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YASUDA Takushi

    Department of Medicine　Professor/Senior Staff
Last Updated :2024/04/19

Researcher Information

Degree

  • (BLANK)（Osaka University）

J-Global ID

Research Interests

  • extended surgery   cancer vaccine   術前治療   食道癌   PET   Neoadjuvan therapy   esophageal carcinoma   

Research Areas

  • Life sciences / Digestive surgery

Academic & Professional Experience

  • 2013/05 - Today  Kinki University Faculty of MedicineDepartment of Surgery, Division of Esophago-Gastric Surgeryprofessor
  • 2007/04 - 2013/04  Kinki University Faculty of MedicineDepartment of Surgery, Division of Esophago-Gastric SurgeryAssociate Professor
  • 2006/07 - 2007/03  Kinki University School of MedicineDepartment of Surgery, Division of Esophago-Gastric SurgeryAssociate Professor
  • 2005/04 - 2006/06  Osaka University Graduate SchoolDepartment of Gastroenterological Surgery助手
  • 2000/01 - 2005/03  Osaka University Graduate School病態制御外科助手
  • 2000 - 2003  Assistant Professor, Dpt. of Surgery and
  • 1999/06 - 1999/12  Osaka Medical Center for Cancer and Cadiovasucular DiseasesDepartment of Surgery医長
  • 1998/04 - 1999/05  Osaka Medical Center for Cancer and Cadiovasucular DiseasesDepartment of Surgery診療主任
  • 1994/04 - 1998/03  Osaka Medical Center for Cancer and Cadiovasucular DiseasesDepartment of Surgery医員
  • 1992/03 - 1994/03  Osaka UniversityHospital医員
  • 1987/07 - 1990/06  Osaka Medical Center for Cancer and Cadiovasucular DiseasesDepartment of Surgeryresident
  • 1986/07 - 1987/06  Osaka UniversityHospital医員（研修医）
  • Osaka University
  • Clinical Oncology Graduate School of Medicine,

Education

  •        - 1986  Osaka University  Faculty of Medicine  Medical School
  •        - 1986  Osaka University  Faculty of Medicine

Association Memberships

  • The Japanese Gastroenterological Association   日本バイオセラピィ学会   日本がん転移学会   食道学会   日本気管食道科学会   日本臨床外科学会   日本消化器内視鏡学会   日本癌学会   日本消化器病学会   日本胸部外科学会   日本癌治療学会   日本消化器外科学会   日本外科学会   米国臨床腫瘍学会（ASCO）   国際食道疾患会議（ISDE）   日本内視鏡外科学会   日本臨床腫瘍学会   日本嚥下学会   日本外科代謝栄養学会   日本外科系連合学会   日本胃癌学会   

Published Papers

  • Keijiro Sugimura; Koji Tanaka; Takahito Sugase; Kota Momose; Takashi Kanemura; Kotaro Yamashita; Tomoki Makino; Osamu Shiraishi; Masaaki Motoori; Makoto Yamasaki; Hiroshi Miyata; Kazumasa Fujitani; Takushi Yasuda; Masahiko Yano; Hidetoshi Eguchi; Yuichiro Doki
    Annals of surgical oncology 2024/02 
    BACKGROUND: The standard treatment for advanced esophageal cancer with synchronous distant metastasis is systemic chemotherapy or immunotherapy. Conversion surgery is not established for esophageal cancer with synchronous distant metastasis. This study aimed to investigate the clinical impact of conversion surgery for esophageal cancer with synchronous distant metastasis after induction therapy. METHODS: This multi-institutional retrospective study enrolled 66 patients with advanced esophageal cancer, including synchronous distant metastasis, who underwent induction chemotherapy or chemoradiotherapy followed by conversion surgery between 2005 and 2021. Short- and long-term outcomes were investigated. RESULTS: Distant lymph node (LN) metastasis occurred in 51 patients (77%). Distant organ metastasis occurred in 15 (23%) patients. There were 41 patients with metastatic para-aortic LNs, and 10 patients with other metastatic LNs. Organs with distant metastasis included the lung in seven patients, liver in seven patients, and liver and lung in one patient. For 61 patients (92%), R0 resection was achieved. The postoperative complication rate was 47%. The in-hospital mortality rate was 1%, and the 3- and 5-year overall survival (OS) rates for all the patients were 32.4% and 24.4%, respectively. The OS rates were similar between the patients with distant LN metastasis and the patients with distant organ metastasis (3-year OS: 34.9% vs. 26.7%; P = 0.435). Multivariate analysis showed that pathologic nodal status is independently associated with a poor prognosis (hazard ratio, 2.43; P = 0.005). CONCLUSIONS: Conversion surgery after chemotherapy or chemoradiotherapy for esophageal cancer with synchronous distant metastasis is feasible and promising. It might be effective for improving the long-term prognosis for patients with controlled nodal status.
  • Masanori Tokunaga; Nozomu Machida; Junki Mizusawa; Seiji Ito; Hiroshi Yabusaki; Motohiro Hirao; Masaya Watanabe; Hiroshi Imamura; Takahiro Kinoshita; Takushi Yasuda; Jun Hihara; Haruhiko Fukuda; Takaki Yoshikawa; Narikazu Boku; Masanori Terashima
    Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2024/01 
    BACKGROUND: This randomized phase II study explored the superiority of trastuzumab plus S-1 plus cisplatin (SP) over SP alone as neoadjuvant chemotherapy (NAC) for HER2-positive resectable gastric cancer with extensive lymph node metastasis. METHODS: Eligible patients with HER2-positive gastric or esophagogastric junction cancer and extensive lymph node metastasis were randomized to receive three or four courses of preoperative chemotherapy with SP (arm A) or SP plus trastuzumab (arm B). Following gastrectomy, adjuvant chemotherapy with S-1 was administered for 1 year in both arms. The primary endpoint was overall survival, and the sample size was 130 patients in total. The trial is registered with the Japan Registry of Clinical Trials, jRCTs031180006. RESULTS: This report elucidates the early endpoints, including pathological findings and safety. The study was terminated early due to slow patient accruals. In total, 46 patients were allocated to arm A (n = 22) and arm B (n = 24). NAC was completed in 20 patients (91%) in arm A and 23 patients (96%) in arm B, with similar incidences of grade 3-4 hematological and non-hematological adverse events. Objective response rates were 50% in arm A and 84% in arm B (p = 0·065). %R0 resection rates were 91% and 92%, and pathological response rates (≥ grade 1b in Japanese classification) were 23% and 50% (p = 0·072) in resected patients, respectively. CONCLUSIONS: Trastuzumab can be safely added to platinum-containing doublet chemotherapy as NAC, and it has the potential to contribute to higher antitumor activity against locally advanced, HER2-positive gastric or esophagogastric junction cancer with extensive nodal metastasis.
  • Atsushi Yasuda; Yutaka Kimura; Hiroaki Kato; Tomoya Nakanishi; Masashi Koda; Yoko Hiraki; Takaomi Hagi; Osamu Shiraishi; Masayuki Shinkai; Motohiro Imano; Takushi Yasuda
    Updates in surgery 2024/01 
    Recent reports have described the practicality of laparoscopic intragastric surgery (l-IGS) as an alternative for resecting submucosal tumors (SMTs) near the esophagogastric junction (EGJ), where excision using an exogastric approach would be difficult. However, even using IGS to perform a full-thickness resection of SMTs that are in or extremely close to the EGJ is very difficult to do safely and avoid disrupting or causing stenosis of the EGJ, without advanced experience. This study retrospectively examined the usefulness of l-IGS for gastric SMTs located in or extremely close to the EGJ. Fourteen patients with gastric SMTs < 2 cm of the EGJ and underwent l-IGS were eligible for this study. We examined the tumor location, operative time, intraoperative hemorrhage, degree of deformation, gastroesophageal reflux disease, perioperative complications, and recurrence. Furthermore, we compared patients with tumors in the EGJ with those with tumors near the EGJ and patients in whom three-port l-IGS was performed with those who underwent single-incision laparoscopic surgery. The average tumor size, operative time, intraoperative hemorrhage, and postoperative hospitalization of the 14 patients were 30.9 ± 21.3 mm, 125.2 ± 31.1 min, 30.7 ± 103.3 mL, and 9.2 ± 3.1 d, respectively. No differences in these parameters according to the type of l-IGS or tumor location were observed. All patients underwent l-IGS without complications and were free from EGJ deformation or esophagitis. We believe that l-IGS is useful for gastric SMTs located < 2 cm of the EGJ as it can be safely performed for difficult tumor locations and does not cause deformation of the EGJ.
  • Hiroki Mizusawa; Osamu Shiraishi; Masashi Shiraishi; Ryuji Sugiya; Tamotsu Kimura; Akira Ishikawa; Takushi Yasuda; Yuji Higashimoto
    Medicine 102 (41) e35547  2023/10 
    The low attenuation area percentage (LAA%) is gaining popularity. LAA% is an index of quantitative emphysema on computed tomography (CT) imaging of the chest. This study aims to retrospectively investigate whether preoperative LAA% is associated with postoperative prognosis in patients with esophageal cancer who were scheduled for esophagectomy. From January 2016 to March 2020, 105 patients with esophageal cancer underwent esophagectomy via right thoracotomy and neoadjuvant chemotherapy. A Synapse Vincent volume analyzer (Fujifilm Medical, Tokyo, Japan) was used for measurement. The software automatically quantified LAA% using a threshold of less than - 950 Hounsfield units on CT images of lung regions. Cox proportional hazard analyses were performed in univariable and multivariable forms. Estimates of the receiver operating curve are used to determine the cutoff value for death of LAA%, and the binary value is then inserted into Cox proportional hazard analyses. The preoperative LAA% cutoff value was ≥ 6.3%. Patients with a preoperative LAA% ≥6.3% had a significantly worse prognosis than those with a preoperative LAA% of < 6.3%. LAA% ≥6.3% (hazard ratio: 6.76; 95% confidence interval: 2.56-17.90, P < .001) was the most influential preoperative factor for overall survival after esophagectomy in multivariate Cox proportional hazard analyses. LAA% is one of the preoperative risk factors for survival after esophagectomy and an indicator of lung condition using routinely performed preoperative CT images. We quantified the extent of preoperative emphysema in patients with esophageal cancer, who were scheduled for surgery, and for the first time, reported LAA% as one of the preoperative risk factors for survival after esophagectomy.
  • Masayuki Shinkai; Motohiro Imano; Masashi Kohda; Tomoya Nakanishi; Yoko Hiraki; Takaomi Hagi; Hiroaki Kato; Osamu Shiraishi; Atsushi Yasuda; Masanobu Tsubaki; Shozo Nishida; Takushi Yasuda
    Langenbeck's archives of surgery 408 (1) 291 - 291 2023/07 
    PURPOSE: Gastric cancer patients with peritoneal metastasis (PM) are generally treated with systemic chemotherapy. When PM has disappeared because of chemotherapy, radical gastrectomy (so-called conversion surgery) is usually performed. We have previously reported the efficacy of conversion surgery, but there are no reports examining the efficacy of palliative gastrectomy for patients with residual PM after chemotherapy. The purpose of this study was to investigate the efficacy of palliative surgery for gastric cancer patients with PM who still have residual peritoneal dissemination after chemotherapy. METHODS: Twenty-five gastric cancer patients with PM confirmed by laparoscopy and who had received chemotherapy but who still had residual PM were included in this study. Among the 25 patients, palliative surgery was performed in 20 patients (PS group) and chemotherapy was continued in 5 patients (CTx group), and their therapeutic outcomes were compared. RESULTS: In the PS group, total and distal gastrectomies were performed. Clavien-Dindo grade I postoperative complications occurred in two patients (10%). There were no treatment-related deaths. Postoperative chemotherapy was performed all cases. In the PS group, the median survival time (MST) reached 22.5 months, with 1- and 2-year overall survival (OS) rates of 95% and 45%, respectively, whereas in the CTx group, the MST was 15.8 months, and the 1- and 2-year OS rates were 60% and 0%, respectively. The PS group had significantly longer OS than the CTx group (P=0.044). CONCLUSIONS: Palliative surgery is safe and may prolong survival in gastric cancer patients with residual PM after chemotherapy.
  • Kenji Minatoya; Yukio Sato; Yasushi Toh; Tomonobu Abe; Shunsuke Endo; Yasutaka Hirata; Michiko Ishida; Hisashi Iwata; Takashi Kamei; Nobuyoshi Kawaharada; Shunsuke Kawamoto; Kohji Kohno; Hiraku Kumamaru; Goro Matsumiya; Noboru Motomura; Rie Nakahara; Morihito Okada; Hisashi Saji; Aya Saito; Hideyuki Shimizu; Kenji Suzuki; Hirofumi Takemura; Tsuyoshi Taketani; Hiroya Takeuchi; Wataru Tatsuishi; Hiroyuki Yamamoto; Takushi Yasuda; Masayuki Watanabe; Naoki Yoshimura; Masanori Tsuchida; Yoshiki Sawa
    General thoracic and cardiovascular surgery 71 (10) 595 - 628 2023/07
  • Yuto Kubo; Tomoki Makino; Makoto Yamasaki; Koji Tanaka; Kotaro Yamashita; Osamu Shiraishi; Keijiro Sugimura; Hiroshi Miyata; Masaaki Motoori; Kazumasa Fujitani; Atsushi Takeno; Motohiro Hirao; Yutaka Kimura; Taroh Satoh; Masahiko Yano; Hidetoshi Eguchi; Takushi Yasuda; Yuichiro Doki
    Annals of surgical oncology 30 (9) 5899 - 5907 2023/06 
    BACKGROUND: Three-course neoadjuvant chemotherapy (NAC) followed by surgery has become a standard of care for locally advanced esophageal cancer (EC). However, some patients occasionally experience a poor tumor response to the third course and have a poor clinical outcome. METHODS: An exploratory analysis of data from the authors' recent multicenter randomized phase 2 trial compared patients with locally advanced EC who received two courses (n = 78) and those who received three courses (n = 68) of NAC. The association between tumor response and clinico-pathologic factors, including survival, was evaluated to identify risk factors in the three-course group. RESULTS: Of 68 patients who received three courses of NAC, 28 (41.2%) had a tumor reduction rate lower than 10% during the third course. This rate was associated with unfavorable overall survival (OS) and progression-free survival (PFS) compared with a tumor reduction rate of 10% or higher (2-year OS rate: 63.5% vs. 89.3%, P = 0.007; 2-year PFS rate: 52.6% vs. 79.7%, P = 0.020). The independent prognostic factors for OS were tumor reduction rate lower than 10% during the third course (hazard ratio [HR], 2.735; 95% confidence interval [CI] 1.041-7.188; P = 0.041) and age of 65 years or older (HR, 9.557, 95% CI 1.240-73.63; P = 0.030). Receiver operating characteristic curve and multivariable logistic regression analyses identified a tumor reduction rate lower than 50% after the first two courses as an independent predictor of a tumor reduction rate lower than 10% during the third course of NAC (HR, 4.315; 95% CI 1.329-14.02; P = 0.015). CONCLUSION: Continuing NAC through a third course may worsen survival for patients who do not experience a response to the first two courses in locally advanced EC.
  • Yuto Kubo; Tomoki Makino; Makoto Yamasaki; Koji Tanaka; Kotaro Yamashita; Osamu Shiraishi; Keijiro Sugimura; Hiroshi Miyata; Masaaki Motoori; Kazumasa Fujitani; Atsushi Takeno; Motohiro Hirao; Yutaka Kimura; Taroh Satoh; Masahiko Yano; Hidetoshi Eguchi; Takushi Yasuda; Yuichiro Doki
    Annals of surgical oncology 30 (9) 5910 - 5911 2023/06
  • 食道摘出再建術後に横隔機能障害を呈した一症例 超音波画像診断装置を用いた横隔膜機能評価
    水澤 裕貴; 白石 匡; 杉谷 竜司; 野口 雅矢; 神吉 健吾; 白石 治; 安田 卓司; 木村 保; 東本 有司
    大阪府理学療法学術大会学会誌 (公社)大阪府理学療法士会 35 116 - 116 1880-7631 2023/06
  • Takuya Sugimoto; Satomi Atobe; Yukiko Kado; Akira Takahashi; Masaaki Motoori; Keijiro Sugimura; Hiroshi Miyata; Masahiko Yano; Koji Tanaka; Yuichiro Doki; Osamu Shiraishi; Takushi Yasuda; Takashi Asahara
    Journal of medical microbiology 72 (6) 2023/06 
    Introduction. Our synbiotics (Lacticaseibacillus paracasei strain Shirota, Bifidobacterium breve strain Yakult, and galacto-oligosaccharides: LBG) helps mitigate serious adverse events such as febrile neutropenia (FN) and diarrhoea in oesophageal cancer patients receiving neoadjuvant chemotherapy (NAC). Unfortunately, LBG therapy does not benefit all patients.Hypothesis/Gap Statement. Identification of the gut microbiota species involved in adverse events during chemotherapy could help predict the onset of adverse events. Identification of the gut microbiota that influence the efficacy of LBG could also help establish a diagnostic method to identify patients who will respond to LBG before the initiation of therapy.Aim. To identify the gut microbiota involved in adverse events during NAC and that affect the efficacy of LBG therapy.Methodology. This study was ancillary to a parent randomized controlled trial in which 81 oesophageal cancer patients were recruited and administered either prophylactic antibiotics or LBG combined with enteral nutrition (LBG+EN). The study included 73 of 81 patients from whom faecal samples were collected both before and after NAC. The gut microbiota was analysed using 16S rRNA gene amplicon sequencing and compared based on the degree of NAC-associated adverse events. Furthermore, the association between the counts of identified bacteria and adverse events and the mitigation effect of LBG+EN was also analysed.Results. The abundance of Anaerostipes hadrus and Bifidobacterium pseudocatenulatum in patients with no FN or only mild diarrhoea was significantly higher (P<0.05) compared to those with FN or severe diarrhoea. Moreover, subgroup analyses of patients receiving LBG+EN showed that the faecal A. hadrus count before NAC was significantly associated with a risk of developing FN (OR, 0.11; 95 % CI, 0.01-0.60, P=0.019). The faecal A. hadrus count after NAC was positively correlated with intestinal concentrations of acetic acid (P=0.0007) and butyric acid (P=0.00005).Conclusion. Anaerostipes hadrus and B. pseudocatenulatum may be involved in the ameliorating adverse events and can thus be used to identify beforehand patients that would benefit from LBG+EN during NAC. These results also suggest that LBG+EN would be useful in the development of measures to prevent adverse events during NAC.
  • Atsushi Yasuda; Yutaka Kimura; Osamu Shiraishi; Masayuki Shinkai; Motohiro Imano; Takushi Yasuda
    International journal of surgery case reports 106 108156 - 108156 2023/05 
    INTRODUCTION AND IMPORTANCE: Laparoscopic wedge resection has been widely performed for gastric gastrointestinal stromal tumors (GISTs). However, because GISTs in the esophagogastric junction (EGJ) are prone to deformity and postoperative functional disorders, laparoscopic resection is technically very difficult and rarely reported. Herein, we report a case of a GIST in the EGJ successfully treated by laparoscopic intragastric surgery (IGS). CASE PRESENTATION: A 58-year-old man with a GIST, which was intragastric growth type, 2.5 cm in diameter, located in the EGJ, and confirmed by upper gastrointestinal endoscope and endoscopic ultrasound-guided fine needle aspiration biopsy. We successfully performed IGS and the patient was discharged without complications. CLINICAL DISCUSSION: Using laparoscopic wedge resection by exogastric approach, it is problematic to resect a gastric SMT located at the EGJ because of the difficulty in viewing the surgical field and additional concerns of deformation of the EGJ. We suppose IGS as a suitable method for such tumors. CONCLUSION: Laparoscopic IGS for gastric GIST was useful in terms of safety and convenience even though the tumor was in the ECJ.
  • 食道癌集学的治療における手術の位置づけ 食道癌における根治化学放射線治療後の再発症例に対するサルベージ手術の治療成績の検討 多施設後方視研究
    菅生 貴仁; 金村 剛志; 武岡 奉均; 山本 昌明; 新野 直樹; 原 尚志; 大森 健; 藤井 善章; 向井 洋介; 三賀森 学; 長谷川 慎一郎; 原口 直紹; 秋田 裕史; 西村 潤一; 和田 浩志; 松田 宙; 安井 昌義; 安田 卓司; 土岐 祐一郎; 宮田 博志
    日本外科学会定期学術集会抄録集 (一社)日本外科学会 123回 SY - 4 2023/04 [Refereed]
  • Shu Aoyama; Masaaki Motoori; Makoto Yamasaki; Osamu Shiraishi; Hiroshi Miyata; Motohiro Hirao; Atsushi Takeno; Keijiro Sugimura; Tomoki Makino; Koji Tanaka; Takuya Hamakawa; Kotaro Yamashita; Yutaka Kimura; Kazumasa Fujitani; Takushi Yasuda; Masahiko Yano; Yuichiro Doki
    Esophagus : official journal of the Japan Esophageal Society 20 (2) 225 - 233 2023/04 
    BACKGROUND: Neoadjuvant therapy followed by surgery is the standard treatment for locally advanced esophageal cancers. During neoadjuvant therapy, tumor-induced esophageal stenosis or adverse events often cause weight loss. However, little is known about the effects of weight loss during neoadjuvant therapy on postoperative complications or prognosis. We investigated the association between weight loss during neoadjuvant chemotherapy, postoperative infectious complications, and prognosis. METHODS: Data from OGSG1003, a randomized phase-II trial comparing two regimens of neoadjuvant chemotherapy, cisplatin and fluorouracil plus Adriamycin and cisplatin and fluorouracil plus docetaxel, for locally advanced esophageal squamous cell carcinoma were used. Body weight was measured before neoadjuvant chemotherapy and esophagectomy. Multivariate analysis for infectious complications and prognosis was performed. RESULTS: The study included 134 patients. The median weight loss during neoadjuvant chemotherapy was 2.83% (-2.07% to 6.29%). Postoperative infectious complications were observed in 37 patients who had a significantly higher weight loss during neoadjuvant chemotherapy (5.18% vs. 1.90%, P = 0.002). Multivariate analysis revealed that > 5% of weight loss during neoadjuvant chemotherapy was the only independent factor associated with postoperative infectious complications (odds ratio 2.69, 95% confidence interval 1.12-6.46, P = 0.027). Weight loss during neoadjuvant chemotherapy was significantly associated with worse recurrence-free survival in the univariate analysis (log-rank test, P = 0.002), but this association was marginal in the multivariate analysis (hazard ratio 1.73, 95% confidence interval 0.98-3.08, P = 0.058). CONCLUSIONS: Severe weight loss during neoadjuvant chemotherapy was an independent risk factor for postoperative infectious complications. Weight maintenance during neoadjuvant chemotherapy may reduce the incidence of postoperative infectious complications.
  • Seiichiro Mitani; Hisato Kawakami; Osamu Shiraishi; Hiroaki Kanemura; Shinichiro Suzuki; Koji Haratani; Hidetoshi Hayashi; Kimio Yonesaka; Yasutaka Chiba; Takushi Yasuda; Kazuhiko Nakagawa
    Esophagus : official journal of the Japan Esophageal Society 20 (2) 290 - 290 2023/01
  • Osamu Shiraishi; Hiroaki Kato; Kota Momose; Yoko Hiraki; Atsushi Yasuda; Masayuki Shinkai; Motohiro Imano; Takushi Yasuda
    Oncology 101 (3) 203 - 212 2023 
    INTRODUCTION: This study aimed to clarify the impact of the average relative dose intensity (RDI) of neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-NAC) for resectable locally advanced esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: To identify the optimal RDI, recurrence-free survival (RFS) and cumulative incidence function (CIF) for recurrence were calculated in low and high RDI groups with any cut-off points. The optimal RDI was defined as the highest RDI administered with a significant increase in either RFS or CIF. The clinicopathological characteristics of the two groups divided by optimal RDI were investigated. The preoperative prognostic factors associated with RFS were confirmed by multivariable Cox proportional hazards model. RESULTS: Among the 150 eligible patients treated with DCF-NAC from 2010 to 2020, 3-year RFS and CIF were 56.3% and 37.8% in 90 patients in the less than 80% RDI group (<80% RDI) and 73.3% and 26.7% in 60 patients in the more than or equal to 80% RDI group (≥80% RDI), respectively. The optimal cut-off RDI was identified as 80%. The <80% RDI group included older individuals, a lower value of creatinine clearance, a higher Charlson Comorbidity Index, reduced RDI at first course, and grade 1-0 in the histopathological tumor response than the ≥80% RDI group. R0 resection and postoperative complication rates were equal in both groups. Cox proportional hazards model identified the response rate and RDI as predictors of RFS. CONCLUSION: An average RDI of more than or equal to 80% improved prognosis in patients receiving DCF-NAC for ESCC.
  • Seiichiro Mitani; Hisato Kawakami; Osamu Shiraishi; Hiroaki Kanemura; Shinichiro Suzuki; Koji Haratani; Hidetoshi Hayashi; Kimio Yonesaka; Yasutaka Chiba; Takushi Yasuda; Kazuhiko Nakagawa
    Esophagus : official journal of the Japan Esophageal Society 20 (2) 281 - 289 2022/12 
    BACKGROUND: Neoadjuvant docetaxel plus cisplatin and 5-FU (NAC-DCF) and adjuvant nivolumab monotherapy are the standard care for locally advanced resectable esophageal squamous cell carcinoma (ESCC). However, no effective biomarkers have been found in perioperative setting. We investigated how programmed death-ligand 1 (PD-L1) changes before and after NAC-DCF and how it relates to the therapeutic effect of NAC-DCF in resectable ESCC. METHODS: PD-L1 expression in paired diagnostic biopsy and surgically resected tissues from ESCC patients who underwent surgical resection after receiving two or three NAC-DCF cycles was evaluated. PD-L1 positivity was defined as a combined positive score (CPS) of 10% ≤ . Gene expression analysis was conducted using samples before NAC-DCF. RESULTS: Sixty-six paired samples from 33 patients were included in PD-L1 expression analysis, and 33 Pre-NAC samples acquired by diagnostic biopsy were included in gene expression analysis. Pretreatment, 3 (9%), 13 (39%), and 17 (52%) patients harbored tumors with CPS ranges of < 1%, 1%-10%, and 10% ≤ , respectively. After NAC-DCF, 5 (15%), 15 (45%), and 13 (39%) tumors presented CPS ranges of < 1%, 1%-10%, and 10% ≤ , respectively. The concordance rate between Pre-and Post-NAC-DCF samples was 45%. Patients with PD-L1-negative tumors both before and after NAC-DCF (n = 9) had shorter survival and different gene expression profile characterized by upregulation in WNT signaling or neutrophils. CONCLUSIONS: A substantial PD-L1 expression alteration was observed, resulting in low concordance rate before and after NAC-DCF. Tumors persistently lacking PD-L1 had distinct gene expression profile with worse clinical outcomes, raising the need for further investigation.
  • ガーゼ装着シリコンディスクを用いたズレない腹腔鏡下胃切除時の肝圧排の工夫
    加藤 寛章; 安田 篤; 平木 洋子; 中西 智也; 百瀬 洸太; 白石 治; 新海 政幸; 安田 卓司
    日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 27 (7) 2338 - 2338 1344-6703 2022/12
  • Hikari Teranishi; Atsushi Yasuda; Motohiro Imano; Yoko Hiraki; Kota Momose; Hiroaki Kato; Osamu Shiraishi; Masayuki Shinkai; Yutaka Kimura; Takushi Yasuda
    Gan to kagaku ryoho. Cancer & chemotherapy 49 (13) 1512 - 1514 0385-0684 2022/12 
    Intraperitoneal chemotherapy, in which an anticancer drug is administered directly into the abdominal cavity through an intraperitoneal access port(IP port), is one of the treatment options for advanced gastric cancer with peritoneal metastasis. Herein, we report a case of sheath-like obstruction of the entire catheter of the IP port due to tissue reaction within a short period of time after IP port implantation. The case was a 35-year-old woman with advanced type 4 gastric cancer with peritoneal dissemination. The IP port was placed and intravenous and intraperitoneal chemotherapy using S-1 plus paclitaxel was started. However, in the middle of the second course, the entire catheter was covered with a fibrous capsule and a sheath-like obstruction occurred, so the IP port was removed and a new IP port was reinserted. One of the IP port troubles is obstruction, but such short-term and special obstruction is rare, and the cause is considered to be a foreign body reaction of the catheter.
  • Tetsuro Toriumi; Masanori Terashima; Junki Mizusawa; Yuya Sato; Yukinori Kurokawa; Shuji Takiguchi; Yuichiro Doki; Hisashi Shinohara; Shin Teshima; Takushi Yasuda; Seiji Ito; Takaki Yoshikawa; Takeshi Sano; Mitsuru Sasako
    European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 49 (4) 838 - 844 2022/11 
    BACKGROUND: Peritoneal, lymph node, and hematogenous recurrence patterns are common after potentially curative surgery for gastric cancer. However, clinicopathological characteristics associated with each recurrence type have rarely been comprehensively reported among patients who received a unified treatment strategy and follow-up protocol. Understanding these recurrence patterns would help with early detection of recurrence and a personalized follow-up plan. We investigated the initial recurrence patterns after curative gastrectomy using data from the randomized clinical JCOG1001 trial. METHODS: Of 1204 patients enrolled in JCOG1001, 932 pStage II/III patients were included. Initial recurrence dates and patterns were recorded by attending physicians according to the protocol. Risk factors for hematogenous, lymph node, and peritoneal recurrence were determined by univariable and multivariable analyses using the Fine-Gray model. RESULTS: Overall, 253 patients developed recurrence. Hematogenous recurrence was the most frequent pattern (n = 115), followed by peritoneal (n = 104) and lymph node recurrence (n = 70). Differentiated type (p = 0.0028), pT4 (p = 0.0466), and pN3 (p < 0.0001) were associated with hematogenous recurrence; however, D2+ lymphadenectomy reduced it (p = 0.0161). Patients with large (≥5 cm) tumors (p = 0.0312), pT4 (p < 0.0001), pN3 (p = 0.0013), and undifferentiated histologic type (p = 0.0001) had significantly higher rates of peritoneal recurrence. Extended lymph node metastasis (pN3) was the only risk factor (p < 0.0001) for lymph node recurrence. CONCLUSIONS: Clinicopathological features differed according to the recurrence patterns. Vigilant follow-up with an understanding of recurrence patterns might be beneficial for some high-risk patients.
  • Hayato Kaida; Takushi Yasuda; Osamu Shiraishi; Hiroaki Kato; Yutaka Kimura; Kohei Hanaoka; Minoru Yamada; Yuko Matsukubo; Masakatsu Tsurusaki; Kazuhiro Kitajima; Satoshi Hattori; Kazunari Ishii
    BMC cancer 22 (1) 1176 - 1176 2022/11 
    BACKGROUND: Induction or adjuvant therapies are not always beneficial for thoracic esophageal squamous cell carcinoma (ESCC) patients, and it is thus important to identify patients at high risk for postoperative ESCC recurrence. We investigated the usefulness of the total metabolic tumor volume (TMTV) for predicting the postoperative recurrence of thoracic ESCC. METHODS: We retrospectively analyzed the cases of 163 thoracic ESCC patients (135 men, 28 women; median age of 66 [range 34-82] years) treated at our hospital in 2007-2012. The TMTV was calculated from the fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in the primary lesion and lymph node metastases. The optimal cut-off values for relapse and non-relapse were obtained by the time-dependent receiver operating curve analyses. Relapse-free survival (RFS) was evaluated by the Kaplan-Meier method, and between-subgroup differences in survival were analyzed by log-rank test. The prognostic significance of metabolic parameters and clinicopathological variables was assessed by a Cox proportional hazard regression analysis. The difference in the failure patterns after surgical resection was evaluated using the χ2-test. RESULTS: The optimal cut-off value of TMTV for discriminating relapse from non-relapse was 3.82. The patients with a TMTV ≥3.82 showed significantly worse prognoses than those with low values (p < 0.001). The TMTV was significantly related to RFS (model 1 for preoperative risk factors: TMTV: hazard ratio [HR] =2.574, p = 0.004; model 2 for preoperative and postoperative risk factors: HR = 1.989, p = 0.044). The combination of the TMTV and cN0-1 or pN0-1 stage significantly stratified the patients into low-and high-risk recurrence groups (TMTV cN0-1, p < 0.001; TMTV pN0-1, p = 0.004). The rates of hematogenous and regional lymph node metastasis were significantly higher in the patients with TMTV ≥3.82 than those with low values (hematogenous metastasis, p < 0.001, regional lymph node metastasis, p = 0.011). CONCLUSIONS: The TMTV was a more significantly independent prognostic factor for RFS than any other PET parameter in patients with resectable thoracic ESCC. The TMTV may be useful for the identifying thoracic ESCC patients at high risk for postoperative recurrence and for deciding the patient management.
  • Kazuchika Ohno; Motomi Nasu; Hidetoshi Matsui; Yoshifumi Baba; Takushi Yasuda; Jun Sakuma; Kenichiro Ikeda; Takashi Maruo; Takumi Okuda; Norihiko Narita; Hisayuki Kato; Taiji Kawasaki; Hiroshi Sato; Kunihiko Tokashiki; Naoki Akisada; Hajime Ishinaga; Ken Akashi; Kenji Okami; Kosuke Murayama; Soichiro Yamamoto; Yuji Kumakura; Kenro Kawada; Akihiro Shiotani; Takahiro Asakage
    Esophagus : official journal of the Japan Esophageal Society 19 (4) 576 - 585 2022/10 
    BACKGROUND: Cervical esophageal cancer (CEC) carries a poor prognosis; however, due to its low incidence, optimal treatment for CEC remains to be established. The purpose of this study was to clarify the current status of treatment of CEC in Japan and obtain evidence for establishing the appropriate treatment method. PATIENTS AND METHODS: We asked specialist training facilities accredited by the Japanese Broncho-Esophageal Society to register data on CEC cases that received curative treatment from January 2009 to December 2014, and conducted a retrospective review of the clinical data of 302 cases registered from 27 facilities. RESULTS: In regard to the initial therapy, of the 302 patients, 33 had undergone endoscopic resection, 41 had undergone surgery, 67 had received induction chemotherapy (IC), and 143 had received chemoradiotherapy (CRT). There were no significant differences in the 5-year overall survival rates among the patient groups that had received surgery, IC or CRT as the initial treatment; advanced stage and recurrent nerve invasion were identified as independent poor prognostic factors. Among the patients who had received IC or CRT as laryngeal-preserving surgery was not indicated at the time of the initial diagnosis, the functional laryngeal preservation rate at the end of the observation period was 34.8%. CONCLUSION: Even in patients with advanced CEC, there is the possibility of preserving the larynx by adopting IC or CRT. However, if the laryngeal function cannot be preserved, there is a risk of complications from aspiration pneumonia, so that the choice of treatment should be made carefully.
  • マルチオミクス機械学習による食道癌の化学療法効果予測因子(Multi-omic machine learning predictor of chemotherapy response of esophageal cancer)
    笹川 翔太; 加藤 寛章; 長岡 孝治; トッド・ジョンソン; 前嶋 和紘; 大川 裕貴; 垣見 和宏; 安田 卓司; 中川 英刀
    日本癌学会総会記事 (一社)日本癌学会 81回 J - 2055 0546-0476 2022/09
  • Hiroshi Miyata; Keijiro Sugimura; Takashi Kanemura; Tomohira Takeoka; Takahito Sugase; Koji Tanaka; Tomoki Makino; Kotaro Yamashita; Makoto Yamasaki; Masaaki Motoori; Osamu Shiraishi; Yutaka Kimura; Takushi Yasuda; Masahiko Yano; Yuichiro Doki
    Annals of surgical oncology 29 (9) 5657 - 5665 2022/09 
    BACKGROUND: Outcomes of salvage surgery after failed definitive chemoradiation (CRT) for esophageal cancer have been well defined. However, only a few studies have focused on salvage esophagectomy for recurrent disease after CRT. METHODS: In 227 patients with esophageal cancer who underwent salvage esophagectomy after definitive CRT, consisting of 116 patients who underwent esophagectomy for persistent disease (the persistent group) and 111 patients who underwent esophagectomy for recurrent disease (the recurrent group), the short- and long-term outcomes were investigated. RESULTS: The rates of any postoperative complication were similar between the groups (49.1% in the persistent group vs. 49.5% in the recurrent group, p = 0.951), although there was a higher rate of anastomotic leakage in the recurrent group (p = 0.027). Thirty-day mortality was also similar between the groups (1.7% in the persistent group vs. 0.9% in the recurrent group, p = 0.587). The 3-year and 5-year overall survival rates were 33.7% and 28.0% in the persistent group and 48.7% and 41.7% in the recurrent group, respectively (p = 0.0175). In the recurrent group, clinically nodal status before CRT as well as pathologically nodal status and time to relapse were identified as independent prognostic factors. In the persistent group, pT and resection margin were identified as independent factors associated with survival. CONCLUSIONS: The present study showed that salvage surgery for recurrent disease can provide acceptable short- and long-term outcomes. Considering clinically and pathologically nodal status and time to relapse, adjuvant therapy might be offered for patients who underwent salvage esophagectomy for recurrent disease after definitive CRT.
  • Shota Sasagawa; Hiroaki Kato; Koji Nagaoka; Changbo Sun; Motohiro Imano; Takao Sato; Todd A Johnson; Masashi Fujita; Kazuhiro Maejima; Yuki Okawa; Kazuhiro Kakimi; Takushi Yasuda; Hidewaki Nakagawa
    Cell reports. Medicine 3 (8) 100705 - 100705 2022/08 
    Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers and is primarily treated with platinum-based neoadjuvant chemotherapy (NAC). Some ESCCs respond well to NAC. However, biomarkers to predict NAC sensitivity and their response mechanism in ESCC remain unclear. We perform whole-genome sequencing and RNA sequencing analysis of 141 ESCC biopsy specimens before NAC treatment to generate a machine-learning-based diagnostic model to predict NAC reactivity in ESCC and analyzed the association between immunogenomic features and NAC response. Neutrophil infiltration may play an important role in ESCC response to NAC. We also demonstrate that specific copy-number alterations and copy-number signatures in the ESCC genome are significantly associated with NAC response. The interactions between the tumor genome and immune features of ESCC are likely to be a good indicator of therapeutic capability and a therapeutic target for ESCC, and machine learning prediction for NAC response is useful.
  • Hiroaki Kanemura; Hidetoshi Hayashi; Shuta Tomida; Junko Tanizaki; Shinichiro Suzuki; Yusuke Kawanaka; Asuka Tsuya; Yasushi Fukuda; Hiroyasu Kaneda; Keita Kudo; Takayuki Takahama; Ryosuke Imai; Koji Haratani; Yasutaka Chiba; Tomoyuki Otani; Akihiko Ito; Kazuko Sakai; Kazuto Nishio; Kazuhiko Nakagawa
    JTO clinical and research reports 3 (8) 100373 - 100373 2022/08 
    Introduction: Despite a considerable benefit of adding immune checkpoint inhibitors (ICIs) to platinum-based chemotherapy for patients with extensive-stage SCLC (ES-SCLC), a durable response to ICIs occurs in only a small minority of such patients. Methods: A total of 135 patients with ES-SCLC treated with chemotherapy either alone (chemo-cohort, n = 71) or together with an ICI (ICI combo-cohort, n = 64) was included in this retrospective study. Tumors were classified pathologically as inflamed or noninflamed on the basis of programmed death-ligand 1 expression and CD8+ tumor-infiltrating lymphocyte density. Immune-related gene expression profiling was performed, and predicted neoantigen load was determined by whole-exome sequencing. Results: Among patients in the ICI combo-cohort, median progression-free survival was 10.8 and 5.1 months for those with inflamed (n = 7) or noninflamed (n = 56) tumors, respectively (log-rank test p = 0.002; hazard ratio of 0.26). Among the 89 patients with immune-related gene expression profiling data available, inflamed tumors had a higher T cell-inflamed GEP score than did noninflamed tumors (-0.18 versus -0.58, p < 0.001). The 12-month progression-free survival rate was 16.1% and 0% for patients in the ICI combo-cohort harboring tumors with a high (n = 26) or low (n = 18) frameshift neoantigen load, respectively. A high-frameshift neoantigen load was associated with up-regulation of gene signatures related to antigen presentation and costimulatory signaling. A durable clinical benefit of ICI therapy was observed only in patients with inflamed tumors and a high-frameshift neoantigen load. Conclusions: Expression of programmed death-ligand 1, CD8+ T cell infiltration, and a high-frameshift neoantigen load are associated with clinical benefit of ICI therapy in ES-SCLC. Clinical trial registration: UMIN000041056.
  • Ayana Okamoto; Ken Kamata; Takeshi Miyata; Tomoe Yoshikawa; Rei Ishikawa; Tomohiro Yamazaki; Atsushi Nakai; Shunsuke Omoto; Kosuke Minaga; Kentaro Yamao; Mamoru Takenaka; Yasutaka Chiba; Toshiharu Sakurai; Naoshi Nishida; Masayuki Kitano; Masatoshi Kudo
    CLINICAL ENDOSCOPY KOREAN SOC GASTROINTESTINAL ENDOSCOPY 55 (4) 558 - 563 2234-2400 2022/07 
    Background/Aims: Bispectral index (BIS) monitors process and display electroencephalographic data and are used to assess the depth of anesthesia. This study retrospectively evaluated the usefulness of BIS monitoring during endoscopic ultrasonography (EUS).Methods: This study included 725 consecutive patients who underwent EUS under sedation with propofol. BIS monitoring was used in 364 patients and was not used in 361. The following parameters were evaluated: (1) median dose of propofol; (2) respiratory and circulatory depression; (3) occurrence of body movements; (4) awakening score 8 at the time; and (5) awakening score 2 hours after leaving the endoscopy room.Results: The BIS group received a significantly lower median dose of propofol than the non-BIS group (159.2 mg vs. 167.5 mg; p=0.015) in all age groups. For patients aged >= 75 years, the reduction in heart rate was significantly lower in the BIS group than in the non-BIS group (1.2% vs. 9.1%; p=0.023). Moreover, the occurrence of body movements was markedly lower in the BIS group than in the non-BIS group (8.5% vs. 39.4%; p<0.001).Conclusions: During EUS examination, BIS monitoring is useful for maintaining a constant depth of anesthesia, especially in patients 75 years of age or older.
  • Atsushi Nakai; Ken Kamata; Tomoko Hyodo; Takaaki Chikugo; Akane Hara; Yasuo Otsuka; Hidekazu Tanaka; Tomoe Yoshikawa; Rei Ishikawa; Ayana Okamoto; Tomohiro Yamazaki; Shunsuke Omoto; Kosuke Minaga; Kentaro Yamao; Mamoru Takenaka; Yasutaka Chiba; Tomohiro Watanabe; Ippei Matsumoto; Yoshifumi Takeyama; Masatoshi Kudo
    Endoscopic Ultrasound Medknow 11 (5) 401 - 406 2303-9027 2022/07 [Refereed]
     
    BACKGROUND: The value of contrast-enhanced harmonic EUS (CH-EUS) for diagnosis of portal vein invasion in patients with pancreatic cancer was evaluated. PATIENTS AND METHODS: This single-center, retrospective study included consecutive patients with pancreatic cancer who underwent both surgical resection after preoperative EUS, CH-EUS, and contrast-enhanced computed tomography (CE-CT) examinations between April 2015 and August 2017. CH-EUS evaluation was performed during the late phase. Portal vein invasion on EUS and CH-EUS was defined as no continuity in the line of the vessel wall. Definition of portal vein invasion on CE-CT was based on the Loyer's criteria. The accuracy of three modalities for diagnosis of invasion into the portal vein was compared using the McNemar's test. RESULTS: Eighty-eight patients (mean age: 71.0 years, ratio of male to female: 48:40) were eligible. Postoperative pathological results were as follows: seven cases of portal vein invasion; 81 cases without. Diagnostic accuracy of EUS, CH-EUS, and CE-CT for diagnosing invasion into the portal vein was 72.7%, 93.2%, and 81.8%, respectively. The differences between CH-EUS and CE-CT (P = 0.0094) and CH-EUS and EUS (P = 0.0022) were significant. EUS and CE-CT were comparable. CONCLUSION: CH-EUS is useful for diagnosis of portal vein invasion by pancreatic cancer.
  • 食道摘出再建術を実施した食道癌患者における術後Performance Statusと術後生存率との関連について
    水澤 裕貴; 東本 有司; 白石 匡; 杉谷 竜司; 野口 雅矢; 白石 治; 安田 卓司; 木村 保
    大阪府理学療法学術大会学会誌 (公社)大阪府理学療法士会 34 50 - 50 1880-7631 2022/06
  • 食道摘出再建術を実施した食道癌患者における術後Performance Statusと術後生存率との関連について
    水澤 裕貴; 東本 有司; 白石 匡; 杉谷 竜司; 野口 雅矢; 白石 治; 安田 卓司; 木村 保
    大阪府理学療法学術大会学会誌 (公社)大阪府理学療法士会 34 50 - 50 1880-7631 2022/06
  • Yasuo Otsuka; Ken Kamata; Tomoko Hyodo; Takaaki Chikugo; Akane Hara; Hidekazu Tanaka; Tomoe Yoshikawa; Rei Ishikawa; Ayana Okamoto; Tomohiro Yamazaki; Atsushi Nakai; Shunsuke Omoto; Kosuke Minaga; Kentaro Yamao; Mamoru Takenaka; Yasutaka Chiba; Tomohiro Watanabe; Takuya Nakai; Ippei Matsumoto; Yoshifumi Takeyama; Masatoshi Kudo
    Surgical Endoscopy Springer Science and Business Media LLC 36 (5) 3254 - 3260 0930-2794 2022/05 [Refereed]
     
    BACKGROUND: The value of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for T-staging in patients with extrahepatic bile duct cancer was evaluated. METHODS: This single-center, retrospective study included consecutive patients with extrahepatic bile duct cancer who underwent surgical resection after preoperative EUS, CH-EUS, and contrast-enhanced CT (CE-CT) examinations between June 2014 and August 2017. The capacity of these modalities for T-staging of extrahepatic bile duct cancer was evaluated by assessing invasion beyond the biliary wall into the surrounding tissue, gallbladder, liver, pancreas, duodenum, portal vein system (portal vein and/or superior mesenteric vein), inferior vena cava, and hepatic arteries (proper hepatic artery, right. and/or left. hepatic artery). Blind reading of EUS, CH-EUS, and CE-CT images was performed by two expert reviewers each. RESULTS: 38 patients were eligible for analysis, of which eight had perihilar bile duct cancer and 30 had distal bile duct cancer. Postoperative T-staging was T1 in 6, T2 in 16, and T3 in 16 cases. CH-EUS was superior to CE-CT for diagnosing invasion beyond the biliary wall into surrounding tissue (92.1% vs. 45.9%, P = 0.0002); the ability to detect invasion to other organs did not differ significantly between the two modalities. The accuracy of CH-EUS for T-staging of tumors was better than that of CE-CT (73.7% vs. 39.5%, P = 0.0059). CH-EUS tended to have a better accuracy than EUS for the diagnosis of invasion beyond the biliary wall into the surrounding tissue (92.1% vs. 78.9%, P = 0.074) and T-staging (73.7% vs. 60.5%, P = 0.074). CONCLUSION: CH-EUS is useful for T-staging of extra hepatic bile duct cancer, especially in terms of invasion beyond the biliary wall into the surrounding tissue.
  • Masaaki Motoori; Keijiro Sugimura; Koji Tanaka; Osamu Shiraishi; Yutaka Kimura; Hiroshi Miyata; Makoto Yamasaki; Tomoki Makino; Yasuhiro Miyazaki; Mitsuru Iwama; Kotaro Yamashita; Mai Niikura; Takuya Sugimoto; Takashi Asahara; Kazumasa Fujitani; Takushi Yasuda; Yuichiro Doki; Masahiko Yano
    Clinical nutrition (Edinburgh, Scotland) 41 (5) 1112 - 1121 2022/05 
    BACKGROUND & AIMS: Established supportive care to reduce the toxicity of neoadjuvant chemotherapy (NAC) is lacking. This multicenter randomized study compared the administration of synbiotics combined with enteral nutrition (EN) versus that of prophylactic antibiotics as supportive care treatment for patients with esophageal cancer undergoing NAC. METHODS: Patients with advanced esophageal cancer scheduled to receive NAC were randomly administered either prophylactic antibiotics (antibiotic group) or synbiotics combined with EN (Syn + EN group). The primary endpoint was the febrile neutropenia (FN) incidence during the first course, and the secondary endpoints were other adverse events, changes in intestinal environment, including fecal microbiota, organic acid concentrations, pH, and chemotherapy tolerability. RESULTS: Eighty-one patients were enrolled. The FN incidence was nonsignificantly lower (P = 0.088) in the Syn + EN group. The incidences of grade 4 neutropenia and grades 2-4 diarrhea were significantly lower in the Syn + EN group (P = 0.014 and 0.033, respectively). Relative dose intensity was significantly higher in the Syn + EN group (92.0 ± 10.9%) than in the antibiotic group (83.2 ± 18.2%) (P = 0.01). Alpfa diversity was significantly higher in the Syn + EN group than in the antibiotic after chemotherapy (P = 0.002). The numbers of Bifidobacterium (P < 0.05), Lacticaseibacillus (P < 0.001), and Enterobacteriaceae (P < 0.001) and the concentration of acetic acid (P < 0.001) were significantly higher in the Syn + EN group than in the antibiotic group after chemotherapy. The severity of diarrhea and occurrence of FN were significantly correlated with Clostridioides difficile abundance and were significantly inversely correlated with acetic acid concentration after chemotherapy. CONCLUSIONS: Synbiotics combined with EN may be an alternative supportive care treatment to prophylactic antibiotics in patients with cancer undergoing toxic chemotherapy (https://jrct.niph.go.jp; jRCTs051180153).
  • Ken Kamata; Makiko Kinoshita; Ikuharu Kinoshita; Hajime Imai; Takeshi Ogura; Hisakazu Matsumoto; Kosuke Minaga; Yasutaka Chiba; Mamoru Takenaka; Masatoshi Kudo; Masayuki Kitano
    International journal of clinical oncology 2022/04 
    OBJECTIVES: This study evaluated the efficacy of endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) in combination with EUS-guided celiac ganglia neurolysis (EUS-CGN) for pancreatic cancer-associated pain. METHODS: This multicenter prospective trial was registered in the University Hospital Medical Information Network (UMIN000031228). Fifty-one consecutive patients with pancreatic cancer-associated pain who presented at one of five Japanese referral centers between February 2018 and March 2021 were enrolled. EUS-CGN was added in cases of visible celiac ganglia. The primary endpoint was effectiveness, defined as a decrease in the numerical rating scale (NRS) by ≥ 3 points. NRS data were prospectively acquired at 1 week after the procedure to evaluate its effectiveness and the extent of pain relief. RESULTS: The technical success rates of EUS-CPN and EUS-CGN were 100% and 80.4%, respectively. The overall efficacy rate was 82.4% [90% confidence interval (CI) 71.2-90.5, P < 0.0001]. The complete pain relief rate was 27.4%. The adverse events rate was 15.7%. The average pain relief period was 72 days. The efficacy rate was higher in the EUS-CPN plus EUS-CGN group than in the EUS-CPN alone group. EUS-CPN plus EUS-CGN was superior to EUS-CPN alone for achieving complete pain relief (P = 0.045). EUS-CGN did not improve the average length of the pain relief period. CONCLUSIONS: EUS-CPN combined with EUS-CGN is safe, feasible, and effective for pain relief in patients with pancreatic cancer. The patients who received additional EUS-CGN had a better short-term response. CLINICAL TRIAL NUMBER: UMIN000031228.
  • 高齢者の上部消化管癌に対する治療方針 高齢者食道癌に対する術前補助療法を含めた手術治療の短期長期成績
    山下 公太郎; 田中 晃司; 牧野 知紀; 金村 剛志; 百瀬 洸太; 浜川 卓也; 竹野 淳; 白石 治; 西塔 拓郎; 山本 和義; 高橋 剛; 黒川 幸典; 中島 清一; 宮田 博志; 平尾 素宏; 安田 卓司; 江口 英利; 土岐 祐一郎
    日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 WS - 7 2022/04
  • Yohei Nose; Kotaro Yamashita; Tomohira Takeoka; Kota Momose; Takuro Saito; Koji Tanaka; Kazuyoshi Yamamoto; Tomoki Makino; Tsuyoshi Takahashi; Yukinori Kurokawa; Makoto Yamasaki; Osamu Shiraishi; Hiroshi Miyata; Takushi Yasuda; Masahiko Yano; Hidetoshi Eguchi; Yuichiro Doki
    Annals of surgical oncology 2022/03
  • 新規開発レジメンを用いた治療成績から考えた胃癌に有用なバイオマーカーとは HER2陽性胃癌に対するS-1/CDDP+/-trastuzumabによるネオアジュバント化学療法(JCOG1301C)(What is the useful biomarker for gastric cancer based on the therapeutic outcomes using the newly developed regimens? Neoadjuvant chemotherapy of S-1/CDDP +/- trastuzumab for HER2-positive gastric cancer(JCOG1301C))
    Aizawa Masaki; Tokunaga Masanori; Machida Nozomu; Mizusawa Junki; Yabusaki Hiroshi; Yasui Hirohumi; Hirao Motohiro; Watanabe Masaya; Yasuda Takushi; Kinoshita Takahiro; Imamura Hiroshi; Hihara Jun; Kataoka Tomoko; Boku Narikazu; Yoshikawa Takaki; Sano Takeshi; Sasako Mitsuru; Terashima Masanori
    日本胃癌学会総会記事 (一社)日本胃癌学会 94回 177 - 177 2022/03
  • Hidetoshi Hayashi; Shunichi Sugawara; Yasushi Fukuda; Daichi Fujimoto; Satoru Miura; Keiichi Ota; Yuichi Ozawa; Satoshi Hara; Junko Tanizaki; Koichi Azuma; Shota Omori; Motoko Tachihara; Kazumi Nishino; Akihiro Bessho; Yasutaka Chiba; Koji Haratani; Kazuko Sakai; Kazuto Nishio; Nobuyuki Yamamoto; Kazuhiko Nakagawa
    Clinical cancer research : an official journal of the American Association for Cancer Research 28 (5) 893 - 902 2022/03 
    PURPOSE: Although the efficacy of programmed cell death-1 (PD-1) blockade is generally poor for non-small cell lung cancer (NSCLC) with activating mutations of the epidermal growth factor receptor (EGFR) gene, EGFR tyrosine kinase inhibitors (TKIs) may improve the tumor immune microenvironment. We performed a randomized study to assess whether nivolumab improves outcome compared with chemotherapy in such patients previously treated with EGFR-TKIs. PATIENTS AND METHODS: Patients with EGFR-mutated NSCLC who acquired EGFR-TKI resistance not due to a secondary T790M mutation of EGFR were randomized 1:1 to nivolumab (n = 52) or carboplatin-pemetrexed (n = 50). The primary endpoint was progression-free survival (PFS). RESULTS: Median PFS and 1-year PFS probability were 1.7 months and 9.6% for nivolumab versus 5.6 months and 14.0% for carboplatin-pemetrexed [log-rank P < 001; hazard ratio (HR) of 1.92, with a 60% confidence interval (CI) of 1.61-2.29]. Overall survival was 20.7 and 19.9 months [HR, 0.88 (95% CI, 0.53-1.47)], and response rate was 9.6% and 36.0% for nivolumab and carboplatin-pemetrexed, respectively. No subgroup including patients with a high tumor mutation burden showed a substantially longer PFS with nivolumab than with carboplatin-pemetrexed. The T-cell-inflamed gene expression profile score (0.11 vs. -0.17, P = 0.036) and expression of genes related to cytotoxic T lymphocytes or their recruitment were higher in tumors that showed a benefit from nivolumab. CONCLUSIONS: Nivolumab did not confer a longer PFS compared with carboplatin-pemetrexed in the study patients. Gene expression profiling identified some cases with a favorable tumor immune microenvironment that was associated with nivolumab efficacy.
  • Yohei Nose; Kotaro Yamashita; Tomohira Takeoka; Kota Momose; Takuro Saito; Koji Tanaka; Kazuyoshi Yamamoto; Tomoki Makino; Tsuyoshi Takahashi; Yukinori Kurokawa; Makoto Yamasaki; Osamu Shiraishi; Hiroshi Miyata; Takushi Yasuda; Masahiko Yano; Hidetoshi Eguchi; Yuichiro Doki
    Annals of surgical oncology 29 (6) 3604 - 3612 2022/02 
    BACKGROUND: Ghrelin has been reported to reduce postoperative weight loss by improving appetite and food intake in patients undergoing upper gastrointestinal surgery. OBJECTIVE: We aimed to investigate whether growth hormone induction, another essential effect of ghrelin, may attenuate skeletal muscle loss in patients during postoperative starvation. METHODS: Esophageal cancer patients were randomized to receive a continuous intravenous infusion of high-dose ghrelin (HD; 0.5 µg/kg/h), low-dose ghrelin (LD; 0.25 µg/kg/h), or placebo for 7 days after surgery. During this period, oral feeding was not introduced but the patients received the same parenteral and enteral nutrition. We investigated the effects of ghrelin on body weight, skeletal muscle mass, nutritional status, and hormone levels. RESULTS: Overall, 73 patients were enrolled in this study. The rate of weight loss on postoperative day (POD) 7 relative to that before surgery was significantly lower in the HD group than in the placebo group (HD vs. placebo: -0.61% vs. 1.8%, p = 0.030). The rate of muscle loss in the erector spinae muscle on POD 7 in the HD and LD groups was significantly lower than that in the placebo group (HD vs. placebo: 2.8% vs. 8.5%, p < 0.001; LD vs. placebo: 4.9% vs. 8.5%, p = 0.028). The levels of growth hormone on PODs 1, 3, and 7, and insulin-like growth factor 1 on PODs 3, 7, and 14 were significantly higher in patients who received ghrelin. CONCLUSION: Continuous ghrelin administration could attenuate skeletal muscle loss in esophageal cancer patients during postoperative starvation.
  • Yohei Nose; Kotaro Yamashita; Tomohira Takeoka; Kota Momose; Takuro Saito; Koji Tanaka; Kazuyoshi Yamamoto; Tomoki Makino; Tsuyoshi Takahashi; Yukinori Kurokawa; Makoto Yamasaki; Osamu Shiraishi; Hiroshi Miyata; Takushi Yasuda; Masahiko Yano; Hidetoshi Eguchi; Yuichiro Doki
    Annals of surgical oncology 29 (6) 3613 - 3614 2022/02
  • Osamu Shiraishi; Takushi Yasuda; Hiroaki Kato; Kota Momose; Yoko Hiraki; Atsushi Yasuda; Masayuki Shinkai; Motohiro Imano
    Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 26 (4) 725 - 732 2022/02 
    BACKGROUND: This study was performed to verify the superiority of a new "non-tensioning method" for avoiding stricture of the cervical esophagogastric anastomosis by circular stapling compared with the conventional method. METHODS: In total, 395 consecutive patients who underwent McKeown esophagectomy with gastric conduit (GC) reconstruction were reviewed. A 4 cm-wide GC was created and pulled up at the cervical site through the retrosternal route. The esophagogastrostomy site of the GC was planned as far caudally as possible on the greater curvature side. In the conventional technique, the stapler was fired while pulling the GC to avoid tissue slack. In the non-tensioning technique, the stapler was fired through the natural thickness of the stomach wall. The length of the blind end was changed from 4 to 2 cm in the non-tensioning technique. Anastomotic leakage and stricture formation were compared between the two techniques, and adjustment was performed using propensity score matching. RESULTS: The conventional group comprised 315 patients, and the non-tensioning group comprised 80 patients. Anastomotic leakage occurred in 22 (7%) and 2 (2.5%) patients, respectively (P = 0.134) [and in 9 (2.9%) and 2 (2.5%) patients, respectively, if leakage at the blind end was excluded]. Anastomotic stricture occurred in 92 (29.2%) and 3 (3.8%) patients, respectively (P < 0.001). The propensity score-matching analysis including 79 pairs of patients confirmed a lower stricture rate in the non-tensioning than conventional group (2.5% vs. 29.1%, P < 0.001). CONCLUSIONS: The non-tensioning technique significantly reduced the incidence of anastomotic stricture compared with the conventional technique.
  • Tomoki Makino; Makoto Yamasaki; Koji Tanaka; Kotaro Yamashita; Shinya Urakawa; Tomo Ishida; Osamu Shiraishi; Keijiro Sugimura; Hiroshi Miyata; Masaaki Motoori; Kazumasa Fujitani; Atsushi Takeno; Motohiro Hirao; Yutaka Kimura; Taroh Satoh; Masahiko Yano; Hidetoshi Eguchi; Yuichiro Doki; Takushi Yasuda
    British journal of cancer 126 (11) 1555 - 1562 2022/02 
    BACKGROUND: The optimal number of neoadjuvant chemotherapy (NAC) cycles remains to be established for treating oesophageal squamous cell carcinoma (ESCC). We compared two versus three courses of NAC for treating locally advanced ESCC in a multi-institutional, randomised, Phase II trial. METHODS: We randomly assigned 180 patients with locally advanced ESCC at 6 institutions to either two (N = 91) or three (N = 89) courses of DCF (docetaxel 70 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 5 days) every 3 weeks, prior to surgery. The primary endpoint was 2-year progression-free survival (PFS) with an intention-to-treat analysis. RESULTS: Patient background parameters were well-balanced. The R0 resection rates were 98.9 and 96.5% in the two- and three-course groups, respectively (P = 0.830). In resected cases, the two- and three-course groups had comparable pN0 rates (P = 0.225) and histological responses (P = 0.898). The 2-year PFS rate was also comparable between the two groups (71.4 vs. 71.1%, P = 0.669). Among subgroups based on baseline characteristics, only patients aged under 65 years old showed a tendency for better survival with the three-course treatment (hazard ratio = 2.612, 95% confidence interval: 1.012-7.517). CONCLUSIONS: Two courses of a DCF regimen showed potential as an optional NAC treatment for locally advanced ESCC. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry of Japan (identification number UMIN 000015788).
  • Yoshinori Yane; Jin-Ichi Hida; Yasutaka Chiba; Yusuke Makutani; Hokuto Ushijima; Yasumasa Yoshioka; Masayoshi Iwamoto; Toshiaki Wada; Koji Daito; Tadao Tokoro; Kazuki Ueda; Junichiro Kawamura
    Scientific reports 12 (1) 916 - 916 2022/01 [Refereed]
     
    The use of temporary diverting stoma has become more common in low colorectal anastomosis to reduce anastomotic complications. Surgical site infection (SSI) at the stoma closure site has been one of the most frequent postoperative complications. The aim of this study was to compare the short-term outcomes between conventional primary suture closure and negative pressure wound therapy with instillation and dwelling (NPWTi-d) therapy following purse-string suturing, using propensity score matching analysis. We retrospectively evaluated the medical records of 107 patients who underwent stoma closure between January 2016 and October 2020. The primary outcome was the proportion of SSI. The secondary outcome was the day of postoperative length of stay. Propensity score matching with one-to-one match was performed for reducing treatment selection bias. Of a total of 107 patients, 67 patients had been treated with conventional primary closure and 40 with NPWTi-d therapy. The propensity score matching derived 37 pairs. The respective SSI proportions were 0% and 16.2% in the groups with NPWTi-d and primary closure (P = 0.025). The respective median days of postoperative hospital stay were 9.0 and 10.0 in the groups with NPWTi-d and primary closure (P = 0.453). NPWTi-d therapy with purse-string suturing was effective in reducing SSI after stoma closure.
  • Masayuki Shinkai; Motohiro Imano; Yoko Hiraki; Kota Momose; Hiroaki Kato; Osamu Shiraishi; Atsushi Yasuda; Masanobu Tsubaki; Shozo Nishida; Takushi Yasuda
    Langenbeck's archives of surgery 407 (3) 975 - 983 2022/01 
    PURPOSE: The prognosis of gastric cancer patients with peritoneal metastasis (PM) remains dismal with standard systemic chemotherapy. Intraperitoneal (i.p.) chemotherapy with paclitaxel (PTX) has local effects on intra-abdominal cancer cells. According to this phenomenon, we have developed regimens combining single i.p. PTX administration with systemic chemotherapy. This treatment strategy is very promising; however, the effect of "conversion surgery" in patients responding to this chemotherapy is unclear. Therefore, we performed a retrospective study to evaluate the safety and efficacy of conversion surgery for gastric cancer patients with PM. METHODS: We enrolled 52 gastric cancer patients with PM who were treated with single i.p. PTX plus systemic chemotherapy between 2005 and 2015. Conversion surgery was performed where PM was eliminated by combination chemotherapy. RESULTS: Among 52 gastric cancer patients, the disappearance of PM was confirmed in 33 patients (63.5%). Gastrectomy with D2 lymph node dissection was performed in all these patients. Histological response of grade ≥ 1b was achieved in 13 patients (39%). Clavien-Dindo grade II postoperative complications occurred in three patients (9%). There were no treatment-related deaths. The median survival time and 1-, 3-, and 5-year overall survival rates of the 33 patients who underwent conversion surgery were 30.7 months and 78.8%, 36.3%, and 24.2%, respectively, and those of the 19 patients who did not undergo surgery were 12.5 months and 52.6%, 5.2%, and 0%, respectively. CONCLUSION: Conversion surgery is safe and may prolong survival for gastric cancer patients with PM who have responded to single i.p. PTX plus systemic chemotherapy.
  • Yusuke Makutani; Hisato Kawakami; Takahiro Tsujikawa; Kanako Yoshimura; Yasutaka Chiba; Akihiko Ito; Junichiro Kawamura; Koji Haratani; Kazuhiko Nakagawa
    Frontiers in oncology 12 956270 - 956270 2022 
    Matrix metalloproteinase 14 (MMP14) expression is implicated in progression of colorectal cancer, but its role in the tumor microenvironment (TME) has been unclear. The relevance of MMP14 to colorectal cancer progression was explored by analysis of transcriptomic data for colorectal adenocarcinoma patients (n = 592) in The Cancer Genome Atlas. The role of MMP14 in the TME was investigated in a retrospective analysis of tumor samples from 86 individuals with stage III colorectal cancer by single cell-based spatial profiling of MMP14 expression as performed by 12-color multiplex immunohistochemistry (mIHC). Analysis of gene expression data revealed that high MMP14 expression was associated with tumor progression and implicated both cancer-associated fibroblasts (CAFs) and tumor-associated macrophages in such progression. Spatial profiling by mIHC revealed that a higher percentage of MMP14+ cells among intratumoral CAFs (MMP14+ CAF/CAF ratio) was associated with poorer relapse-free survival. Multivariable analysis including key clinical factors identified the MMP14+ CAF/CAF ratio as an independent poor prognostic factor. Moreover, the patient subset with both a high MMP14+ CAF/CAF ratio and a low tumor-infiltrating lymphocyte density showed the worst prognosis. Our results suggest that MMP14+ CAFs play an important role in progression of stage III colorectal cancer and may therefore be a promising therapeutic target.
  • Kimio Yonesaka; Junko Tanizaki; Osamu Maenishi; Koji Haratani; Hisato Kawakami; Kaoru Tanaka; Hidetoshi Hayashi; Kazuko Sakai; Yasutaka Chiba; Asuka Tsuya; Hiroki Goto; Eri Otsuka; Hiroaki Okida; Maki Kobayashi; Ryoto Yoshimoto; Masanori Funabashi; Yuuri Hashimoto; Kenji Hirotani; Takashi Kagari; Kazuto Nishio; Kazuhiko Nakagawa
    Clinical cancer research : an official journal of the American Association for Cancer Research 28 (2) 390 - 403 2021/12 
    PURPOSE: EGFR-tyrosine kinase inhibitor (TKI) is a standard first-line therapy for activated EGFR-mutated non-small cell lung cancer (NSCLC). Treatment options for patients with acquired EGFR-TKI resistance are limited. HER3 mediates EGFR-TKI resistance. Clinical trials of the HER3-targeting antibody-drug conjugate patritumab deruxtecan (HER3-DXd) demonstrated its anticancer activity in EGFR-mutated NSCLC; however, the mechanisms that regulate HER3 expression are unknown. This study was conducted with the aim to clarify the mechanisms underlying HER3 regulation in EGFR-mutated NSCLC tumors and explored the strategy for enhancing the anticancer activity of HER3-DXd in EGFR-mutated NSCLC. EXPERIMENTAL DESIGN: Paired tumor samples were obtained from 48 patients with EGFR-mutated NSCLC treated with EGFR-TKI(s). HER3 expression was immunohistochemically quantified with H-score, and genomic alteration and transcriptomic signature were tested in tumors from pretreatment to post-EGFR-TKI resistance acquisition. The anticancer efficacy of HER3-DXd and osimertinib was evaluated in EGFR-mutated NSCLC cells. RESULTS: We showed augmented HER3 expression in EGFR-mutated tumors with acquired EGFR-TKI resistance compared with paired pretreatment samples. RNA sequencing revealed that repressed PI3K/AKT/mTOR signaling was associated with HER3 augmentation, especially in tumors from patients who received continuous EGFR-TKI therapy. An in vitro study also showed that EGFR-TKI increased HER3 expression, repressed AKT phosphorylation in multiple EGFR-mutated cancers, and enhanced the anticancer activity of HER3-DXd. CONCLUSIONS: Our findings help clarify the mechanisms of HER3 regulation in EGFR-mutated NSCLC tumors and highlight a rationale for combination therapy with HER3-DXd and EGFR-TKI in EGFR-mutated NSCLC.
  • Keijiro Sugimura; Hiroshi Miyata; Koji Tanaka; Tomoki Makino; Atsushi Takeno; Osamu Shiraishi; Masaaki Motoori; Makoto Yamasaki; Yutaka Kimura; Motohiro Hirao; Kazumasa Fujitani; Takushi Yasuda; Masaki Mori; Hidetoshi Eguchi; Masahiko Yano; Yuichiro Doki
    Annals of surgery 274 (6) e465-e472  2021/12 
    OBJECTIVE: We conducted a multicenter randomized prospective phase 2 trial of chemoradiotherapy (CRT) versus chemotherapy (CT) as initial induction therapy for conversion surgery (CS) in clinical T4b esophageal cancer. We compared treatment effects and adverse events (AEs). SUMMARY BACKGROUND DATA: Although induction followed by CS is potentially curative for T4b esophageal cancer, the optimal initial induction treatment is unclear. METHODS: Ninety-nine patients with T4b esophageal cancer were randomly allocated to chemoradiotherapy (Group A, n = 49) or CT (Group B, n = 50) as initial induction treatment. CRT consisted of radiation (50.4 Gy) with cisplatin and 5-fluorouracil. CT consisted of 2 cycles of docetaxel plus cisplatin and 5-fluorouracil (DCF). CRT or CT was followed by CS if resectable. If unresectable, the patient received the other treatment as secondary treatment. CS was performed if resectable after secondary treatment. The primary end point was 2-year overall survival. RESULTS: In Group A, CS was performed in 34 (69%) and 7 patients (14%) after initial and secondary treatment. In Group B, CS was performed in 25 (50%) and 17 patients (34%) after initial and secondary treatment. The R0 resection rate after initial and secondary treatment was similar (78% vs 76%, P = 1.000). AEs including leukopenia, neutropenia, febrile neutropenia, and diarrhea were significantly more frequent in Group B. Group A had better histological complete response of the primary tumor (40% vs 17%, P = 0.028) and histological nodal status (P = 0.038). CONCLUSION: Upfront CRT was superior to upfront CT in terms of pathological effects and AEs. The Japan Registry of Clinical Trials (s051180164).
  • 【ここが知りたい、表在型Barrett食道腺癌】治療編 表在型Barrett食道腺癌の外科的治療
    安田 篤; 白石 治; 平木 洋子; 百瀬 洸太; 加藤 寛章; 新海 政幸; 今野 元博; 安田 卓司
    消化器内視鏡 (株)東京医学社 33 (11) 1769 - 1774 0915-3217 2021/11
  • Kentaro Yamao; Masakatsu Tsurusaki; Kota Takashima; Hidekazu Tanaka; Akihiro Yoshida; Ayana Okamoto; Tomohiro Yamazaki; Shunsuke Omoto; Ken Kamata; Kosuke Minaga; Mamoru Takenaka; Takaaki Chikugo; Yasutaka Chiba; Tomohiro Watanabe; Masatoshi Kudo
    Diagnostics (Basel, Switzerland) 11 (10) 2021/10 
    BACKGROUND: Pancreatic cancer (PC) exhibits extremely rapid growth; however, it remains largely unknown whether the early stages of PC also exhibit rapid growth speed equivalent to advanced PC. This study aimed to investigate the natural history of early PCs through retrospectively assessing pre-diagnostic images. METHODS: We examined the data of nine patients, including three patients with carcinoma in situ (CIS), who had undergone magnetic resonance cholangiopancreatography (MRCP) to detect solitary main pancreatic duct (MPD) stenosis >1 year before definitive PC diagnosis. We retrospectively analyzed the time to diagnosis and first-time tumor detection from the estimated time point of first-time MPD stenosis detection without tumor lesion. RESULTS: The median tumor size at diagnosis and the first-time tumor detection size were 14 and 7.5 mm, respectively. The median time to diagnosis and first-time tumor detection were 26 and 49 months, respectively. CONCLUSIONS: No studies have investigated the PC history, especially that of early PCs, including CIS, based on the initial detection of MPD stenosis using MRCP. Assessment of a small number of patients showed that the time to progression can take several years in the early PC stages. Understanding this natural history is very important in the clinical setting.
  • 食道癌術前後の大腰筋断面積変化量は術後1年の予後予測因子となる
    水澤 裕貴; 東本 有司; 白石 匡; 杉谷 竜司; 武田 優; 石川 朗; 白石 治; 安田 卓司; 木村 保; 福田 寛二
    日本呼吸ケア・リハビリテーション学会誌 (一社)日本呼吸ケア・リハビリテーション学会 31 (Suppl.) 163s - 163s 1881-7319 2021/10
  • Shinji Mine; Yukinori Kurokawa; Hiroya Takeuchi; Masanori Terashima; Takushi Yasuda; Kazuhiro Yoshida; Hiroshi Yabusaki; Yasuhiro Shirakawa; Kazumasa Fujitani; Takeshi Sano; Yuichiro Doki; Yuko Kitagawa
    Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 25 (2) 430 - 437 2021/09 
    BACKGROUND: Esophagogastric junction (EGJ) cancers are resected thorough esophagectomy or gastrectomy, with the incidence of postoperative complications influenced by the chosen procedure. METHODS: In this prospective nationwide multicenter study, patients with cT2-T4 EGJ cancers were enrolled before surgery. Based on the protocol, surgeons performed a transthoracic esophagectomy (TTE) or a transhiatal gastrectomy (THG) and dissected all lymph nodes prespecified as the standardized procedure. Postoperative complications were correlated with the clinical factors in each procedure. RESULTS: A total of 345 patients were eligible for this study. TTE and THG were performed in 120 and 225 patients, respectively. Complications of Clavien-Dindo ≥ Grade II were found in 115/345 (33.3%) patients. Recurrent laryngeal nerve palsy was found only in the TTE group (p < 0.001). The incidence of other complications was not significantly different between the two groups. High body mass index (BMI) in the TTE group, male sex, and longer esophageal invasion in the THG group were significantly correlated with complications ≥ Grade II (p = 0.049, 0.037, and 0.019, respectively). Anastomotic leakage was most frequently observed (12.2%). Tumor size in the THG group (p = 0.02) was significantly associated with leakage. All six patients with ≥ Grade IV leakage underwent THG, whereas, none of the patients in the TTE group had leakage ≥ Grade IV (2.7% vs. 0%, p = 0.096). CONCLUSIONS: Surgical resection should be performed with utmost care, particularly in patients with a high BMI undergoing TTE, and in patients with larger tumors, longer esophageal invasion, or male patients undergoing THG.
  • Kotaro Yamashita; Yasuhiro Miyazaki; Daisaku Nakatani; Yasunori Masuike; Koji Tanaka; Keijiro Sugimura; Tomoki Makino; Osamu Shiraishi; Tsuyoshi Takahashi; Yukinori Kurokawa; Makoto Yamasaki; Hiroshi Miyata; Yutaka Kimura; Hiroyuki Araki; Tomomi Yamada; Takushi Yasuda; Masahiko Yano; Hidetoshi Eguchi; Yuichiro Doki
    Anticancer research 41 (8) 3875 - 3884 2021/08 
    BACKGROUND/AIM: An excessive postoperative inflammatory response is correlated with the development of pneumonia and an unfavourable prognosis in patients undergoing esophagectomy for esophageal cancer. We assessed the influence of OSK-0028, a synthetic human ghrelin on inflammatory response and energy metabolism, on the postoperative course of patients following radical esophagectomy. PATIENTS AND METHODS: Esophageal cancer patients were randomly assigned to low-dose (LD; 0.25 μg/kg/h) or high-dose (HD; 0.5 μg/kg/h) intravenous OSK-0028 or placebo for 7 days after esophagectomy. The primary endpoint was serum interleukin-6 level on postoperative day (POD) 3. RESULTS: A total of 75 patients were enrolled (23 LD, 26 HD, 26 placebo). The median interleukin-6 levels on POD 3 were 40.95, 35.85, and 64.50 pg/ml in the placebo, LD, and HD groups, respectively, with no significant differences (p=0.78). Postoperative complications did not differ between groups. Bodyweight loss was significantly lower in patients receiving OSK-0028 than in those receiving placebo (-0.17% vs. 1.78%, p=0.043). CONCLUSION: Although OSK-0028 did not attenuate inflammatory response after esophagectomy, it prevented postoperative bodyweight loss.
  • Koji Tanaka; Makoto Yamasaki; Keijiro Sugimura; Osamu Shiraishi; Masaaki Motoori; Takuya Hamakawa; Atsushi Takeno; Kotaro Yamashita; Tomoki Makino; Yutaka Kimura; Hiroshi Miyata; Motohiro Hirao; Hidetoshi Eguchi; Takushi Yasuda; Masahiko Yano; Yuichiro Doki
    Annals of surgical oncology 28 (8) 4402 - 4410 2021/08 
    BACKGROUND: The impact of thoracic duct (TD) resection on prognosis is controversial. This study aimed to examine the impact of TD resection. METHODS: In this six-institution, matched-cohort study, 2269 consecutive patients with esophageal squamous cell carcinoma who underwent esophagectomy between 2000 and 2017 were enrolled for analysis of long-term outcomes, including overall survival (OS), disease-free survival (DFS), cause-specific survival (CSS), and recurrence patterns. RESULTS: Based on a propensity score, 642 TD-resected and 642 TD-preserved patients with all stages of disease were selected. At 5 years, the TD-resected group had an OS of 57.7%, a DFS of 50.9%, and a CSS of 62.2%. These rates were significantly higher than the corresponding rates of 48.7% (p = 0.0078), 41.0% (p = 0.0297), and 55.3% (p = 0.0473) in the TD-preserved group. The OS in the TD-preserved and TD-resected groups was similar for the patients with cStage 1 or 2 (p = 0.6265), but it was significantly higher in the TD-resected group for the patients with cStage 3 or 4 (p = 0.0052). The incidence of total recurrence did not differ between the two groups. However, the incidence of hematogenous recurrence in the TD-resected group (19.0%) was significantly lower than in the TD-preserved group (26.2%) (p = 0.0021). For cT4a tumors, the incidence of local recurrence in the TD-resected group (2.4%) was significantly lower than in the TD-preserved group (18.4%) (p = 0.0183). CONCLUSIONS: Performance of TD resection may help to improve prognosis, especially for patients with advanced esophageal squamous cell carcinoma, by reducing hematogenous and local recurrence. Prospective trials are needed to determine whether prophylactic TD resection has a positive impact on the prognosis of patients with esophageal cancer.
  • Takushi Yasuda; Osamu Shiraishi; Hiroaki Kato; Yoko Hiraki; Kota Momose; Atsushi Yasuda; Masayuki Shinkai; Yutaka Kimura; Motohiro Imano
    Esophagus : official journal of the Japan Esophageal Society 18 (3) 468 - 474 2021/07 
    BACKGROUND: A challenge in esophageal reconstruction after esophagectomy is that the distance from the neck to the abdomen must be replaced with a long segment obtained from the gastrointestinal tract. The success or failure of the reconstruction depends on the blood flow to the reconstructed organ and the tension on the anastomotic site, both of which depend on the reconstruction distance. There are three possible esophageal reconstruction routes: posterior mediastinal, retrosternal, and subcutaneous. However, there is still no consensus as to which route is the shortest. METHODS: The length of each reconstruction route was retrospectively compared using measurements obtained during surgery, where the strategy was to pull up the gastric conduit through the shortest route. The proximal reference point was defined as the left inferior border of the cricoid cartilage and the distal reference point was defined as the superior border of the duodenum arising from the head of the pancreas. RESULTS: This study involved 112 Japanese patients with esophageal cancer (102 men, 10 women). The mean distances of the posterior mediastinal, retrosternal, and subcutaneous routes were 34.7 ± 2.37 cm, 32.4 ± 2.24 cm, and 36.3 ± 2.27 cm, respectively. The retrosternal route was significantly shorter than the other two routes (both p < 0.0001) and shorter by 2.31 cm on average than the posterior mediastinal route. The retrosternal route was longer than the posterior mediastinal route in only 5 patients, with a difference of less than 1 cm. CONCLUSION: The retrosternal route was the shortest for esophageal reconstruction in living Japanese patients.
  • Atsushi Yasuda; Yutaka Kimura; Yoko Hiraki; Kota Momose; Hiroaki Kato; Osamu Shiraishi; Masayuki Shinkai; Motohiro Imano; Haruhiko Imamoto; Takushi Yasuda
    Asian journal of endoscopic surgery 14 (3) 658 - 664 2021/07 
    INTRODUCTION: Control of postoperative gastroesophageal reflux (GER) is a critical consideration for patients who undergo proximal gastrectomy. This report describes a new and simple reconstruction method by esophagogastrostomy with placement of the remnant stomach into the lower mediastinum (EG-PRIME). This approach not only suppresses postoperative GER, but it can also be easily performed by total laparoscopy. Detailed herein are the methods for EG-PRIME and the results for three patients with cancer of the upper gastric body. MATERIALS AND SURGICAL TECHNIQUE: At the start of the EG-PRIME surgical procedure, a pseudo-fornix and lozenge-shaped gastric conduit were made by cutting the stomach diagonally. Next, the pseudo-fornix was inserted into the esophageal hiatus to form a new angle of His. Then overlap anastomosis was performed and the entry site was closed longitudinally. The outcomes assessed were operative time, intraoperative blood loss, postoperative complications and GER according to 24-hour pH monitoring. DISCUSSION: The operative times were 339, 288 and 236 minutes; in two patients, intraoperative blood loss was 260 and 343 mL, and in the third, blood loss was minimal. No postoperative complications were observed in any of the three patients. The degree of the GER resulting in fraction time pH<4 was 9.0%, 0.3%, and 2.9%, respectively. No esophagitis by upper gastrointestinal endoscopy was observed in any patient. This EG-PRIME method was technically feasible for reconstruction after proximal gastrectomy by total laparoscopy. This approach may be as simple and useful as esophagogastrostomy for preventing postoperative GER, but more experience with this method is required.
  • 白石 治; 安田 卓司; 加藤 寛章; 百瀬 洸太; 平木 洋子; 安田 篤; 新海 政幸; 今野 元博; 木村 豊
    臨床外科 (株)医学書院 76 (6) 669 - 675 0386-9857 2021/06 
    ＜文献概要＞ポイント ◆郭清の前に周囲組織の授動を十分に行い,郭清組織を衝立化する.◆残すべき神経走行を確認し,切離ラインのデザインを決める.◆残す神経からの枝を鋭的に神経沿いに切離することで,衝立化された郭清組織から神経はスライドするように外れていく.
  • 安田 卓司; 白石 治; 加藤 寛章; 百瀬 洸太; 木村 豊
    手術 金原出版(株) 75 (7) 1125 - 1133 0037-4423 2021/06
  • 白石 治; 安田 卓司; 加藤 寛章; 百瀬 洸太; 平木 洋子; 安田 篤; 新海 政幸; 今野 元博; 木村 豊
    臨床外科 (株)医学書院 76 (6) 669 - 675 0386-9857 2021/06 
    ＜文献概要＞ポイント ◆郭清の前に周囲組織の授動を十分に行い,郭清組織を衝立化する.◆残すべき神経走行を確認し,切離ラインのデザインを決める.◆残す神経からの枝を鋭的に神経沿いに切離することで,衝立化された郭清組織から神経はスライドするように外れていく.
  • Ryosuke Kita; Hiroshi Miyata; Keijiro Sugimura; Koji Tanaka; Tomoki Makino; Kotaro Yamashita; Makoto Yamasaki; Masaaki Motoori; Osamu Shiraishi; Yutaka Kimura; Takushi Yasuda; Masahiko Yano; Yuichiro Doki
    Clinical nutrition (Edinburgh, Scotland) 40 (6) 4380 - 4385 2021/06 
    BACKGROUND & AIMS: Reductions in skeletal muscle mass during neoadjuvant therapy can have a negative effect on short- and long-term outcomes in patients with esophageal cancer. However, effective treatment for suppressing reductions in skeletal muscle mass during neoadjuvant therapy has not been established. METHODS: Eighty-seven patients were included in this study who were enrolled in a previous randomized study comparing the effects of enteral nutrition (EN) and parenteral nutrition (PN) on chemotherapy-related toxicities during neoadjuvant chemotherapy in esophageal cancer patients. Changes in skeletal muscle mass during neoadjuvant therapy were compared between the two groups. RESULTS: Skeletal muscle mass index (SMI) decreased from 45.8 cm2/m2 before treatment to 43.7 cm2/m2 after neoadjuvant chemotherapy in 87 patients (p = 0.092). The total calorie intake during neoadjuvant therapy was equal between the two groups. SMI reduction was significantly smaller in the EN group than in the PN group (-1.4 cm2/m2 vs -3.0 cm2/m (Gebski et al., 2007) [2], p < 0.001). EN support was identified as the only independent factor adversely associated with severe SMI reduction (p < 0.001). Patients with low SMI after neoadjuvant chemotherapy were more susceptible to postoperative complications than patients with moderate SMI (47.6% vs 16.7%, p = 0.007), especially pulmonary complications (31.8% vs 10.8%, p = 0.003). Patients with low SMI after neoadjuvant chemotherapy tended to show worse prognosis than patients with moderate SMI (5-year overall survival rate: 43.8% vs 62.1%, p = 0.194). CONCLUSIONS: Compared with PN support, EN support during neoadjuvant chemotherapy suppressed reductions in skeletal muscle mass in patients with esophageal cancer.
  • Hayato Kaida; Kazuhiro Kitajima; Masatoyo Nakajo; Mana Ishibashi; Tomoyuki Matsunaga; Ryogo Minamimoto; Kenji Hirata; Koya Nakatani; Ao Hung; Satoshi Hattori; Takushi Yasuda; Kazunari Ishii
    European journal of nuclear medicine and molecular imaging 48 (11) 3666 - 3682 2021/05 
    PURPOSE: To investigate the usefulness of the positron emission tomography response criteria in solid tumors 1.0 (PERCIST1.0) for predicting tumor response to neoadjuvant chemotherapy and prognosis and determine whether PERCIST improvements are necessary for esophageal squamous cell carcinoma (ESCC) patients. PATIENTS AND METHODS: We analyzed the cases of 177 ESCC patients and examined the association between PERCIST and their pathological responses. Associations of whole-PERCIST with progression-free survival (PFS) and overall survival (OS) were evaluated by a Kaplan-Meier analysis and Cox proportional hazards model. To investigate potential PERCIST improvements, we used the survival tree technique to understand patients' prognoses. RESULTS: There were significant correlations between the pathologic response and PERCIST of primary tumor (p < 0.001). The optimal cutoff value of the primary tumors' SULpeak response to classify pathologic responses was -50.0%. The diagnostic accuracy of SULpeak response was 87.3% sensitivity, 54.1% specificity, 68.9% accuracy, positive predictive value 60.5%, and negative predictive value 84.1%. Whole-PERCIST was significantly associated with PFS and OS. The survival tree results indicated that a high reduction of the whole SULpeak response was significantly correlated with the patients' prognoses. The cutoff values for the separation of prognoses were - 52.5 for PFS and - 47.1% for OS. CONCLUSION: PERCIST1.0 can help predict tumor responses and prognoses. However, 18F-FDG-PET/CT tends to underestimate residual tumors in histopathological response evaluations. Modified PERCIST, in which the partial metabolic response is further classified by the SULpeak response (-50%), might be more appropriate than PERCIST1.0 for evaluating tumor responses and stratifying high-risk patients for recurrence and poor prognosis.
  • Tomohiro Yamazaki; Mamoru Takenaka; Shunsuke Omoto; Tomoe Yoshikawa; Rei Ishikawa; Ayana Okamoto; Atsushi Nakai; Kosuke Minaga; Ken Kamata; Kentaro Yamao; Yoriaki Komeda; Tomohiro Watanabe; Naoshi Nishida; Keiko Kamei; Ippei Matsumoto; Yoshifumi Takeyama; Takaaki Chikugo; Yasutaka Chiba; Masatoshi Kudo
    Journal of clinical medicine 10 (9) 2021/04 
    This study aimed to investigate whether the incorporation of contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) into the international consensus guidelines (ICG) for the management of intraductal papillary mucinous neoplasm (IPMN) could improve its malignancy diagnostic value. In this single-center retrospective study, 109 patients diagnosed with IPMN who underwent preoperative CH-EUS between March 2010 and December 2018 were enrolled. We analyzed each malignancy diagnostic value (sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV)) by replacing fundamental B-mode EUS with CH-EUS as the recommended test for patients with worrisome features (WF) (the CH-EUS incorporation ICG) and comparing the results to those obtained using the 2017 ICG. The malignancy diagnostic values as per the 2017 ICG were 78.9%, 42.3%, 60.0%, and 64.7% for Se, Sp, PPV, and NPV, respectively. The CH-EUS incorporation ICG plan improved the malignancy diagnostic values (Se 78.9%/Sp, 53.8%/PPV, 65.2%/NPV 70.0%). CH-EUS may be useful in determining the appropriate treatment strategies for IPMN.
  • Osamu Shiraishi; Takushi Yasuda; Hiroaki Kato; Kota Momose; Yoko Hiraki; Atsushi Yasuda; Masayuki Shinkai; Yutaka Kimura; Motohiro Imano
    Annals of surgical oncology 28 (11) 6366 - 6375 2021/03 
    INTRODUCTION: We compare planned salvage surgery after definitive chemoradiotherapy (SALV) versus neoadjuvant chemoradiotherapy plus surgery (NCRS) for borderline resectable T4 esophageal squamous cell carcinoma. PATIENTS AND METHODS: A total of 37 patients underwent planned SALV, and 20 underwent NCRS from 2004 to 2017. The short-term outcome measures were the R0 resection rate, complications, and treatment-related mortality. The long-term outcome measures were the 5-year overall survival rate and causes of death. RESULTS: R0 resection rate was similar between the SALV and NCRS groups (81% versus 85%). The incidence of postoperative pneumonia (35% versus 18%) and treatment-related mortality rate (9% versus 0%) tended to be higher in the SALV. ypT grade 2-3 (65% versus 30%, p = 0.012) and Clavien-Dindo grade ≥ IIIb complications (32% versus 0%, p = 0.008) were significantly more frequent in the SALV group. The groups had similar 5-year overall survival (26% versus 27%). The causes of death in the SALV and NCRS groups were primary esophageal cancer in 35% and 55% of patients, respectively, and pulmonary-related mortality in 24% and 5%, respectively. Multivariable Cox regression analysis revealed the following significant poor prognostic factors: stable disease as the clinical response, preoperative body mass index (BMI) of < 18.5 kg/m2, ypN stage 1-3, and R1-2 resection. CONCLUSIONS: SALV was associated with a higher incidence of late pulmonary-related mortality but had a stronger antitumor effect than NCRS. Consequently, the survival rate was similar between the groups. Surgery is recommended for patients with a partial response and preoperative BMI of ≥ 18.5 kg/m2.
  • Osamu Shiraishi; Tomoki Makino; Makoto Yamasaki; Koji Tanaka; Kotaro Yamashita; Tomo Ishida; Keijiro Sugimura; Hiroshi Miyata; Masaaki Motoori; Kazumasa Fujitani; Atsushi Takeno; Motohiro Hirao; Yutaka Kimura; Taroh Satoh; Masahiko Yano; Yuichiro Doki; Takushi Yasuda
    Esophagus : official journal of the Japan Esophageal Society 18 (4) 825 - 834 2021/03 
    OBJECTIVE: To compare short-term outcomes between two- vs. three courses of neoadjuvant chemotherapy (NAC) to clarify the optimal treatment for esophageal squamous cell cancer (ESCC) in a multicenter, randomized, phase II trial. BACKGROUND: An optimal number of NAC cycles remains to be established for locally advanced ESCC. METHODS: Patients with locally advanced ESCC were randomly assigned to either two (N = 91) or three (N = 89) courses of DCF (70 mg/m2 intravenous docetaxel and 70 mg/m2 intravenous cisplatin on day 1, and a continuous 700 mg/m2 fluorouracil infusion for 5 days) every 3 weeks followed by surgery. We compared the two groups for perioperative parameters, adverse events, and the response to NAC. RESULTS: The two- and three-course groups showed similar completion rates and overall NAC dose reductions. Although the two-course group showed significantly lower overall grades 3-4 leukopenia and anemia compared to the three-course group, the two groups had similar overall toxicity rates. Postoperative complications were not significantly different between the two groups, except arrhythmia (13 vs. 0%, P = 0.0007). Only two postoperative in-hospital deaths occurred in the three-course group, due to sepsis following severe pneumonia. Compared to the two-course group, the three-course group was associated with a significantly better clinical response (42.9 vs. 65.2%, P = 0.0027) and a relatively higher rate of pathological complete response (9.1 vs. 15.3%, P = 0.212). CONCLUSION: Both two- and three-course DCF regimens in the NAC setting seemed to be equally feasible in locally advanced ESCC patients. Additional DCF courses led to a better NAC response without increasing the incidence of adverse events or postoperative morbidity. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry of Japan (Identification Number UMIN 000015788).
  • Keijiro Sugimura; Makoto Yamasaki; Takushi Yasuda; Masahiko Yano; Motohiro Hirao; Kazumasa Fujitani; Yutaka Kimura; Hiroshi Miyata; Masaaki Motoori; Atsushi Takeno; Osamu Shiraishi; Tomoki Makino; Takayuki Kii; Koji Tanaka; Taro Satoh; Masaki Mori; Yuichiro Doki
    Annals of gastroenterological surgery WILEY-V C H VERLAG GMBH 5 (1) 75 - 82 2475-0328 2021/01 
    Aim: The aim is to report the long-term outcomes of preoperative cisplatin and fluorouracil plus docetaxel (DCF) vs Adriamycin (ACF) for resectable esophageal squamous cell carcinoma (ESCC). Previously, this trial showed that DCF is associated with prolonged recurrence-free survival (RFS). Methods: Patients were randomly assigned to two cycles of ACF (35 mg/m2 of Adriamycin, 70 mg/m2 of cisplatin intravenously on day 1, and 700 mg/m2 of fluorouracil infusion for 7 days) every 4 weeks or DCF (70 mg/m2 of docetaxel, 70 mg/m2 of cisplatin intravenously on day 1, and 700 mg/m2 of fluorouracil infusion for 5 days) every 3 weeks, followed by surgery. The primary endpoint was RFS. The secondary endpoint was overall survival (OS). Results: Between October 2011 and October 2013, 162 patients at 10 institutions were enrolled in the study, 162 of whom were eligible and randomly assigned to the two groups. The median follow-up for surviving patients was 69.8 months. The 5-year RFS was significantly better in the DCF group than in the ACF group (59.9% vs 40.7%, hazard ratio [HR] 0.55; 95% confidence interval [CI], 0.35-0.86; P = .009) and the 5-year OS was significantly better in the DCF group than in the ACF group (63.5% vs 49.4%, HR, 0.61; 95% CI, 0.38-0.96; P = .03). The benefit of DCF chemotherapy on survival was significantly greater in the subgroups with more advanced clinical T and N stage. Conclusions: Cisplatin and fluorouracil plus docetaxel are associated with better RFS and OS than ACF in resectable ESCC patients.
  • Yoko Hiraki; Yutaka Kimura; Motohiro Imano; Hiroaki Kato; Mitsuru Iwama; Osamu Shiraishi; Atsushi Yasuda; Masayuki Shinkai; Tomoki Makino; Masaaki Motoori; Makoto Yamasaki; Hiroshi Miyata; Takao Satou; Taroh Satoh; Hiroshi Furukawa; Masahiko Yano; Yuichiro Doki; Takushi Yasuda
    Surgery today 51 (1) 118 - 126 2021/01 [Refereed]
     
    PURPOSE: The purpose of this study is to determine the clinical significance of micrometastases after neoadjuvant chemotherapy (NAC) and the difference in controlling micrometastases using different NAC regimens in resectable advanced esophageal squamous cell carcinoma (ESCC). METHODS: We analyzed patients with ESCC who underwent esophagectomy with lymph node dissection after NAC with Adriamycin + cisplatin + 5-fluorouracil (ACF) or docetaxel + cisplatin + 5-fluorouracil (DCF). Micrometastasis was defined as a single isolated cancer cell or cluster of cancer cells on the cervical, recurrent nerve, or abdominal LNs as shown by immunohistochemical staining with anti-cytokeratin antibody (AE1/AE3). The associations between micrometastases, recurrence, prognosis, and regimen differences were investigated. RESULTS: One hundred and one cases (ACF group: 51 cases; DCF group: 50 cases) were analyzed. Micrometastases occurred in 24 patients (23.8%): 17/51 (33.3%) in the ACF group and 7/50 (13.5%) in the DCF group (p = 0.0403). The 5-year recurrence-free survival (RFS) rates for patients without (n = 77) and with (n = 24) micrometastases were 62 and 32%, respectively, (hazard ratio, 2.158; 95% confidence interval, 1.170-3.980; stratified log-rank test, p = 0.0115). A multivariate analysis showed that stage pN1 or higher and micrometastases were significant risk factors affecting RFS. CONCLUSION: In resectable advanced ESCC, controlling micrometastases in the LNs after NAC varied by regimen and may be associated with preventing ESCC recurrence.
  • 白石 治; 安田 卓司; 加藤 寛章; 百瀬 洸太; 平木 洋子; 安田 篤; 新海 政幸; 木村 豊; 今野 元博
    外科 (株)南江堂 82 (13) 1297 - 1302 0016-593X 2020/12 
    ＜文献概要＞食道癌の機能温存縮小手術のめざすところは,生活の質(QOL)と根治性を両立した手術である.頸部食道癌では,舌骨上筋群の温存と下筋群の切離,反回神経麻痺を回避して嚥下能を維持し,輪状咽頭筋切離により最大限に口側切離距離を確保し,喉頭温存手術を可能とする.胸部中下部食道癌では,上縦隔リンパ節転移を認めないことを条件に,嚥下能の低下した高齢者や脳梗塞既往患者を対象に頸部操作を省略できる高位胸腔内胃管再建術を適応する.
  • 食道癌術後患者に対する、安全・簡便・低侵襲な経腸栄養ルートの造設法 内視鏡的経皮経胃管腸瘻造設
    加藤 寛章; 白石 治; 平木 洋子; 岩間 密; 安田 篤; 新海 政幸; 木村 豊; 今野 元博; 安田 卓司
    学会誌JSPEN (一社)日本臨床栄養代謝学会 2 (Suppl.1) 452 - 452 2020/11
  • Osamu Shiraishi; Hiroaki Kato; Mitsuru Iwama; Yoko Hiraki; Atsushi Yasuda; Ying-Feng Peng; Masayuki Shinkai; Yutaka Kimura; Motohiro Imano; Takushi Yasuda
    Surgical endoscopy 34 (11) 4967 - 4974 2020/11 [Refereed]
     
    BACKGROUND: Feeding jejunostomy (FJ) is a common treatment to support patients with esophageal cancer after esophagectomy. However, severe FJ-related complications, such as bowel obstruction, occasionally occur. We investigated the ability of our simple, novel FJ technique, the "curtain method," to prevent bowel obstruction. METHODS: In laparoscopic surgery, the main mechanism of bowel obstruction involves torsion of the mesentery accompanied by migration of the intestine across the fixed FJ through the space surrounded by a triangle comprising the ligament of Treitz, fixed FJ, and spleen rather than adhesion. Our "curtain method" involves closure of this triangle zone with omentum, and the appearance of the lifted omentum resembles a curtain. Sixty patients treated with this modified FJ were retrospectively compared with 13 patients treated with conventional FJ in terms of the incidence of bowel obstruction, peritonitis, stoma site infection, and catheter obstruction. RESULTS: From 2013 to 2017, 60 patients underwent esophagectomy and gastric conduit reconstruction accompanied by modified laparoscopic FJ. The median observation period, including the period after tube removal, was 644 days. No FJ-associated bowel obstruction, the prevention of which was the primary aim, occurred in any patient. Likewise, no peritonitis or dislodgement occurred. Eight patients (13%) developed a stoma site infection with granulation. The feeding tube became occluded in 11 patients (18%); however, a new feeding tube was reinserted under fluoroscopy for all of these patients. From 2003 to 2012, 13 patients underwent conventional FJ. The median observation period was 387 days. Three patients (23%) developed bowel obstruction by torsion 71 to 134 days after the first surgery, and all were treated by emergency operations. Other FJ-related complications were not different from those in the modified FJ group. CONCLUSION: Our simple, novel technique, the "curtain method," for prevention of laparoscopic FJ-associated bowel obstruction after esophagectomy is a safe additional surgery.
  • Ken Kamata; Reiko Ashida; Satoru Yasukawa; Yasutaka Chiba; Nobuyasu Fukutake; Hiroko Nebiki; Akira Kurita; Makoto Takaoka; Takeshi Ogura; Hideyuki Shiomi; Masanori Asada; Hiroaki Yasuda; Minoru Shigekawa; Akio Yanagisawa; Masatoshi Kudo; Masayuki Kitano
    Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 20 (7) 1428 - 1433 2020/10 [Refereed]
     
    OBJECTIVES: Preoperative grading of pancreatic neuroendocrine tumors (PanNET) is challenging. The aim of this study was to prospectively evaluate the use of a 25-gauge needle with a core trap for diagnosis and grading of PanNET. METHODS: This multicenter prospective trial was registered with the University Hospital Medical Information Network (UMIN000021409). Consecutive patients with suspected PanNET between June 2016 and November 2017 were enrolled. All patients underwent endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) using a 25-gauge needle with a core trap. Samples obtained after the first needle pass were used for central pathological review. EUS-FNB was evaluated in terms of (i) technical success rate, (ii) adequacy for histological evaluation, (iii) complication rate during the procedure, and (iv) concordance between PanNET grading on EUS-FNB and that after analysis of the resected tumor. RESULTS: Fifty-two patients were enrolled. Of the 36/52 patients who underwent surgical resection, 31 were finally diagnosed with PanNET and were eligible for analysis. The technical success rate of EUS-FNB was 100%. The rate of adequacy for histological evaluation was 90.3%. There were no complications related to EUS-FNB. The concordance rate between PanNET grading on EUS-FNB and that after analysis of the resected tumor was 82.6% (95% confidence interval = 61.22-95.05, P = 0.579). CONCLUSIONS: EUS-FNB using a 25-gauge needle with a core trap is feasible, providing histological samples are of sufficient quality for diagnosis and grading of PanNET.
  • Osamu Shiraishi; Takushi Yasuda; Hiroaki Kato; Mitsuru Iwama; Yoko Hiraki; Atsushi Yasuda; Masayuki Shinkai; Yutaka Kimura; Motohiro Imano
    Annals of surgical oncology 27 (11) 4433 - 4440 2020/10 [Refereed]
     
    PURPOSE: We retrospectively investigated the risk factors for mediastinal lymph node (MLN) metastasis in esophagogastric junction (EGJ) cancer with an epicenter within 2 cm above and below the anatomical cardia, including both adenocarcinoma (AC) and squamous cell carcinoma (SCC). METHODS: Fifty patients who underwent initial surgery for EGJ cancer from January 2002 to December 2013 were included in this study. We defined metastatic lymph nodes as pathological metastases in resected specimens and recurrence within 2 years postoperatively. RESULTS: Thirty-four patients had AC and 16 had SCC; 24 patients underwent transhiatal resection and 26 underwent transthoracic resection. MLN metastasis was observed in 13 patients (26%) regardless of the histological type, 9 of whom had metastasis in the upper and middle mediastinum. Metastasis occurred when the esophageal invasion length (EIL) exceeded 20 mm. In addition, 10/13 patients had stage pN2-3 cancer. Multivariable analysis identified EIL ≥ 20 mm and stage pN2-3 as significant risk factors for MLN metastasis. The 5-year overall survival was 38% and 65% in the MLN-positive and -negative groups, respectively (p = 0.12). Multivariable Cox regression analysis showed that only stage pN2-3, and not the presence of MLN metastasis, was a significantly poor prognostic factor. CONCLUSION: MLN metastasis in EGJ cancer may have a close association with the EIL of the tumor, but the presence of MLN metastasis itself was not a poor prognostic factor. The significance and indications for MLN dissection should be clarified in prospective clinical trials.
  • Takushi Yasuda; Kohei Nishiki; Yoko Hiraki; Hiroaki Kato; Mitsuru Iwama; Osamu Shiraishi; Atsushi Yasuda; Masayuki Shinkai; Yutaka Kimura; Yasushi Sukegawa; Yasutaka Chiba; Motohiro Imano; Kazuyoshi Takeda; Takao Satou; Hitoshi Shiozaki; Yusuke Nakamura
    Annals of surgery 275 (1) e155-e162  2020/08 
    OBJECTIVES: To elucidate the efficacy of adjuvant vaccine monotherapy using 3 Human Leukocyte Antigen (HLA)-A24-restricted tumor-specific peptide antigens for ESCC, upregulated lung cancer 10, cell division cycle associated 1, and KH domain-containing protein overexpressed in cancer 1. SUMMARY OF BACKGROUND DATA: ESCC patients with pathologically positive nodes (pN(+)) have a high risk for postoperative recurrence, despite curative resection after preoperative therapy. Subclinical micrometastases are an appropriate target for cancer vaccine. METHODS: This is a non-randomized prospective phase II clinical trial (UMIN000003557). ESCC patients curatively resected after preoperative therapy with pN(+) were allocated into the control and vaccine groups (CG and VG) according to the HLA-A status. One mg each of three epitope peptides was postoperatively injected 10 times weekly followed by 10 times biweekly to the VG. The primary and secondary endpoints were relapse-free survival (RFS) and esophageal cancer-specific survival (ECSS), respectively. RESULTS: Thirty were in the CG and 33 in the VG. No significant difference was observed in RFS between the CG and VG (5-year RFS: 32.5% vs 45.3%), but the recurrence rate significantly decreased with the number of peptides which induced antigen-specific cytotoxic T lymphocytes. The VG showed a significantly higher 5-year ECSS than the CG (60.0% vs 32.4%, P = 0.045) and this difference was more prominent in patients with CD8 and programmed death-ligand 1 double negative tumor (68.0% vs 17.7%, P = 0.010). CONCLUSIONS: Our cancer peptide vaccine might improve the survival of ESCC patients, which is warranted to be verified in the phase III randomized controlled study.
  • Satoru Motoyama; Eri Maeda; Masahiko Yano; Takushi Yasuda; Masaichi Ohira; Yoshiaki Kajiyama; Takahiro Higashi; Yuichiro Doki; Hisahiro Matsubara
    Esophagus : official journal of the Japan Esophageal Society 17 (2) 141 - 148 2020/04 [Refereed]
     
    BACKGROUND: It will be important for the Japan Esophageal Society (JES) to show an evident advantage of its institution certification system. To achieve this essential task, we used nationally acquired big data to re-analyze 5-year survival information. METHODS: In 2008-2009, there were 4897 thoracic esophageal cancer patients who underwent esophagectomy and were registered in the National Database of Hospital-based Cancer Registries. We divided these patients into two groups, those who underwent surgery at an Authorized Institute for Board Certified Esophageal Surgeons (AIBCES) or a Non-AIBCES. We then compared the patient backgrounds and 5-year survival rates between these two groups, with and without propensity score matching. RESULTS: There were 3080 (63%) patients who underwent esophagectomy at an AIBCES and 1817 (37%) who underwent surgery at a Non-AIBCES. Comparison of the Kaplan-Meier survival curves using log-rank tests indicated a significant difference between the AIBCES and Non-AIBCES groups at all cStages (cStages I-IV). Multivariable Cox proportional hazard analysis stratified by clinical stage and adjuvant treatment revealed that AIBCES vs. Non-AIBCES is a significant independent factor (adjusted HR 0.78) for survival. After propensity score matching ensuring the backgrounds of the two groups being equivalent, there were significant differences in the 5-year survival rates for patients with cStages I-III disease between the AIBCES and Non-AIBCES groups. CONCLUSIONS: There is a survival advantage to undergoing esophagectomy at an AIBCES. The institute certification system from the JES will contribute to the future establishment of a more appropriate surgery delivery system for thoracic esophageal cancer.
  • Osamu Shiraishi; Hiroaki Kato; Mituru Iwama; Yoko Hiraki; Atsushi Yasuda; Ying-Feng Peng; Masayuki Shinkai; Yutaka Kimura; Motohiro Imano; Takushi Yasuda
    Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus 33 (2) 1120-8694 2020/03 [Refereed]
     
    Unexpected dysphagia is an important problem affecting life prognosis in patients who have undergone an esophagectomy for esophageal cancer. For nutritional support in patients suffering from dysphagia after a previous esophagectomy, a simplified percutaneous endoscopic transgastric conduit feeding jejunostomy approach was developed that can be performed regardless of the patient's condition. The feasibility of this procedure in 25 patients with esophageal cancer who underwent three-stage esophagectomy with retrosternal gastric conduit reconstruction from April 2009 to December 2016 was evaluated retrospectively. Under fluoroscopy, a percutaneous endoscopic transgastric conduit feeding jejunostomy catheter (9 French) was introduced into the jejunum in the epigastric region using the Seldinger's technique. The following patient data were analyzed retrospectively: operating time, complications, reasons for oral intake difficulty, and clinical data describing patients' nutritional status before and 1 month after percutaneous endoscopic transgastric conduit jejunostomy treatment, such as serum albumin and clinical course. Median patients' age was 68 years (range 50-76 years). Indications for the procedure were late swallowing dysfunction (n = 12), early swallowing dysfunction secondary to surgical complication (n = 8), anastomotic leakage (n = 3), and anorexia (n = 2). Causes of late swallowing dysfunction were radiation injury (n = 8), advanced age (n = 2), or cerebral infarction (n = 2). The median operating time was 29 minutes (range 14-82 minutes). Four patients developed mild erosions at the stoma secondary to bile reflux along the side of the catheter. No patient experienced severe complications such as ileus and peritonitis. Patients were treated for a median of 160 days (range 18-3106 days) with percutaneous endoscopic transgastric conduit jejunostomy. Patient's serum albumin significantly increased from 2.8 to 3.3 g/dl in 1 month. Of the eight patients with early swallowing dysfunction, six successfully regained sufficient oral nutrition after receiving enteral feeding nutritional management. Although all except one late swallowing dysfunction patient could not discontinue tube feeding, five patients were long-term survivors at the time this report was written. This jejunostomy procedure is simple, safe, and useful for patients with unexpected dysphagia and accompanying malnutrition after esophagectomy.
  • Atsushi Yasuda; Takushi Yasuda; Haruhiko Imamoto; Yoko Hiraki; Kohta Momose; Hiroaki Kato; Mitsuru Iwama; Osamu Shiraishi; Masayuki Shinkai; Motohiro Imano; Yutaka Kimura
    Surgical case reports 6 (1) 44 - 44 2020/02 [Refereed]
     
    BACKGROUND: Granular cell tumors (GCT) in the gastrointestinal tract are rare. Herein, we describe a case of a gastric GCT diagnosed preoperatively by endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) and successfully resected by single-incision laparoscopic surgery (SILS). CASE PRESENTATION: A 46-year-old Japanese woman had a tumor located in the angle of the stomach that was approximately 1.5 cm in diameter. Abdominal computed tomography (CT) revealed a submucosal tumor (SMT), which was finally diagnosed as a gastric GCT using EUS-FNAB. The tumor was not identified by CT 1 year and 4 months before diagnosis; therefore, because there was a possibility that the tumor was malignant, we performed surgical wedge resection using SILS. The patient had an uneventful recovery postoperatively and was discharged without complications 3 days after surgery. The tumor was pathologically diagnosed as a benign GCT that remained within the muscular layer. No recurrence or complications have occurred in the first 16 months since the surgery. CONCLUSION: Because gastric GCTs are generally benign and are rarely associated with lymph node metastasis, SILS seems to be a safe and feasible surgical approach for treating GCTs.
  • TAKASHI KUROSAKI; HISATO KAWAKAMI; SEIICHIRO MITANI; RYOHEI KAWABATA; TAKAYUKI TAKAHAMA; YOSHIKANE NONAGASE; SOICHI FUMITA; TOMOHIRO OZAKI; YASUTAKA CHIBA; TAKAO TAMURA; KAZUHIKO NAKAGAWA
    In Vivo Anticancer Research USA Inc. 34 (4) 1921 - 1929 0258-851X 2020
  • Munmee Dutta; Hidewaki Nakagawa; Hiroaki Kato; Kazuhiro Maejima; Shota Sasagawa; Kaoru Nakano; Aya Sasaki-Oku; Akihiro Fujimoto; Raúl Nicolás Mateos; Ashwini Patil; Hiroko Tanaka; Satoru Miyano; Takushi Yasuda; Kenta Nakai; Masashi Fujita
    PeerJ 8 e9294  2020 [Refereed]
     
    Esophageal squamous cell carcinoma (ESCC) is the predominant type of esophageal cancer in the Asian region, including Japan. A previous study reported mutational landscape of Japanese ESCCs by using exome sequencing. However, somatic structural alterations were yet to be explored. To provide a comprehensive mutational landscape, we performed whole genome sequencing (WGS) analysis of biopsy specimens from 20 ESCC patients in a Japanese population. WGS analysis identified non-silent coding mutations of TP53, ZNF750 and FAT1 in ESCC. We detected six mutational signatures in ESCC, one of which showed significant association with smoking status. Recurrent structural variations, many of which were chromosomal deletions, affected genes such as LRP1B, TTC28, CSMD1, PDE4D, SDK1 and WWOX in 25%-30% of tumors. Somatic copy number amplifications at 11q13.3 (CCND1), 3q26.33 (TP63/SOX2), and 8p11.23 (FGFR1) and deletions at 9p21.3 (CDKN2A) were identified. Overall, these multi-dimensional view of genomic alterations improve the understanding of the ESCC development at molecular level and provides future prognosis and therapeutic implications for ESCC in Japan.
  • Satoru Motoyama; Hiroyuki Yamamoto; Hiroaki Miyata; Masahiko Yano; Takushi Yasuda; Masaichi Ohira; Yoshiaki Kajiyama; Yasushi Toh; Masayuki Watanabe; Yoshihiro Kakeji; Yasuyuki Seto; Yuichiro Doki; Hisahiro Matsubara
    Esophagus : official journal of the Japan Esophageal Society 17 (1) 41 - 49 1612-9059 2020/01 [Refereed]
     
    BACKGROUND: In 2009, the Japan Esophageal Society (JES) established a system for certification of qualified surgeons as "Board Certified Esophageal Surgeons" (BCESs) or institutes as "Authorized Institutes for Board Certified Esophageal Surgeons" (AIBCESs). We examined the short-term outcomes after esophagectomy, taking into consideration the certifications statuses of the institutes and surgeons. METHODS: This study investigated patients who underwent esophagectomy for thoracic esophageal cancer and who were registered in the Japanese National Clinical Database (NCD) between 2015 and 2017. Using hierarchical multivariable logistic regression analysis adjusted for patient-level risk factors, we determined whether the institute's or surgeon's certification status had greater influence on surgery-related mortality or postoperative complications. RESULTS: Enrolled were 16,752 patients operated on at 854 institutes by 1879 surgeons. There were significant differences in the backgrounds and incidences of postoperative complications and surgery-related mortality rates between the 11,162 patients treated at AIBCESs and the 5590 treated at Non-AIBCESs (surgery-related mortality rates: 1.6% vs 2.8%). There were also differences between the 6854 patients operated on by a BCES and the 9898 treated by a Non-BCES (1.7% vs 2.2%). Hierarchical logistic regression analysis revealed that surgery-related mortality was significantly lower among patients treated at AIBCESs. The institute's certification had greater influence on short-term surgical outcomes than the operating surgeon's certification. CONCLUSIONS: The certification system for surgeons and institutes established by the JES appears to be appropriate, as indicated by the improved surgery-related mortality rate. It also appears that the JES certification system contributes to a more appropriate medical delivery system for thoracic esophageal cancer in Japan.
  • 木村 豊; 白石 治; 岩間 密; 加藤 寛章; 川上 尚人; 奥野 達哉; 平木 洋子; 安田 篤; 新海 政幸; 今野 元博; 中川 和彦; 安田 卓司
    癌と化学療法 (株)癌と化学療法社 46 (13) 2173 - 2175 0385-0684 2019/12 
    腎機能低下を伴う進行食道癌に対して術前化学療法(NAC)として5-FU+DTX+nedaplatin(NED)(UDON)療法を施行し、その有用性をretrospectiveに検討した。クレアチニン・クリアランス(Ccr)が50mL/min未満の進行食道癌5例を対象として、NACとしてUDON療法[5-FU640mg/m2(day1〜5)、NED72mg/m2(day1)、DTX28mg/m2(day1、15)、休薬2週間を1コース]を2コース施行した後に根治手術を施行した。化学療法の有害事象(AE)を評価し、臨床的な効果について検討した。患者背景は、男性4例、女性1例、年齢の中央値(範囲)79(58〜80)歳、performance status(PS)1:3、PS2:2例であった。腫瘍の主占居部位は、Ce 1、Ut 1、Mt 3例、進行度はcStage IIA1、IIIA2、IIIC2例であった。grade(Gr)3以上のAEは、好中球減少、低Na血症がそれぞれ2例、発熱性好中球減少、下痢がそれぞれ1例であった。抗腫瘍効果は部分奏効4例、安定1例、組織学的効果は、Gr 1a:Gr 1b=2:3であった。腎機能低下のため高用量CDDP投与が困難な進行食道癌患者に対するNACとして、UDON療法は有用である。(著者抄録)
  • 木村 豊; 大東 弘治; 安田 篤; 加藤 寛章; 上田 和毅; 今本 治彦; 川村 純一郎; 安田 卓司
    近畿大学医学雑誌 近畿大学医学会 44 (3-4) 121 - 131 0385-8367 2019/12 
    消化器癌に対するロボット支援下手術(RS)は、2018年4月に胃癌に対する腹腔鏡下胃切除術(幽門側胃切除術)、腹腔鏡下噴門側胃切除術、腹腔鏡下胃全摘術の他に、食道癌に対する胸腔鏡下食道悪性腫瘍手術、直腸癌に対する腹腔鏡下直腸切除・切断術が保険収載され、今後ますます普及、発展していくことが予想される。RSで使用されるda Vinci Surgical Systemの利点として、手振れ防止機能、高解像度の3D内視鏡、多関節の鉗子、縮尺機能などがあげられる。一方、触覚がない、高額であるなどの欠点が指摘されているが、様々な科学技術の発展とともにRSも進歩していくことが期待される。消化器癌に対するRSに関して、一般的には時間はかかるが、出血量は少なく、合併症も低減できる可能性が報告されている。しかし、始まったばかりの手術であるため、エビデンスはまだ不十分であり、今後は、安全に行っていくともにエビデンスを構築していくことが求められている。(著者抄録)
  • 木村 豊; 大東 弘治; 安田 篤; 加藤 寛章; 上田 和毅; 今本 治彦; 川村 純一郎; 安田 卓司
    近畿大学医学雑誌 近畿大学医学会 44 (3-4) 121 - 131 0385-8367 2019/12 [Refereed]
     
    消化器癌に対するロボット支援下手術(RS)は、2018年4月に胃癌に対する腹腔鏡下胃切除術(幽門側胃切除術)、腹腔鏡下噴門側胃切除術、腹腔鏡下胃全摘術の他に、食道癌に対する胸腔鏡下食道悪性腫瘍手術、直腸癌に対する腹腔鏡下直腸切除・切断術が保険収載され、今後ますます普及、発展していくことが予想される。RSで使用されるda Vinci Surgical Systemの利点として、手振れ防止機能、高解像度の3D内視鏡、多関節の鉗子、縮尺機能などがあげられる。一方、触覚がない、高額であるなどの欠点が指摘されているが、様々な科学技術の発展とともにRSも進歩していくことが期待される。消化器癌に対するRSに関して、一般的には時間はかかるが、出血量は少なく、合併症も低減できる可能性が報告されている。しかし、始まったばかりの手術であるため、エビデンスはまだ不十分であり、今後は、安全に行っていくともにエビデンスを構築していくことが求められている。(著者抄録)
  • Yutaka Kimura; Osamu Shiraishi; Mitsuru Iwama; Hiroaki Kato; Hisato Kawakami; Tatsuya Okuno; Yoko Hiraki; Atsushi Yasuda; Masayuki Shinkai; Motohiro Imano; Kazuhiko Nakagawa; Takushi Yasuda
    Gan to kagaku ryoho. Cancer & chemotherapy 46 (13) 2173 - 2175 0385-0684 2019/12 [Refereed]
     
    BACKGROUND: In Japan, pre-operative 5-FU and cisplatin(CDDP)(FP)combination therapy has been the standard neoadjuvant chemotherapy(NAC)for advanced resectable esophageal cancer(EC); furthermore, the efficacy of the docetaxel (DTX)-containing triplet regimen, FP plus DTX, has been reported. However, patients with impaired renal function should not receive high-dose CDDP. We have been developing a non-CDDP-containing triplet regimen, comprising 5-FU, DTX, and nedaplatin(NED)(UDON), on a phase Ⅰ/Ⅱtrial basis. This retrospective study aimed to investigate the safety and efficacy of NAC with UDON in advanced EC patients with impaired renal function. METHODS: Five patients with advanced resectable EC with impaired renal function were enrolled in this study. Patients received NAC(5-FU, 640mg/m / 2, days 1-5; DTX, 28 mg/m2, days 1 and 15; and NED, 72mg/m2, day 1, q28, 2 courses); following this, they underwent esophagectomy. The primary endpoint was response rate, and the secondary endpoint was adverse event(AE). RESULTS: The median age was 79 years (range: 58-80 years). The ECOG performance status was 1/2 : 3/2. The main tumor locations were Ce/Ut/Mt : 1/1/3 and the cStages were ⅡA/ⅢA/ⅢC : 1/2/2. The RR(CR/PR/SD/PD : 0/4/1/0)was 80%. The pathological response was grade 1a/1b : 2/3. Major grade 3 or 4 AEs included neutropenia(40%), febrile neutropenia(20%), diarrhea(20%), and hyponatremia( 40%). There was no treatment-related death or reoperation. CONCLUSIONS: NAC with UDON might be feasible and effective in patients with advanced resectable EC with impaired renal function, who are ineligible for high-dose CDDP administration. We are planning a phaseⅡclinical study based on the present results.
  • 加藤 寛章; 白石 治; 岩間 密; 安田 篤; 新海 政幸; 木村 豊; 安田 卓司
    臨床外科 (株)医学書院 74 (11) 94 - 97 0386-9857 2019/10
  • Koji Haratani; Hidetoshi Hayashi; Takayuki Takahama; Yasushi Nakamura; Shuta Tomida; Takeshi Yoshida; Yasutaka Chiba; Takahiro Sawada; Kazuko Sakai; Yoshihiko Fujita; Yosuke Togashi; Junko Tanizaki; Hisato Kawakami; Akihiko Ito; Kazuto Nishio; Kazuhiko Nakagawa
    Journal for immunotherapy of cancer 7 (1) 251 - 251 2019/09 [Refereed]
     
    BACKGROUND: Immune checkpoint inhibitors (ICIs) confer a survival benefit in many cancer types. Given that the survival outcome for cancer of unknown primary site (CUP) remains poor, we investigated the potential of CUP for immunotherapy. METHODS: A total of 164 patients with CUP (favorable subset, 34 patients; unfavorable subset, 130 patients) who were treated between January 2009 and March 2017 was identified from a review of medical records at Kindai University Hospital. They included 92 patients for whom pretreatment tumor tissue was available both for determination of programmed cell death-ligand 1 expression and tumor-infiltrating lymphocyte (TIL) density by immunohistochemistry (IHC) and for immune-related gene expression profiling (irGEP). The results of irGEP for CUP were compared with published data for ICI-treated solid cancers classified into progressive disease (PD) and non-PD subsets according to their best response to ICIs. RESULTS: The median overall survival of all CUP patients was 29.3 months (95% confidence interval [CI], 15.7-not reached) and 7.1 months (95% CI, 5.0-9.4) for favorable and unfavorable subsets, respectively. IHC and irGEP revealed that pretreatment immune activity-including expression of immune checkpoint molecules-for CUP was similar to that for ICI-responsive malignancies (antitumor immune cell signatures: CUP versus PD, P = 0.002-0.067; CUP versus non-PD, P = 0.591-0.999), although VEGFA expression was associated with suppression of antitumor immunity in CUP (P = 0.008, false discovery rate = 0.010). In addition, one case of CUP in the unfavorable subset that was associated with prominent PD-L1 expression on TILs and showed a durable response to nivolumab is presented. CONCLUSIONS: The survival outcome of CUP remains unsatisfactory. However, our clinical and immune profiling of CUP has revealed a potential to benefit from immunotherapy, with ICIs thus being a potential option for CUP treatment.
  • Masanori Terashima; Yoshiaki Iwasaki; Junki Mizusawa; Hiroshi Katayama; Kenichi Nakamura; Hitoshi Katai; Takaki Yoshikawa; Yuichi Ito; Masahide Kaji; Yutaka Kimura; Motohiro Hirao; Makoto Yamada; Akira Kurita; Masakazu Takagi; Narikazu Boku; Takeshi Sano; Mitsuru Sasako; Akinori Takagane; Keisuke Koeda; Shin Teshima; Tsuneaki Fujitani; Norimasa Fukushima; Naoyuki Matsushita; Hase Kazuo; Yoshiyuki Kawashima; Takahiro Kinoshita; Mikito Inokuchi; Masanori Ueno; Ikuo Wada; Hiroshi Yabusaki; Yasuyuki Kawauchi; Kaoru Miyashita; Seiji Ito; Hiroaki Hata; Yuichiro Doki; Takushi Yasuda; Ken Omori; Masahiro Goto; Hiroshi Imamura
    GASTRIC CANCER SPRINGER 22 (5) 1044 - 1052 1436-3291 2019/09 
    Background The prognosis of patients with linitis plastica (type 4) and large (>= 8 cm) ulcero-invasive-type (type 3) gastric cancer is extremely poor, even after extended surgery and adjuvant chemotherapy. Given the promising results of our previous phase II study evaluating neoadjuvant chemotherapy (NAC) with S-1 plus cisplatin (JCOG0210), we performed a phase III study to confirm the efficacy of NAC in these patients, with the safety and surgical results are presented here. Methods Eligible patients were randomized to gastrectomy plus adjuvant chemotherapy with S-1 (Arm A) or NAC followed by gastrectomy + adjuvant chemotherapy (Arm B). The primary endpoint was the overall survival (OS). This trial is registered at the UMIN Clinical Trials Registry as C000000279. Results From February 2007 to July 2013, 300 patients were randomized (Arm A 149, Arm B 151). NAC was completed in 133 patients (88%). Major grade 3/4 adverse events during NAC were neutropenia (29.3%), nausea (5.4%), diarrhea (4.8%), and fatigue (2.7%). Gastrectomy was performed in 147 patients (99%) in Arm A and 139 patients (92%) in Arm B. The operation time was significantly shorter in Arm B than in Arm A (median 255 vs. 240 min, respectively; p = 0.024). There were no significant differences in Grade 2-4 morbidity and mortality (25.2% and 1.3% in Arm A and 15.8% and 0.7% in Arm B, respectively). Conclusions NAC for type 4 and large type 3 gastric cancer followed by D2 gastrectomy can be safely performed without increasing the morbidity or mortality.
  • Yukinori Kurokawa; Hiroya Takeuchi; Yuichiro Doki; Shinji Mine; Masanori Terashima; Takushi Yasuda; Kazuhiro Yoshida; Hiroyuki Daiko; Shinichi Sakuramoto; Takaki Yoshikawa; Chikara Kunisaki; Yasuyuki Seto; Shigeyuki Tamura; Toshio Shimokawa; Takeshi Sano; Yuko Kitagawa
    Annals of surgery 274 (1) 120 - 127 0003-4932 2019/08 [Refereed]
     
    MINI: A prospective nationwide multicenter study revealed that total gastrectomy and para-aortic nodal dissection were not needed for esophagogastric junction tumors. Subtotal esophagectomy with dissection of upper mediastinal station 106recR should be selected if esophageal involvement exceeds 4.0 cm. Lower mediastinal station 110 should be dissected if esophageal involvement exceeds 2.0 cm. OBJECTIVE: The aim of the study was to determine the optimal extent of lymph node dissection for the 2 histological types of esophagogastric junction (EGJ) tumors based on the incidence of metastasis in a prospective nationwide multicenter study. BACKGROUND: Because most previous studies were retrospective, the optimal surgical procedure for EGJ tumors has not been standardized. METHODS: Patients with cT2-T4 adenocarcinoma or squamous cell carcinoma located within 2.0 cm of the EGJ were enrolled before surgery. Surgeons dissected all lymph nodes prespecified in the protocol, using either the abdominal transhiatal or right transthoracic approach. The primary endpoint was the metastasis rate of each lymph node. Lymph nodes were classified according to metastasis rate, as follows: category-1 (strongly recommended for dissection), rate more than 10%; category-2 (weakly recommended for dissection), rate from 5% to 10%; and category-3 (not recommended for dissection), rate less than 5%. RESULTS: Between 2014 and 2017, 1065 patients with EGJ tumor were screened, and 371 were enrolled. Among 358 patients who underwent surgical resection, category-1 nodes included abdominal stations 1, 2, 3, 7, 9, and 11p, whereas category-2 nodes included abdominal stations 8a, 19, and lower mediastinal station 110. If esophageal involvement exceeded 2.0 cm, station 110 was assigned to category-1. Among 98 patients who had either adenocarcinoma with esophageal involvement over 3.0 cm or squamous cell carcinoma, there were no category-1 nodes in the upper/middle mediastinal field, whereas category-2 nodes included upper mediastinal station 106recR and middle mediastinal station 108. When esophageal involvement exceeded 4.0 cm, station 106recR was assigned to category-1. CONCLUSION: The study accurately identified the distribution of lymph node metastases from EGJ tumors and the optimal extent of subsequent lymph node dissection.
  • 食道癌に対する術前化学療法後のリンパ節における微小転移の臨床的意義
    平木 洋子; 木村 豊; 今野 元博; 加藤 寛章; 岩間 密; 白石 治; 安田 篤; 新海 政幸; 土岐 祐一郎; 安田 卓司
    日本消化器外科学会総会 (一社)日本消化器外科学会 74回 P2 - 3 2019/07
  • 気道系浸潤高度振興食道癌に対する手術
    Takushi Yasuda
    手術 73 (4) 379 - 390 2019/03 [Refereed]
  • Kimio Yonesaka; Yoshihisa Kobayashi; Hidetoshi Hayashi; Yasutaka Chiba; Tetsuya Mitsudomi; Kazuhiko Nakagawa
    Oncology reports 41 (2) 1059 - 1066 1021-335X 2019/02 [Refereed]
     
    Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‑TKIs) are efficacious drugs for non‑small cell lung cancers (NSCLCs) with EGFR‑activating mutations. Afatinib, a second‑generation EGFR‑TKI and osimertinib, a third‑generation EGFR‑TKI, are both standard therapies for patients with these types of cancer. Each drug possesses distinct binding sites for the tyrosine kinase domain of EGFR. The present study examined the efficacy of single and combination TKI therapy using in vitro growth inhibition assays of Ba/F3 cells with an EGFR‑activating Del19 mutation. Afatinib or osimertinib treatment alone markedly inhibited cell proliferation in Ba/F3 cells, although drug‑resistant cells eventually appeared with secondary EGFR mutations (either T790M or C797S, respectively) as determined by direct sequencing. Notably a combination of afatinib and osimertinib eradicated Ba/F3 cells with no development of resistance. We also evaluated the efficacy of afatinib, osimertinib, and a combination of the two, using drug‑resistant cells with T790M or C797S mutations. Osimertinib was effective for treating Ba/F3 cells with the T790M mutation, whereas afatinib was moderately effective against C797S Ba/F3 cells. However, subsequent treatment, even when both drugs were used in combination, could not completely eradicate the Ba/F3 population and doubly resistant cells with a variety of triple mutations were generated, including Del19/T790M/C797S. In conclusion, an initial treatment with a combination of osimertinib and afatinib is potentially more effective for eradicating mutant EGFR‑dependent cells than sequential drug use. This should be tested in future clinical trials to establish whether such a combination would be effective for the treatment of NSCLC.
  • Satoru Motoyama; Eri Maeda; Masahiko Yano; Takushi Yasuda; Masaichi Ohira; Yuichiro Doki; Yasushi Toh; Takahiro Higashi; Hisahiro Matsubara
    Esophagus : official journal of the Japan Esophageal Society 16 (1) 114 - 121 1612-9059 2019/01 [Refereed]
     
    BACKGROUND: Since 2013, The Japan Esophageal Society has been certifying "Authorized Institute for Board Certified Esophageal Surgeon (AIBCES)" to contribute to improving national medical care by enhancing the professional knowledge and skills of esophageal surgeons. However, the appropriateness on this certification system has not yet been verified. Our aim was to assess the appropriateness of the institute certification system for esophageal surgeries used by the medical society. METHODS: Using data from the National Database of Hospital-based Cancer Registries, we analyzed the 5-year overall survival rates among 2135 patients with thoracic esophageal cancer who underwent an esophagectomy at 53 AIBCES or 141 non-AIBCES. RESULTS: There were 1343 (63%) patients who underwent surgery at an AIBCES and 792 (37%) who underwent surgery at a non-AIBCES. Registered patients were followed up for a median of 53 (range 1-88) months. Over the followed-up period examined, 670 (50%) patients treated at an AIBCES died and 455 (57%) treated at a non-AIBCES died. Comparison of the Kaplan-Meier survival curves indicated that patients with cStage II or cStage III disease treated at an AIBCES had significantly better 5-year survival rates than those treated at a non-AIBCES (55.4% vs. 44.9% and 38.0% vs. 30.3%, respectively). Univariate and multivariate analyses stratified based on stages and adjuvant therapies revealed that institute certification (AIBCES vs. non-AIBCES) is a significant independent factor for 5-year survival. CONCLUSIONS: The institute certification system used by the Japan Esophageal Society may be appropriate, as indicated by improved 5-year survival outcomes. The institute certification system has the potential to contribute to a more appropriate medical delivery system in the future.
  • Masayuki Shinkai; Motohiro Imano; Yasutaka Chiba; Mitsuru Iwama; Osamu Shiraisi; Atsushi Yasuda; Masanobu Tsubaki; Shozo Nishida; Yutaka Kimura; Takushi Yasuda
    Journal of surgical oncology 119 (1) 56 - 63 0022-4790 2019/01 [Refereed]
     
    BACKGROUND: We carried out a phase II trial to evaluate the feasibility and efficacy of neoadjuvant chemotherapy comprising a single intraperitoneal administration of paclitaxel, followed by intravenous administrations of paclitaxel and cisplatin with S-1 for clinical stage III gastric cancer. METHODS: Patients with potentially resectable gastric cancer were eligible. A laparoscopic survey was performed to confirm CY0 and P0. Intraperitoneal paclitaxel (60 mg/m 2 ) was administered, followed by systemic chemotherapy. Surgery was performed after two cycles of chemotherapy. The primary endpoint was the response rate of chemotherapy. Secondary endpoints were adverse events, pathological response rate, and overall survival rate. RESULTS: Twenty patients were enrolled. Planned cycles were completed in all patients. Grade 3/4 leukopenia and grade 3/4 neutropenia were observed in four (20%) and seven (35%) patients, respectively. The overall response rate was 70% (partial response: 14, stable disease: 5, progressive disease: 1). All patients underwent R0 gastrectomy with D2 lymph-node dissection, with no surgery-related deaths. The pathological response rate was 65% (13 of 20). The 3- and 5-year overall survival rates were 90.0% and 77.1%, respectively. CONCLUSIONS: Neoadjuvant chemotherapy including intraperitoneal paclitaxel followed by sequential intravenous paclitaxel and cisplatin with S-1 for resectable advanced gastric cancer is feasible and effective.
  • FDG PET/CTによる食道癌術前化学療法の予後解析
    甲斐田 勇人; 白石 治; 岩間 密; 加藤 寛章; 木村 豊; 花岡 宏平; 山田 穣; 北島 一宏; 細野 眞; 安田 卓司; 石井 一成
    核医学 (一社)日本核医学会 55 (Suppl.) S200 - S200 0022-7854 2018/11 [Refereed]
  • Masayuki Shinkai; Motohiro Imano; Yasutaka Chiba; Yoko Hiraki; Hiroaki Kato; Mitsuru Iwama; Osamu Shiraishi; Atsushi Yasuda; Masahiro Tsubaki; Shozo Nishida; Yutaka Kimura; Takushi Yasuda
    Anticancer research 38 (10) 5975 - 5981 2018/10 [Refereed]
     
    AIM: To conduct a phase II study of single intraperitoneal (i.p.) administration of paclitaxel followed by paclitaxel, cisplatin, and S-1 (PCS) chemotherapy for patients with gastric cancer with peritoneal metastasis (PM). PATIENTS AND METHODS: Staging laparotomy was performed to confirm PM. Initially, patients received i.p. paclitaxel. Beginning 7 days later, PCS was given every 3 weeks followed by second-look laparoscopy. Primary and secondary endpoints were the overall survival (OS) rate, and response rate and patient safety, respectively. RESULTS: Seventeen patients were enrolled. The overall response rate was 70.5% (12/17). Grade 3/4 toxic effects included neutropenia and leukopenia. After chemotherapy, PM disappearance was confirmed in 11 patients. Gastrectomy was eventually performed in 11 patients. The 1-year OS rate was 82.4% and the median survival time was 23.9 months considering the overall cohort. CONCLUSION: Combination chemotherapy with i.p. paclitaxel and PCS is well tolerated and effective in patients with gastric cancer with PM.
  • Masayuki Shinkai; Motohiro Imano; Yasutaka Chiba; Yoko Hiraki; Hiroaki Kato; Mitsuru Iwama; Osamu Shiraisi; Atsushi Yasuda; Masahiro Tsubaki; Shozo Nishida; Yutaka Kimura; Takushi Yasuda
    Anticancer research 38 (10) 5969 - 5974 2018/10 [Refereed]
     
    BACKGROUND/AIM: A preliminary study evaluating the feasibility of single intraperitoneal (IP) administration of paclitaxel followed by paclitaxel and cisplatin with S-1 (PCS) systemic chemotherapy for cytology-positive (CY1) gastric cancer. PATIENTS AND METHODS: Staging laparoscopy was performed to confirm CY1 and P0 status. Initially, patients received IP paclitaxel. Beginning 7 days later PCS was given every 3 weeks followed by second-look laparoscopy. RESULTS: Nine patients were enrolled. The toxic effects of IP and systemic chemotherapy were acceptable. After chemotherapy, 8 patients converted from CY1P0 to CY0P0 and 1 patient from CY1P0 to CY1P1. Gastrectomy was performed on 8 patients except for the CY1P1 patient. Four patients were alive without recurrence. The 2-year overall and progression-free survival rates were 76% and 65%, respectively. CONCLUSION: Combination chemotherapy with IP paclitaxel and sequential PCS is safe and may be effective for CY1 gastric cancer.
  • Takushi Yasuda
    Annals of surgical oncology Springer New York LLC 25 (8) 2127 - 2128 1534-4681 2018/08 [Refereed]
  • Takushi Yasuda; Osamu Shiraishi; Mitsuru Iwama; Tomoki Makino; Hiroaki Kato; Yutaka Kimura
    The Journal of thoracic and cardiovascular surgery Mosby Inc. 156 (2) 859 - 866 1097-685X 2018/08 [Refereed]
     
    BACKGROUND: The incidence of metachronous esophageal squamous cell cancer (ESCC) after head and neck cancer (HNC) and in elderly patients has increased. Both elderly ESCC patients and ESCC patients after HNC surgery are at potential risk for dysphagia, and for the latter, surgery in the neck is difficult. An intrathoracic anastomosis that bypasses the cervical procedure is preferable to preserve swallowing function and reduce surgical risk. In gastrectomized patients, because the stomach cannot be used as a substitute, securing graft blood supply is critical, but microvascular anastomosis cannot be easily added in procedures for intrathoracic posterior mediastinal reconstruction. Thus, we have developed a novel technique for esophageal reconstruction in gastrectomized patients who are elderly or who had undergone HNC surgery, enabling concomitant intrathoracic anastomosis and microvascular anastomosis. The purpose of this study was to evaluate the usefulness and safety of this technique. METHODS: The jejunal or ileocolic graft is first pulled up through the anterior mediastinum and is then passed into the right thoracic cavity via a small hole made in the anterior mediastinal pleura. The graft is finally anastomosed with the remnant esophagus in the upper posterior mediastinum. Thereafter, microvascular anastomosis is performed in the retrosternal space. RESULTS: Four patients underwent this new reconstruction procedure with no significant postoperative complications, good swallowing function postoperatively, and no retention of food in the graft. CONCLUSIONS: This novel transmediastinal reconstruction technique is a possible option for highly selected patients to enable intrathoracic anastomosis and the addition of microvascular anastomosis.
  • Kosuke Minaga; Mamoru Takenaka; Ayana Okamoto; Shunsuke Omoto; Takeshi Miyata; Hajime Imai; Masatoshi Kudo
    Endoscopy Georg Thieme Verlag 50 (7) E153 - E154 1438-8812 2018/07
  • 切除可能食道癌に対する術前化学療法としてのDCFとACF療法の多施設共同ランダム化比較試験 Annals of Oncology
    山崎 誠; 安田 卓司; 矢野 雅彦; 平尾 素宏; 小林 研二; 藤谷 和正; 田村 茂行; 木村 豊; 宮田 博志; 本告 正明; 白石 治; 牧野 知紀; 佐藤 太郎; 森 正樹; 土岐 祐一郎
    日本外科学会定期学術集会抄録集 (一社)日本外科学会 118回 785 - 785 2018/04
  • 腹腔鏡下胃全摘と比較した腹腔鏡下噴門側胃切除(食道残胃吻合)のメリット(残胃を残す意義)(Advantage of proximal gastrectomy compared with total gastrectomy in laparoscopic surgery)
    安田 篤; 木村 豊; 平木 洋子; 加藤 寛章; 岩間 密; 白石 治; 新海 政幸; 今野 元博; 今本 治彦; 古河 洋; 安田 卓司
    日本胃癌学会総会記事 (一社)日本胃癌学会 90回 283 - 283 2018/03
  • Tomoya Yokota; Takushi Yasuda; Hiroyuki Kato; Isao Nozaki; Hiroshi Sato; Yoshinori Miyata; Yoshifumi Kuroki; Ken Kato; Yasuo Hamamoto; Yasuhiro Tsubosa; Hirofumi Ogawa; Yoshinori Ito; Yuko Kitagawa
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY SPRINGER JAPAN KK 23 (1) 73 - 80 1341-9625 2018/02 [Refereed]
     
    We conducted a multicenter phase II trial assessing chemoselection with docetaxel plus 5-fluorouracil and cisplatin induction chemotherapy and subsequent conversion surgery for locally advanced, unresectable esophageal cancer. The aim of this study was to validate the concordance of clinical T diagnosis among physicians in the cases of this trial.Computed tomography scans and esophagoscopic images of 48 patients taken at baseline were centrally reviewed by 6 senior physicians with experience in esophageal oncology. Individual reviewers voted for definitive T4, relative T4, relative T3, or definitive T3. Discordant diagnoses between reviewers were resolved by the majority opinion. The reviewers were blinded to patient clinical outcome data and to the vote of the other reviewers.Ninety percent of cases were diagnosed as clinical T4 by investigators, while 33.3-75.0% (median 70.8%) of cases were judged to be T4 by 6 reviewers. Discordant diagnosis between investigators and reviewers occurred in 33% (16/48) of all cases (Cohen's kappa coefficient 0.0519), including 12 cases where curative resection was considered possible (48%, n = 25) and 4 cases where curative resection was considered impossible (17%, n = 23). Critical discordance (one reviewer voted for definitive T3 but the other voted for definitive T4, and vice versa) between reviewers occurred in 0-12.5% of cases (median 2.1%).There were inter-observer variations in clinical diagnosis of the T category of locally advanced, unresectable esophageal cancer. Accurate clinical diagnosis of T classification is required for determining the optimum treatment for each patient.
  • Junko Tanizaki; Koji Haratani; Hidetoshi Hayashi; Yasutaka Chiba; Yasushi Nakamura; Kimio Yonesaka; Keita Kudo; Hiroyasu Kaneda; Yoshikazu Hasegawa; Kaoru Tanaka; Masayuki Takeda; Akihiko Ito; Kazuhiko Nakagawa
    Journal of Thoracic Oncology Elsevier Inc 13 (1) 97 - 105 1556-1380 2018/01 [Refereed]
     
    Objective The aim of this study was to identify baseline peripheral blood biomarkers associated with clinical outcome in patients with NSCLC treated with nivolumab. Methods Univariable and multivariable analyses were performed retrospectively for 134 patients with advanced or recurrent NSCLC treated with nivolumab to evaluate the relationship between survival and peripheral blood parameters measured before treatment initiation, including absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute monocyte count, and absolute eosinophil count (AEC), as well as serum C-reactive protein and lactate dehydrogenase levels. Progression-free survival, overall survival, and response rate were determined. Results Among the variables selected by univariable analysis, a low ANC, high ALC, and high AEC were significantly and independently associated with both better progression-free survival (p = 0.001, p = 0.04, and p = 0.02, respectively) and better overall survival (p = 0.03, p = 0.03, and p = 0.003, respectively) in multivariable analysis. Categorization of patients according to the number of favorable factors revealed that those with only one factor had a significantly worse outcome than those with two or three factors. A similar trend was apparent for patients with a programmed death 1 ligand tumor proportion score less than 50%, whereas all patients with a score of 50% or higher had at least two favorable factors. Conclusions A baseline signature of a low ANC, high ALC, and high AEC was associated with a better outcome of nivolumab treatment, with the number of favorable factors identifying subgroups of patients differing in survival and response rate.
  • Takeo Fukagawa; Hitoshi Katai; Junki Mizusawa; Kenichi Nakamura; Takeshi Sano; Masanori Terashima; Seiji Ito; Takaki Yoshikawa; Norimasa Fukushima; Yasuyuki Kawachi; Takahiro Kinoshita; Yutaka Kimura; Hiroshi Yabusaki; Yasunori Nishida; Yoshiaki Iwasaki; Sang-Woong Lee; Takashi Yasuda; Mitsuru Sasako; on behalf of the Stomach Cancer Study Group of the Japan Clinical Oncology Group
    Gastric Cancer Springer Tokyo 21 (1) 68 - 73 1436-3305 2018/01 [Refereed]
     
    Background: Neoadjuvant chemotherapy (NAC) followed by radical surgery is a promising strategy to improve survival of patients with stage III gastric cancer, but is associated with the risk of preoperative overdiagnosis by which patients with early disease may receive unnecessary intensive chemotherapy. Methods: We assessed the validity of a preoperative diagnostic criterion in a prospective multicenter study. Patients with gastric cancer with a clinical diagnosis of T2/T3/T4, M0, except for diffuse large tumors and extensive bulky nodal disease, were eligible. Prospectively recorded clinical diagnoses (cT category, cN category) were compared with postoperative pathological diagnoses (pT category, pN category, and pathological stage). The primary endpoint was the proportion of pathological stage I tumors among those diagnosed as cT3/T4, which we expected to be 5% or less. Results: Data from 1260 patients enrolled from 53 institutions were analyzed. The proportion of pathological stage I tumors in those with a diagnosis of cT3/T4 (primary endpoint) was 12.3%, which was much higher than the prespecified value. The positive predictive value and the sensitivity for pathological stage III tumors were 43.6% and 87.8% respectively. The sensitivity and specificity of contrast-enhanced CT for lymph node metastasis were 62.5% and 65.7% respectively. After exploring several diagnostic criteria, we propose, for future NAC trials in Japan, a diagnosis of “cT3/T4 with cN1/N2/N3,” by which inclusion of pathological stage I tumors was reduced to 6.5%, although its sensitivity for pathological stage III tumors decreased to 64.5%. Conclusion: Clinical diagnosis of T3/T4 tumors was not an optimal criterion to select patients for intensive NAC trials because more than 10% of patients with pathological stage I disease were included. We propose the criterion “cT3/T4 and cN1/N2/N3” instead.
  • スキルス胃がんが疑われた早期胃癌の切除例
    中野博史; 古河洋; 中室誠; 近藤禎晃; 大久保遊平; 星本真弘; 太田善夫; 佐藤隆夫; 木村豊; 今野元博; 安田卓司
    癌と化学療法 45 (12) 2018 [Refereed]
  • 臓器把持用クリップを活用した肥満患者に対する腹腔鏡下胃切除術の工夫
    木村 豊; 安田 篤; 加藤 寛章; 岩間 密; 白石 治; 新海 政幸; 今本 治彦; 安田 卓司
    日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 22 (7) EP191 - 07 1344-6703 2017/12
  • Yasuda A; Yasuda T; Kato H; Iwama M; Shiraishi O; Hiraki Y; Tanaka Y; Shinkai M; Imano M; Kimura Y; Imamoto H
    Surgical case reports 3 (1) 79 - 79 2017/12 [Refereed]
     
    BACKGROUND: An incisional hernia in a case of antethoracic pedicled jejunal flap esophageal reconstruction after esophagectomy is a very rare occurrence, and this hernia was distinctive in that the reconstructed jejunum had passed through the hernial orifice; a standard surgical treatment for such a presentation has not been established. Herein, we describe a case of repair using mesh prosthesis for an atypical and distinctive incisional hernia after antethoracic pedicled jejunal flap esophageal reconstruction. CASE PRESENTATION: A 77-year-old woman with a history of subtotal esophagectomy who had undergone antethoracic pedicled jejunal flap reconstruction complained of epigastric prominence and discomfort without pain. On examination, she had an abdominal protrusion between the xiphoid process and the umbilicus that contained the small bowel. Computed tomography showed that the fenestration of the abdominal wall that was intentionally created for jejunum pull-up was dehisced in a region measuring 9 × 15 cm and the small intestine protruded through it into the subcutaneous space without strangulation. Because the hernial orifice was too large and the reconstructed jejunum was passing through the hernial orifice in this case, we applied a parastomal hernia repair method that was modified from the inguinal hernia repair using the Lichtenstein technique. After 3 years and 5 months following surgery, the patient has recovered without hernia recurrence or other complications. CONCLUSION: We consider this to be the first case of repair using Composix mesh prosthesis for repair of an atypical and distinctive incisional hernia after an antethoracic pedicled jejunal flap reconstruction. This method seems to be useful and could potentially be widely adopted as the surgical treatment for this condition.
  • 木村 豊; 間狩 洋一; 三上 城太; 平木 洋子; 加藤 寛章; 岩間 密; 白石 治; 安田 篤; 新海 政幸; 今野 元博; 今本 治彦; 藤田 淳也; 古河 洋; 安田 卓司
    癌と化学療法 (株)癌と化学療法社 44 (12) 1080 - 1082 0385-0684 2017/11 
    はじめに:進行再発胃癌の二次治療として推奨されているramucirumab(RAM)+paclitaxel(PTX)療法の特徴的な有害事象(AE)として蛋白尿があげられる。今回、RAM+PTX療法によりgrade(gr)3の蛋白尿を来したためRAMを中止し、PTX単剤を続行し、奏効を得た高齢の再発胃癌の1例を経験した。症例:77歳、女性。76歳時に胃癌のため幽門側胃切除術、D2郭清を施行され、粘液癌、T4aN3H0P0CY0M0、fStage IIICであった。S-1による1年間の補助化学療法後、術後1年4ヵ月目に腹膜転移再発を来した。二次治療としてRAM(8mg/kg:第1、15日)+PTX(80mg/m2:第1、8、15日)を開始した。2コース目にgr3の尿蛋白(定性3+、尿中蛋白/Cr比8.30)を認めたためRAMを中止し、以後はPTX単剤の投与を施行した。RAM中止後に蛋白尿は速やかに改善し、2コース後のCT検査で腹水は減少、4コース後には腹水は消失した。考察:RAMの適正使用ガイドでは、投与前には尿蛋白定性検査を行い、2+以上では尿蛋白定量検査を行い、3g以上では投与の中止が推奨されている。本症例では、適正使用ガイドに則りPTX単剤を続行することによって奏効を得た。(著者抄録)
  • 新海 政幸; 今野 元博; 平木 洋子; 加藤 寛章; 岩間 密; 白石 治; 安田 篤; 木村 豊; 今本 治彦; 古河 洋; 安田 卓司
    癌と化学療法 (株)癌と化学療法社 44 (12) 1355 - 1357 0385-0684 2017/11 
    背景と目的:CY1P0胃癌の予後を改善する目的にpaclitaxel(PTX)腹腔内投与とPTX、cisplatin(CDDP)、S-1(PCS)3剤による全身化学療法を施行したので報告する。対象と方法:審査腹腔鏡によりCY1P0と診断した症例に対し、PTX腹腔内投与、逐次化学療法としてPCS療法を施行。2コース施行時にRECIST評価法にてPDでなければ、再度審査腹腔鏡を施行した。結果:症例は4例、腹腔内投与および全身化学療法によるGrade3以上の有害事象として1例に白血球減少、好中球減少を認めた。奏効度はPR1例、SD3例。全例に再度審査腹腔鏡を施行した。4例ともCY0P0にdown stageしていたため、D2郭清を伴う胃切除術を施行した。術後合併症は食道空腸吻合部の縫合不全1例と膵液瘻1例を認めた。組織学的治療効果判定はGrade 1a 3例、Grade 1b 1例。長期成績:肝再発1例、#16リンパ節再発を1例に認め原病死するも腹膜再発はなく、残り2例は無再発生存中である。結語:P0CY1胃癌に対する本治療法の有害事象は認容範囲であり、長期生存例も認めた。(著者抄録)
  • 岩間 密; 木村 豊; 白石 治; 加藤 寛章; 平木 洋子; 田中 裕美子; 安田 篤; 新海 政幸; 今野 元博; 今本 治彦; 安田 卓司
    癌と化学療法 (株)癌と化学療法社 44 (12) 1720 - 1722 0385-0684 2017/11 
    気管に浸潤したT4食道癌に対し化学放射線療法(CRT)と化学療法による集学的治療により、R0切除し得た症例を経験したので報告する。症例は75歳、男性。嗄声を自覚し、上部消化管内視鏡検査で胸部上部(Ut)に3型腫瘍を認め、CT検査でNo.106recRリンパ節(LN)の胸膜・気管浸潤を認めたため、食道扁平上皮癌、Ut、cT4b(No.106recR-気管)N1M0、cStage IIIC(UICC 7th)と診断した。5-FU+CDDP(CF)療法を併用したCRT(60Gy)を施行したがT4解除には至らず、docetaxel+CF(DCF)療法を2コース追加した。内視鏡上はほぼCRで、No.106recR LNも著明に縮小してFDG-PETの集積も消失したためT4解除と判断し、サルベージ手術を行った。Utの腫瘍からNo.106recR LNにかけては高度の瘢痕化を呈するも気管や反回神経の剥離は可能で、合併切除せずともR0切除が可能であった。T4局所進行食道癌に対しては、CRTにDCF療法を加えた集学的治療でT4解除が得られた後に手術を行うことで、安全かつ臓器機能の温存や予後の改善が期待できると考えられた。(著者抄録)
  • 平木 洋子; 加藤 寛章; 白石 治; 田中 裕美子; 岩間 密; 安田 篤; 新海 政幸; 木村 豊; 今野 元博; 今本 治彦; 安田 卓司
    癌と化学療法 (株)癌と化学療法社 44 (12) 1723 - 1725 0385-0684 2017/11 
    播種や他臓器浸潤が疑われる巨大胃gastrointestinal stromal tumor(GIST)に対して、イマチニブによる術前化学療法後に腫瘍切除を行った症例を経験したので報告する。症例は69歳、男性。急速に増大する腹部膨満感を主訴に受診した。CT検査にて壁外結節を伴い膵臓、脾臓と広範囲に接する巨大な胃原発を疑う嚢胞性腫瘤を認め、超音波内視鏡下穿刺吸引細胞診にてGISTと診断された。前治療なしでの手術では、術中の偽被膜破損や他臓器合併切除のリスクがあると判断し、術前化学療法としてイマチニブ400mg/日を6ヵ月間内服した。腫瘍活性が低下したが嚢胞部分の大きさが変化せず、腹部膨満の訴えが強いため手術を行った。イマチニブは術前1週間前に休薬し、合併切除や偽被膜破損なく腫瘍摘出術を行うことができ、術後2週目からイマチニブを再開した。術後経過は順調で、術後1年8ヵ月経過して無再発生存中である。(著者抄録)
  • 安田 篤; 安田 卓司; 木村 豊; 加藤 寛章; 平木 洋子; 岩間 密; 白石 治; 新海 政幸; 今野 元博; 今本 治彦
    癌と化学療法 (株)癌と化学療法社 44 (12) 1943 - 1945 0385-0684 2017/11 
    cStage II/III食道癌に対する治療戦略は術前化学療法(neoadjuvant chemotherapy:NAC)+根治手術が標準であるが、深い潰瘍症例などでは腫瘍穿通が生じて治療戦略を変更せざるを得ない状況に陥ることも経験される。今回、進行食道癌症例に対してNACを施行し、腫瘍壊死のため大動脈穿通のリスクを来したため緊急手術を施行して危険を回避し得た1症例を報告する。症例は62歳、女性。胸部つまり感と吐血を認め、内視鏡検査にて胸部食道癌(扁平上皮癌、cT4N2M0)と診断された。docetaxel+CDDP+5-FU(DCF)によるNACを施行したが2コース終了後に腫瘍が大動脈へ穿通寸前であることが判明し、緊急手術にて右開胸食道亜全摘、胸骨後経路細径胃管再建を行った。本症例は腫瘍がBotallo靱帯へ浸潤して根治切除はできなかったが、胸腔内穿通による縦隔炎や大動脈穿通などの危機的状態を回避することができた。進行癌の集学的治療では、常にoncologic emergencyに対する緊急対応を想定し、発症時には迅速に対処することが肝要と考えられた。(著者抄録)
  • Mitsuru Iwama; Yutaka Kimura; Osamu Shiraishi; Hiroaki Kato; Yoko Hiraki; Yumiko Tanaka; Atsushi Yasuda; Masayuki Shinkai; Motohiro Imano; Haruhiko Imamoto; Takushi Yasuda
    Gan to kagaku ryoho. Cancer & chemotherapy 44 (12) 1720 - 1722 0385-0684 2017/11 
    Prognosis of locally advanced esophageal cancer is poor. The greatest prognostic factor of locally advanced esophageal cancer is a local control. We experienced a case of T4 locally advanced thoracic esophageal cancer who was successfully resected without any combined resection after multimodality therapy. A male in 75-year-old. was diagnosed with type 3 locally advanced upper thoracic esophageal cancer whose metastatic right recurrent laryngeal lymph node invaded into the trachea. Definitive chemoradiation therapy(CRT)was performed, leading to a significant shrinkage of the main tumor, but T4 lesion remained. Next, adding DCF therapy(docetaxel, CDDP and 5-FU), a relief of T4 was finally obtained. Then, salvage surgery with subtotalesophagectomy and retrosternalesophagealreconstruction with gastric tube was performed, resulting in R0 resection without any combined resection. The postoperative course was uneventful, and the patient has been alive without recurrence for 1 year after surgery. In locally advanced cancer, focusing on T4 downstaging, it is significantly important in terms of safety, curativity and organ preservation to perform surgery after a sure sign of T4 relief by multimodality therapy.
  • 幕谷 悠介; 白石 治; 岩間 密; 平木 洋子; 加藤 寛章; 安田 篤; 新海 政幸; 今野 元博; 木村 豊; 今本 治彦; 安田 卓司
    癌と化学療法 (株)癌と化学療法社 44 (12) 1577 - 1579 0385-0684 2017/11 [Refereed]
     
    症例は76歳、男性。69歳時に胸部食道癌に対し右開胸食道亜全摘術、胸骨後経路胃管再建術を施行され、術中に心室細動から心停止を来した既往があった。今回、上部消化管内視鏡検査にて再建胃管幽門前庭部小彎の3型胃管癌(中分化型腺癌、cT2N0M0、cStage IIA)と診断された。高度のるい痩(BMI 15kg/m2)があり、間質性肺炎に対するステロイドの長期間の内服、前回手術時の心停止の既往があり、胸骨縦切開胃管全摘術を行うにはリスクが極めて高いと判断した。そのため胃管幽門側部分切除術とし、#4d、#6リンパ節は右胃大網動静脈をすだれ状に郭清し口側胃管への血流を温存、右胃動脈は切離し、#5リンパ節を郭清して病巣を摘出した。周術期に合併症はなく、術後40日目に退院となった。予備力の非常に乏しい患者には、根治性と安全性のバランスを考慮した本術式の選択が有用であったと考えられる。(著者抄録)
  • Yusuke Makutani; Osamu Shiraishi; Mitsuru Iwama; Yoko Hiraki; Hiroaki Kato; Atsushi Yasuda; Masayuki Shinkai; Motohiro Imano; Yutaka Kimura; Haruhiko Imamoto; Takushi Yasuda
    Gan to kagaku ryoho. Cancer & chemotherapy 44 (12) 1577 - 1579 0385-0684 2017/11 [Refereed]
     
    A 76-year-old man was admitted to our hospital for treatment of gastric tube cancer(cT2N0M0, cStage II A)detected by a screening upper gastrointestinal endoscopy. Seven years previously, he had undergone subtotal esophagectomy for esophageal cancer with gastric pull-up via the retrosternal route. At that time, he experienced cardiopulmonary arrest due to ventric- ular tachycardia. He was in a state of poor nutrition(BMI 15 kg/m2). Therefore, reducing operative stress as much as possible, minimizing complications after surgery, and aiming for a satisfactory postoperative course are all important goals. Based on his past history, we performed distal gastrectomy(resection of the distal part of the gastric tube)without excision of the right gastroepiploic artery. The postoperative course was uneventful. He was discharged 40 days after surgery. By considering the risks of surgery due to cardiac dysfunction and malnutrition, we were able to provide effective and safe therapy for the patient.
  • Yoko Hiraki; Hiroaki Kato; Osamu Shiraishi; Yumiko Tanaka; Mitsuru Iwama; Atsushi Yasuda; Masayuki Shinkai; Yutaka Kimura; Motohiro Imano; Haruhiko Imamoto; Takushi Yasuda
    Gan to kagaku ryoho. Cancer & chemotherapy 44 (12) 1723 - 1725 0385-0684 2017/11 [Refereed]
     
    The usefulness and safety of imatinibfor neoadjuvant chemotherapy for resectable gastrointestinal stromal tumor(GIST) has not been established. We reported a case of a huge GIST of the stomach that was safely resected following preoperative imatinibtherapy. A 69-year-old man was hospitalized with abdominal fullness which increased rapidly from a month ago. A CT scan showed a huge tumor containing solid and cystic component which was accompanied by an extra-wall nodule. The tumor was strongly suspected to be originated from the stomach and EUS-FNA revealed GIST. We diagnosed GIST of the stomach and initiated preoperative adjuvant chemotherapy with imatinib because there was a risk for the break of tumor capsule and composite resection of the other organs without prior chemotherapy. After the administration of imatinib4 00 mg/day for 6months, the solid component was decreased in size and its' activity by PET-CT had declined, but the size of the cystic component was not changed and the patient's complaint of fullness was not reduced. Then, after a week cessation of imatinib, we performed surgical removal of the tumor with partial gastrectomy without surgical complication during and after the operation. Imatinibwas resumed 2 weeks later postoperatively and 1 year and 8 months has passed since the operation without recurrence. Neoadjuvant chemotherapy with imatinibhas the potential to become an important therapeutic option for the treatment of huge GISTs.
  • Atsushi Yasuda; Takushi Yasuda; Yutaka Kimura; Hiroaki Kato; Yoko Hiraki; Mitsuru Iwama; Osamu Shiraishi; Masayuki Shinkai; Motohiro Imano; Haruhiko Imamoto
    Gan to kagaku ryoho. Cancer & chemotherapy 44 (12) 1943 - 1945 0385-0684 2017/11 [Refereed]
     
    According to the Guidelines for Diagnosis and Treatment of Carcinoma of the Esophagus in Japan, the standard treatment of esophageal cancer with cStage II / III is preoperative chemotherapy and radical resection. But when the tumor has deep ulcer, the perforation of it is sometimes occurred due of the anti-tumor effect and we are forced to change the standard treatment. In this time, we report a case of emergency resection of esophageal cancer which is on the brink of perforation after neoadjuvant chemotherapy. A 62-year-old woman had locally advanced esophageal cancer(cT4N2M0)and performed neoadjuvant chemotherapy(NAC). After 2 courses of NAC, the patient got into critical condition that the esophageal cancer was on the brink of perforation, thus we immediately performed emergency resection of the tumor. Unfortunately, the tumor was not completely resected because of invasion to the Botallo ligament, but we were able to avoid a critical state such as mediastinitis or penetration to the aorta. In multimodality therapy for locally advanced tumor, immediate response to oncologic emergency is significantly required, impacting on the prognosis and quality of life.
  • Kosuke Minaga; Mamoru Takenaka; Masayuki Kitano; Yasutaka Chiba; Hajime Imai; Kentaro Yamao; Ken Kamata; Takeshi Miyata; Shunsuke Omoto; Toshiharu Sakurai; Tomohiro Watanabe; Naoshi Nishida; Masatoshi Kudo
    SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES SPRINGER 31 (11) 4764 - 4772 0930-2794 2017/11 [Refereed]
     
    Treatment of unresectable malignant hilar biliary stricture (UMHBS) is challenging, especially after failure of repeated transpapillary endoscopic stenting. Endoscopic ultrasonography-guided intrahepatic biliary drainage (EUS-IBD) is a recent technique for intrahepatic biliary decompression, but indications for its use for complex hilar strictures have not been well studied. The aim of this study was to assess the feasibility and safety of EUS-IBD for UMHBS after failed transpapillary re-intervention. Retrospective analysis of all consecutive patients with UMHBS of Bismuth II grade or higher who, between December 2008 and May 2016, underwent EUS-IBD after failed repeated transpapillary interventions. The technical success, clinical success, and complication rates were evaluated. Factors associated with clinical ineffectiveness of EUS-IBD were explored. A total of 30 patients (19 women, median age 66 years [range 52-87]) underwent EUS-IBD for UMHBS during the study period. Hilar biliary stricture morphology was classified as Bismuth II, III, or IV in 5, 13, and 12 patients, respectively. The median number of preceding endoscopic interventions was 4 (range 2-14). EUS-IBD was required because the following procedures failed: duodenal scope insertion (n = 4), accessing the papilla after duodenal stent insertion (n = 5), or achieving desired intrahepatic biliary drainage (n = 21). Technical success with EUS-IBD was achieved in 29 of 30 patients (96.7%) and clinical success was attained in 22 of these 29 (75.9%). Mild peritonitis occurred in three of 30 (10%) and was managed conservatively. Stent dysfunction occurred in 23.3% (7/30). There was no procedure-related mortality. On multivariable analysis, Bismuth IV stricture predicted clinical ineffectiveness (odds ratio = 12.7, 95% CI 1.18-135.4, P = 0.035). EUS-IBD may be a feasible and effective rescue alternative with few major complications after failed transpapillary endoscopic re-intervention in patients with UMHBS, particularly for Bismuth II or III strictures.
  • Ken Kamata; Mamoru Takenaka; Masayuki Kitano; Shunsuke Omoto; Takeshi Miyata; Kosuke Minaga; Kentaro Yamao; Hajime Imai; Toshiharu Sakurai; Tomohiro Watanabe; Naoshi Nishida; Takaaki Chikugo; Yasutaka Chiba; Haruhiko Imamoto; Takushi Yasuda; Andrea Lisotti; Pietro Fusaroli; Masatoshi Kudo
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY WILEY 32 (10) 1686 - 1692 0815-9319 2017/10 [Refereed]
     
    Background and Aim: The study aims to evaluate contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for the differential diagnosis of submucosal tumors (SMT) of the upper gastrointestinal tract. Methods: Between June 2008 and May 2015, 157 consecutive patients with submucosal lesions of the upper gastrointestinal tract were evaluated by CH-EUS. This was a single-center retrospective analysis of prospectively collected data in a registry. The data from 73 patients who later underwent surgical resection were analyzed in this study. Surgical specimens served as the final diagnoses. The two CH-EUS variables of blood flow (hyper-enhancement vs hypo-enhancement) and homogeneity of enhancement pattern were evaluated. Results: The final diagnoses were 58 gastrointestinal stromal tumors (GISTs) and 15 benign SMTs (two lipomas, five leiomyomas, five schwannomas, two glomus tumors, and one ectopic pancreas). On CH-EUS, 49 of 58 (84.5%) GISTs presented with hyper-enhancement, whereas 4 of 15 (26.7%) benign SMTs showed hyper-enhancement; 21 of 58 (36.2%) GISTs showed inhomogeneous contrast enhancement, while only 2 of 15 (13.3%) benign SMTs demonstrated inhomogeneous contrast enhancement. If hyper-enhancement was considered to indicate GISTs, the sensitivity, specificity, and accuracy were 84.5%, 73.3%, and 82.2%, respectively. If inhomogeneous enhancement was considered to indicate GISTs, the sensitivity, specificity, and accuracy were 36.2%, 86.7%, and 46.6%, respectively. In lesions of less than 2cm, hyper-enhancement was a more sensitive indicator of GISTs than inhomogeneous enhancement. Conclusions: Hyper-enhancement and inhomogeneous enhancement were found to be a characteristic of GISTs. CH-EUS was useful for discrimination of benign SMTs from GISTs.
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  • 白石 治; 加藤 寛章; 岩間 密; 平木 洋子; 安田 篤; 新海 政幸; 木村 豊; 今野 元博; 今本 治彦; 安田 卓司
    消化器内視鏡 (株)東京医学社 29 (9) 1757 - 1764 0915-3217 2017/09 
    食道胃接合部癌はこれまでは食道癌、胃癌としておのおの扱われてきたため、その手術治療方針は確立されていない。術式決定の鍵となるのは開胸に関わる縦隔リンパ節、胃全摘に関わる胃大彎側のリンパ節、転移率の高い傍大動脈リンパ節(#16a2lat)の郭清の要否である。これまでの報告と自験例を合わせて検討すると、縦隔リンパ節転移は食道浸潤位置と関連があり、胃大彎リンパ節(#4d)は転移頻度が低く、進行癌では大動脈周囲リンパ節(#16a2lat)は転移をきたしやすい。現在、本邦では西分類食道胃接合部癌に対して、扁平上皮癌および食道浸潤長30mmを超える腺癌は"右開胸食道亜全摘+上中下縦隔リンパ節郭清"、30mmを超えない腺癌は"経裂孔的下部食道切除+下縦隔リンパ節郭清"、16a2latリンパ節の追加郭清、胃全摘は規定しない方針で前向き介入臨床試験が進んでおり、結果が待たれるところである。(著者抄録)
  • Volumetric parameterを用いた食道癌切除患者の予後因子の検討
    甲斐田 勇人; 石井 一成; 細川 知紗; 柳生 行伸; 任 誠雲; 兵頭 朋子; 山田 穣; 細野 眞; 安田 卓司; 村上 卓道
    核医学 (一社)日本核医学会 54 (Suppl.) S193 - S193 0022-7854 2017/09
  • Yutaka Kimura; Hiroshi Yano; Takashi Iwazawa; Junya Fujita; Shoichiro Fujita; Kazuyoshi Yamamoto; Takushi Yasuda
    SURGERY TODAY SPRINGER 47 (9) 1080 - 1085 0941-1291 2017/09 [Refereed]
     
    Purpose Many surgeons in Japan use 1-day nasogastric tube (NGT) decompression after gastrectomy as a standard procedure. This prospective randomized study aimed to define whether 1-day NGT decompression is necessary after distal gastrectomy. Methods The subjects were 233 patients with gastric cancer, randomized into two groups immediately after distal gastrectomy: one group received 1-day NGT decompression (NGT group, n = 119) and the other did not (no-NGT group, n = 114). The primary outcome measure was postoperative surgery-related and respiratory complications, whereas secondary measures were the postoperative course to recovery and patient complaints. Results The incidence of surgery-related complications did not differ significantly between the NGT and no-NGT groups (21.0 and 19.2%, respectively; p = 0.87). The rate of respiratory complications was 6.7% in the NGT group and 7.0% in the no-NGT group (p > 0.99). The time to passage of first flatus and the postoperative hospital stay did not differ between the groups. Twenty-five patients in the NGT group and none in the no-NGT group complained of nasopharyngeal discomfort ( p < 0.0001). Conclusion Considering the physical discomfort caused by the NGT, we believe that routine 1-day NGT decompression is unnecessary after distal gastrectomy.
  • 岩間密; 安田卓司; 白石治; 加藤寛章; 平木洋子; 田中裕美子; 安田篤; 新海政幸; 今野元博; 木村豊; 今本治彦
    胸部外科 70 (8) 720‐727 - 727 0021-5252 2017/07 
    Patients with esophageal cancer are often treated with definitive chemoradiotherapy (dCRT). Regardless of arrival at dCRT, the risk of local/regional recurrence during follow-up is significant. Many patient are faced with limited options for therapy once dCRT has failed. Salvage surgery is the only way for complete cure of patients with local/regional recurrent esophageal cancer after dCRT. However, salvage surgery has a significant high risk of fatal complications. We examine our preventive measures to reduce the incidence of postoperative complications after salvage surgery for thoracic esophageal cancer. The points of our preventive measures are them; I. the ingenuity of surgery, II. the securement of blood supply for the respiratory tract, III. standard lymphadenectomy, IV. countermeasures of anastomotic failure, V. countermeasures of dead space, VI. countermeasures of respiratory complications, VII. perioperative managements. Salvage surgery is a reasonable option to treat patients with local/regional recurrence after failed dCRT. Our preventive mesures are effective, therefore, we have to make the further technological developments and the safety of salvage surgery.
  • 高齢社会の癌治療 高齢者胸部食道癌手術におけるリスク因子と対策
    白石 治; 田中 由美子; 加藤 寛章; 岩間 密; 安田 篤; 新海 政幸; 木村 豊; 今野 元博; 今本 治彦; 安田 卓司
    日本気管食道科学会会報 (NPO)日本気管食道科学会 68 (2) 115 - 115 0029-0645 2017/04
  • 白石 治; 加藤 寛章; 岩間 密; 新海 政幸; 木村 豊; 安田 卓司
    手術 金原出版(株) 71 (5) 743 - 751 0037-4423 2017/04
  • 【消化器癌手術に必要な拡大視による局所微細解剖アトラス】 Esophageal Surgery 高度進行食道癌の切除可能性を見極める拡大視による局所微細解剖
    白石 治; 加藤 寛章; 岩間 密; 新海 政幸; 木村 豊; 安田 卓司
    手術 金原出版(株) 71 (4) 389 - 397 0037-4423 2017/03
  • Ken Kamata; Mamoru Takenaka; Atsushi Nakai; Shunsuke Omoto; Takeshi Miyata; Kosuke Minaga; Tomohiro Matsuda; Kentaro Yamao; Hajime Imai; Yasutaka Chiba; Toshiharu Sakurai; Tomohiro Watanabe; Naoshi Nishida; Takaaki Chikugo; Ippei Matsumoto; Yoshifumi Takeyama; Masatoshi Kudo
    Oncology S. Karger AG 93 (1) 102 - 106 0030-2414 2017 [Refereed]
  • Yoriaki Komeda; Hiroshi Kashida; Toshiharu Sakurai; Yutaka Asakuma; George Tribonias; Tomoyuki Nagai; Masashi Kono; Kosuke Minaga; Mamoru Takenaka; Tadaaki Arizumi; Satoru Hagiwara; Shigenaga Matsui; Tomohiro Watanabe; Naoshi Nishida; Takaaki Chikugo; Yasutaka Chiba; Masatoshi Kudo
    Oncology S. Karger AG 93 (1) 49 - 54 0030-2414 2017 [Refereed]
  • M. Yamasaki; T. Yasuda; M. Yano; M. Hirao; K. Kobayashi; K. Fujitani; S. Tamura; Y. Kimura; H. Miyata; M. Motoori; O. Shiraishi; T. Makino; T. Satoh; M. Mori; Y. Doki
    ANNALS OF ONCOLOGY OXFORD UNIV PRESS 28 (1) 116 - 120 0923-7534 2017/01 [Refereed]
     
    Background: This phase II trial evaluated the efficacy of cisplatin and fluorouracil (CF)-based combination neoadjuvant chemotherapy on the outcome of patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). We compared the recurrence-free survival (RFS) associated with CF plus Adriamycin (ACF) with that associated with CF plus docetaxel (DCF) to select an alternative regimen in a new phase III trial investigating the optimal neoadjuvant treatment of patients with ESCC. Patients and methods: Patients with resectable advanced ESCC were randomly assigned to either ACF (Adriamycin 35 mg/m(2), cisplatin 70 mg/m(2) i. v. on day 1, fluorouracil 700 mg/m(2) continuous infusion for 7 days) every 4 weeks or DCF (docetaxel 70 mg/m(2), cisplatin 70 mg/m(2) i. v. on day 1, fluorouracil 700 mg/m(2) continuous infusion for 5 days) every 3 weeks. Surgery was scheduled after completion of two cycles of chemotherapy. The primary end point was RFS, analyzed by the intention-to-treat. Results: Between October 2011 and October 2013, 162 patients at 10 institutions were enrolled in the study, all of whom were eligible and randomly assigned to the two groups (81 to the ACF group and 81 to the DCF group). The R0 resection rates for the ACF and DCF groups were equivalent (95.9% versus 96.2%, P = 0.93). The 2-year RFS and overall survival rates for DCF versus ACF were 64.1% versus 42.9% (hazard ratio 0.53, 95% confidence interval 0.33-0.83, P = 0.0057) and 78.6% versus 65.4% (P = 0.08), respectively. Conclusion: Compared with ACF, DCF chemotherapy was associated with prolonged RFS for
  • 【胃癌・食道癌のリンパ節郭清のすべて】 食道癌に対する頸部リンパ節郭清
    白石 治; 岩間 密; 加藤 寛章; 平木 洋子; 田中 裕美子; 中野 敬次; 安田 篤; 新海 政幸; 木村 豊; 今野 元博; 今本 治彦; 安田 卓司
    消化器外科 (株)へるす出版 40 (1) 17 - 29 0387-2645 2017/01
  • Hiroshi Miyata; Masahiko Yano; Takushi Yasuda; Makoto Yamasaki; Kohei Murakami; Tomoki Makino; Kohei Nishiki; Keijiro Sugimura; Masaaki Motoori; Osamu Shiraishi; Masaki Mori; Yuichiro Doki
    NUTRITION ELSEVIER SCIENCE INC 33 204 - 210 0899-9007 2017/01 [Refereed]
     
    Objectives: Omega-3 (omega-3) fatty acids have potential positive effects during chemotherapy, such as body weight maintenance and muscle mass preservation. However, little is known about the effect this supplement might have on reducing chemotherapy-induced toxicities. The aim of this study was to determine the usefulness of omega-3 fatty acid supplementation in the reduction of chemotherapy-related toxicities. Methods: Sixty-one patients undergoing neoadjuvant chemotherapy for esophageal cancer randomly received omega-3-rich enteral nutrition (EN; n = 31) or omega-3-poor EN support (n = 30) for 15 d during chemotherapy. The daily dosage of omega-3 fatty acids was 900 mg in the omega-3-rich group and 250 mg in the omega-3-poor group. The primary endpoint was the frequency of grade 3/4 neutropenia, and secondary endpoints included other chemotherapy-related adverse events, body weight, and inflammatory markers. Results: The total and dietary intake calories during chemotherapy were equal in both groups. There was no significant difference in the body weight change after chemotherapy between the two groups. There was no significant difference in the incidence of grade 3/4 leukopenia and neutropenia (P > 0.05). However, stomatitis was significantly less frequent in the omega-3-rich group, than in the omega-3-poor group (P = 0.018). Grade 3/4 diarrhea occurred relatively less frequently in the omega-3-rich group than in the omega-3-poor group; however, this difference was not significant (16.1% versus 36.7%, respectively, P = 0.068). Increases in the aspartate aminotransferase and alanine aminotransferase levels were seen significantly less frequently in the omega-3-rich group than in the omega-3-poor group (P = 0.012 and P = 0.015, respectively). Conclusions: 6)-3-rich EN support decreased the frequency of chemotherapy-induced mucosal toxicities, such as stomatitis and diarrhea, and exhibited a hepatoprotective effect during chemotherapy, compared with the omega-3-poor EN support. (C) 2016 Elsevier Inc. All rights reserved.
  • Osamu Shiraishi; Makoto Yamasaki; Tomoki Makino; Masaaki Motoori; Hiroshi Miyata; Masayuki Shinkai; Yutaka Kimura; Motohiro Hirao; Kazumasa Fujitani; Shigeyuki Tamura; Kenji Kobayashi; Masahiko Yano; Yuichiro Doki; Takushi Yasuda
    ONCOLOGY KARGER 92 (2) 101 - 108 0030-2414 2017 [Refereed]
     
    Background: Neoadjuvant chemotherapy for resectable advanced esophageal squamous cell carcinoma (ESCC) requires reassessment. We have conducted a trial aiming at the comparison between DCF and ACF concerning perioperative adverse events. Methods: Patients were randomly assigned to receive either DCF [docetaxel 70 mg/m(2), cisplatin 70 mg/m(2) on day 1, and 5-fluorouracil (5-FU) 700 mg/m(2) for 5 days] every 3 weeks or ACF (adriamycin 35 mg/m(2), cisplatin 70 mg/m(2) on day 1, and 5-FU 700 mg/m(2) for 7 days) every 4 weeks. Each group consisted of 81 patients. Two cycles of preoperative chemotherapy were planned, after which patients underwent subtotal esophagectomy via a right thoracotomy with lymphadenectomy. Chemotherapy- and surgery-related adverse effects were assessed. Results: Grade 3-4 neutropenia and febrile neutropenia occurred in 90 and 39% of patients, respectively, in the DCF group compared with 69 and 17% of patients, respectively, in the ACF group (p<0.01). Perioperative complications did not differ significantly between the groups. The overall response rates of DCF and ACF were 61 and 40%, respectively, while the histopathological complete responses were 15 and 3%, respectively (p<0.01). Conclusion: The DCF and ACF regimens were found to be equally feasible in patients with resectable advanced ESCC; however, DCF delivered an antitumor effect and therefore potentially improved the long-term outcomes. (C) 2016 S. Karger AG, Basel
  • 安田 卓司
    臨床外科 (株)医学書院 71 (13) 1469 - 1475 0386-9857 2016/12
  • 【周囲神経・血管・リンパ節までまるわかり!外科ナース・研修医のための消化器の手術&臓器のはたらき】 (2章)食道 だから食道手術後はどう注意する?
    加藤 寛章; 安田 卓司
    消化器外科Nursing (株)メディカ出版 (2016秋季増刊) 42 - 43 1341-7819 2016/10
  • 【周囲神経・血管・リンパ節までまるわかり!外科ナース・研修医のための消化器の手術&臓器のはたらき】 (2章)食道 食道の働きと解剖
    加藤 寛章; 安田 卓司
    消化器外科Nursing (株)メディカ出版 (2016秋季増刊) 30 - 41 1341-7819 2016/10
  • 安田 卓司
    臨床外科 (株)医学書院 71 (9) 1104 - 1112 0386-9857 2016/09 
    ＜ポイント＞合併切除に伴う手術・合併症リスクと浸潤部以外の手術の根治性のバランスを考慮したうえで適応を決定する.心膜や肺への部分浸潤が疑われるときは,積極的に合併切除したほうが術野展開と根治性の面で有利である.気道系の合併切除では,切除部および周囲の大血管の被覆,死腔充填と気管・気管支の血流確保が重要である.(著者抄録)
  • Ken Kamata; Masayuki Kitano; Satoru Yasukawa; Masatoshi Kudo; Yasutaka Chiba; Takeshi Ogura; Kazuhide Higuchi; Nobuyasu Fukutake; Reiko Ashida; Tomoaki Yamasaki; Hiroko Nebiki; Satoru Hirose; Noriyuki Hoki; Masanori Asada; Shujiro Yazumi; Makoto Takaoka; Kazuichi Okazaki; Fumihiro Matsuda; Yoshihiro Okabe; Akio Yanagisawa
    Endoscopy Georg Thieme Verlag 48 (7) 632 - 638 1438-8812 2016/07 [Refereed]
     
    Background and study aims: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with 25-gauge needles yields small volume samples that are mainly processed for cytology. Using 25-gauge needles with a core trap may overcome this limitation. This trial compared 25-gauge needles with and without a core trap in terms of their ability to obtain histologic samples from solid pancreatic masses. Patients and methods: Consecutive patients with solid pancreatic masses who presented to eight Japanese referral centers for EUS-FNA in April-September 2013 were randomized to undergo sampling with a 25-gauge needle with a core trap (ProCore) or a standard 25-gauge needle. Tissue samples were fixed in formalin and processed for histologic evaluation. For the purpose of this study only samples obtained with the first needle pass were used for comparison of: (i) accuracy for the diagnosis of malignancy, (ii) rate of samples with preserved tissue architecture adequate for histologic evaluation, and (iii) sample cellularity. Results: A total of 214 patients were enrolled. Compared to the first pass with a standard needle (n=108), the first pass with the ProCore needle (n=106) provided samples that were more often adequate for histologic evaluation (81.1% vs. 69.4% P=0.048) and had superior cellularity (rich/moderate/poor, 36%/27%/37% vs. 19%/26%/55% P=0.003). There were no significant differences between the two needles in sensitivity (75.6% vs. 69.0%, P=0.337) and accuracy (79.2% vs. 75.9%, P=0.561) for the diagnosis of malignancy. Conclusions: In patients with solid pancreatic masses, a 25-gauge EUS-FNA needle with a core trap provides histologic samples of better quality than a standard 25-gauge needle. There was no difference in accuracy for the diagnosis of malignancy between the needles. Clinical trial number: UMIN000010021.
  • 田中 裕美子; 白石 治; 熊野 正士; 曽我部 俊介; 岩間 密; 安田 篤; 新海 政幸; 今野 元博; 今本 治彦; 村上 卓道; 奥野 清隆; 安田 卓司
    近畿大学医学雑誌 近畿大学医学会 41 (1-2) 27 - 38 0385-8367 2016/06 
    切除困難な局所進行食道癌cT4(大動脈)も化学療法(ChT)/化学放射線療法(CRT)の進歩に伴い治癒切除率が向上し、より精度の高い深達度診断が求められている。我々は通常の仰臥位CTでのcT4診断(Picus角(PA)≧90度)に加え、重力差を利用した腹臥位CTとの比較による動的評価法を考案し、その有用性を検討した。対象は初診時仰臥位造影CTでcT3以深の食道癌22例(cT3/T4=17/5)35測定、全例ChT/CRTを先行し18例で手術を施行。腫瘍-大動脈壁間距離(T-A D)とPAを仰/腹CTで測定し、最終深達度(fT4=R1、2、fT3.5=R0 and著明な瘢痕化(+)、fT3=R0 and瘢痕化(-)、非手術例はEUS所見)と比較した。全35測定の平均後縦隔前後径(下縦隔)は仰/腹の順に12.3/26.0mmで、PA<60度(21測定)の平均T-A DとPAは3.0/4.4mm、23.2/16度と腹臥位で距離は延長し角度は縮小した(p<0.05)。治療前PA≧60度の10例はfT3/T3.5/T4=5/2/3。fT3は腹臥位で全例PAは減少しT-A Dも3/5例で延長、fT3.5はいずれかが不変、fT4は両方不変であった。以上より、仰/腹CTにおけるT-A D/PAの比較はT3(両方変化)、T3.5(いずれか不変)、T4(両方不変)を鑑別できる可能性が示唆された。(著者抄録)
  • Takushi Yasuda; Tomoki Makino; Osamu Shiraishi; Shunsuke Sogabe
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MOSBY-ELSEVIER 151 (6) E95 - E97 0022-5223 2016/06 [Refereed]
  • 【新/アトラスで学ぶ達人の手術】 食道・胃の手術 胸部食道癌手術 根治的化学放射線療法後のサルベージ手術
    安田 卓司
    消化器外科 (株)へるす出版 39 (5) 506 - 517 0387-2645 2016/04
  • 消化器外科手術アトラス 右開胸食道亜全摘術 縦隔からの反回神経周囲リンパ節徹底郭清
    白石 治; 田中 裕美子; 曽我部 俊介; 岩間 密; 安田 篤; 新海 政幸; 今野 元博; 今本 治彦; 安田 卓司
    消化器外科 (株)へるす出版 39 (4) 373 - 384 0387-2645 2016/04
  • 白石 治; 田中 裕美子; 曽我部 俊介; 加藤 寛章; 岩間 密; 安田 篤; 新海 政幸; 今野 元博; 今本 治彦; 塩崎 均; 安田 卓司
    消化器内視鏡 (株)東京医学社 28 (1) 115 - 121 0915-3217 2016/01 
    本稿では、喉頭温存手術の適応限界とその術式を紹介した。頸部食道癌は喉頭、気管と密接な解剖学的問題があり、切離マージンの根治性と術後嚥下障害リスクの安全性の問題から喉頭温存手術の適応は限られている。そこで、筆者らは喉頭温存手術の適応を限界まで広げるために術式の工夫を考案した。まずは、輪状咽頭筋、下咽頭収縮筋下縁を切離することで、喉頭気管と頸部食道の剥離は輪状軟骨上縁付近まで延長でき、最大限に切離マージンを確保できる。次に、舌骨上筋群には剥離操作を入れず舌骨下筋群を全切離し、術後の喉頭挙上の妨げになる瘢痕、癒着を回避することで誤嚥を減少させ安全性を確保できる。これらをもってすると、喉頭温存手術の適応限界は下咽頭から食道入口部に内視鏡を進め、内腔が広がり始める狭窄帯下端から尾側の病巣まで、CTでは輪状軟骨下縁まで及んでいない病巣である。本論にその詳細を記述した。(著者抄録)
  • Yumiko Tanaka; Motohiro Imano; Shunsuke Sogabe; Mitsuru Iwama; Osamu Shiraishi; Atsushi Yasuda; Masayuki Shinkai; Haruhiko Imamoto; Hiroshi Furukawa; Takushi Yasuda
    Japanese Journal of Gastroenterological Surgery Japanese Society of Gastroenterological Surgery 49 (9) 857 - 866 1348-9372 2016 
    A 71-year-old man underwent staging laparoscopy for HER2-positive advanced gastric cancer staging laparoscopy revealed peritoneal dissemination. He received neoadjuvant chemotherapy including trastuzumab (T-mab). After the chemotherapy, he underwent staging laparoscopy again. Peritoneal dissemination was not found, and he underwent total gastrectomy (D2) and splenectomy. Pathological diagnosis was poorly differentiated adenocarcinoma invading the submucosa. Harvested lymph nodes were all free of metastasis. Peritoneal dissemination and peritoneal cytology was negative. After curative resection, combination therapy of S-1 and T-mab was administered. At 8 months after the gastric cancer surgery, nausea appeared. Serum CEA concentration was elevated. Recurrent signs were not found on chest and abdominal enhanced CT. He was urgently hospitalized for decreased level of consciousness. Enhanced MRI revealed abnormal enhancement effects of the pia mater of the cerebellum, midbrain and right temporal lobe. Because there were not infection signs, infectious meningitis was denied. Meningeal carcinomatosis was diagnosed from progress, and he died 12 days after being diagnosed. Meningeal carcinomatosis is a rare complication of gastric cancer, and its prognosis is poor. There are a wide variety of symptoms in meningeal carcinomatosis. In some cases, a definitive diagnosis is very difficult. We considered it important to report our experience to emphasize the need to include meningeal carcinomatosis in the differential diagnoses for patients presenting with cerebral and cranial signs.
  • 【外科修練医必修 新外科専門医到達のための特別講義】 救命・救急医療 ショック
    新海 政幸; 安田 卓司
    外科 (株)南江堂 77 (12) 1480 - 1484 0016-593X 2015/11
  • Atsushi Yasuda; Takushi Yasuda; Haruhiko Imamoto; Hiroaki Kato; Kohei Nishiki; Mitsuru Iwama; Tomoki Makino; Osamu Shiraishi; Masayuki Shinkai; Motohiro Imano; Hiroshi Furukawa; Kiyokata Okuno; Hitoshi Shiozaki
    GASTRIC CANCER SPRINGER 18 (4) 850 - 858 1436-3291 2015/10 [Refereed]
     
    An optimal reconstruction method for proximal gastrectomy (PG) remains elusive. Esophagogastrostomy (EG) is technically simple but suffers from the disadvantage of gastroesophageal reflux. Jejunal interposition (JI) has a low rate of gastroesophageal reflux, but the procedure is more complicated, and delayed gastric emptying is a problem. We created a modified EG and have used the modified technique for PG since 2006. The procedure involves shaping the remnant stomach into a gastric conduit. The EG is performed high on the anterior wall, and the conduit is kept straight by applying a circular stapler inserted from the anterior wall of the antrum. The tip of the gastric conduit is then inserted into the lower mediastinum, creating a sharp angle of His. In this retrospective cohort study, the clinical and physiological outcomes were compared between 25 patients who underwent this procedure and 21 patients who underwent JI from 2001 to 2005. Laparoscopic procedures were performed more frequently, and residual food and bile reflux were less common in the EG group than in the JI group. No significant differences in remnant gastritis or reflux esophagitis were observed between the two groups. However, the late complication of intestinal obstruction occurred only in the JI group. The modified EG technique has advantages over the JI technique because of its simplicity and low incidence of residual food and bile reflux. The next step would be to explore this technique further by a prospective multi-institutional study to confirm the reproducibility of its benefits. Miniabstract: The modified EG technique has advantages over the JI technique because of its simplicity, high rate of laparoscopy use, and low incidence of gastroesophageal reflux.
  • 白石 治; 田中 裕美子; 曽我部 俊介; 岩間 密; 安田 篤; 新海 政幸; 今野 元博; 今本 治彦; 塩崎 均; 安田 卓司
    臨床外科 (株)医学書院 70 (9) 1083 - 1089 0386-9857 2015/09 
    ＜ポイント＞pT3,pN2,鎖骨上リンパ節陽性例,ly+,v+であったものが,再発高リスク群であり,また再発の70%が術後1年内に確認され,88%が2年内に確認された.リンパ節再発が最も多く,次に血行性再発が多い.また血行性転移の内訳は肺が33%,肝が30%,次いで骨が17%を占めた.寛解,長期生存できる可能性があるのは,頸部および縦隔のリンパ節や肺の1〜2個の転移再発であり,可能ならば積極的に切除を検討する.(著者抄録)
  • Takushi Yasuda; Masayuki Shinkai; Osamu Shiraishi; Shunsuke Sogabe
    International Journal of Surgery Case Reports Elsevier Ltd 14 112 - 116 2210-2612 2015/08 [Refereed]
     
    Abstract Introduction The only way for complete cure of advanced esophageal cancer with invasion to the mid-trachea is anterior mediastinal tracheostomy (AMT), which has a significantly high risk of fatal complications. The shorter tracheal stump is beneficial for good blood supply, but complicates to create a tracheostomy. Presentation of case A 71-year-old patient with a history of advanced cervical esophageal cancer who was treated with definitive chemoradiotherapy 3 years earlier had local recurrence on the left side of the trachea despite salvage lymphadenectomy for solitary left paratracheal lymph node recurrence 1 year earlier. AMT involving a resection of nearly the whole trachea was needded for complete resection. However, the recurrenced tumor was localized on the tracheal left side. We designed the new surgical procedure to preserve a longer segment of the unaffected right tracheal wall by diagonal cut (3.6 cm longer than on the left side) while maintaining adequate blood flow by preserving the right lateral vascular pedicle in a state of connecting with the right lobe of the thyroid gland and the right tracheal stump. The postoperative course was uneventful, and at 1 year postoperatively, no tumor recurrence has been detected. Discussion Preservation of the lateral vascular pedicle enables a longer tracheal stump by securing sufficient blood supply and a longer tracheal stump in AMT, even when unilateral, enables to create tracheostomy more surely, preventing fatal complications. Conclusion This novel procedure should be considered in cases with tumor invasion extending into the lower mid-trachea that is limited to one side.
  • Takushi Yasuda; Masahiko Yano; Hiroshi Miyata; Makoto Yamasaki; Shuji Takiguchi; Yoshiyuki Fujiwara; Yuichiro Doki
    ANNALS OF SURGICAL ONCOLOGY SPRINGER 22 (8) 2599 - 2607 1068-9265 2015/08 [Refereed]
     
    Patients with resectable thoracic esophageal squamous cell cancer (TESCC) and positron emission tomography (PET)-positive lymph nodes (PET-N positive) are likely to have a parts per thousand yen3 pathological lymph node metastases (pLNMs) and show a higher rate of postoperative recurrence despite curative resection than PET-N-negative TESCC patients. We examined the prognostic significance of F-18-fluorodeoxyglucose uptake into lymph node metastases after neoadjuvant chemotherapy (NAC) for PET-N positive TESCC and aimed to propose the optimal NAC response criteria for these patients. Fifty-one patients with PET-N positive TESCC underwent two courses of NAC followed by surgery. Metabolic responses of primary tumors and LNs were prospectively evaluated and associations with clinicopathological data and patient survival assessed by univariate and multivariate analyses. After NAC, 21 patients were post-treatment (post-) PET-N positive and 30 post-PET-N negative. A significantly (p < 0.001) high proportion of the post-PET-N-negative group had a parts per thousand currency sign2 pLNMs than the post-PET-N positive group (86.7 vs. 28.6 %). The PET-N negative group also had a significantly lower distant metastasis rate (23.3 vs. 75.0 %) and higher 5-year relapse-free survival (RFS) rate (69.0 vs. 20.0 %). Univariate and multivariate Cox's proportional hazard regression analyses identified post-PET-N negative status as the only significant favorable predictive factor for low postoperative recurrence (p = 0.015) independent of the primary tumor response. PET-N negative status predicts a parts per thousand currency sign2 pLNMs and longer RFS in resectable TESCC patients even after NAC. Therefore, post-PET-N status, not the effects on the primary tumor, is a critical NAC treatment response criterion for evaluating prognosis and guiding subsequent treatment.
  • 岩間 密; 今野 元博; 安田 卓司
    臨床腫瘍プラクティス (株)ヴァンメディカル 11 (3) 204 - 209 1880-3083 2015/08 
    ＜View Points!＞4型胃癌における最も大きな予後規定因子は腹膜播種である。我々は4型胃癌をはじめ進行胃がんにおける腹膜播種制御を目的に、以下の2つの治療戦略を計画した。■局所効果により将来の腹膜播種再発予防を期待した術前化学放射線療法(OGSG1205、OGSG1301)■漿膜浸潤胃癌症例に対し腹腔内微小転移を対象とした周術期腹腔内化学療法(GAPS study)(著者抄録)
  • 安田卓司; 白石治; 岩間密; 錦耕平; 曽我部俊介; 新海政幸
    手術 金原出版 69 (7) 1003 - 1012 0037-4423 2015/06
  • Kazuki Ishikawa; Kiyoshi Nakamatsu; Osamu Shiraishi; Takushi Yasuda; Yasumasa Nishimura
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY SPRINGER JAPAN KK 20 (3) 531 - 537 1341-9625 2015/06 [Refereed]
     
    The clinical results of definitive-dose preoperative chemoradiotherapy (CRT) of 50 Gy/25 fractions/5 weeks for unresectable esophageal cancer were analyzed. Inclusion criteria were unresectable esophageal squamous cell carcinoma with T4b or mediastinal lymph nodes invading to the trachea or aorta. Radiation therapy of 50 Gy/25 fractions/5 weeks was combined concurrently with two courses of FP therapy (CDDP 70 mg/m(2) + 5-FU 700 mg/m(2)/d x 5 days: day 1-5, day 29-33). Tumor response was evaluated 4 weeks after completion of RT. Subtotal esophagectomy was planned 6-8 weeks after RT. Thirty patients (26 male and 4 female) aged from 50-78 years (median 66) were enrolled between 2008 and 2011. The clinical stages according to the 7th edition of UICC were stages II/III/IV, 1/23/6; T1/2/3/4, 1/1/4/24; and N0/1/2/3, 3/25/1/1. All 30 patients completed RT of 50 Gy/25 fractions. Initial tumor responses were 21 patients with resectable disease, 7 with unresectable disease, and 2 with progressive disease. Subtotal esophagectomy was performed in 18 (60 %) of the 30 patients. Pathological complete response was obtained in five (28 %) patients. There were two patients with hospitalization death after surgery (11 %). Six of the 7 patients who still had unresectable disease were treated with 1-3 courses of docetaxel, CDDP and 5-FU. Three patients treated without surgery showed long-term survival. The 3-year loco-regional control rate and the 3-year overall survival rate for the 30 patients were 70 and 49 %, respectively. Definitive-dose preoperative CRT was feasible, and is a promising treatment strategy for unresectable esophageal cancer.
  • Kohei Nishiki; Yumiko Tanaka; Shunsuke Sogabe; Mitsuru Iwama; Tomoki Makino; Osamu Shiraishi; Atsushi Yasuda; Masayuki Shinkai; Motohiro Imano; Haruhiko Imamoto; Hiroshi Furukawa; Takushi Yasuda
    Japanese Journal of Cancer and Chemotherapy Japanese Journal of Cancer and Chemotherapy Publishers Inc. 42 (6) 739 - 742 0385-0684 2015/06 [Refereed]
     
    A 58-year-old woman was diagnosed with scirrhous gastric cancer suspected because of lymphangitis carcinomatosa. She was treated with 10 courses of S-1+CDDP chemotherapy. After 3 years and 6 months, CR was obtained and she underwent curative total gastrectomy with D2 lymph node dissection plus resection of the spleen and transverse colon. The pathological results of the resected specimen were tub2 > por, pT1a, N1 (No. 7), MO, CYO, P0, and HER2 (3+). After surgical treatment, supraclavicular lymph node metastasis occurred, and the patient underwent trastuzumab+capecitabine therapy, which resulted in CR for 1 year and 6 months. Thus, for unresectable scirrhous gastric cancer, multidisciplinary therapy such as longterm chemotherapy including trastuzumab and surgery is useful.
  • 癌性リンパ管症併発を疑うスキルス胃癌に対し化学療法にてCR後根治切除し長期生存中の1例
    錦 耕平; 田中 由美子; 曽我部 俊介; 岩間 密; 牧野 知紀; 白石 治; 安田 篤; 新海 政幸; 今野 元博; 今本 治彦; 古河 洋; 安田 卓司
    癌と化学療法 (株)癌と化学療法社 42 (6) 739 - 742 0385-0684 2015/06 
    症例は58歳、女性。癌性リンパ管症を伴うスキルス胃癌に対し、S-1+CDDP化学療法10コース施行しCRを得た。3年6ヵ月後に根治切除施行。切除標本の病理結果はtub2>por、pT1a、N1(No.7)、M0、CY0、P0、HER2(3+)であった。その後、鎖骨上窩リンパ節再発を来し、trastuzumab+capecitabine併用化学療法施行。1年6ヵ月、画像上病巣は認めていない。切除不能スキルス胃癌に対しても長期にわたる化学療法、手術治療など集学的治療が有用であると考えられた。(著者抄録)
  • Ying-Feng Peng; Motohiro Imano; Tatsuki Itoh; Takao Satoh; Yasutaka Chiba; Haruhiko Imamoto; Masahiro Tsubaki; Shozo Nishida; Takushi Yasuda; Hiroshi Furukawa
    JOURNAL OF SURGICAL ONCOLOGY WILEY-BLACKWELL 111 (8) 1041 - 1046 0022-4790 2015/06 [Refereed]
     
    Background and ObjectivesWe carried out a phase II trial to evaluate the feasibility, efficacy, and tolerability of perioperative chemotherapy including single intraperitoneal(IP) administration of paclitaxel(PTX) followed by intravenous(IV) administrations of PTX with S-1 in a neoadjuvant setting for serosa-positive gastric cancer. MethodsPatients with cT4a gastric cancer were enrolled. A laparoscopic survey was performed before study inclusion for the confirmation of serosal invasion, negative lavage cytology, and negative peritoneal metastasis. IP PTX (80mg/m(2)) was administered, followed by systemic chemotherapy. Surgery was performed after the completion of chemotherapy. The primary endpoint was the treatment completion rate. Results37 patients were recruited. The treatment completion rate was 67.6% (25/37; 90% CI, 52.8-80.1%), which was significantly higher than 50%; we set this as a threshold value (P=2.4% [one-sided]). 14 patients had target lesions; of these, 10 showed a partial response (71.4%), three had stable disease (21.4%), and one had progressive disease(7.2%). The response rate was 71.4% (10/14). All patients underwent gastrectomy with D2 lymph node dissection. The 3- and 5-year OS rates were 78.0 and 74.9%, respectively. ConclusionsPerioperative chemotherapy including neoadjuvant IP PTX followed by sequential IV PTX with S-1 for serosa-positive gastric cancer is feasible, safe, and efficient. J. Surg. Oncol. 2015 111:1041-1046. (c) 2015 Wiley Periodicals, Inc.
  • Takushi Yasuda; Masahiko Yano; Hiroshi Miyata; Makoto Yamasaki; Ichiro Higuchi; Shuji Takiguchi; Yoshiyuki Fujiwara; Yuichiro Doki
    SURGERY TODAY SPRINGER 45 (3) 335 - 345 0941-1291 2015/03 [Refereed]
     
    Purpose F-18-fluorodeoxyglucose positron emission tomography-positive lymph nodes (PET-N positive) in patients with resectable thoracic esophageal squamous cell carcinoma (TESCC) are associated with a high rate of postoperative distant recurrence. The purpose of this study was to evaluate the systemic control and survival benefit of neoadjuvant chemotherapy (NAC, cisplatin + doxorubicin + 5-fluorouracil) in these patients. Methods Of 77 patients with resectable TESCC who were PET-N positive, we evaluated 51 treated with NAC + surgery in this study and 26 who had undergone surgery alone (SA) in a previous study. Historical comparisons of the groups were made, and the response to treatment was evaluated in the NAC group. Results The NAC group had a higher rate of pN0-1 and a lower rate of postoperative recurrence (p < 0.0001 and p < 0.024, respectively) than the SA group; however, their relapse-free survival (RFS) rates were not significantly different. The NAC group had a significantly higher RFS in cT1/T2 cases, but showed similar survival in cT3 cases. On the other hand, post-treatment PET-N-negative patients had a higher RFS (p = 0.008) and a lower rate of distant recurrence (p = 0.021), even with cT3 disease. A multi-variate analysis identified the post-treatment PET-N evaluation to be the only significant predictor of the RFS in cT3 cases. Conclusions NAC significantly suppressed postoperative recurrence in TESCC PET-N-positive patients, but the survival benefit was unclear. However, post-treatment PET-N-negative patients were likely responders to NAC.
  • Makoto Yamasaki; Hiroshi Miyata; Takushi Yasuda; Osamu Shiraishi; Tsuyoshi Takahashi; Masaaki Motoori; Masahiko Yano; Hitoshi Shiozaki; Masaki Mori; Yuichiro Doki
    WORLD JOURNAL OF SURGERY SPRINGER 39 (2) 433 - 440 0364-2313 2015/02 [Refereed]
     
    Reconstruction after esophagectomy is mainly performed through the retrosternum (RS) or posterior mediastinum (PM). However, the best approach is not clear. This study aimed to assess the impact of the route of gastric conduit reconstruction, after esophagectomy for esophageal squamous cell carcinoma (ESCC), on post-operative outcomes. We analyzed 298 patients who underwent radical esophagectomy for ESCC at three high volume centers between 2008 and 2009. Among them, the RS was selected in 166 patients and PM in 118; while, the antethoracic route was used in 14 patients. Post-operative morbidity, mortality, and long-term outcome were compared. There were no differences between patients of the two routes with respect to operative blood loss (RS: 753 +/- A 519, PM: 748 +/- A 414 g) and post-operative complications, including pulmonary problems (RS: 15 %, PM: 10.2 %) and anastomotic leakage (RS: 9.0 %, PM: 5.1 %); although, the operating time (RS: 566 +/- A 97, PM: 472 +/- A 79 min; p < 0.0001) was shorter in the PM group than the RS group. The percentage weight loss after surgery was significantly less in the PM group than the RS group at 1 year (8.6 vs. 11.1 %; p = 0.025); although, the percentage at discharge was not different between the groups (PM: 4.9 %, RS: 6.3 %; p = 0.072). Multivariate analysis identified pre-operative body weight and the reconstruction route as significant and independent factors associated with 1-year weight loss. The results indicate gastric tube reconstruction through the posterior mediastinal route after esophagectomy may relieve post-operative 1-year malnutrition without increasing post-operative complications.
  • 食道再建術－(1)胃
    安田 卓司
    臨床食道学 1 187 - 191 2015 [Refereed]
  • 安田 卓司; 白石 治; 岩間 密; 錦 耕平; 安田 篤; 新海 政幸
    手術 金原出版(株) 69 (1) 1 - 12 0037-4423 2015/01
  • Shunsuke Sogabe; Yosuke Togashi; Hiroaki Kato; Akihiro Kogita; Takuro Mizukami; Yoichi Sakamoto; Eri Banno; Masato Terashima; Hidetoshi Hayashi; Marco A. de Velasco; Kazuko Sakai; Yoshihiko Fujita; Shuta Tomida; Takushi Yasuda; Yoshifumi Takeyama; Kiyotaka Okuno; Kazuto Nishio
    MOLECULAR CANCER THERAPEUTICS AMER ASSOC CANCER RESEARCH 13 (12) 3098 - 3106 1535-7163 2014/12 [Refereed]
     
    The prognosis for patients with unresectable advanced or recurrent gastric cancer remains poor. The identification of additional oncogenes with influences similar to those of epidermal growth factor receptor gene mutations, upon which the growth of cancer cells is dependent, is needed. In this study, we evaluated sensitivity to MEK inhibitors (GSK1120212 and PD0325901) in several gastric cancer cell lines in vitro and found three poorly differentiated gastric cancer cell lines that were hypersensitive to the inhibitors. The sequence analyses in these three cell lines revealed that one cell line had a novel MEK1 mutation, while the other two had previously reported KRAS and MEK1 mutations, respectively; the gene statuses of the other resistant cell lines were all wild-type. Experiments using MEK1 expression vectors demonstrated that the MEK1 mutations induced the phosphorylation of ERK1/2 and had a transforming potential, enhancing the tumorigenicity. The MEK inhibitor dramatically reduced the phosphorylation of ERK1/2 and induced apoptosis in the cell lines with MEK1 mutations. In vivo, tumor growth was also dramatically decreased by an inhibitor. One of the 46 gastric cancer clinical samples that were examined had a MEK1 mutation; this tumor had a poorly differentiated histology. Considering the addiction of cancer cells to active MEK1 mutations for proliferation, gastric cancer with such oncogenic MEK1 mutations might be suitable for targeted therapy with MEK inhibitors. (C)2014 AACR.
  • Atsushi Yasuda; Haruhiko Imamoto; Hiroshi Furukawa; Motohiro Imano; Takushi Yasuda; Kiyokata Okuno
    Japanese Journal of Cancer and Chemotherapy Japanese Journal of Cancer and Chemotherapy Publishers Inc. 41 (12) 2322 - 2325 0385-0684 2014/11 [Refereed]
     
    We report 2 rare cases of afferent loop syndrome caused by obstruction at the jejuno-jejunostomy site in the Roux-en-Y loop after total gastrectomy, which was successfully treated by endoscopic balloon dilatation of the anastomotic stenosis. Case 1: A 62-year-old woman presented with malaise and lower abdominal distension 6 months after laparoscopy-assisted total gastrectomy with Roux-en-Y reconstruction. She was diagnosed with afferent loop syndrome CT imaging indicated marked dilatation of the afferent loop, with membranous obstruction at the jejuno-jejunostomy site in the Roux-en-Y loop. Although almost complete occlusion was noted at the jejuno-jejunostomy site, the obstruction was successfully relieved by endoscopic balloon dilation using Tandem™ XL Triple Lumen ERCP Cannula (Boston Scientific)®. Case 2: A 70-year-old man presented with malaise and lower abdominal distension 3 years after laparoscopy-assisted total gastrectomy with Roux-en-Y reconstruction. He was diagnosed with afferent loop syndrome CT imaging indicated complete obstruction at the jejunojejunostomy site in the Roux-en-Y loop. As in case 1, the obstruction was successfully treated by endoscopic balloon dilatation of the occluded anastomosis.
  • 胃全摘後Roux-en-Y脚吻合部の完全狭窄による輸入脚症候群に対し内視鏡的拡張術にて治療完遂し得た2例の報告
    安田 篤; 今本 治彦; 古河 洋; 今野 元博; 安田 卓司; 奥野 清隆
    癌と化学療法 (株)癌と化学療法社 41 (12) 2322 - 2325 0385-0684 2014/11 
    はじめに:われわれは極めてまれなY脚吻合部のほぼ完全閉塞よる輸入脚症候群に対し、侵襲の少ない内視鏡的バルーン拡張術にて狭窄を解除し得た2症例を経験したので報告する。症例1:62歳、女性。腹腔鏡補助下胃全摘、Roux-en-Y再建施行後6ヵ月目で全身倦怠と下腹部の膨満感出現、CTで輸入脚の著明な拡張変化を認め、輸入脚症候群と診断した。Y脚吻合部はほぼ完全狭窄の状態であったが、透明キャップとタンデムXL ERCPカニューレ(Boston Scientific)を用いて内視鏡的バルーン拡張術を完遂し得た。症例2:70歳、男性。腹腔鏡補助下胃全摘施行後3年目で軽度全身倦怠と易疲労、下腹部の膨満が出現、採血結果は特に異常を認めなかったが、CTで輸入脚の著明な拡張を認め、輸入脚症候群と診断した。Y脚吻合部完全狭窄であったが同様に透明キャップとタンデムカニューレを用いて内視鏡的バルーン拡張術を完遂し得た。まとめ:本疾患は迅速な対応が求められる場合が多いが、治療方法はできる限り低侵襲なものを選択すべきである。内視鏡的処置はその一つとして試みるべき手技と考える。(著者抄録)
  • Tomoki Makino; Takushi Yasuda; Osamu Shiraishi; Hitoshi Shiozaki
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MOSBY-ELSEVIER 148 (5) E211 - E212 0022-5223 2014/11 [Refereed]
  • Yosuke Togashi; Tokuzo Arao; Hiroaki Kato; Kazuko Matsumoto; Masato Terashima; Hidetoshi Hayashi; Marco A. de Velasco; Yoshihiko Fujita; Hideharu Kimura; Takushi Yasuda; Hitoshi Shiozaki; Kazuto Nishio
    ONCOTARGET IMPACT JOURNALS LLC 5 (10) 2962 - 2973 1949-2553 2014/05 [Refereed]
     
    Chromosomal band 11q13 seems to be one of the most frequently amplified lesions in human cancer, including esophageal squamous cell cancer (ESCC). The oral cancer overexpressed 1 (ORAOV1) gene has been identified within this region, but its detailed biological function in human ESCC remains largely unclear. In our clinical samples of stage III ESCC, ORAOV1 amplification was observed in 49 of 94 cases (53%). ORAOV1 amplification was significantly associated with a poorly differentiated histology and tumors located in the upper or middle esophagus. Patients with ORAOV1 amplification tended to have a shorter survival period, although the difference was not significant. To investigate the function of ORAOV1, we created ORAOV1-overexpressed ESCC cell lines that exhibited increased cellular proliferation and colony formation, compared with in vitro controls. In vivo, ORAOV1-overexpressed cells exhibited a significantly increased tumorigenicity and a significantly larger tumor volume and poorer differentiation than controls. The peptide mass fingerprinting technique demonstrated that ORAOV1 bound to pyrroline-5-carboxylate reductase (PYCR), which is associated with proline metabolism and reactive oxygen species (ROS) production. Then, ORAOV1-overexpressed cell lines were resistant to stress treatment, which was cancelled by PYCR-knockdown. In addition, the ORAOV1-overexpressed cell line had a higher intracellular proline concentration and a lower ROS level. Our findings indicate that the ORAOV1 gene is frequently amplified in ESCC, enhances tumorigenicity and tumor growth, and is associated with a poorly differentiated tumor histology via proline metabolism and ROS production. ORAOV1 could be a novel target for the treatment of ESCC.
  • Takushi Yasuda; Yasuhiro Nakamori; Osamu Shiraishi; Atsushi Yasuda; Ying-Feng Peng; Masayuki Shinakai; Motohiro Imano; Haruhiko Imamoto; Hitoshi Shiozaki
    ESOPHAGUS SPRINGER JAPAN KK 11 (2) 99 - 107 1612-9059 2014/04 [Refereed]
     
    Background Postoperative pneumonia is the most common complication after esophagectomy and is closely associated with swallowing dysfunction and silent aspiration. Silent aspiration in the elderly is associated with decreased secretion of substance P (SP), which controls the swallowing and cough reflexes. The majority of patients with esophageal cancer are elderly. We hypothesized that surgical stress would decrease SP secretion, thereby increasing the risk of postoperative aspiration after esophagectomy, and prospectively investigated. Methods Thirty patients with esophageal cancer scheduled to undergo esophagectomy were enrolled in the study. Plasma and salivary SP concentrations and cough reflex sensitivity were measured before surgery and on postoperative days 2 and 7 to examine the association with postoperative aspiration. Results Postoperative silent aspiration was observed in 6 patients, 4 of whom developed pneumonia. Plasma SP concentration did not change significantly during the perioperative period. Salivary SP concentration and cough reflex sensitivity could not be measured in nearly one-third of patients because of postoperative dry mouth and unwillingness of patients to undergo measurement, respectively; thus, these perioperative changes could not be assessed. Preoperative plasma and salivary SP concentrations had a significant association with postoperative aspiration on univariate analysis and multivariate logistic regression analysis using variables selected by stepwise forward selection identified preoperative plasma SP concentration as the only significant risk factor for postoperative aspiration (p = 0.023). Conclusion Definitive results supporting our hypothesis could not be obtained. However, multivariate analysis suggested that decreased preoperative plasma SP concentration is likely associated with postoperative silent aspiration after esophagectomy.
  • 白石 治; 牧野 知紀; 安田 卓司
    臨床外科 (株)医学書院 69 (2) 141 - 146 0386-9857 2014/02 
    われわれがめざす普遍的な目的は,患者を根治へ導くことである.食道胃接合部癌の腫瘍学的見地に基づき至適郭清範囲を同定し,根治性を優先した術式を決定する必要がある.縦隔リンパ節転移は組織型にかかわらず解剖学的位置によるリンパ流に規定され,食道浸潤長が20mmを超えるものには高い縦隔リンパ節転移リスクがある.これらには"右開胸食道亜全摘2領域郭清"が必要であり,縦隔転移を認めた例でも開胸手術による5年全生存率は47%で,長期生存は可能である.わが国においては右開胸食道亜全摘術の安全性は確立されており,リスク回避のために開胸を避ける必要はない.今後,根治性を最優先する立場に立って症例を蓄積し,より正確なリンパ節転移状況を把握し,真の治療方針を構築する必要がある.(著者抄録)
  • 白石 治; 錦 耕平; 岩間 密; 牧野知紀; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 塩崎 均; 安田卓司
    日本気管食道科学会会報 (NPO)日本気管食道科学会 65 (2) 144 - 147 0029-0645 2014 
    頸部食道癌に対し、喉頭温存を重視した治療戦略として、導入化学放射線療法の中間判定による治療選択と、次のような術式工夫を行い、良好な成績が得られているので報告した。1)喉頭温存手術の適応を拡大するため、輪状咽頭筋と下咽頭収縮筋下端を輪状軟骨付着部で切離することにより、輪状軟骨上縁までの食道剥離を可能とする。2)術後嚥下障害を回避するため、手術のさい舌骨上筋群には皮弁剥離操作をしないことで瘢痕を予防し、舌骨下筋群を胸骨付着部で全切離することで喉頭下方牽引力を取り除き、温存した舌骨上筋群で喉頭を挙上させることにより安全性を確保する。3)移植空腸を長めに採取し、犠牲腸管余剰腸間膜で気管全体を被覆し、死腔を埋めて気管を保護し感染を防ぐことにより気管壊死を予防する。4)再建腸管は緊張をもって直線的に再建することで通過性を良くし、誤嚥を予防する。
  • 頸部食道癌に対する喉頭温存根治術．
    白石 治; 錦 耕平; 岩間 密; 牧野知紀; 塩崎 均; 安田卓司
    手術 臨時増刊号 消化器癌定型手術の標準手技アトラス 68 367 - 375 2014
  • Hajime Ishikawa; Motohiro Imano; Osamu Shiraishi; Atsushi Yasuda; Ying-Feng Peng; Masayuki Shinkai; Takushi Yasuda; Haruhiko Imamoto; Hitoshi Shiozaki
    GASTRIC CANCER SPRINGER 17 (1) 173 - 180 1436-3291 2014/01 [Refereed]
     
    Lymphocyte antigen 6 complex locus K (LY6K) has been identified as a tumor-associated antigen in lung cancers and esophageal squamous cell carcinomas. The immunogenicity of LY6K-177 peptide vaccine therapy has been demonstrated in patients with advanced esophageal cancer. This study extends this treatment to gastric cancer. LY6K expression in clinical samples obtained from gastric cancer patients was examined by immunochemistry. As a phase I clinical trial, the safety and immunogenicity of LY6K-177 peptide vaccine emulsified with Montanide ISA 51 was evaluated in six patients with unresectable advanced gastric cancer. LY6K-177 peptide (1 mg in 1 ml sterile saline) was emulsified with incomplete Freund's adjuvant (1 ml) and intracutaneously administered to the inguinal region or axilla. One treatment course comprised four vaccinations, performed weekly for the first and second treatment courses and biweekly for the third treatment course. LY6K expression was confirmed in 85 % of gastric cancer tissues. Induration and redness at the vaccination site (grade I), possibly a delayed-type hypersensitivity reaction, was observed in all patients; however, no systemic toxicology was identified in any patient throughout the observation period. Three of the six patients had stable disease, and a tumor contraction effect was observed in one patient. LY6K was expressed in 85 % of observed gastric cancers. Vaccination with LY6K-177 peptide/Montanide ISA 51 appeared to be tolerated by advanced gastric cancer patients, and moreover anticancer efficacy was suggested. This trial was registered with ClinicalTrial.gov (no. NCT00845611).
  • 安田 篤; 今野 元博; 今本 治彦; 安田 卓司; 古河 洋; 塩崎 均
    近畿大学医学雑誌 近畿大学医学会 38 (3-4) 149 - 152 0385-8367 2013/12 
    はじめに 近年の新規抗癌剤出現により、進行癌に対するいくつかの集学的治療が行われているが、その一つとして術前化学療法+手術の有用性が報告されている。今回我々は2型噴門部進行胃癌に対してTS-1/CDDPによる術前化学療法を施行した結果、病理組織学的にCRを得た症例を経験したので報告する。症例 67歳男性、健診にて胃病変を指摘され、近医にてGIF施行したところ噴門部後壁に2型胃癌認めたため当科紹介となった。経過 当初、画像診断で肝転移を伴う高度進行胃癌(T4aN1H1Stage IV)と診断してTS-1/CDDPの化学療法を3クール施行した。効果判定では主病変と所属リンパ節は著明に縮小したが、肝病変は治療効果を認めず、血管腫の可能性も出てきたため肝部分切除+胃全摘術を行った。摘出病理標本では原発巣、リンパ節ともに癌細胞は認めず、肝病変は硬化性血管腫であったため、pathological CRと判断した。術後経過は良好で、退院後adjuvant chemotherapyとしてTS-1内服を1年半施行、26ヵ月経過した現在、無再発にて経過観察中である。(著者抄録)
  • Motohiro Imano; Tatsuki Itoh; Takao Satou; Atsushi Yasuda; Kohei Nishiki; Hiroaki Kato; Osamu Shiraishi; Ying-Feng Peng; Masayuki Shinkai; Masahiro Tsubaki; Takushi Yasuda; Haruhiko Imamoto; Shozo Nishida; Yoshifumi Takeyama; Hiroshi Furkawa; Kiyokata Okuno; Hitoshi Shiozaki
    Targeted Oncology 8 (4) 231 - 235 1776-2596 2013/12 [Refereed]
     
    Intraperitoneally administrated epithelial cellular adhesion molecule (EpCAM) monoclonal antibody is a therapeutic agent in patients with malignant effusion in several types of carcinoma. However, the role of EpCAM in peritoneal metastasis (PM) lesions and primary lesions of gastric cancer (GC) is still unclear. Therefore, in this study, we investigated EpCAM expression in GC patients with PM. We investigated the expression of EpCAM in 35PM lesions and 104 biopsy samples as primary lesions. Immunohistochemical staining was performed using the Ventana Benchmark XT (Roche Diagnostics) system. EpCAM expression was evaluated by calculating the total immunostaining score, which is the product of the proportion score and the intensity score. Overexpression was defined as a total score greater than 4. All PM specimens showed overexpression of EpCAM, and GC cells in both the surface layer and the deep layer of the PM showed a high expression of EpCAM. Meanwhile, in the biopsy sample, the expression of EpCAM ranged from none to strong. The EpCAM score results for PM specimens and biopsy samples were 11.0 ± 2.0 and 6.9 ± 3.9, respectively. The difference between the scores was statistically significant (P < 0.05). The intraperitoneally administrated EpCAM antibody might have a anti-cancer effect in PM lesions of GC. Additionally, it can be assumed that only GC cells which express a high level of EpCAM might metastasize to the peritoneum. © 2012 Springer-Verlag France.
  • Takushi Yasuda
    Acta Med Kinki Univ Kinki University Medical Association 38 (2) 69 - 78 0386-6092 2013/12 [Refereed]
     
    [Abstract] The preferred organ for reconstruction after esophagectomy is the stomach, but the procedures vary even for a gastric pull-up reconstruction. In this article, I review the major reports on the most popular procedures, specifically in relation to the following three aspects ofthe surgeries and examine the optimal gastric reconstruction technique at present. Size of gastric substitute : Compared with whole-stomach (WS) reconstruction, gastric tube (GT) reconstruction tended to have comparable incidence of anastomotic leakage, less chest discomfort, and a lower incidence of reflux esophagitis. As for physiological function of the gastric substitute, opinions differed as to the value of each : the WS preserves the entire gastric wall vascular network and has a larger capacity, enabling the patient to take sufficient calories by eating more meals, while the smallervolume and lower compliance of the gastric tube wall provides a rapid increase in intragastric pressure that facilitates gastric emptying after food intake and lowers compression of the lung and heart, thereby minimizing the ability of intrathoracic negative pressure to cause duodenogastric reflux. In GT, longer length and complete clearance of the lymph nodes between the subcardia and gastric angle are also great advantages for tension-free anastomosis and curativity. This review suggests that the GT is a superior esophageal substitute. Reconstruction route : Comparing the posteriormediastinal (PM) and retrosternal (RS) routes, PM is shorter, which is an advantage for tension-free anastomosis, but is susceptible to intrathoracic negative pressure and carries a risk of secondary dysphagia due to locoregional recurrence. On the other hand, the RS route facilitates irradiation of locoregional recurrence with less fear of adverse effects on the gastric conduit. Some authors reported the RS route had a higher rate of anastomotic leakage, although this review finds the rate is likely to be similar between the two routes. At present, RS is recommended in the palliative setting.Level of anastomosis : Comparison of cervical anastomosis (CA) and thoracic anastomosis (TA) revealed that CS enabled a 1.5 to 2.5 cm longer resection of the proximal esophagus, which was reported to decrease the risk of anastomotic recurrence. However, recent studies showed comparable survival rates for CA and TA groups. No significant difference was observed in the anastomotic leakage rate between the two groups. Currently, esophageal reconstruction methods after esophagectomy should be determined on an individual basis, after careful consideration of the merits and risks of each procedure and technique.
  • 安田 篤; 今本 治彦; 安田 卓司; 新海 政幸; 今野 元博; 古河 洋; 奥野 清隆; 塩崎 均
    日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 18 (6) 657 - 664 1344-6703 2013/11 
    [目的]高齢者胃切除症例に対する腹腔鏡下手術の安全性と有用性を検討した.[対象]当科で施行した80歳以上の胃切除症例を腹腔鏡群(Lap群)58例と開腹群(Open群)59例に分け,術中の呼吸変動と血圧変動,術後合併症などを検討した.[結果]術中血圧変動は両群間に有意差を認めず,術中のETCO2はLap群で若干の高値であったが,術後高炭酸ガス血症が遷延することはなかった.術後合併症はOpen群25.4%,Lap群13.8%で,最も割合の多かった呼吸器合併症はLap群5.2%,Open群8.5%であった.[結論]高齢者胃癌症例に対する腹腔鏡下手術は術後合併症,特に呼吸器合併症に対して有利と思われ,有用な治療法として筆者らは現在積極的に導入している.(著者抄録)
  • 大学病院における周術期肺血栓塞栓症のリスクマネジメント
    保田 知生; 岩間 密; 武本 智樹; 村瀬 貴昭; 松本 正孝; 加藤 寛章; 中多 靖幸; 亀井 敬子; 石川 原; 杉浦 史哲; 中居 卓也; 安田 卓司; 光冨 徹哉; 竹山 宜典; 奥野 清隆
    日本臨床外科学会雑誌 日本臨床外科学会 74 (増刊) 308 - 308 1345-2843 2013/10
  • 最近のVTE(静脈血栓塞栓症)の予防と治療 当院における中心静脈穿刺に伴う深部静脈血栓症の現状
    岩間 密; 保田 知生; 白石 治; 武本 昌子; 杉浦 史哲; 錦 耕平; 安田 卓司; 竹山 宜典; 奥野 清隆
    日本臨床外科学会雑誌 日本臨床外科学会 74 (増刊) 417 - 417 1345-2843 2013/10
  • 【食道胃接合部癌の診断と治療】 治療 手術治療 食道外科の立場から(開胸して行う場合) 至適郭清範囲から決まる術式選択
    白石 治; 安田 卓司
    消化器外科 (株)へるす出版 36 (11) 1597 - 1606 0387-2645 2013/10
  • 【主要な手術・治療・処置を徹底図解! 消化器外科の術式別ケア はやわかりノート】 (第1部)開胸・開腹・内視鏡手術編(第1章) 食道疾患 頸部食道がん手術(遊離空腸再建術)
    牧野 知紀; 白石 治; 安田 卓司
    消化器外科Nursing (株)メディカ出版 (2013秋季増刊) 42 - 46 1341-7819 2013/10
  • 安田 卓司
    臨床外科 (株)医学書院 68 (11) 6 - 16 0386-9857 2013/10
  • 食道癌根治術施行患者に対する呼吸リハビリテーションの効果
    前田 和成; 本田 憲胤; 東本 有司; 白石 匡; 杉谷 竜司; 山縣 俊之; 安田 卓司; 西山 理; 東田 有智; 福田 寛二
    日本呼吸ケア・リハビリテーション学会誌 (一社)日本呼吸ケア・リハビリテーション学会 23 (Suppl.) 231s - 231s 1881-7319 2013/09
  • Hiroaki Kato; Tokuzo Arao; Kazuko Matsumoto; Yoshihiko Fujita; Hideharu Kimura; Hidetoshi Hayashi; Kouhei Nishiki; Mitsuru Iwama; Osamu Shiraishi; Atsushi Yasuda; Masayuki Shinkai; Motohiro Imano; Haruhiko Imamoto; Takushi Yasuda; Kiyotaka Okuno; Hitoshi Shiozaki; Kazuto Nishio
    International journal of oncology SPANDIDOS PUBL LTD 42 (4) 1151 - 8 1019-6439 2013/04 [Refereed]
     
    Molecular targeted therapy is expected to be a promising therapeutic approach for the treatment of esophageal squamous cell carcinoma (ESCC); however, the gene amplification status of molecular targeted genes in ESCC remains largely unclear. The gene amplification of EGFR, HER2, FGFR2 and MET was examined using a real-time PCR-based copy number assay of 245 ESCC surgical specimens of formalin-fixed, paraffin-embedded samples. Fluorescence in situ hybridization (FISH) and comparative genomic hybridization analyses verified the results of the copy number assay. EGFR mutation was detected using the Scorpions-ARMS method. The EGFR status and drug sensitivity to an EGFR tyrosine kinase inhibitor was then evaluated in vitro. Gene amplification of EGFR and HER2 was observed in 7% (16/244) and 11% (27/245) of the ESCC specimens. A multivariate analysis revealed that HER2 amplification was a significant predictor of a poor prognosis in patients with stage III post-operative ESCC. The L861Q type of EGFR mutation with hypersensitivity to EGFR tyrosine kinase inhibitor was found in one of the eight ESCC cell lines and one del745 type of EGFR mutation was identified in 107 clinical samples. In addition, we demonstrated for the first time that FGFR2 amplification was observed in 4% (8/196) of the ESCC specimens. MET amplification was observed in 1% (2/196). In conclusion, the frequent gene amplification of EGFR, HER2 and FGFR2 and the presence of active EGFR mutations were observed in ESCC specimens. Our results strongly encourage the development of molecular targeted therapy for ESCC.
  • Motohiro Imano; Hiroshi Furukawa; Masaki Yokokawa; Yasumasa Nishimura; Yukinori Kurokawa; Taroh Satoh; Daisuke Sakai; Takushi Yasuda; Haruhiko Imamoto; Toshimasa Tujinaka; Toshio Shimokawa; Hitoshi Shiozaki
    Japanese journal of clinical oncology 43 (4) 431 - 5 0368-2811 2013/04 [Refereed]
     
    A Phase I/II trial of radiotherapy administered concurrently with TS-1 plus cisplatin has been initiated in Japanese patients with clinical resectable type 4 or large type 3 gastric cancer. The aim of this trial is to determine the recommended dose of TS-1 and cisplatin combined with radiotherapy at a fixed dose in the Phase I study, and to evaluate the efficacy and safety in the Phase II study. The primary endpoint for Phase II is the pathological complete response rate, assessed using surgically resected specimens. Secondary endpoints are the response rate, progression-free survival, overall survival, operation transitional rate, R0 resection rate, rate of treatment completion, rate of down-staging and rates of postoperative complications and adverse events. In Phase II, a total of 30 patients will be enrolled in the Osaka Gastrointestinal Cancer Chemotherapy Study Group trial over a period of 6 years.
  • Takushi Yasuda; Masahiko Yano; Hiroshi Miyata; Makoto Yamasaki; Shuji Takiguchi; Yoshiyuki Fujiwara; Yuichiro Doki
    World journal of surgery 37 (2) 416 - 23 0364-2313 2013/02 [Refereed]
     
    BACKGROUND: Recently, reports from the West have indicated three-field lymphadenectomy (3FL) for esophageal cancer increases the accuracy of tumor staging and survival. However, this cervical procedure is likely to lead to swallowing dysfunction and aspiration, which are barriers to introducing this procedure in clinical practice. METHODS: Our goal is to elucidate the etiology of swallowing dysfunction after 3FL and devise a remedy. First, based on evaluation of swallowing function in ten patients with two-field lymphadenectomy (2FL) and ten with 3FL, we hypothesized that the scarred sternohyoid and sternothyroid muscles might be impairing laryngeal elevation after 3FL; thus, complete division of the bilateral infrahyoid muscles attached to the sternum (CDBIMS) could be an effective remedy. Next, the utility of this additive procedure was examined in 20 patients with 3FL. Swallowing function was evaluated by the distance of total laryngeal elevation (TLE) and the frequency of incomplete airway protection (IAP) (laryngeal penetration or aspiration) on videofluoroscopic study. RESULTS: The average TLE and frequency of IAP were, respectively, 0.37 cm and 70 % in the 3FL group, showing significant deterioration (p < 0.001 and 0.025), in contrast to 1.79 cm and 20 % in the 2FL group. The 3FL + CDBIMS group showed significant improvements in the average TLE and the frequency of IAP (1.70 cm and 25 %), compared with the 3FL group (p < 0.001 and 0.018). Multivariate logistic regression identified additive CDBIMS as a significant suppressor of IAP after 3FL. CONCLUSIONS: Laryngeal elevation was significantly impaired after 3FL. Adding CDBIMS might improve swallowing function in these patients.
  • Keiko Kamei; Takeo Yasuda; Takuya Nakai; Yoshifumi Takeyama
    Case Reports in Gastroenterology S. Karger AG 7 (3) 433 - 437 1662-0631 2013 [Refereed]
     
    We report a rare case of adenocarcinoma of the duodenum arising from Brunner's gland. A 70-year-old man with a history of hypertension was referred to us with the complaint of abdominal discomfort. Upper gastrointestinal endoscopy revealed an irregular elevated mucosa and a submucosal tumor with delle in the duodenal bulb. Biopsy specimens revealed adenocarcinoma (the former) and hyperplasia (the latter). We could not agree with the patient about performing pancreaticoduodenectomy, so under the diagnosis of primary duodenal carcinoma, we performed resection of the bulbus and the antrum. Pathological examination showed that one of the tumors was consistent with normal Brunner's glands, Brunner's gland hyperplasia and adenocarcinoma arising from Brunner's glands. The patient's postoperative course was good, but 15 months after, he developed lymph node recurrence at the site of the pancreas head. Under the diagnosis of lymph node metastasis of duodenal cancer, we performed pancreaticoduodenectomy this time. Pathological examination confirmed our preoperative diagnosis. The patient remained well after the surgery for 2 years.
  • データ解説1-5
    安田 卓司
    Frontiers in Gastroenterology 18 54 - 63 2013 [Refereed]
  • 安田 卓司; 塩崎 均
    手術 金原出版(株) 66 (13) 1815 - 1825 0037-4423 2012/12
  • 安田 篤; 今本 治彦; 加藤 寛章; 今野 元博; 安田 卓司; 塩崎 均
    日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 17 (6) 789 - 795 1344-6703 2012/12 
    心不全・肥満を伴った成人Bochdalek孔ヘルニアを経験したので報告する.患者は47歳,女性.2010年2月から急性心不全にて当院循環器内科で加療中であった.咳嗽と心窩部痛にてCT検査を施行し,Bochdalek孔ヘルニアと診断され当科を紹介された.腹腔鏡下に手術を開始したがヘルニア内容の癒着や内臓脂肪による視野不良のために施行困難となり,hand-assisted laparoscopic surgery(HALS)に変更した.その後脱出した横行結腸,大網を還納し,ヘルニア門を縫合閉鎖,さらにpolypropylene meshで補完して手術を完遂した.24ヵ月経った現在,再発は認めていない.自験例のような肥満・癒着症例,心合併症症例で完全腹腔鏡下での修復術が困難な場合に,HALSは良好な視野で安全かつ低侵襲に施行でき,有用な手技と考える.(著者抄録)
  • Motohiro Imano; Takao Satou; Tatsuki Itoh; Atsushi Yasuda; Hiroaki Kato; Masayuki Shinkai; Ying-Feng Peng; Masahiro Tsubaki; Takushi Yasuda; Haruhiko Imamoto; Shozo Nishida; Yoshifumi Takeyama; Kiyokata Okuno; Hitoshi Shiozaki
    TARGETED ONCOLOGY SPRINGER 7 (4) 213 - 216 1776-2596 2012/12 [Refereed]
     
    The prognosis of gastric cancer patients with peritoneal metastasis is very poor. Recent findings suggest that use of trastuzumab, a monoclonal antibody-based agent that targets human epidermal growth factor receptor 2 (HER2), may improve the prognosis of gastric cancer patients with HER2 overexpression and/or gene amplification. However, whether these mechanisms of HER2 upregulation are present in gastric cancer patients with peritoneal metastasis is unclear. The status of HER2 expression in a cohort of samples obtained from 35 gastric cancer patients with peritoneal metastasis was investigated using immunohistochemistry and fluorescence in situ hybridization. In 18 cases, we also investigated the influence of induction chemotherapy on HER2 overexpression. The frequency of HER2 overexpression and gene amplification was 2.9 % (1/35) in peritoneal metastatic lesions. There was concurrence in HER2 status in the samples examined prior to and following induction of chemotherapy. Most samples from the gastric cancer patients with peritoneal metastasis did not show HER2 amplification and/or overexpression. Although our study size was small, these results suggest that trastuzumab, which is critically dependent on HER2 expression, might not be an effective agent for these patients. Consequently, other therapeutic approaches for these patients must be developed.
  • Motohiro Imano; Atsushi Yasuda; Tatsuki Itoh; Takao Satou; Ying-Feng Peng; Hiroaki Kato; Masayuki Shinkai; Masahiro Tsubaki; Yasutaka Chiba; Takushi Yasuda; Haruhiko Imamoto; Shozo Nishida; Yoshifumi Takeyama; Kiyokata Okuno; Hiroshi Furukawa; Hitoshi Shiozaki
    JOURNAL OF GASTROINTESTINAL SURGERY SPRINGER 16 (12) 2190 - 2196 1091-255X 2012/12 [Refereed]
     
    We conducted a phase II study involving a single administration of intraperitoneal chemotherapy with paclitaxel followed by sequential systemic chemotherapy with S-1+ paclitaxel for advanced gastric cancer patients with peritoneal metastasis. Gastric cancer patients with peritoneal metastasis were enrolled. Paclitaxel (80 mg/m(2)) was administered intraperitoneally at staging laparoscopy. Within 7 days, patients received systemic chemotherapy with S-1 (80 mg/m(2)/day on days 1-14) plus paclitaxel (50 mg/m(2) on days 1 and 8), followed by 7-days rest. The responders to this chemotherapy underwent second-look laparoscopy, and gastrectomy with D2 lymph node dissection was performed in patients when the disappearance of peritoneal metastasis had been confirmed. The primary endpoint of the study was overall survival rate. Thirty-five patients were enrolled. All patients were confirmed as having localized peritoneal metastasis by staging laparoscopy. Eventually, gastrectomy was performed in 22 patients. The median survival time of the total patient population and those patients in which gastrectomy was performed was 21.3 and 29.8 months, respectively. The overall response rate was 65.7 % for all patients. The frequent grade 3/4 toxic effects included neutropenia and leukopenia. Sequential intraperitoneal and intravenous paclitaxel plus S-1 was well tolerated in gastric cancer patients with peritoneal metastasis.
  • T. Yasuda; K. Sugimura; M. Yamasaki; H. Miyata; M. Motoori; M. Yano; H. Shiozaki; M. Mori; Y. Doki
    DISEASES OF THE ESOPHAGUS OXFORD UNIV PRESS INC 25 (8) 687 - 693 1442-2050 2012/11 [Refereed]
     
    Gastro-tracheobronchial fistula (GTF) is a rare but life-threatening complication specifically observed after esophagectomy and reconstruction using posterior mediastinal gastric tube. Ten cases of GTF were encountered in three hospitals in 20002009. Their clinicopathological, surgical, and postoperative care are summarized, together with a review of previously reported cases. GTF was classified as anastomotic leakage (n= 5), gastric necrosis (n= 4), and gastric ulcer type (n= 1). The anastomotic leakage type appeared about 2 weeks (postoperative day [POD]: 835) after esophagectomy, was located in the cervical or higher thoracic trachea. Breathing and pneumonia were controlled by tracheal tube placed in the distal of fistula. The gastric necrosis type was noted in patients who developed necrosis of the upper part of the gastric tube and abscess formation behind the tracheal wall, at POD 2036 around the carina, the site of pronounced ischemia. Due to the large fistula around the carina, emergency surgery with muscle patch repair was frequently required for the control of aspiration pneumonia. Patients of the gastric ulcer type had peptic ulcer in the lesser curvature of the gastric tube, which perforated into the right bronchus long after surgery (POD 630). With respect to tracheobronchial factors, preoperative chemoradiation (three cases) and pre-tracheal node dissection (three cases) tended to increase the risk of GTF. Closure of GTF by surgery (muscle patch repair) was successful in four cases and by nonsurgical treatment in three cases. In one case, stable oral intake was achieved by bypass operation without closure of GTF. Hospital death occurred in three cases. Understanding the pathogenesis and treatment options of GTF is important for surgeons who deal with esophageal cancer.
  • Motohiro Imano; Ying-Feng Peng; Tatsuki Itoh; Masayasu Nishikawa; Takao Satou; Atsushi Yasuda; Keisuke Inoue; Hiroaki Kato; Masayuki Shinkai; Masahiro Tsubaki; Takushi Yasuda; Haruhiko Imamoto; Shozo Nishida; Hiroshi Furukawa; Yoshifumi Takeyama; Kiyokata Okuno; Hitoshi Shiozaki
    ANTICANCER RESEARCH INT INST ANTICANCER RESEARCH 32 (9) 4071 - 4075 0250-7005 2012/09 [Refereed]
     
    Aim: A preliminary study with the aim of evaluating the safety and efficacy of a single intraperitoneal administration of paclitaxel, combined with intravenous administration of paclitaxel plus S-1, was carried out in gastric cancer patients with peritoneal metastasis. Patients and Methods: Paclitaxel was administered intraperitoneally at 80 mg/m(2). After one to two weeks, S-1 was administered at 80 mg/m(2)/day for 14 consecutive days, followed by seven days' rest. Paclitaxel was administered intravenously at 50 mg/m(2) on days 1 and 8. The safety, pharmacokinetic analysis and efficacy of this therapy were investigated. Results: Fifteen patients were enrolled in this study. The toxic effects of the intraperitoneal chemotherapy were mild. The toxic effects with the systemic chemotherapy were acceptable. The ratio of (AUC peri)/(AUC pla) was 1065:1 in the pharmacokinetic analysis. The one-year overall survival rate was 10/15 (66.7%). Conclusion: A single intraperitoneal administration of paclitaxel combined with intravenous administration of paclitaxel plus S-1 is a well-tolerated and feasible treatment for patients with gastric cancer with peritoneal metastasis.
  • Hajime Ishikawa; Motohiro Imano; Osamu Shiraishi; Atsushi Yasuda; Ying-Feng Peng; Masayuki Shinkai; Takushi Yasuda; Haruhiko Imamoto; Kazuyoshi Takeda; Hitoshi Shiozaki
    ESOPHAGUS SPRINGER TOKYO 9 (2) 105 - 112 1612-9059 2012/06 [Refereed]
     
    Up-regulated gene in lung cancer 10 (URLC10), confirmed to be lymphocyte antigen 6 complex locus K and defined as an oncoantigen, has been identified as a tumor-associated antigen by systematic analysis of expression levels of thousands of genes in lung cancer tissues and esophageal squamous cell carcinoma tissues, which were compared with those of normal human tissues by use of cDNA microarray analysis. Human leukocyte antigen (HLA)-A*2402-positive dendritic cells pulsed with URLC10-derived epitope peptide induced CD8(+) cytotoxic T lymphocytes to exert specific cytotoxicity against the HLA-A*2402-positive URLC10-expressing esophageal carcinoma cell lines. In a phase I clinical trial we evaluated the safety and immunogenicity of a URLC10-177 peptide vaccine emulsified with Montanide ISA51 for patients with unresectable advanced esophageal cancer. One milligram of URLC10-177 peptide in 1 mL sterile saline was emulsified with 1 mL incomplete Freund's adjuvant and administered subcutaneously to the inguinal region or axilla of the patients. One course of treatment comprised four vaccinations, which were performed every week in the first and second treatment courses and subsequently every 2 weeks after the first vaccination in the third treatment course. Redness and induration of the skin were the only adverse events at the injection site and were believed to be a delayed-type hypersensitivity (DTH) reaction against the peptide vaccine. A URLC10-177-specific immune reaction in the enzyme-linked immunospot assay was detected in three of four DTH-positive patients (75 %) and in one of three DTH-negative patients (33 %). Furthermore, patients who had a DTH reaction seemed to survive longer than those who had no DTH reaction. URLC10-177 peptide/Montanide vaccine therapy was well tolerated and induced a URLC10-177 peptide-specific immune response. Therapeutic URLC10-177 peptide vaccination is expected to have clinical benefit in prolonging the survival of patients with unresectable advanced esophageal cancer.
  • Hiroshi Miyata; Masahiko Yano; Takushi Yasuda; Rie Hamano; Makoto Yamasaki; Eihou Hou; Masaaki Motoori; Osamu Shiraishi; Koji Tanaka; Masaki Mori; Yuichiro Doki
    CLINICAL NUTRITION CHURCHILL LIVINGSTONE 31 (3) 330 - 336 0261-5614 2012/06 [Refereed]
     
    Background & aims: Enteral nutrition (EN) is provided for patients with cancer. However, Little is known about the clinical efficacy of EN support during chemotherapy in patients with cancer. Methods: Ninety-one patients who received neoadjuvant chemotherapy (5-fluorouracil, cisplatin and adriamycin) for esophageal cancer were enrolled to receive either EN (n = 47) or PN (n = 44) at random. The primary endpoint was the incidence of chemotherapy-related toxicities during chemotherapy. Results: Total and dietary intake calories during chemotherapy were equal in the two groups. There were no significant differences in serum albumin level and body weight change after chemotherapy between the two groups. There was no significant difference in tumor response to chemotherapy between the two groups (EN: 51%, PN: 55%, p = 0.886). Leukopenia and neutropenia of grade 3 or 4, defined according to the Common Toxicities Criteria of the National Cancer Institute, were significantly less frequent in the EN group than PN group (leukopenia: 17% vs 41%, p = 0.011, neutropenia: 36% vs 66%, p = 0.005). Lymphopenia and thrombocytopenia tended to be less frequent in the EN group, albeit insignificantly. Conclusions: Compared with PN support, EN support during neoadjuvant chemotherapy reduced the incidence of chemotherapy-related hematological toxicities in patients with esophageal cancers. The clinical trial registration number: UMIN000004483 (C) 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
  • Takuhito Tada; Yasutaka Chiba; Kayoko Tsujino; Haruyuki Fukuda; Yasumasa Nishimura; Masaki Kokubo; Shunichi Negoro; Shinzoh Kudoh; Masahiro Fukuoka; Kazuhiko Nakagawa; Yoichi Nakanishi
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS ELSEVIER SCIENCE INC 83 (1) 327 - 331 0360-3016 2012/05 [Refereed]
     
    Purpose: A Phase I study to determine a recommended dose of thoracic radiotherapy using accelerated hyperfractionation for unresectable non-small-cell lung cancer was conducted. Methods and Materials: Patients with unresectable Stage III non-small-cell lung cancer were treated intravenously with carboplatin (area under the concentration curve 2) and paclitaxel (40 mg/m(2)) on Days 1, 8, 15, and 22 with concurrent twice-daily thoracic radiotherapy (1.5 Gy per fraction) beginning on Day 1 followed by two cycles of consolidation chemotherapy using carboplatin (area under the concentration curve 5) and paclitaxel (200 mg/m(2)). Total doses were 54 Gy in 36 fractions, 60 Gy in 40 fractions, 66 Gy in 44 fractions, and 72 Gy in 48 fractions at Levels 1 to 4. The dose-limiting toxicity, defined as Grade >= 4 esophagitis and neutropenic fever and Grade >= 3 other nonhematologic toxicities, was monitored for 90 days. Results: Of 26 patients enrolled, 22 patients were assessable for response and toxicity. When 4 patients entered Level 4, enrollment was closed to avoid severe late toxicities. Dose-limiting toxicities occurred in 3 patients. They were Grade 3 neuropathy at Level 1 and Level 3 and Grade 3 infection at Level 1. However, the maximum tolerated dose was not reached. The median survival time was 28.6 months for all patients. Conclusions: The maximum tolerated dose was not reached, although the dose of radiation was escalated to 72 Gy in 48 fractions. However, a dose of 66 Gy in 44 fractions was adopted for this study because late toxicity data were insufficient. (C) 2012 Elsevier Inc.
  • Takushi Yasuda; Ichiro Higuchi; Masahiko Yano; Hiroshi Miyata; Makoto Yamasaki; Shuji Takiguchi; Yoshiyuki Fujiwara; Jun Hatazawa; Yuichiro Doki
    ANNALS OF SURGICAL ONCOLOGY SPRINGER 19 (2) 652 - 660 1068-9265 2012/02 [Refereed]
     
    Induction therapy is not always beneficial for all patients. Therefore, it is important to identify the patients with a high rate of recurrence. The occurrence of lymph node metastases (LNMs) strongly influences the postoperative survival in patients with esophageal cancer. We investigated the usefulness of an LN evaluation by initial F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in prediction of postoperative recurrence for patients with resectable esophageal squamous cell carcinoma (ESCC). A total of 76 ESCC patients who did not undergo induction therapy, but who did receive a curative resection were divided into PET-node (PET-N) positive (n = 26) and negative (n = 50) groups according to the presence or absence of FDG uptake in LNs. The PET-N status was compared with the size and the number of LNMs, as well as with the survival and failure patterns. PET positive LNs involved a significantly larger size of metastatic nests than PET negative LNs (P = 0.002). The PET-N negative group showed a higher proportion of patients with 2 or fewer LNMs (92.0%), a higher 5-year relapse-free survival (75.1%) and a higher overall survival (70.0%), and a lower postoperative recurrence (24.0%) than the 15.4, 29.6, 30.3, and 69.2% values in the PET-N positive group, respectively, (P < 0.005). Multivariate analyses identified the PET-N status to be the most significant preoperative risk factor for postoperative recurrence (P = 0.031). The preoperative PET-N status in patients with resectable ESCC was significantly associated with the size and the number of LNMs and was therefore found to reliably identify the high-risk population for postoperative recurrence.
  • Masaaki Motoori; Masahiko Yano; Takushi Yasuda; Hiroshi Miyata; Ying Feng Peng; Makoto Yamasaki; Osamu Shiraishi; Koji Tanaka; Osamu Ishikawa; Hitoshi Shiozaki; Yuichiro Doki
    ONCOLOGY KARGER 83 (2) 91 - 100 0030-2414 2012 [Refereed]
     
    Objectives: Chemotherapy may cause various toxicities as well as impair immunological function. However, little is known about the relationship between toxicities and immunological parameters or the effect of enteral nutrition (EN) on immunological status during chemotherapy. Methods: 91 patients who received neoadjuvant chemotherapy (NACT) for esophageal cancer were randomly assigned to receive either EN or parenteral nutrition (PN). Immunological parameters, including total lymphocyte count (TLC), type 1 and type 2 CD4-positive T cells (Th1/Th2) balance, human leukocyte antigen (HLA)-DR expression on monocytes, natural killer cell activity, and phytohemagglutinin-stimulated lymphocyte proliferation were measured at baseline and day 14 of the first chemotherapy cycle. Results: In the PN group, patients with grade 3-4 neutropenia showed significantly lower TLC, HLA-DR expression, and Th1/Th2 balance at day 14 compared to those with grade 0-2 neutropenia. Among pretherapeutic factors, Th1/Th2 balance was the only factor significantly associated with the severity of neutropenia. Concerning the comparison of immunological parameters between the EN and PN groups, HLA-DR expression at day 14 was significantly higher in the EN group. Conclusions: Baseline Th1/Th2 balance predicted the severity of neutropenia, and EN significantly reduced the decline of monocyte HLA-DR expression in patients with esophageal cancer receiving NACT. Copyright (C) 2012 S. Karger AG, Basel
  • Motohiro Imano; Haruhiko Imamoto; Tatsuki Itoh; Takao Satou; Ying-Feng Peng; Atsushi Yasuda; Hiroaki Kato; Osamu Shiraishi; Masayuki Shinkai; Takushi Yasuda; Yoshifumi Takeyama; Kiyokata Okuno; Hitoshi Shiozaki
    JOURNAL OF SURGICAL ONCOLOGY WILEY-BLACKWELL 105 (1) 43 - 47 0022-4790 2012/01 [Refereed]
     
    Background The aim of this study was to examine the safety, pharmacokinetics, and cytological efficacy against free intraperitoneal cancer cells of intraperitoneal chemotherapy (IPC) with paclitaxel after gastrectomy with en-bloc D2 lymph node dissection (GD2) in cases of gastric cancer with peritoneal carcinomatosis (PC) and/or positive cytological findings in peritoneal washings (CFPW). Methods: Twenty-one patients with gastric cancer with PC and/or positive CFPW who underwent GD2 were treated with early, post-operative, intraperitoneal paclitaxel. Intra-chemotherapeutic toxicity and operative complication were measured using the common toxicity criteria of the National Cancer Institute, version 3.0. Intraperitoneal and plasma paclitaxel concentrations were measured using a high-performance liquid chromatography assay. Results: Grade 3 anemia occurred in two patients (9.5%) and neutropenia was observed in three patients (14.3%). No grade 4 toxicity was observed. A grade 2 operative complication was a superficial surgical site infection (4.8%) that was treated with antibiotics. Cytologically, no viable cancer cells were observed in the intra-abdominal fluid 24 hr after intraperitoneal administration of paclitaxel. The intraperitoneal/plasma area under the drug concentration-time curve (AUC) ratio was 596.9:1. Conclusion: IPC with paclitaxel after GD2 is a safe and cytologically effective treatment modality for free intraperitoneal cancer cells. However, additional data are required to determine the effect on survival. J. Surg. Oncol. 2012;105:43-47. (C) 2011 Wiley Periodicals, Inc.
  • Motohiro Imano; Kiyotaka Okuno; Tatsuki Itoh; Takao Satou; Eizaburo Ishimaru; Takushi Yasuda; Jin-Ichi Hida; Haruhiko Imamoto; Yoshifumi Takeyama; Hitoshi Shiozaki
    The American surgeon SOUTHEASTERN SURGICAL CONGRESS 77 (11) 1515 - 20 0003-1348 2011/11 [Refereed]
     
    Even after radical surgery for stage II and stage III colorectal cancer, metachronous liver metastasis is frequently observed. The aim of this study was to identify the risk of metachronous liver metastasis with retrospective clinicopathological study. Immunohistochemistry was performed to evaluate the expression of Osteopontin (OPN), CD-68, and CD105 in 41 cases of stage II and stage III colorectal cancer tissue. Stage II and stage III colorectal cancer patients who had undergone R0 resection were classified into two groups: with metachronous liver metastasis (m-LM; n = 17) and without liver metastases (control; n = 24). Additionally, double-immunofluorescence staining was performed using antibodies to OPN and CD68. OPN-positive cells were frequently colocalized with CD68 immunoreactivity. OPN and microvascular density expression in the central area were significantly higher in the m-LM (OPN; control 4.3 ± 0.56, m-LV 10.8 ± 1.48, P < 0.05; microvascular density control 18.5 ± 2.86, m-LV 31.4 ± 4.39, P < 0.05), while CD68 expression in the invasive margin was significantly higher in the control group (control 98.9 ± 7.31, m-LV 28.2 ± 3.18, P < 0.05). These results suggest that the risk of metachronous liver metastasis could be well predicted by immunohistochemical staining of OPN in the central areas, and CD68 in the invasive margins of tumors.
  • 錦 耕平; 安田 卓司; 塩崎 均
    日本臨床 (株)日本臨床社 69 (増刊6 食道癌) 392 - 398 0047-1852 2011/08
  • Masaaki Motoori; Masahiko Yano; Takushi Yasuda; Hiroshi Miyata; YingFeng Peng; Makoto Yamasaki; Osamu Shiraishi; Toru Masuzawa; Koji Tanaka; Osamu Ishikawa; Hitoshi Shiozaki; Yuichiro Doki
    ESOPHAGUS SPRINGER TOKYO 8 (2) 81 - 87 1612-9059 2011/06 [Refereed]
     
    Background Neoadjuvant chemotherapy (NACT) followed by surgery is a promising treatment strategy for advanced esophageal cancer. Response to NACT is a strong predictor for prognosis, but no studies have examined the relationship between toxicity and efficacy of NACT. Methods We retrospectively analyzed the treatment results of 105 patients with clinically node-positive esophageal cancer treated with NACT followed by surgery and examined the correlation between adverse events and treatment efficacy. Chemotherapeutic response was evaluated by the reduction rate of the primary tumor in CT scans. Adverse events were graded using the Common Terminology Criteria for Adverse Events version 3. Results The clinical response rate was 40%, and responders displayed a significantly better survival than nonresponders. Major adverse events (grade 3 or 4) during NACT were leukopenia (24.8%), neutropenia (42.9%), nausea (30.5%), and mucositis (27.9%). There were no chemotherapy-related deaths. In a univariate analysis, responders had significantly more severe adverse events including leukopenia, neutropenia, anemia, thrombocytopenia, and nausea than nonresponders. A multivariate analysis demonstrated that neutropenia was the only independent factor significantly associated with a clinical response (P = 0.027). Concerning prognosis, patients with grade 2-4 neutropenia showed significantly better survival than those with grade 0-1 neutropenia. Conclusion Antitumor efficacy of NACT for advanced esophageal cancer is significantly associated with the severity of neutropenia. To elucidate the mechanisms underlining these observations, pharmacokinetic and genetic chemosensitivity analyses are needed in future studies.
  • Takushi Yasuda; Hitoshi Shiozaki
    SURGERY TODAY SPRINGER 41 (6) 745 - 753 0941-1291 2011/06 [Refereed]
     
    The present best practice for performing esophageal reconstruction using colon tissue was investigated in this review. The left colon has advantages in that it has less variation in blood supply and a smaller diameter than the right colon; however, the rate of graft necrosis is higher for the left colon. Additional microvascular anastomosis, which is unnecessary in most cases, may be able to resolve these issues. The colon graft should be reconstructed in an isoperistaltic fashion whenever possible in order to prevent regurgitation and improve food transit. The posterior mediastinum has the advantage of being the shortest route, but it also has the major disadvantage that graft necrosis can be severe or fatal if it occurs. In palliative or advanced cases, a retrosternal or subcutaneous route is preferred, because the posterior mediastinum is a tumor bed. However, in these cases partial excision of the manubrium and the left clavicula should be considered to release compression of the graft at the thoracic inlet. Consequently, the selection of the colon graft should be flexible and be based on the inspection of blood supply and the length needed, and thereafter microvessel anastomosis should be added in cases where graft ischemia might occur.
  • Takushi Yasuda; Hitoshi Shiozaki
    ANNALS OF THORACIC AND CARDIOVASCULAR SURGERY MEDICAL TRIBUNE INC 17 (2) 103 - 109 1341-1098 2011/04 [Refereed]
     
    The pedicled colon segment is widely accepted as a substitute to the gastric tube in esophageal reconstruction of cases where the stomach is not available. The usefulness of reconstruction with a pedicled jejunum has also been reported in recent years. In order to make a long jejunal graft, at least the second and third jejunal vessels have to be severed. However, this leads to a decrease of circulation in the pedicled jejunum. This poor circulation was primarily responsible for the high rates of gangrene and mortality (22.2% and 46.5%, respectively) in the beginnings of jejunal reconstruction. Advances in microsurgery have now enabled surgeons to overcome these disadvantages, as a result, both the rates of gangrene and mortality have decreased to almost zero since the addition of microvascular anastomosis with the jejunal vessels and the internal thoracic vessels. At present, the reconstruction using a pedicled jejunum is a safe operation that provides such advantages as a low incidence of intrinsic disease, more active transport of food, and a lower rate of regurgitation by peristalsis, compared with the reconstruction using the pedicled colon. The disadvantage of the procedure is the relatively high rate of anastomotic leakage (11.1% to 19.2%). Improvements in the surgical procedures to overcome this disadvantage are, therefore, needed before it can be recommended without any reservations.
  • Makoto Yamasaki; Hiroshi Miyata; Koji Tanaka; Osamu Shiraishi; Masaaki Motoori; Y. F. Peng; Takushi Yasuda; Masahiko Yano; Hitoshi Shiozaki; Masaki Mori; Yuichiro Doki
    ONCOLOGY KARGER 80 (5-6) 307 - 313 0030-2414 2011 [Refereed]
     
    Objective: Esophageal squamous cell carcinoma (ESCC) is refractory to current therapeutic regimens and more effective therapies are imperative. To this end, we conducted a multicenter phase I/II trial of docetaxel, cisplatin, and fluorouracil (DCF) combination chemotherapy for ESCC. Methods: The study subjects were 46 patients with advanced or recurrent ESCC. Treatment included docetaxel at 60, 70, and 75 mg/m(2), cisplatin at 70 mg/m(2) on day 1, and daily fluorouracil at 700 mg/m(2) on days 1 through 5. The recommended dose of docetaxel was determined in phase I, while the response rate (RR) and progression-free survival rates were analyzed in phase II. Results: The recommended dose was determined to be 70 mg/m(2) in phase I. In phase II, the RR was 72.5%. Interim analysis showed median and 1-year progression-free survival of 14 months and 55.6%, respectively. Grade 3/4 toxicities of leukopenia and neutropenia occurred in 72.5 and 90% of patients, respectively. No treatment-related death was recorded. Surgical resection was subsequently performed in 20 patients after chemotherapy, and curative resection was achieved in 19. Conclusion: DCF was tolerable and effective for advanced and recurrent ESCC. Such findings might encourage a change in the treatment strategy for ESCC. Copyright (C) 2011 S. Karger AG, Basel
  • M. Imano; H. Imamoto; T. Itoh; T. Satou; Y. F. Peng; A. Yasuda; H. Kato; K. Nishiki; O. Shiraishi; M. Shinkai; M. Tsubaki; T. Yasuda; S. Nishida; Y. Takeyama; K. Okuno; H. Shiozaki
    EUROPEAN SURGICAL RESEARCH KARGER 47 (4) 254 - 259 0014-312X 2011 [Refereed]
     
    Background: There is no standard treatment available for gastric cancer patients whose sole 'non-curative factor' is positive cytological findings in peritoneal washings (CFPW). The aim of this study was to examine the safety, pharmacokinetics and efficacy for free intraperitoneal cancer cells of intraperitoneal chemotherapy with paclitaxel after gastrectomy with en bloc D2 lymph node dissection in cases of gastric cancer with positive CFPW. Methods: Ten patients with gastric cancer who underwent gastrectomy and systemic lymphadenectomy with D2 dissection, without any other non-curative factors besides positive CFPW, were treated with early postoperative intraperitoneal paclitaxel. Intra-chemotherapeutic toxicity and operative complications were measured using NCI-CTC version 3.0. Intraperitoneal and plasma paclitaxel concentrations were measured using a high-performance liquid chromatographic assay. Results: Grade 3/4 toxic effects included anemia (20%) and neutropenia (10%) that required no treatment. Operative complications were, for example, superficial surgical site infections (10%) that were treated with antibiotics. No viable cancer cells were observed in the intra-abdominal fluid 24 h after intraperitoneal administration of paclitaxel. The intraperitoneal/plasma area under the drug concentration-time curve ratio was 2,003.3: 1. Conclusion: Intraperitoneal chemotherapy with paclitaxel is a safe and effective treatment modality for free intraperitoneal cancer cells. Copyright (C) 2011 S. Karger AG, Basel
  • Masaaki Motoori; Ichiro Takemasa; Makoto Yamasaki; Takamichi Komori; Atsushi Takeno; Hiroshi Miyata; Shuji Takiguchi; Yoshiyuki Fujiwara; Takushi Yasuda; Masahiko Yano; Nariaki Matsuura; Kenichi Matsubara; Morito Monden; Masaki Mori; Yuichiro Doki
    INTERNATIONAL JOURNAL OF ONCOLOGY SPANDIDOS PUBL LTD 37 (5) 1113 - 1120 1019-6439 2010/11 [Refereed]
     
    To improve the prognosis of advanced esophageal cancer, neoadjuvant chemotherapy (NACT) followed by surgery is a promising treatment strategy. NACT has been shown to improve the prognosis of responders. However, non-responders not only suffer from side-effects, but they also lose precious time to take advantage of other possible treatments. Therefore, it is crucial to establish a reliable method that allows prediction of response before chemotherapy. A biopsy sample can provide valuable information on the biological characteristics of an individual esophageal cancer, which can affect chemosensitivity. Comprehensive gene expression profiling (GEP) using oligonucleotide microarray covering 30,000 human probes was performed in 50 pretreatment endoscopic biopsy samples from 25 patients with esophageal squamous cell cancer (ESCC) who underwent cisplatin-based chemotherapy (two samples per patient). Chemotherapeutic responses were evaluated by the reduction rate of the tumor area on CT scans. Responders were defined as patients with reduction rates of >= 50% and non-responders were defined as patients with <50% decrease. The diagnostic system, that predicts responses to chemotherapy, was constructed with the 199 most informative genes, and showed 82% of accuracy. Furthermore, the predictive performance of this system was confirmed using an additional ten samples with an accuracy of 80%. This study shows that GEP of pretreatment ESCC biopsy samples has the potential to predict responses to chemotherapy.
  • M. Imano; T. Itoh; T. Satou; Y. Sogo; H. Hirai; H. Kato; A. Yasuda; Y. F. Peng; M. Shinkai; T. Yasuda; H. Imamoto; K. Okuno; H. Shiozaki; H. Ohyanagi
    EJSO ELSEVIER SCI LTD 36 (10) 963 - 968 0748-7983 2010/10 [Refereed]
     
    Background: We performed short-term neoadjuvant chemotherapy (s-NAC) to examine whether anticancer drugs can change the proliferative ability of cancer cells in gastric cancer patients. Methods: Chemotherapy was performed for 72 h before gastrectomy in 63 gastric cancer patients. Patients were classed into four groups: Group F, 16 cases who received a single administration of 5-fluorouracil (5-FU); Group C, 15 cases who received a single administration of cis-diamminedichloroplatinum (CDDP; cisplatin); Group FC, 16 cases who received both 5-FU+CDDP; and a Control group, 16 cases who did not receive chemotherapy. We reviewed neoadjuvant biopsy tissue and gastric cancer tissue delivered by operation in these cases. The TUNEL method and immunohistochemistry with an anti-MIB-1 antibody were used to evaluate cellular apoptosis and proliferative ability, respectively. The apoptotic index (Al) and an MIB-1 index (MI) were also calculated. Results: There were no differences in Al or MI in biopsy tissue between the groups. The Al of gastric cancer tissue in Group FC was significantly higher than in the other groups (P < 0.01). The MI of Group FC was significantly lower than in the other groups (P < 0.05). In addition, after s-NAC operation there was a significant inhibition of proliferative potency and an induction of apoptosis in Group FC. Conclusion: Combination of CDDP and 5-FU reduced proliferative potency and increased cellular apoptosis in gastric cancer cells. (C) 2010 Elsevier Ltd. All rights reserved.
  • 安田 卓司
    近畿大学医学雑誌 近畿大学医学会 35 (2) 67 - 75 0385-8367 2010/06
  • 【食道癌手術 困難症例・偶発症対処の秘策】 頸部食道癌喉頭温存手術
    白石 治; 安田 卓司; 今本 治彦; 新海 政幸; 彭 英峰; 塩崎 均
    手術 金原出版(株) 64 (7) 977 - 984 0037-4423 2010/06
  • Hironori Shigeoka; Haruhiko Imamoto; Yasumasa Nishimura; Taro Shimono; Hiroshi Furukawa; Hiroshi Imamura; Takushi Yasuda; Hitoshi Shiozaki
    WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY BAISHIDENG PUBLISHING GROUP INC 2 (6) 282 - 286 1948-5204 2010/06 [Refereed]
     
    This report presents a case of highly advanced gastric cancer that achieved a histologically complete response (CR) to preoperative chemoradiotherapy with S-1 plus low-dose Cisplatin. A 60-year-old male patient underwent FDG positron emission tomography (PET) during a routine health examination. The patient was found to have swollen paraaortic lymph nodes. Shortly thereafter, he was diagnosed with gastric carcinoma with a type 2 tumor in the antrum with paraaortic lymph node metastases based on FDG-PET, endoscopic examination and abdominal computed tomography. After the completion of chemoradiation therapy (CRT), the tumor and the paraaortic lymph node metastases disappeared. The patient underwent surgery 5 wk after the completion of CRT, including a subtotal gastrectomy with Rouxen- Y reconstruction, D3 lymph node dissection and a left adrenalectomy. No cancer cells were detected in the resected specimen either in the primary lesion or lymph nodes, thus confirming a pathologically CR to CRT (CR grade 3). The patient has been stable and well without any evidence of recurrence for 48 mo after surgery. Such a preoperative CRT regimen might therefore be very effective for treatment of some advanced gastric cancers. (C) 2010 Baishideng. All rights reserved.
  • 白石 治; 安田 卓司; 今本 治彦; 新海 政幸; 彭 英峰; 塩崎 均
    手術 金原出版(株) 64 (5) 631 - 637 0037-4423 2010/05
  • 新海 政幸; 安田 卓司; 塩崎 均
    外科治療 (株)永井書店 102 (増刊) 490 - 494 0433-2644 2010/04 
    胸部食道癌切除後の再建臓器は胃が標準的である。しかし胃癌合併例や胃切除後状態などで胃管を使用できない場合がある。一般的には胃の次には結腸を使用している施設が多いが、当院では内胸動静脈を支配血管とした血管吻合を付加することにより、空腸を安全かつ十分な距離を挙上できるようになることから、胸壁前食道空腸吻合術を第一選択としている。本術式は結腸を利用するよりはるかに単純で安全である。(著者抄録)
  • 中森 康浩; 安田 卓司; 今本 治彦; 加藤 寛章; 岩間 密; 白石 治; 安田 篤; 彭 英峰; 新海 政幸; 今野 元博; 塩崎 均
    近畿大学医学雑誌 近畿大学医学会 35 (1) 31 - 40 0385-8367 2010/03 
    高齢者が多く侵襲度の高い食道癌術後の誤嚥性肺炎は最も危険な合併症のひとつである。高齢者の誤嚥はサブスタンスP(SP)の分泌低下による咳嗽反射低下がその要因とされている。食道癌周術期における血中SP濃度と咳反射の推移および誤嚥/肺炎の発症との関連を明らかにする。胸部食道癌手術予定で文書により同意が得られた26例を対象とした。術前、術後2日目(POD2)、術後7日目(POD7)に血中SP濃度測定、クエン酸誘発咳嗽反射閾値検査を行い、誤嚥/肺炎の発症との関連を前向き臨床研究で検討する。血中SPの平均値は術前、POD2、POD7の順に108.2pg/ml、66.8pg/ml、62.2pg/mlと推移しPOD2に大きく低下した。クエン酸誘発咳嗽反射閾値は測定可能の23例中19例(82.6%)でPOD2に閾値の上昇(15例)または最大のレベル10(4例)を示した。65歳以上のE群と65歳未満のY群に分けて検討したところ肺炎は3例(E群:2例、Y群:1例)、不顕性誤嚥を2例(E群)に認め、全例POD2に咳嗽反射閾値の上昇をみた。E群の誤嚥/肺炎の4例はいずれも術前血中SP濃度は40pg/ml以下でPOD2においても上昇をみなかった。食道癌術後の誤嚥/肺炎とのリスク因子を検討した結果、E群において術前の血中SP濃度≦40pg/mlが最も有意なリスク因子と判明した(p=0.008)。食道癌術後は血中SP濃度の低下と咳嗽反射閾値の上昇により誤嚥性肺炎を容易に発症する状態にある。65歳以上で術前の血中SP濃度≦40pg/mlは術後の誤嚥/肺炎に対するハイリスク群と考えられた。(著者抄録)
  • Makoto Yamasaki; Hiroshi Miyata; Yoshiyuki Fujiwara; Shuji Takiguchi; Kiyokazu Nakajima; Toshirou Nishida; Takushi Yasuda; Jin Matsuyama; Masaki Mori; Yuichiro Doki
    ANNALS OF SURGICAL ONCOLOGY SPRINGER 17 (2) 634 - 642 1068-9265 2010/02 [Refereed]
     
    Background. Response to chemotherapy and anatomical spread are significant prognostic factors in patients with esophageal squamous cell carcinoma (ESCC) treated by chemotherapy then surgery. Predicting the response to chemotherapy would allow significant optimization of cancer treatment. Methods. Genomic mutation and protein expression of p53 were investigated retrospectively by polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) and immunohistochemistry (IHC) using biopsy specimens from 77 ESCC patients before chemotherapy with 5-fluorouracil, adriamycin, and cisplatin. p53 status was correlated with various clinicopathological factors. Thereafter, we performed a prospective study of 20 consecutive patients to test our prediction model. Results. The retrospective study showed mutant p53 genotype and positive p53 IHC staining in 46.8 and 55.8% of patients, respectively, which was not associated with patient's clinicopathological findings including initial tumor stage. Objective response to chemotherapy was observed in 65.9% of patients with wild genotype, but in only 16.7% of patients with mutant genotype. Patients with mutations in p53 therefore showed significantly poorer prognosis than those without mutant p53. In contrast, p53 IHC staining did not correlate with response to chemotherapy, curative resection rate or prognosis. In the prospective study, p53 mutation was seen in 50% (10/20) of patients and was again consistently associated with poorer response to chemotherapy and poorer prognosis. Conclusions. p53 genotype of pretreatment biopsy is a potentially useful predictor of response to chemotherapy and prognosis in ESCC patients. This information might be valuable to clinicians in deciding on the optimal clinical strategy in patients with ESCC.
  • 頚部食道切除後の再建法（音声再建を含む）
    白石 治; 安田卓司; 塩﨑 均
    食道外科up-to-date 204 - 216 2010 [Refereed]
  • Motohiro Imano; Takao Satou; Tatsuki Itoh; Yoshifumi Takeyama; Atsushi Yasuda; Ying-Feng Peng; Masayuki Shinkai; Seiji Haji; Chikao Yasuda; Takuya Nakai; Takushi Yasuda; Haruhiko Imamoto; Kiyotaka Okuno; Hitoshi Shiozaki; Harumasa Ohyanagi
    AMERICAN SURGEON SOUTHEASTERN SURGICAL CONGRESS 76 (1) 91 - 95 0003-1348 2010/01 [Refereed]
     
    Mucin glycoproteins from the gallbladder epithelium are thought to contribute to the matrix or nucleus of gallstones and other biomineralization systems. The involved acidic glycoproteins have been reported in bile and gallstones. In addition, osteopontin (Opn) is a noncollagenous acidic bone matrix glycoprotein that possesses calcium-binding properties. To investigate the role of Opn in pigment gallstone formation, the involvement of Opn in pigment gallstone formation was studied immunohistochemically in the gallbladder wall and in the stones. Staining for Opn was strongly positive in the epithelium of stone-laden gallbladders and in their stones. The stone-laden gallbladders were infiltrated by macrophages, which intensely stained for Opn. Sections of the pigment stones, under low magnification, showed a lamellar pattern of Opn immunolabeling and showed a reticular pattern under high magnification. Our results indicate that Opn, an acidic glycoprotein from the gallbladder epithelium, seems to be involved in lithiasis. Opn from macrophages and/or the epithelium seems to help form the matrix protein.
  • Motohiro Imano; Takao Satou; Tatsuki Itoh; Kenichi Sakai; Eizaburo Ishimaru; Atsushi Yasuda; Ying-Feng Peng; Masayuki Shinkai; Fumiharu Akai; Takushi Yasuda; Haruhiko Imamoto; Kiyokata Okuno; Hiroyuki Ito; Hitoshi Shiozaki; Harumasa Ohyanagi
    JOURNAL OF GASTROINTESTINAL SURGERY SPRINGER 13 (9) 1577 - 1582 1091-255X 2009/09 [Refereed]
     
    Osteopontin (OPN) is significantly overexpressed in a variety of malignancies. However, little is known concerning the significance of OPN expression in human cancers. Thus, the aim of this study was to determine the relationship between the degree of OPN expression, the proliferative activity of cancer cells, and the clinicopathological findings for surgically resected gastric cancer. We evaluated the immunohistochemical expression of OPN in 85 specimens of cancer. Additionally, we investigated a cancer cell proliferative index using an anti-MIB-1 antibody and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling staining. Levels of OPN expression in gastric cancers were classified into three groups. To compare the relationship between OPN expression and clinicopathological findings, the features of cancer lesions were classified using the TNM Classification of Malignant Tumors, 6th Edition. Immunohistochemical examination of OPN expression in gastric cancer revealed diffuse granular staining in the cytoplasm. High OPN expression was observed in 37 of 85 carcinomas. Strong OPN expression was significantly associated with a low apoptotic index, a high proliferative index, depth of invasion, lymphatic invasion, and venous invasion. Pathologically, intestinal type carcinoma showed strong expression of OPN. These data suggested that OPN may play an important role in the invasiveness and the progressive nature of gastric cancer.
  • Masaaki Motoori; Ichiro Takemasa; Makoto Yamasaki; Takamichi Komori; Atsushi Takeno; Hiroshi Miyata; Shuji Takiguchi; Yoshiyuki Fujiwara; Takushi Yasuda; Masahiko Yano; Nariaki Matsuura; Kenichi Matsubara; Morito Monden; Masaki Mori; Yuichiro Doki
    INTERNATIONAL JOURNAL OF ONCOLOGY SPANDIDOS PUBL LTD 35 (2) 265 - 271 1019-6439 2009/08 [Refereed]
     
    Advanced esophageal cancer has been recently treated by multimodal therapy including preoperative chemotherapy or chemoradiotherapy and surgery. A biopsy sample provides a valuable specimen for understanding the biological characteristics of individual esophageal cancer. Pretreatment prediction of the response to chemotherapy or radiotherapy based on biological characteristics using biopsy samples is a desirable goal. In using biopsy samples for molecular analysis, there are two problems; the proportion of cancer cells and the intratumor heterogeneity. This study was conducted to investigate the feasibility of using endoscopic biopsy samples of esophageal squamous cell cancer (ESCC) for comprehensive gene expression profiling (GEP). Comprehensive GEP was performed in 40 bulky ESCC specimens and 10 normal esophageal epithelial specimens from patients who underwent esophageal resection and 52 endoscopic ESCC biopsy samples from 26 patients (two samples per one patient). Unsupervised hierarchical cluster analysis showed distinct profiles between the bulky ESCC specimens and normal epithelial specimens. Also, unsupervised hierarchical cluster analysis revealed distinct profiles between the biopsy ESCC samples and normal epithelial specimens. Moreover, a couple of biopsy samples taken from different locations of the same tumor were closely clustered together. That is, biopsy ESCC samples were distinguished from normal esophageal epithelial specimens and the intratumor heterogeneity of GEP was smaller than intertumor heterogeneity. GEP using biopsy ESCC samples is feasible and has the potential to represent the biological properties.
  • 武本智樹; 安田卓司; 中森康浩; 西山厚子; 岩間 密; 白石 治; 安田 篤; 彭 英峰; 新海政幸; 平井紀彦; 今野元博; 今本治彦; 塩﨑 均
    近畿大学医学会誌 近畿大学医学部 34 (1) 25 - 33 0385-8367 2009 [Refereed]
     
    [抄録]反回神経リンパ節(106recLN) の転移診断に基づく胸部食道癌手術における頸部郭清の個別化戦略において，術中転移診断を迅速病理診断に因ることの妥当性を検討した.対象はCTおよびFDG-PETで頸部・上縦隔LN転移陰性の胸部中・下部(Mt/ Lt)食道癌40例で，術中1～2個の106recLN を迅速病理診断し，転移陰性例は頚部郭清を省略して，その診断精度と根治性を検討した.術中迅速病理診断の結果， 106recLN転移陽性は15例，陰性は25例で，陽性例で6例(40％)，陰性例で1例(4％)の頚部LN転移/再発を認めた.術中検索した106recLNの診断は術後病理と全例一致したが，陰性例で，頚部再発の1例を含む4例にて術中未検索のLNに転移を認めた. 4例の転移巣は全て長径1mm以上で，検索していれば十分診断可能であった.術後病理診断によれば，頚部LN転移/再発は106recLN転移陽性群では19例中7例(36.8％)に対し，陰性群の21例では1例もなかった. 5年生存率は3領域群:66.7％， 2領域群:71.3％で有意差は無く，再発形式も同等であった.以上より，頚部・上縦隔LN転移陰性のMt/Lt食道癌における106recLNの術中転移診断による頚部郭清の個別化は，根治性の劣化も無く妥当であった. 106recLNの術中転移診断は複数個で行うことが肝要で，診断は病理診断で十分と考えられた.
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  • 食道癌根治的化学放射線療法（CRT）後遺残・再発腫瘍に関する臨床病理学的検討
    武本智樹; 安田卓司; 中森康浩; 西山厚子; 岩間 密; 白石 治; 安田 篤; 彭 英峰; 新海政幸; 平井紀彦; 今野元博; 今本治彦; 塩﨑 均
    近畿大学医学会誌 34 (2) 113 - 122 2009 [Refereed]
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  • Tomoki Makino; Yuichiro Doki; Hiroshi Miyata; Takushi Yasuda; Makoto Yamasaki; Yoshiyuki Fujiwara; Shuji Takiguchi; Ichiro Higuchi; Jun Hatazawa; Morito Monden
    SURGERY MOSBY-ELSEVIER 144 (5) 793 - 802 0039-6060 2008/11 [Refereed]
     
    Background. Neoadjuvant chemotherapy (NACT) targets lymph node metastasis (LN), as well as the primary tumor (PT) in esophageal squamous cell carcinomas (ESCC). F-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) reflects viable tumor volume and may be more useful for evaluating NACT responses than conventional radiography. Moreover, FDG-PET may elucidate the clinical significance of NACT responses for LN, which is not always identical to those for PT. Patients and Methods. We retrospectively investigated prognostic factors in 38 node-positive ESCC patients who had undergone NACT (5-fluorouracil, adriamycin, and cisplatin) and surgical resection. The NACT response was evaluated separately by both PET and computed tomography (CT) for each PT and LN. Results. Although NACT effect for PT and LN was similar by PET evaluation (SUVmax reduction; average 70.58% vs 71.57%), they did not show significant correlation, revealing discordance for 13 (34.2%) patients when SUVmax reduction of more than 70% was classified as a PET responder. An opposite relationship existed in that the pre-NACT SUVmax of PT was significantly lower in PET responders than in PET non-responders (9.92 +/- 4.3 vs 12.96 +/- 3.8, P=.032), while that of LN tenden to be higher in responders than in non responders (5.70 +/- 3.2 vs 3.77 +/- 0.9, P=.072). Multivariate analysis identified the number of PET-positive LN (P=.018, HR=5.464) and PET response for PT (P=015, HR=4.620) and for LN (P=.028, HR=3.854) as independent prognostic predictors. The NACT response for PT or LN on CT evaluation was not a significant prognostic predictors. The NACT response for PT or LN on CT for evaluation was not a significant prognostic predictor. Conclusion. PET is superior to CT for evaluating the NACt response from the viewpoint of survival analysis. The NACT response should be evaluated for both LN and PT because of their different behaviors during chemotherapy. Further studies of larger sample number should be conducted in the future. (Surgery 2008;144:793-802.)
  • Ichirou Higuchi; Takushi Yasuda; Masahiko Yano; Yuichirou Doki; Hiroshi Miyata; Mitsuaki Tatsumi; Hironori Fukunaga; Shuji Takiguchi; Yoshiyuki Fujiwara; Jun Hatazawa; Morito Monden
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MOSBY-ELSEVIER 136 (1) 205 - U114 0022-5223 2008/07 [Refereed]
     
    Objective: Patients with advanced esophageal squamous cell carcinoma receive neoadjuvant chemotherapy or chemoradiotherapy to improve survival, but benefits are observed only in those with histologic response. Positron emission tomography with fludeoxyglucose F 18 ( INN fludeoxyglucose [ (18)F]) detects accumulation of glucose analog in viable cancer cells. This study investigated the usefulness of positron emission tomography with fludeoxyglucose F 18 in assessment of response of advanced esophageal squamous cell carcinoma to neoadjuvant treatment to establish new criteria to predict postoperative long-term survival. Methods: Fifty patients with locally advanced esophageal squamous cell carcinoma who received neoadjuvant therapy ( chemotherapy 35, chemoradiotherapy 15) underwent positron emission tomography with fludeoxyglucose F 18 before surgical resection in evaluation of posttreatment maximum standardized uptake value, residual tumor size ( maximum square area of longitudinal axis), histologic response, and postoperative survival. Results: After treatment, uptake was not noted in 21 patients ( posttreatment maximum standardized uptake value <2.5, negative) but was detected in 29 (>= 2.5, positive). Residual tumor size ranged from 0 to 54.0 mm(2) for negative results and 55.0 to 676.0 mm(2) for positive, clearly distinguishing histologic major response from nonresponse. The negative group demonstrated significantly higher 5-year cause-specific survival ( 67.7%) and lower hematogenous recurrence ( 4.8%) than the 36.5% and 37.0% values in the positive group, ( P <.0042 and P = .0083, respectively). Univariate Cox regression analyses identified posttreatment maximum standardized uptake value ( cutoff 2.5) as the only preoperative prognostic factor ( P = .0071). Conclusion: Posttreatment positron emission tomography with fludeoxyglucose F 18 reliably predicted histologic response and postoperative survival in advanced esophageal squamous cell carcinoma. This tool could potentially be used to tailor optimal treatment according to individual responses.
  • Akiko Yoshioka; Hiroshi Miyata; Yuichiro Doki; Takushi Yasuda; Makoto Yamasaki; Masaaki Motoori; Kazuyuki Okada; Jin Matsuyama; Youichi Makari; Itsuro Sohma; Shuji Takiguchi; Yoshiyuki Fujiwara; Morito Monden
    ONCOLOGY REPORTS PROFESSOR D A SPANDIDOS 19 (5) 1099 - 1107 1021-335X 2008/05 [Refereed]
     
    The activation of the PI3K/Akt/mTOR pathway plays an important role in tumorigenesis and resistance to anticancer drugs. The aim of this study was to elucidate the role of the Akt/mTOR pathway in chemoresistance and the prognosis of patients with esophageal squamous cell carcinoma (ESCC) who received preoperative chemotherapy. We evaluated p-Akt and p-mTOR expression by immuno-histochemistry in the surgical specimens of 143 ESCC (51 patients with and 92 without preoperative chemotherapy). In 37 patients of the former group, paired tissue samples obtained before and after chemotherapy were examined immunohistochemically. The incidence of p-Akt expression was higher in ESCC with than without chemotherapy (51.0 vs. 25.0%, p=0.0018). Although p-Akt expression was not associated with an advanced tumor stage, a comparison between before and after chemotherapy demonstrated an increased p-Akt expression during chemotherapy (p=0.0348). The p-Akt expression did not correlate with survival in ESCC without chemotherapy, but was associated with poor prognosis in those with chemotherapy (p=0.0058). In particular, an increased p-Akt expression during chemotherapy was associated with poor survival (p=0.0022). Notably, the p-mTOR expression did not correlate with p-Akt expression (p=0.1482). The depth of the tumor invasion, clinical response and p-Akt expression correlated with the prognosis of 51 ESCC with chemotherapy. A multivariate analysis showed that p-Akt expression was the only independent predictor of poor prognosis in ESCC patients with chemotherapy. p-Akt expression increases after chemotherapy in ESCC and a high expression correlates with poor prognosis. Our results suggest that the activation of Akt is a potentially useful therapeutic target in ESCC patients treated with chemotherapy.
  • Kazuyuki Okada; Masahiko Yano; Yuichiro Doki; Takashi Azama; Hiroshi Iwanaga; Hirofumi Miki; Mitsuo Nakayama; Hiroshi Miyata; Shuji Takiguchi; Yoshiyuki Fujiwara; Takushi Yasuda; Norio Ishida; Morito Monden
    JOURNAL OF SURGICAL RESEARCH ACADEMIC PRESS INC ELSEVIER SCIENCE 145 (1) 5 - 12 0022-4804 2008/03 [Refereed]
     
    Background. The biological clock regulates circadian rhythm and is important for sustaining homeostasis. Here we examined the response of biological clock genes to systemic inflammatory stimulation. Materials and methods. At 08:00 h (= Zeitgeber time [ZT] 01), male Wistar rats (7-wk-old) maintained on a 12:12 h light:dark cycle (light on 07:00-19:00 h) received intravenous injection of 1 mg/kg lipopolysaccharide (LPS group) or 0.3 mL saline (control group). They were then sacrificed every 4 h (09:00 h ZT 02, 13:00 h = ZT 06, 17:00 h = ZT 10, 21:00 h ZT 14, 01:00 h = ZT 18,05:00 h = ZT 22) over a 2-d period, and blood, brain, and liver samples were obtained for analysis (n = 4 at each time for each group). The expression levels of clock gene, rPer2, and those of clock controlled gene, rDBP, were quantified in the suprachiasmatic nucleus by in situ hybridization, while those of rPerl, rPer2, rDBP, rPPARA, and rFKBP51 in the liver were determined by quantitative RT-PCR. Results. In the suprachiasmatic nucleus of control rats, rPer2 and rDBP mRNA expression levels showed robust circadian patterns with peak levels at ZT 06 and ZT 10, respectively. LPS significantly suppressed both genes on day I but recovery was noted on day 2. Similarly, LPS significantly suppressed rPer1, rPer2, rDBP, rPPARA, and rFKBP51 mRNA expression levels in the liver on day 1 but recovery was noted on day 2, whereas a robust circadian pattern was noted in the control group. Conclusion. Our results indicate that LPS causes transient suppression of the biological clock genes and suggest that the biological clock plays an important role in the response to systemic inflammatory stimulation. (c) 2008 Elsevier Inc. All rights reserved.
  • Minami Y; Miyata H; Doki Y; Yano M; Yamasaki M; Takiguchi S; Fujiwara Y; Yasuda T; Monden M
    Gan to kagaku ryoho. Cancer & chemotherapy 35 (3) 437 - 440 0385-0684 2008/03 [Refereed]
     
    Recently, it is reported that a omega-3 fatty acid-containing diet (Racol) enhances innate immunity and reduces mucosal damage in the small intestine during chemotherapy. The aim of this study is to examine the effects of a omega-3 fatty acid-containing diet (Racol) on the toxicity of chemoradiation therapy (CRT) for patients with esophageal cancers. Toxicity of CRT was evaluated in 10 patients who took Rakol at a maximum dose of 600 mL/day during CRT, compared with 10 patients who did not take Rakol. Regarding blood toxicity, the decrease of platelets did not differ between the former and the latter. However, the incidence of grade 2~4 neutropenia was lower in the former than in the latter (p=0.0043). With regard to gastrointestinal toxicity, the incidence of grade 2~4 diarrhea was also lower in the former than in the latter (p=0.0118). Moreover, the incidence of grade 2~4 stomatitis/pharyngitis tended to decrease in patients who took Rakol compared with those who did not (p=0.0812). The current results indicated that a omega-3 fatty acid-containing diet (Racol) may be beneficial to patients with esophageal cancers who receive CRT by reducing CRT toxicity.
  • H. Miyata; Y. Doki; T. Yasuda; M. Yamasaki; I. Higuchi; Y. Makari; J. Matsuyama; T. Hirao; S. Takiguchi; Y. Fujiwara; M. Monden
    DISEASES OF THE ESOPHAGUS BLACKWELL PUBLISHING 21 (2) 144 - 150 1120-8694 2008 [Refereed]
     
    F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) is used for pre-treatment staging and evaluation of response to pre-operative therapy in advanced thoracic esophageal cancers. To evaluate the clinical significance of PET diagnosis of superficial thoracic esophageal cancers, FDG-PET was conducted preoperatively in 41 patients with such cancers without pre-operative therapy. We compared the PET diagnosis with clinicopathological findings with respect to both the primary tumor and lymph node (LN) metastasis. Of the 41 superficial thoracic esophageal cancers, 21 (51.2%) were PET positive for primary tumors. Although tumor length and histological type did not correlate with FDG uptake by primary tumors, non-flat (elevated or depressed) tumors showed significantly stronger FDG uptake than flat ones. Of 28 tumors infiltrating the deep submucosal layer, 19 (67.9%) were PET positive, while only two (15.4%) of 13 tumors infiltrating only the mucosa or shallow submucosal layer were PET positive. MANOVA identified FDG uptake as the only independent risk factor for deep submucosal invasion (odds ratio, 7.407; P = 0.0279). In 13 patients with pathological LN metastasis, although no LN metastasis was detected by FDG-PET, FDG uptake by the primary tumors was the only risk factor for LN metastasis (P = 0.0318). PET-negative tumors tended to reflect longer disease-free survival than PET-positive tumors, although this was not significant. FDG-PET is useful for detecting tumors infiltrating the middle or deep submucosal layer (sm2/sm3), and for predicting LN metastasis in patients with superficial thoracic esophageal cancers. FDG-PET is helpful for decision-making regarding treatment of such patients.
  • Y. Doki; K. Okada; M. Miyata; M. Yamasaki; Y. Fujiwara; S. Takiguchi; T. Yasuda; T. Hirao; H. Nagano; M. Monden
    DISEASES OF THE ESOPHAGUS BLACKWELL PUBLISHING 21 (2) 132 - 138 1120-8694 2008 [Refereed]
     
    For esophageal cancer patients, the gastric tube is the first choice as an esophageal substitute, with the colon or the jejunum being used when the stomach cannot be used. We retrospectively compared these two methods from the viewpoint of peri-operative complications and long-term bodyweight alteration. From 1998 to 2005 53 patients who had undergone subtotal esophagectomy due to thoracic esophageal cancers were given reconstruction with the colon (28 cases) or the jejunum (25 cases). Both intestines were reconstructed via the subcutaneous route and were anastomosed to the internal mammalian artery and vein for a supercharged blood supply. There was no difference in operating time and blood loss. Compared with the colon reconstruction group, the hospital stay of the jejunum reconstruction group was significantly shorter (65 days vs 45 days, P = 0.0120) and the incidence of anastomotic leakage tended to be less (13 cases, 46% vs 6 cases, 24%, P = 0.1507), while other operative morbidity did not differ between the two groups. Bodyweight loss, which is a serious postoperative sequela after esophagectomy, was less in the jejunum group than in the colon group, showing a significant difference at 12 months after surgery. Our retrospective study revealed the jejunum to be superior to the colon for the reconstruction after esophagectomy along with gastrectomy, with respect to anastomotic leakage and bodyweight loss. The next step will be to conduct a prospective large cohort study.
  • 胃癌-基礎と臨床のアップデート 腹膜播種 化学療法-抗癌剤腹腔内投与・全身化学療法併用療法-
    今野 元博; 安田 卓司; 今本 治彦; 塩﨑 均; 大柳 治正
    日本臨床 596 - 602 2008
  • Yong Zhang; Yoshiyuki Fujiwara; Yuichiro Doki; Shuji Takiguchi; Takushi Yasuda; Hiroshi Miyata; Makoto Yamazaki; Chew Yee Ngan; Hirofumi Yamamoto; Qingyong Ma; Morito Monden
    ONCOLOGY KARGER 75 (1-2) 17 - 26 0030-2414 2008 [Refereed]
     
    Objective: Tyrosine kinase B (TrkB) is associated with aggressive behavior and poor prognosis in various cancers. Here we examined the association between TrkB expression and distant metastases/prognosis in gastric carcinoma (GC). Patients and Methods: We analyzed TrkB expression in 161 GC patients by immunohistochemistry and Western blot analysis. The correlation of TrkB mRNA and protein expression levels was examined in 10 patients by RT-PCR assay. Results: TrkB expression was of level 1 in 97 (60.2%) and level 2 in 64 (39.8%) patients. Patients with level 2 expression had a significantly higher incidence of distant metastases (p < 0.0001), well-differentiated tumors (p < 0.005), deeper depth of invasion (p < 0.005) and poorer disease-free and overall survival (p < 0.0001 each) compared to patients with level 1. Multivariate analysis identified the level of TrkB expression as an independent prognostic factor for both disease-free and overall survival (p < 0.01 and p < 0.0001, respectively). Both lymph node metastasis (odds ratio = 10.7) and TrkB expression (odds ratio = 9.3) were independent predictors of distant metastases. Conclusion: A high level of TrkB expression was observed in well-differentiated GC subtypes and is a predictor for distant metastases and prognosis in GC. Copyright (C) 2008 S. Karger AG, Basel.
  • がん化学療法の実際 －進行食道癌の化学療法－
    今野 元博; 安田 卓司; 平井 紀彦; 新海 政幸; 彭 英峰; 安田 篤; 白石 治; 武本 智樹; 岩間 密; 清川 厚子; 中森 康浩; 今本 治彦; 奥野 清隆; 塩﨑 均
    永井書店 103 - 108 2008
  • 松永和秀; 安田卓司; 朝村真一; 彭 英峰; 杉浦史哲; 塩崎 均; 磯貝典孝
    日外科系連合誌 Japanese College of Surgeons 33 (1) 733 - 736 0385-7883 2008 [Refereed]
     
    難治性食道瘻の一次縫合が困難であった２例に対して，大胸筋皮弁パッチグラフトによる瘻孔閉鎖術を施行した。皮島の血行を考慮し，皮島の周囲に多くの脂肪組織を付け，かつ表皮のみをトリミング（真皮は温存）し，最終的に瘻孔のサイズの1.5～２倍（0.5～１cm大き目）の大きさにして，瘻孔を閉鎖した。経口摂取は術後13日目から開始した。術後１カ月目の嚥下造影所見では，検査食通過時，吻合部が若干狭い印象であったが，通過障害は認められず，胃管への移送は良好であった。食事については，患者の誤嚥防止や吻合部への嚥下圧の負担を考慮した嚥下食を提供し，徐々に摂取量と食事形態をアップした。その結果２例とも誤嚥性肺炎や瘻孔の再発をきたすことなく，術後経過は良好であった。
  • 今野 元博; 安田 卓司; 平井 紀彦; 新海 政幸; 彭 英峰; 安田 篤; 白石 治; 武本 智樹; 西川 厚子; 岩間 密; 中森 康浩; 今本 治彦; 伊藤 龍生; 佐藤 隆夫; 奥野 清隆; 塩﨑 均; 大柳 治正
    癌の臨床 (株)篠原出版新社 54 (5) 329 - 336 0021-4949 2008
  • Current status of initial staging and posttreatment response evaluation in esophageal carcinoma
    安田 卓司; 今本 治彦; 塩﨑 均
    日本外科学会雑誌 日本外科学会事務所 109 (1) 3 - 9 2008/01 
    近年の診断技術の進歩は目覚しく、内視鏡機器の開発やFDG-PET（positron emission tomography）、Sentinel node（SN）診断の登場により診断精度は飛躍的に向上した。食道癌治療も低侵襲治療の進歩に伴い治療法の個別化が求められており、正確な進行度診断に基づいて個々に治療を選択していくことが重要である。
    T因子診断において拡大内視鏡とAFI（autofluorescence imaging）・NBI（narrow band imaging）の導入はT1の診断精度を格段に向上させた。T2以深は超音波内視鏡（endoscopic ultrasonography：EUS）とMultidetector CTによる診断が標準である。N因子についてはFDG-PETの有用性が期待されたが偽陰性が多く特異度は高いが感度が低い欠点がある。CTで腫大リンパ節を確認しEUSとFDG-PETで転移診断することが必要である。また近年低侵襲治療の適応決定を目的にラジオアイソトープを用いたSN診断が導入され、今後の研究成果が期待される。M因子においてFDG-PETは全身検索が可能でCTに付加的な情報を提供できるので極めて
  • Hirokazu Taniguchi; Yoshiyuki Fujiwaral; Yuichiro Dokil; Yurika Su Ita; Itsuro Sohma; Hiroshi Miyata; Shuji Takiguchi; Takushi Yasuda; Naruya Tomita; Ryuichi Morishita; Morito Monden
    INTERNATIONAL JOURNAL OF CANCER WILEY-LISS 121 (7) 1609 - 1617 0020-7136 2007/10 [Refereed]
     
    The ets-1 transcription factor plays an important role in cell proliferation, differentiation, apoptosis and tissue remodeling. Aberrant ets-1 expression correlates with aggressive tumor behavior and poorer prognosis in patients with various malignancies. I his study evaluated the efficacy of double-stranded decoy oligonucleotides targeting ets-1-binding cis elements for the suppression of ets-1 in treatment of a peritoneal dissemination model of gastric cancer. In vitro, MTT assay was performed to evaluate the effect of the ets-1 decoy on cell growth. Electrophoretic mobility shift assay (EMSA) was performed to determine ets-1 activity. In vivo, the effect of the ets-1 decoy was investigated in the peritoneal dissemination nude mice model. Disseminated nodules were analyzed immunohistochemically. Ets-1 decoy, but not scrambled decoy, significantly inhibited cell growth in 2 gastric cancer cell lines, which showed overexpression of ets-1 protein by inhibiting the binding activity of ets-1. In the peritoneal dissemination model, the ets-1 decoy significantly suppressed the disseminated nodules, and tended to prolong the survival rate. PCNA index, microvessel density and VEGF expression were also reduced in peritoneal tumors treated with ets-1 decoy. Intraperitoneal injection of ets-1 decoy inhibited peritoneal dissemination of gastric cancer in a nude mice model. The results indicate that the decoy strategy for ets-1 offers a promising therapy for patients with incurable peritoneal dissemination of gastric cancer, most of which show overexpression of ets-1 protein.
  • Yoichi Makari; Takushi Yasuda; Yuichiro Doki; Hiroshi Miyata; Yoshiyuki Fujiwara; Shuji Takiguchi; Jin Matsuyama; Makoto Yamasaki; Takafumi Hirao; Mitsuhiro Koyama Koyama; Hironobu Nakamuara; Morito Monden
    JOURNAL OF SURGICAL ONCOLOGY WILEY-LISS 96 (3) 220 - 229 0022-4790 2007/09 [Refereed]
     
    Background: Redundant blood supply by angiogenesis is a great advantage for the continuous growth of solid tumors. However, with chemotherapy (ChT), it can be disadvantageous due to increased drug delivery. An objective, reproducible, and non-invasive method for evaluating tumor blood supply is offered by perfusion CT. Methods: Fifty-five advanced esophageal cancers (95% squarnous cell carcinomas) were evaluated for hemodynamic parameters, including blood flow (BF), blood volume (BV), and mean transit time (MTT) of primary tumor by perfusion CT scan. Forty-six underwent neoadjuvant therapy (36 ChT and 10 chemoradiotherapy (CRT)) as primary treatment of the cancer and 36 underwent esophagectomy. Results: Clinicopathological parameters were not significantly associated with hemodynamic parameters, except for hematogenic metastasis, which was not frequent (seven patients), but significantly associated with high BF (P = 0.0165). High BF and low MTT correlated significantly with a good response by neoadjuvant therapies (P = 0.0004 and P = 0.0124), while BV did not. The patients with high BF more frequently underwent esophagectomy and displayed better prognosis than those with lower values, while neither BV nor MTT was associated with patient survival. Conclusions: Tumor BF by perfusion CT can partly predict the effect of ChT and CRT and survival. Further large cohort studies in homogeneous patient groups will reveal its clinical usefulness.
  • Shinji Yamamoto; Yasuhiko Tomita; Yoshihiko Hoshida; Eiichi Morii; Takushi Yasuda; Yuichiro Doki; Katsuyuki Aozasa; Hirokazu Uyama; Hideji Nakamura; Morito Monden
    ANNALS OF SURGICAL ONCOLOGY SPRINGER 14 (7) 2141 - 2149 1068-9265 2007/07 [Refereed]
     
    Background: Hepatoma-derived growth factor (HDGF) is thought to play an important role in the development and progression of carcinomas. In the present study, association of HDGF expression with recurrence and prognosis of esophageal carcinoma (EC) was examined. Methods: HDGF expression in 111 patients with EC (101 men and 10 women) with ages ranging from 38 to 82 (median, 61) years was analyzed by immunohistochemistry. Samples in which > 90% of tumor cells exhibited nuclear and cytoplasmic HDGF immunoreactivity at levels greater than or equal to what is observed in the endothelial cells were regarded as HDGF expression level 1, and others as HDGF expression level 0. Results: Thirty-seven of 111 patients showed level 1 HDGF expression. There was no correlation between HDGF expression and other clinicopathologic factors. Patients with level 1 expression showed poorer disease-free and overall survival (P < .05 for both) compared with those with level 0 expression. HDGF expression was an independent prognostic factor for patients with early (pT1-2) stage of the disease, but not for those with advanced (pT3-4) stage. Conclusions: HDGF expression level was shown to be a prognostic factor for EC.
  • Yuichiro Doki; Takushi Yasuda; Hiroshi Miyata; Yoshiyuki Fujiwara; Shuji Takiguchi; Makoto Yamasaki; Yoichi Makari; Jin Matsuyama; Takeshi Masuoka; Morito Monden
    SURGERY TODAY SPRINGER 37 (7) 590 - 595 0941-1291 2007/07 [Refereed]
     
    Thoracic esophageal cancers frequently metastasize to the right recurrent nerve nodes (RRNNs). In fact, huge RRNNs invading the trachea sometimes remain after definitive chemoradiation therapy (CRT), despite complete remission of the primary lesion. We performed salvage lymphadenectomy of a large RRNN combined with partial resection of the trachea in two patients. Using an anterior approach, we removed part of the sternum, clavicle, and the first and second costal cartilage; then, we removed the RRNNs with combined resection of the lateral quarter circumference of the trachea, the esophageal wall, and the recurrent nerve. Reconstruction was done with a musculocutaneous patch of major pectoral muscle to cover the tracheal defect. The only minor complication was venous thrombosis in one patient. Thus, combined removal of the RRNN and trachea was performed safely as a salvage operation after definitive CRT for esophageal squamous cell carcinoma.
  • Ryohei Kawabata; Hisashi Wada; Midori Isobe; Takashi Saika; Shuichiro Sato; Akiko Uenaka; Hiroshi Miyata; Takushi Yasuda; Yuichiro Doki; Yuji Noguchi; Hiromi Kumon; Kazuhide Tsuji; Keiji Iwatsuki; Hiroshi Shiku; Gerd Ritter; Roger Murphy; Eric Hoffman; Lloyd J. Old; Morito Monden; Eiichi Nakayama
    International Journal of Cancer 120 (10) 2178 - 2184 0020-7136 2007/05 [Refereed]
     
    NY-ESO-1 specific humoral responses are frequently observed in patients with various types of NY-ESO-1 antigen expressing tumors. In a large proportion of NY-ESO-1 antibody-positive patients of NY-ESO-1-specific CD8 T-cells can also be detected suggesting that monitoring of the NY-ESO-1 specific humoral immune response may be a relevant and more practical surrogate for estimating the overall immune response against NY-ESO-1 in clinical vaccine studies. We have immunized 9 cancer patients with full length NY-ESO-1 protein formulated with cholesterol-bearing hydrophobized pullulan (CHP-NY-ESO-1) and investigated the humoral immune responses against NY-ESO-1. Seven patients were NY-ESO-1 antibody-negative and 2 patients were positive prior to vaccination. Vaccination with CHP-NY-ESO-1 resulted in the induction or increase of NY-ESO-1 antibody responses in all 9 patients immunized. Epitope analysis revealed 5 regions in the NY-ESO-1 protein molecule that were recognized by antibodies induced after vaccination. The 5 regions were also recognized by antibodies present in nonvaccinated, NY-ESO-1 antibody-positive cancer patients. A peptide spanning amino acids 91-108 was recognized in 6 out of 9 vaccinated patients and in 8 out of 9 nonvaccinated, sero-positive patients, being the most dominant antigenic epitope in NY-ESO-1 for antibody recognition in cancer patients. In conclusion, we showed that CHP-NY-ESO-1 protein vaccination had a potent activity for inducing humoral immune responses against NY-ESO-1 antigen in cancer patients. The antigenic epitopes recognized by antibodies in the vaccinated patients were similar to those recognized in cancer patients with spontaneous humoral immunity against NY-ESO-1. © 2007 Wiley-Liss, Inc.
  • Jin Matsuyama; Yuichiro Doki; Takushi Yasuda; Hiroshi Miyata; Yoshiyuki Fujiwara; Shuji Takiguchi; Makoto Yamasaki; Yoichi Makari; Nariaki Matsuura; Masayuki Mano; Morito Monden
    SURGERY MOSBY-ELSEVIER 141 (5) 570 - 580 0039-6060 2007/05 [Refereed]
     
    Background. Neoadjuvant chemotherapy (NACT) has been postulated but not yet proven to eradicate micrometastases and improve the prognosis of patients with advanced esophageal squamous cell carcinomas (ESCC). Cytokeratin immunohistochemistry of the lymph nodes of ESCC revealed immunohistochemical micrometastases (IHM) and cytokeratin deposits (CO), which are hyalinized denucleated particles considered to be cadavers of carcinoma cells. Successful chemotherapy should convert cancer cells from IHM to CD and improve the status of ESCC patients from systemic disease to regional disease. Methods. Cytokeratin immunostaining of surgically removed lymph nodes was performed for 107 patients with node-positive ESCC, including 32 patients without preoperative treatment (Surgery group) and 75 patients undergoing NACT using CDDP, doxorubicin hydrochroride, and 5-fluorouracil (NACT group). Cytokeratin-positive staining was done for serial hematoxylin-eosin-stained sections and classified as pathologic metastasis, IHM, or CD. Results. CO was observed less frequently in the Surgery group than in the NACT group (6% vs 43%, P < .0001), whereas IHM was more frequent in the former (47% vs 24%, P = .019). IHM was a poor prognostic factor in both groups, whereas U) was a favorable one in the NACT group. The effect of chemotherapy on IHM was classified as eradicated, IHM(-)/CD(+); persistent, IHM(+)/CD(+); no effect, IHM(+)/CD(-); or not informative, IHM(-)/CD(-). This classification correlated well with the clinical response of the primary neoplasm, number of pathologic metastases, and postoperative survival (3-year survival rates: 78%, 18%, 0%, and 38%). IHM/CD was found to be an independent prognostic factor together with the number of pathologic metastases in the multivariate analysis. Conclusions. Disappearance of IHM and the emergence of CD suggest the eradication of micrometastases by NACT The clinical benefit of NACT was apparent for IHM(-)/CD(+) patients with node-positive ESCC.
  • Akiko Uenaka; Hisashi Wada; Midori Isobe; Takashi Saika; Kazuhide Tsuji; Eiichi Sato; Shuichiro Sato; Yuji Noguchi; Ryohei Kawabata; Takushi Yasuda; Yuichiro Doki; Hiromi Kumon; Keiji Iwatsuki; Hiroshi Shiku; Morito Monden; Achim A. Jungbluth; Gerd Ritter; Roger Murphy; Eric Hoffman; Lloyd J. Old; Eiichi Nakayama
    Cancer Immunity Academy of Cancer Immunology 7 1424-9634 2007/04 [Refereed]
     
    We recently showed that vaccination with a complex of cholesterol-bearing hydrophobized pullulan and NY-ESO-1 protein (CHP-NY-ESO-1) elicited antibody responses in 9 of 9 patients vaccinated in a clinical trial. In this study, we performed T cell immunomonitoring and analyzed tumor responses in these patients. To evaluate CD4 and CD8 T cell responses, an IFN-γ secretion assay was used. The assay showed low background and was sensitive for detecting antigen-specific T cells. An increase in the CD4 T cell response was observed in 2 of 2 initially sero-positive and 5 of 7 initially sero-negative patients after vaccination. An increase in the CD8 T cell response was also observed in 2 of 2 sero-positive and 5 of 7 sero-negative patients after vaccination. Analysis of peptides recognized by CD4 and CD8 T cells revealed two dominant NY-ESO-1 regions, 73-114 and 121-144. Tumor responses were observed in 3 esophageal cancer patients and a malignant melanoma patient. In 3 of 4 prostate cancer patients, prostate-specific antigen (PSA) values stabilized during the course of vaccination. The use of whole protein, containing multiple CD4 and CD8 epitopes, may be beneficial for cancer vaccines to prevent tumors from evading the immune response. Copyright © 2007 by Eiichi Nakayama.
  • Naoki Hashimoto; Tikao Yasuda; Masato Inayama; Hidemine Ho; Masayuki Shinkai; Kenshu Kawanishi; Norihiko Hirai; Motohiro Imano; Hironori Shigeoka; Haruhiko Imamoto; Hitoshi Shiozaki
    HEPATO-GASTROENTEROLOGY H G E UPDATE MEDICAL PUBLISHING S A 54 (75) 796 - 798 0172-6390 2007/04 [Refereed]
     
    Background/Aims: Persistence of dyspeptic symptoms after choledochoduodenostomy (CDD) is common. There is evidence that at least some of these symptoms may be attributed to duodenogastric reflux (DGR). The aim of the study was to quantify DGR after CDD.Methodology: A total of 6 patients who had undergone cholecystectomy with a standard side-to-end CDD for choledocholithiasis or Lemmel syndrome were studied by symptom evaluation, biliary scintigraphy and endoscopy at least 6 months after surgery. Duodenogastric reflux was quantified using continuous intravenous infusion of Tc-99m-HIDA.Results: The incidence of DGR after CDD was 67% compared to healthy control. In the majority of the patients the DGR was mild to moderate, but not with the clinical symptoms.Conclusions: 99mTc-HIDA scanning of the hepatobiliary system is a reasonable and reliable method for the quantitative evaluation of DGR. CDD is associated with a high incidence of DGR, but its occurrence does not produce significant clinical symptoms.
  • 【腫瘍外科治療の最前線】 食道の腫瘍性疾患 稀な組織型の食道腫瘍 食道悪性黒色腫、悪性リンパ腫と神経鞘腫
    重岡 宏典; 彭 英峰; 平井 紀彦; 新海 政幸; 川西 賢秀; 今野 元博; 今本 治彦; 安田 卓司; 塩崎 均
    外科治療 (株)永井書店 96 (増刊) 417 - 421 0433-2644 2007/04 
    本邦では食道に発生する悪性腫瘍の大部分は扁平上皮癌であり、少数であるが腺癌もみられる。その他ごくまれな悪性腫瘍として、悪性黒色腫や悪性リンパ腫、GIST、癌肉腫などがあり本稿ではわれわれが経験した食道悪性黒色腫と悪性リンパ腫について述べる。食道の良性腫瘍には筋腫、ポリープ、線維腫、嚢胞、血管腫、乳頭腫、脂肪腫などがあり、平滑筋腫が最も頻度が高く、良性腫瘍の約70%を占める。非常にまれな良性腫瘍として食道神経鞘腫についても紹介する。(著者抄録)
  • Fujiwara Y; Doki Y; Takiguchi S; Yasuda T; Miyata H; Monden M
    Gan to kagaku ryoho. Cancer & chemotherapy 34 (3) 431 - 434 0385-0684 2007/03 [Refereed]
     
    Recently, new and promising antitumor agents such as TS-1, CPT-11, and taxanes have been widely used and have contributed to the survival of unresectable and recurrent gastric cancer patients. However, problems remain in the treatment for patients showing multi-drug resistance to those agents. We have experienced five patients with unresectable and recurrent gastric cancer, treated with combination therapy with bi-weekly docetaxel and 5'-deoxy-5-fluorouridine (5'-DFUR). The therapy was introduced as a 2nd, 3rd, 4th, and 6th chemotherapy regimen. Among five cases, one showed a moderate response and two exhibited stable disease, while two suffered progressive disease. Although the performance status at the start of the therapy was "2" in three cases and "1" in two cases, there were no serious adverse events in any case, and all patients were treated at an outpatient clinic. Three cases were introduced to the regimen as final treatment and survived for 209, 246, and 157 days, respectively. Combination therapy with bi-weekly docetaxel/5'-DFUR can be a promising regimen for gastric patients showing multi-drug resistance and poorer performance status.
  • Takashi Azama; Masahiko Yano; Katsutaka Oishi; Koji Kadota; Kija Hyun; Hiromi Tokura; Shinya Nishimura; Takashi Matsunaga; Hiroshi Iwanaga; Hirofumi Miki; Kazuyuki Okada; Nobuaki Hiraoka; Hiroshi Miyata; Shuji Takiguchi; Yoshiyuki Fujiwara; Takushi Yasuda; Norio Ishida; Morito Monden
    LIFE SCIENCES PERGAMON-ELSEVIER SCIENCE LTD 80 (12) 1100 - 1108 0024-3205 2007/02 [Refereed]
     
    Patients undergoing surgery often develop symptoms of circadian rhythm disorders such as insomnia or delirium. However, the effect of surgery on the biological clock remains unknown. The present study examines the expression of clock genes in peripheral blood mononuclear cells (PBMCs) and measures plasma hormone concentrations in patients with esophageal cancer and early gastric cancer who underwent surgery. Six blood samples per day were collected from 9 patients with esophageal cancer before and after esophagectomy and from 9 patients with early gastric cancer before and after laparoscopy-assisted distal gastrectomy (LADG). The expression profiles of hPer1 and hPer2 mRNAs in PBMCs were determined by real-time RT-PCR. Plasma melatonin and cortisol concentrations were measured by radioimmunoassay. Plasma melatonin levels decreased in both groups throughout the day and plasma cortisol levels changed after surgery. The acrophase of clock gene expression was altered after surgery as follows: hPer1, from 6:19 +/- 1:50 to 13:59 +/- 0:59 (p=0.0003) and from 7:47 +/- 1:27 to 12:33 +/- 1:30 (p=0.0043) and hPer2, from 5:01 +/- 2:59 to 19:30 +/- 2:15 (p < 0.0001) and from 6:49 +/- 1:59 to 13:39 +/- 3:06 (p=0.0171) in patients with esophageal and early gastric cancer, respectively. The post-operative phase change of hPer2 was more prominent after esophagectomy than after LADG. Our results suggest that surgical stress affects the peripheral clock as well as endogenous hormones in humans. (c) 2006 Elsevier Inc. All rights reserved.
  • 左右迷走神経肺枝温存
    安田 卓司; 彭 英峰; 今本 治彦; 塩﨑 均
    消化器外科 へるす出版 30 (2) 159 - 169 2007/02
  • Makoto Yamasaki; Yuichiro Doki; Hiroshi Miyata; Takushi Yasuda; Shuji Takiguchi; Yoshiyuki Fujiwara; Morito Monden
    Japanese Journal of Gastroenterological Surgery Japanese Society of Gastroenterological Surgery 40 (8) 1466 - 1472 1348-9372 2007 [Refereed]
     
    A nonrecurrent inferior laryngeal nerve (NRILN) is a rare anomaly. We report four cases of esophageal cancer with NRILN treated by transthoracic esophagectomy with three-field lymphadenectomy. All had been diagnosed as esophageal cancer. Under a diagnosis of concomitant NRILN based on preoperative computed tomography, we conducted transthoracic esophagectomy with three-field lymphadenectomy. The right subclavian artery on the right between the esophagus and vertebral column was recognizable perioperatively. The right recurrent nerve was not identified at the right subclavian artery during mediastinal dissection, but the NRILN was identified as going directly from the vagal nerve to the larynx during neck lymphadenectomy. The thoracic duct ran between the esophagus and the azygos vein, terminating at the right venous angle. Because the aberrant right subclavian artery is associated with the NRILN, right-sided terminating thoracic duct, etc., surgery must proceed under stringent controll with these abnormalities in mind. In patients with NRILN, cancer tends to metastasize to neck lymph nodes regardless of upper mediastinal lymph nodes, which is why esophagectomy with three-field lymphadenectomy is considered standard in treating thoracic esophageal cancer with NRILN. ©2007 The Japanese Society of Gastroenterological Surgery.
  • 根治的CRT後の食道癌salvage手術の適応と限界
    新海 政幸; 安田 卓司; 清川 厚子; 武本 智樹; 安田 篤; 彭 英峰; 平井 紀彦; 今野 元博; 今本 治彦; 塩﨑 均
    癌の臨床 (53) 605 - 610 2007
  • 腹膜播種を伴う胃癌症例に対するPTX腹腔内投与と逐次S-1+Weekly PTX併用療法
    今野 元博; 今本 治彦; 安田 卓司; 平井 紀彦; 新海 政幸; 彭 英峰; 安田 篤; 武本 智樹; 清川 厚子; 杉浦 史哲; 奥野 清隆; 塩﨑 均; 大柳 治正
    Chemotherapy for Gastric cancer Chemotherapy for Gastric cancer Medical Front Int. Ltd. (2007) 10 - 11 2007
  • スキルス胃癌腹膜播種陽性症例に対するPaclitaxel腹腔内投与と逐次S-1+weekly paclitaxel併用療法
    今野 元博; 安田 卓司; 平井 紀彦; 新海 政幸; 彭 英峰; 安田 篤; 武本 智樹; 清川 厚子; 岩間 密; 中森 康浩; 今本 治彦; 伊藤 龍生; 佐藤 隆夫; 奥野 清隆; 塩﨑 均; 大柳 治正
    消化器科 科学評論社 42 (2) 169 - 175 0289-8756 2007
  • 手術ーここ３０年の変化 食道良性疾患の手術
    今本 治彦; 安田 卓司; 塩﨑 均
    手術 金原出版 60 (10) 1433 - 1439 2006/09
  • Masaaki Motoori; Ichiro Takemasa; Yuichiro Doki; Sakae Saito; Hiroshi Miyata; Shuji Takiguchi; Yoshiyuki Fujiwara; Takushi Yasuda; Masahiko Yano; Yukinori Kurokawa; Takamichi Komori; Makoto Yamasaki; Noriko Ueno; Shigeyuki Oba; Shin Ishii; Morito Monden; Kikuya Kato
    European journal of cancer (Oxford, England : 1990) 42 (12) 1897 - 903 0959-8049 2006/08 [Refereed]
     
    Peritoneal metastasis is the most common cause of tumour progression in advanced gastric cancer. Clinicopathological findings including cytologic examination of peritoneal lavage have been applied to assess the risk of peritoneal metastasis, but are sometimes inadequate for predicting peritoneal metastasis in individuals. Hence, we tried to construct a new prediction system for peritoneal metastasis by using a PCR-based high throughput array with 2304 genes. The prediction system, constructed from the learning set comprised of 30 patients with the most informative 18 genes, classified each case into a 'good signature group' or 'poor signature group'. Then, we confirmed the predictive performance in an additional validation set comprised of 24 patients, and the prediction accuracy for peritoneal metastasis was 75%. Kaplan-Meier analysis with peritoneal metastasis revealed significant difference between these two groups (P=0.0225). By combining our system with conventional clinicopathological factors, we can identify high risk cases for peritoneal metastasis more accurately.
  • K Nishioka; Y Doki; H Miyata; S Tamura; T Yasuda; Y Kimura; K Kishi; K Yoshida; Y Fujiwara; M Yano; M Monden
    JOURNAL OF SURGICAL RESEARCH ACADEMIC PRESS INC ELSEVIER SCIENCE 132 (1) 130 - 135 0022-4804 2006/05 [Refereed]
     
    Background. We have reported G1 progression and cyclooxygenase-2 (COX-2) induction during carcinogenesis of the squamous epithelium of the esophagus. As bile acid induces COX-2 expression and promotes carcinogenesis in the digestive tract, we investigated the effect of bile acid on the proliferation of squamous cell carcinoma of the esophagus (ESCC). Materials and methods. MTT assay, Western blot analysis of COX-2 and cell cycle-related molecules in the G1 phase (Rb, CDC25A, cyclin D1), and CDK2 kinase assay were performed on chenodeoxycholic acid (CDCA) exposure to ESCC cell lines (TE2R, TE3, TE13, TE15). Results. In the presence of gradient bile acid concentration (up to 100 mu M), growth of ESCC cell lines was stimulated at a low concentration (maximally at 20-30 mu M), but suppressed at a higher concentration. Only a low dose of bile acid induced the expression of cyclin D1 and CDC25A and showed high Rb phosphorylation and high CDK2 kinase activity. In contrast, bile acid progressively induced COX-2 expression in a dose-dependent manner, regardless of its biphasic effects on cell proliferation, and a COX-2 specific inhibitor (JTE-522) did not suppress growth stimulation by a low dose of bile acid. Conclusions. Bile acid at a low dose stimulates the proliferation of ESCC by inducing G1-regulating molecules. However, COX-2 expression, which is also induced by bile acid, does not affect cell proliferation. Further work is needed to elucidate its role in carcinogenesis. (c) 2006 Elsevier Inc. All rights reserved.
  • H Miyata; M Yano; Y Doki; T Yasuda; S Yoshioka; Y Sugita; S Takiguchi; Y Fujiwara; M Monden
    JOURNAL OF SURGICAL ONCOLOGY WILEY-LISS 93 (6) 477 - 484 0022-4790 2006/05 [Refereed]
     
    Background and Objectives: The aim of this study was to evaluate the usefulness of intra-operative genetic diagnosis of RN node micrometastasis in the decision-making of 3FL for thoracic esophageal cancers. Methods: Eighty-nine patients with middle and lower thoracic esophageal cancer were enrolled in a prospective Study, in which 3FL was performed when RN node metastasis was revealed by intra-operative histological examination and/or genetic analysis using real-time RT-PCR assay. For other cases, 2FL was performed. Results: Of the 89 patients, 3FL was performed for 33 patients and 2FL for 56 patients. In the 3FL group, RN node metastasis was both histologically and genetically positive in 19 patients, histologically negative and genetically positive in 11, and histologically positive and genetically negative in 3, with cervical node metastasis being detected in 7, 3. and 0 patients, respectively. In the 2FL group, only one patient had cervical node recurrence during the follow-up period. The postoperative survival in this study was equivalent to that of the historical controls (3-year survival rates 63.9% vs. 52.3%, P = 0.1513) of 66 3FL patients when 3FL was the first choice for thoracic esophageal cancers. Conclusions: Intra-operative histological and genetic diagnosis of RN node metastasis, may help avoid unnecessary cervical node resection. A Phase III trial should be done.
  • YASUDA T.; DOKI Y.; MIYATA H.; TAKIGUCHI S.; FUJIWARA Y.; MONDEN M.
    The Journal of the Japan Broncho-esophagological Society The Japan Broncho-esophagological Society 57 (2) 120 - 124 0029-0645 2006/04
  • N Urano; Y Fujiwara; Y Doki; SJ Kim; Y Miyoshi; S Noguchi; H Miyata; S Takiguchi; T Yasuda; M Yano; M Monden
    INTERNATIONAL JOURNAL OF ONCOLOGY PROFESSOR D A SPANDIDOS 28 (2) 375 - 381 1019-6439 2006/02 [Refereed]
     
    Docetaxel, one of the most effective anticancer drugs for gastric cancer, targets beta-tubulin, the major protein in mitotic spindles. Eight isotypes of beta-tubulin, with tissue and organ-specific expression, have been identified in mammalian cells. We examined class III beta-tubulin expression in gastric cancer and assessed its relationship with sensitivity to docetaxel-based chemotherapy. A total of 115 paraffin-embedded gastric tumors were analyzed by immunohistochemistry for class III beta-tubulin expression. Twenty patients with advanced gastric cancer received preoperative docetaxel-based chemotherapy. Their biopsied specimens, obtained by endoscopy before chemotherapy were examined for class III beta-tubulin expression. The relationship between expression and chemosensitivity was assessed. Forty-two (36.4%) of 115 cases were confirmed to be positive for class III beta-tubulin expression. There was no association between clinicopathological status and prognosis. Among the patients positive for class III beta-tubulin expression, only 16.7% showed no response to chemotherapy, while 64.3% responded to the chemotherapy in the negative group. Our results suggest that class III beta-tubulin is a simple and useful predictive marker for the clinical response to docetaxel-based chemotherapy in gastric cancer.
  • Naomi Urano; Yoshiyuki Fujiwara; Yuichirou Doki; Masaki Tsujie; Hirofumi Yamamoto; Hiroshi Miyata; Shuji Takiguchi; Takushi Yasuda; Masahiko Yano; Morito Monden
    Gastric Cancer 9 (1) 44 - 49 1436-3291 2006/02 [Refereed]
     
    Background. The transcriptional factor hypoxia-inducible factor 1α (HIF-1α) controls angiogenesis and metabolism by upregulating hypoxia-induced genes, such as the vascular endothelial growth factor (VEGF) gene and the glucose transporter (GLUT-1) gene. In addition to its regulation by oncogenes or tumor suppressor genes such as HER2, p53, VHL, and PTEN, overexpression of HIF-1α is induced by hypoxia. Increased HIF-1α expression is associated with malignant potential, and with patient prognosis and response to chemoradiotherapy in some cancer types. Methods. We investigated the association between HIF-1α expression and clinicopathological characteristics, including the expression of VEGF and p53 proteins, in gastric cancer. Furthermore, we analyzed the impact of HIF-1α, VEGF, and p53 protein expression on resistance to chemotherapy in advanced gastric cancer. Results. Among 146 specimens from patients with gastric adenocarcinoma, 89 (61.0%), 52 (35.6%), and 102 (69.9%) were positive for HIF-1α, p53, and VEGF expression, respectively. The increased expression of HIF-1α protein correlated significantly with the increased expression of p53 (P < 0.0001) and VEGF (P = 0.0007). However, overexpression of these proteins was not associated with prognosis or clinicopathological status, with the exception of infrequent distant metastases. Furthermore, overexpression of these proteins was not associated with chemosensitivity in these patients with gastric cancer. Conclusion. Our results indicate that overexpression of HIF-1α correlates significantly with p53 and VEGF protein expression in patients with gastric cancer however, this overexpression shows no association with clinicopathological status, patient prognosis, or chemosensitivity. © 2006 by International and Japanese Gastric Cancer Association.
  • Shinji Yamamoto; Yasuhiko Tomita; Yoshihiko Hoshida; Shuji Takiguchi; Yoshiyuki Fujiwara; Takushi Yasuda; Yuichiro Doki; Kenya Yoshida; Katsuyuki Aozasa; Hideji Nakamura; Morito Monden
    Clinical Cancer Research 12 (1) 117 - 122 1078-0432 2006/01 [Refereed]
     
    Purpose: Hepatoma-derived growth factor (HDGF) is a unique nuclear/growth factor and might play an important role in the development and progression of carcinomas. In the present study, association of HDGF expression with recurrence and prognosis of gastric carcinoma was examined. Patients and Methods: HDGF expression in 317 patients with gastric carcinoma (233 males and 84 females) with ages ranging from 26 to 81 years (median, 60 years) was analyzed by immunohistochemistry. Samples with > 90% of tumor cells to express positive immunoreactivity similar to or stronger than that in endothelial cells both for nucleus and cytoplasm were regarded as HDGF index level 2, and others as HDGF index level 1. Results: One hundred and eighty-two cases showed level 1 HDGF expression, whereas 135 cases showed level 2 HDGF expression. Patients with level 2 expression showed higher rates of proximal tumor location (P < 0.0001), large tumor size (P < 0.0001), infiltrative tumor growth (P < 0.0001), presence of vascular and lymphatic invasion (P < 0.0001 for both), presence of lymph node metastasis (P < 0.0001), deep tumor invasion (P < 0.0001), and poorer disease-free and overall survival (P < 0.0001 for both) compared to those with level 1 expression. Multivariate analysis revealed HDGF expression level as an independent prognosticator for disease-free and overall survival. Conclusion: HDGF expression level was shown to be a prognostic factor for gastric carcinoma. © 2006 American Association for Cancer Research.
  • Fujiwara Y; Fujita J; Kan K; Tsukahara K; Takiguchi S; Miyata H; Yasuda T; Doki Y; Monden M
    Gan to kagaku ryoho. Cancer & chemotherapy 33 (1) 45 - 48 0385-0684 2006/01 [Refereed]
     
    The safety of chemotherapy combining TS-1 and weekly paclitaxel for the treatment of unresectable and recurrent gastric cancer was evaluated in this study. Paclitaxel was administered by intravenous drip infusion at a starting dose (level 1) of 50 mg/m2 on days 1, 8, and 15. TS-1 was administered orally at a dose of 40 mg/m2twice a day for 2 weeks (days 1-14) followed by 2 weeks rest. A total of 9 patients were enrolled in this study. Two out of 6 patients treated with level 1 suffered from leukocytopenia and neutropenia, which were determined as dose-limiting toxicity (DLT). Three patients were treated with level 2, in which the dose of paclitaxel was increased up to 60 mg/m2. One of 3 patients suffered from grade 3 diarrhea and one patient from grade 4 leukocytopenia, eutrocytopenia, anemia, and stomatitis, which were determined as DLT. According to these results,level 1 of this regimen was recommended as a safe treatment for gastric cancer patients. A phase II study will be performed to evaluate the efficacy of the combination chemotherapy.
  • S Takiguchi; M Sekimoto; M Yasui; H Miyata; Y Fujiwara; T Yasuda; M Yano; M Monden
    SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES SPRINGER 19 (9) 1204 - 1210 0930-2794 2005/09 [Refereed]
     
    Background: We devised a new method incorporating cyber visual training whereby novices in endoscopic surgery are instructed via repetition of a video-recorded procedure. We then conducted a study designed to investigate the impact of this cyber visual training on the mastery of intracorporeal knot-tying as an endoscopic technique. Methods: For the cyber visual training a 10-min video of the same procedure was replayed at normal, slow, and rapid speeds or presented in a series of still images. The training was undertaken by 36 medical students and 1st year trainee doctors who had had no experience of endoscopic surgery. They were divided into three groups, each of all received the same introductory lecture. Group A was only given training with the instructor for 15 min. Group B trained with the instructor for 15 min and was allowed self-training for 10 min. Group C viewed the cyber video beforehand and then underwent training with the instructor for 15 min. For all participants, the time required to complete a knot-tying task was measured and the level of endoscopic skill before and after the training was assessed using a virtual reality system the minimally Invasive Surgical Trainer-Virtual Reality (MIST - VR), in terms of the following three parameters: time, errors, and efficiency of hand movements. The Steel-Dwass test was used to evaluate the differences among the three groups in task performance. Results: Group C completed the knot-tying task faster than group A (p = 0.0375), but there were significant differences between groups A and B and groups B and C. There were no significant differences in the parameters assessed using the MIST-VR. Conclusions: Our new concept of cyber visual training is effective for mastering the knot-tying technique. This type of training should be widely applicable to other procedures, such as dissection, clipping, and hemostasis.
  • Masaaki Motoori; Ichiro Takemasa; Masahiko Yano; Sakae Saito; Hiroshi Miyata; Shuji Takiguchi; Yoshiyuki Fujiwara; Takushi Yasuda; Yuichiro Doki; Yukinori Kurokawa; Noriko Ueno; Shigeyuki Oba; Shin Ishii; Morito Monden; Kikuya Kato
    International journal of cancer 114 (6) 963 - 8 0020-7136 2005/05 [Refereed]
     
    The prognosis of patients with advanced gastric cancer remains unfavorable. Even after curative resection, 40% of patients with advanced gastric cancer die of recurrence. Conventional clinicopathlogic findings are sometimes inadequate for predicting recurrence in individuals. Hence, we tried to construct a new diagnostic system, which predicts recurrence in patients with advanced gastric cancer after curative resection based on molecular analysis. Gastric cancer progression is a function of multiple genetic events that may affect the expression of large number of genes. We performed gene expression profiling with 2,304 genes in 60 advanced gastric cancer patients who underwent curative resection using a PCR array technique, a high-throughput quantitative RT-PCR technique. The diagnostic system, which was constructed from the learning set comprised of 40 patients with the most informative 29 genes, classified each case into a good-signature or poor-signature group. Then, we confirmed the predictive performance in an additional test set comprised of 20 patients, and the prediction accuracy for recurrence was 75%. Kaplan-Meier analysis revealed significant difference between the good-signature and the poor-signature group (p = 0.0125). Especially in patients with smaller tumor (< or = 5 cm), less developed LN metastasis (N(0,1)), or earlier stage (stages I and II), the prediction accuracy was high (88.9%, 84.6%, or 81.8%, respectively). Our diagnostic system based on systematic analysis of gene expression profiling can predict the recurrence at clinically meaningful level. By combining our system with conventional clinicopathologic factors, we can improve the prediction of recurrence in patients with advanced gastric cancer who underwent curative surgery.
  • Hiroshi Iwanaga; Masahiko Yano; Hirofumi Miki; Kazuyuki Okada; Takashi Azama; Syuji Takiguchi; Yoshiyuki Fujiwara; Takushi Yasuda; Mitsuo Nakayama; Masaru Kobayashi; Katsutaka Oishi; Norio Ishida; Katsuya Nagai; Morito Monden
    Journal of Parenteral and Enteral Nutrition 29 (3) 157 - 161 0148-6071 2005/05 [Refereed]
     
    Background: We previously reported that parenteral nutrition (PN) altered the arcadian rhythm of clock gene expression in the suprachiasmatic nucleus (SCN) and liver of rats. The present study was designed to investigate what factor(s) in the PN solution causes the alteration. Methods: Male Wistar rats, kept under light and dark conditions, were divided into 4 groups after cannulation. The sham operation group received saline solution from 8 AM to 8 PM at the rate of 36 mL/kg/12 hours. The glucose, amino acid, and saline groups received a glucose solution (20% wt/vol glucose, 261 kcal/kg/d, Na+ 50 meq/L and Cl- 50 meq/L), an amino acid solution (4,3% wt/vol 1.78 gN/kg/d, Na +50 meq/L and Cl- 50 meq/L) and a saline solution from 8 AM to 8 PM at a rate of 240 mL/kg/12 hours, respectively. Rats were killed every 4 hours (9 AM = Zeitgeber Time (ZT) 02, 1 PM = ZT06, 5 PM = ZT10, 9 PM = ZT14,1 AM = ZT18, 5 AM = ZT22, n = 3 at each point), and brain and liver samples were removed. rPer2 expression in the SCN and liver was analyzed by in situ hybridization and Northern blotting, respectively. Results: Compared with the sham-operation rats, the peak time of rPer2 expression in the SCN was significantly affected by glucose, amino acid, and saline solutions. Among them, glucose-group rats showed the rPer2 expression most similar to that of diurnal PN. On the other hand, the rPer2 expression in the liver was shifted in the glucose and amino-acid-solution groups. The pattern of rPer2 expressions in the amino acid group was most similar to that of the diurnal PN group. Conclusions: These results indicate that the most potent entrainer for the SCN clock is glucose, whereas that for the liver is amino acid. Copyright © 2005 by the American Society for Parenteral and Enteral Nutrition.
  • Takuji Mori; Yoshiyuki Fujiwara; Masahiko Yano; Takushi Yasuda; Shuji Takiguchi; Hiroshi Miyata; Morito Monden
    Oncology Reports 13 (5) 801 - 805 1021-335X 2005/05 [Refereed]
     
    The presence of peritoneal micrometastasis in the abdomen is a poor prognostic factor in advanced gastric cancer. However, there is no standardized method for detection of peritoneal micrometastases. The aim of this study was to establish an animal model mimicking early phase peritoneal dissemination of advanced gastric cancer and then to use this model to compare the sensitivity and specificity of reverse transcription-polymerase chain reaction (RT-PCR) with peritoneal lavage fluid, randomly collected omentum with or without milky spots stained with activated carbon particles for detection of disseminated cancer cells. MKN-45-EGFP gastric cancer cells (1×103 5×10 3 and 1×104) were injected intraperitoneally into 4-week-old female BALBc nu/nu mice on day 0. Mice were sacrificed at 7 or 14 days postinjection. Peritoneal seeding was assessed by fluorescence stereomicroscopy. The sensitivities of RT-PCR with peritoneal lavage fluid, omentum with or without milky spots, were compared. Peritoneal seeding was confirmed in 8 of 10 mice injected with 1×104 MKN-45-EGFP cells by fluorescence stereomicroscopy. On days 7 and 14, the rate of the detection of CEA mRNA was 0, 50.0, and 87.5% in the omentum, omentum with milky spots and peritoneal lavage fluid, respectively. On days 7 and 14, the average level of CEA mRNA was 0, 51113±28225, and 3556±2842 in the omentum, omentum with milky spots and peritoneal lavage fluid, respectively. Molecular diagnosis using peritoneal lavage fluid is more sensitive than that using the omentum.
  • M Yano; M Taniguchi; T Tsujinaka; Y Fujiwara; T Yasuda; H Shiozaki; M Monden
    HEPATO-GASTROENTEROLOGY H G E UPDATE MEDICAL PUBLISHING S A 52 (62) 481 - 485 0172-6390 2005/03 [Refereed]
     
    Background/Aims: This study examined whether or not preoperative administration of methylprednisolone reduces perioperative systemic inflammatory response and thus can offer clinical benefit to patients. Methodology: Forty patients with thoracic esophageal cancer who were scheduled for esophagectomy with lymphadenectomy were randomly allocated to either of the following two groups: 20 patients received methylprednisolone (500mg/body) in saline 2 hours before surgery and another 20 patients received a placebo (saline alone). The effects on the early clinical course were assessed by rectal intramucosal pH (pHi) as a marker of systemic oxygenation, water balance, serum cytokine levels and the incidence of postoperative complications. The effects on the late clinical course were examined by comparing patient survival time. Results: Rectal pHi value, water balance, blood balance and body weight change did not significantly differ between the two groups. Serum proinflammatory cytokine (interleukin-6 and interleukin-8) levels were significantly higher in the control group than the methylprednisolone group 2 hours after surgery. Serum C-reactive protein was also significantly higher in the control group on postoperative day 2 and 3. No significant differences were seen in the incidence of postoperative complications. Survival curves for the two groups did not statistically differ. Conclusions: Preoperative methylprednisolone significantly reduces inflammatory cytokine response immediately after surgery for esophageal cancer, but its clinical benefit remains unclear.
  • M Yano; T Yasuda; H Miyata; Y Fujiwara; S Takiguchi; M Monden
    JOURNAL OF SURGICAL ONCOLOGY WILEY-LISS 89 (4) 244 - 250 0022-4790 2005/03 [Refereed]
     
    Background and Objectives: Although the histological effectiveness of preoperative chemoradiotherapy against the main tumor is reported to be the strongest prognostic factor for patients with esophageal cancer, it remains unknown whether such chemo-radiotherapy is equally effective against metastatic lymph nodes. Methods: We studied 103 consecutive patients with esophaceal cancer, who were given preoperative chemoradiotherapy followed by surgery. The histological effectiveness against the main tumor of the chemoradiotherapy was correlated with lymph mode metastasis and other clinico-pathological factors. Results: The histological effectiveness against the main tumor was grade 3 in 26 patients, grade 2 in 49 and grade 1 in 28. The number of pathological node-negative patients was 21 (80.8%), 19 (38.8%), and 7 (25.0%) in those having grade 3, 2, and I responses of their main tumors, respectively. The average number of pathological metastatic lymph nodes was 0.19, 1.4, and 4.4 in patients with grade 3, 2, and 1 responses, respectively. Endoscopic biopsy after the chemoradiotherapy could not accurately diagnose the pathological complete response (CR) of the main tumors, with a high false negative rate (60.9%). Conclusions: The effects of chemoradiotherapy against main tumors significantly correlated with nodal status. Most patients with main tumors of pathological CR are node-negative. Patients with a grade 2 response have at most a few positive nodes. Surgery would be most beneficial for such patients. (C) 2005 Wiley-Liss, Inc.
  • M Ikeda; M Sekimoto; S Takiguchi; M Kubota; M Ikenaga; H Yamamoto; Y Fujiwara; M Ohue; T Yasuda; H Imamura; M Tatsuta; M Yano; H Furukawa; M Monden
    ANNALS OF SURGERY LIPPINCOTT WILLIAMS & WILKINS 241 (2) 208 - 216 0003-4932 2005/02 [Refereed]
     
    Objective: The aims of this prospective study were to investigate the true incidence of portal or splenic vein thrombosis (PSVT) after elective laparoscopic splenectomy using contrast-enhanced computed tomography (CT) scan, and outcome of anticoagulant therapy for PSVT. Summary Background Data: Although rare, thrombosis of the portal venous system is considered a possible cause of death after splenectomy. The reported incidence of ultrasonographically detected PSVT after elective open splenectomy ranges from 6.3% to 10%. Methods: Twenty-two patients under-went laparoscopic splenectomy (LS group), and 21 patients underwent open splenectomy (OS group). Preoperative and postoperative helical CT with contrast were obtained in all patients, and the extent of thrombosis was investigated. Prothrombotic disorder was also determined. Results: PSVT occurred in 12 (55%) patients of the LS group, but in only 4 (19%) of the OS group. The difference was significant (P = 0.03). Clinical symptoms appeared in 4 of the 12 LS patients. Thrombosis occurred in the intrahepatic portal vein (n = 9), extrahepatic portal vein (n = 2), mesenteric veins (n = 1), proximal splenic vein (n = 4), and distal splenic vein (n = 8). Prothrombotic disorder was diagnosed in I patient. Anticoagulant therapy was initiated once the diagnosis was established, and complete recanalization, except for distal splenic vein, was observed without any adverse event. Patients with splenomegaly were at high risk of PSVT. Conclusions: PSVT is a more frequent complication of laparoscopic splenectomy than previously reported but can be treated safely following early detection by CT with contrast.
  • M Yano; Y Fujiwara; S Takiguchi; T Yasuda; H Miyata; Miyashiro, I; K Takachi; K Kishi; M Monden
    Proceedings of the 6th International Gastric Cancer Congress MEDIMOND PUBLISHING CO 237 - 241 2005 [Refereed]
     
    Introduction: This study examined the feasibility and efficacy of preoperative intraperitoneal (i.p.) chemotherapy for serosa-infiltrating gastric cancer. Materials and Methods: Twenty-five patients with serosa-infiltrating tumors, as diagnosed by staging laparoscopy, received preoperative i.p. chemotherapy (20 mg of mitomycin C on Day1 and 10 mg of cisplatin for 5 days.) followed by surgical resection. Results: Preoperative T stages (T3 in 21 and T4 in 4) were downstaged postoperatively (T1 in 1, T2 in 10, T3 in 11 and T4 in 3). The 1- and 2-year overall survival was 83.3% and 51.3%, respectively. The median survival time was 24.4 months. The toxicity of the treatment was tolerable and no serious postoperative complication was seen. Conclusions: Preoperative i.p. chemotherapy seems to be a safe and effective therapy for serosa-infiltrating gastric cancer.
  • Shuji Takiguchi; Mitsugu Sekimoto; Yoshiyuki Fujiwara; Hiroshi Miyata; Takushi Yasuda; Yuichiro Doki; Masahiko Yano; Morito Monden
    Surgery today SPRINGER 35 (10) 896 - 9 0941-1291 2005 [Refereed]
     
    An esophagojejunostomy using a circular stapler requires the fixing of an anvil at the esophageal stump. When this placement procedure is laparoscopically performed, purse-string suturing is difficult, and there is a risk of loosening when a conventional needle driver is used. We herein present a simple but effective technique for performing laparoscopic purse-string suturing of the esophageal stump using a semiautomatic suturing device called the Endostitch. Gastrointestinal anvil placement was laparoscopically performed for 10 patients who underwent an esophagojejunostomy following a total gastrectomy. After the lumen of the esophagus was expanded using bowel forceps, the Endostitch was used to place approximately 12 encircling purse-string sutures. An anvil was positioned with support of the esophageal wall at three points with forceps. The Endostitch was used for the ligation with a sufficient degree of tension applied by extracorporeally pulling the sutures through the abdominal wall. The time for placement of the anvil averaged approximately 8 min. The ring formation following anastomosis was favorable in all patients. As a result, we consider our technique to be simple but very effective.
  • Shoichiro Fujita; Hisashi Wada; Achim A. Jungbluth; Shuichiro Sato; Tetsuya Nakata; Yuji Noguchi; Yuichiro Doki; Masayoshi Yasui; Yurika Sugita; Takushi Yasuda; Masahiko Yano; Tosbiro Ono; Yao-Tseng Chen; Masahiko Higashiyama; Sacha Gnjatic; Lloyd J. Old; Eiichi Nakayama; Morito Monden
    Clinical Cancer Research 10 (19) 6551 - 6558 1078-0432 2004/10 [Refereed]
     
    Purpose: Although NY-ESO-1 was isolated from an esophageal carcinoma patient, its expression in this type of cancer and its immunogenicity in esophageal cancer patients have not yet been fully elucidated. We report here the frequency of NY-ESO-1 mRNA and protein expression in esophageal cancer and the presence of NY-ESO-1-specific immune response in patients. Experimental Design: One hundred twenty three esophageal squamous cell carcinoma specimens were analyzed for the expression of NY-ESO-1 mRNA by conventional and real-time reverse transcription-PCR and the expression of protein by immunohistochemistry and Western blot. Sera and peripheral blood lymphocytes from 51 patients were analyzed for the NY-ESO-1 antibody production by enzyme-linked immunosorbent assay and NY-ESO-1 T cell response by enzyme-linked immunospot assay. Survival analyses were also performed. Results: NY-ESO-1 mRNA was expressed in 41 of 123 (33%) esophageal squamous cell carcinoma specimens, and its expression was found at higher frequency in well-differentiated and moderately differentiated type of cancer. No mRNA copy was detected in any of the adjacent normal tissues. Twenty-one of 24 (87.5%) NY-ESO-1 mRNA-positive tumors were stained positively by immunohistochemistry. Correlation between the level of NY-ESO-1 mRNA expression and the degree of immunohistochemistry positivity was observed. Antibody production was observed in 2 patients with famers that showed protein expression. Furthermore, a CD8 T-cell response against NY-ESO-1 was observed in 1 of the 2 seropositive patients. Conclusions: The high expression frequency of NY-ESO-1 mRNA and protein indicates NY-ESO-1 as a feasible vaccine target in esophageal cancer.
  • M Yano; T Yasuda; Y Fujiwara; S Takiguchi; H Miyata; M Monden
    JOURNAL OF SURGICAL ONCOLOGY WILEY-LISS 88 (1) 39 - 43 0022-4790 2004/10 [Refereed]
     
    Background and Objectives: Serosa-infiltrating gastric cancer poses a high risk for peritoneal recurrence. This study examined the feasibility and efficacy of preoperative intraperitoneal (i.p.) chemotherapy for such cancer. Methods: Patients with serosa-infiltrating tumors, diagnosed by conventional examinations as well as by staging laparoscopy, were enrolled in this study. Those with unresectable T4 tumors, visible peritoneal metastasis or distant organ metastasis were excluded. Twenty-five eligible patients received preoperative i.p. chemotherapy, which consisted of i.p. injection of 20 mg of mitomycin C on day I and 10 mg of cisplatin for 5 days, followed by surgery. Results: Of the 25 patients, 24 underwent gastrectomy with lymph node dissection and I underwent palliative gastrojejunostomy. The curability of the surgery was curability A in 6, B in 16, and C in 3. Preoperative T stages (T3 in 21 and T4 in 4) were downstaged postoperatively (T I in 1, T2 in 10, T3 in 11, and T4 in 3). The I - and 2-year overall survival was 83.3 and 51.3%, respectively. The median survival time was 24.4 months. The toxicity of the preoperative treatment was tolerable and no serious postoperative complication was seen. Conclusions: Preoperative i.p. chemotherapy seems to be a safe and effective therapy for serosa-infiltrating gastric cancer. Randomized clinical trials comparing preoperative i.p. chemotherapy followed by surgery and surgery alone are needed. (C) 2004 Wiley-Liss, Inc.
  • Fujiwara Y; Miyata H; Takiguchi S; Yasuda T; Yano M; Monden M
    Gan to kagaku ryoho. Cancer & chemotherapy 31 (11) 1876 - 1878 0385-0684 2004/10 [Refereed]
     
    Recently, new promising anti-tumor agents such as TS-1, taxanes, and CPT-11 have been approved for gastric cancer treatment. These agents showed a better response and may contribute to a patient's survival and quality of life. However, there are cases with advanced and recurrent gastric cancer that are resistive or tolerant to these agents. We report two cases in which the patients had suffered symptomatic local recurrence during the chemotherapy. Consequently, they had been treated with radiotherapy in order to improve their clinical status. We also discuss the significance of radiotherapy in gastric cancer.
  • Kimura Y; Yasuda T; Fujiwara Y; Takiguchi S; Miyata H; Nagano H; Yano M; Monden M
    Gan to kagaku ryoho. Cancer & chemotherapy 31 (11) 1825 - 1827 0385-0684 2004/10 [Refereed]
     
    The prognosis of patients with hepatic metastasis of gastric cancer is poor, and standard therapies for patients are not established. Here we present two cases of hepatic metastasis from gastric cancer. In both cases, no other organ metastasis except the liver was confirmed, in which hepatic arterial infusion chemotherapy with 5-FU, adriamycin and cisplatin (FAP) were performed because TS-1 chemotherapy was not an effective chemotherapy. Case 1: An 80-year-old man had distal gastrectomy for type 2 gastric cancer (Stage II) in January 2001. A liver S8 metastatic recurrence was discovered in the 18th month post operation. After chemotherapy with TS-1 for 5 courses, a hepatic arterial infusion treatment was performed for 7 courses. The effect was PR, but the treatment was canceled because of a catheter obstruction. The patient is living without recurrence. Case 2: This case was a 73-year-old man who had distal gastrectomy for type 0 IIc gastric cancer (Stage IA) in May 1999. Multiple hepatic metastases recurred in the 32nd month post operation. After chemotherapy with TS-1 for 2 courses, a hepatic arterial infusion treatment was performed for 10 courses. The effect was CR, but a peritoneal recurrence was discovered, and a systemic chemotherapy was performed. The patient is living without recrudescence of hepatic metastasis. The hepatic arterial infusion chemotherapy with FAP was effective for gastric cancer patients with liver metastasis because TS-1 chemotherapy was not an effective chemotherapy. It is necessary to consider combined chemotherapy in addition to systemic chemotherapy.
  • Yusuke Oji; Masahiko Yano; Yoko Nakano; Sakie Abeno; Shin-Ichi Nakatsuka; Ai Ikeba; Takushi Yasuda; Yoshiyuki Fujiwara; Shuji Takiguchi; Hirofumi Yamamoto; Seiichiro Fujita; Keisuke Kanato; Ken Ito; Tanyarat Jomgeow; Manabu Kawakami; Akihiro Tsuboi; Toshiaki Shirakata; Sumiyuki Nishida; Naoki Hosen; Yoshihiro Oka; Katsuyuki Aozasa; Morito Monden; Haruo Sugiyama
    Anticancer Research 24 (5 B) 3103 - 3108 0250-7005 2004/09 [Refereed]
     
    Background: The Wilms' tumor gene WT1 is overexpressed in various kinds of solid cancers. However, it remains unclear whether WT1 is expressed in esophageal squamous cell carcinoma. Materials and Methods: Expression of the WT1 gene was examined by real-time RT-PCR in 12 esophageal squamous cell carcinoma (ESCC) and by immunohistochemistry n 9 of these 12 and another 29. Results: Real-time RT-PCR showed that the WT1 mRNA was overexpressed in all of the 12 ESCC examined. Immunohistochemical analysis showed that the WT1 protein was overexpressed in ESCC cells in 36 (95%) of the 38 examined. Furthermore, expression of the WT1 protein was examined in 20 esophageal squamous dysplasia. The WT1 protein was overexpressed in 5 (45%) out of 11 mild dysplasia and in 8 (89%) out of 9 moderate to severe dysplasia. Conclusion: These results may indicate an important role of the WT1 gene in the tumorigenesis of ESCC.
  • Shinji Yamamoto; Yasuhiko Tomita; Yoshihiko Hoshida; Norishige Iizuka; Shinya Kidogami; Hiroshi Miyata; Shuji Takiguchi; Yoshiyuki Fujiwara; Takushi Yasuda; Masahiko Yano; Shoji Nakamori; Masato Sakon; Morito Monden; Katsuyuki Aozasa
    Clinical Cancer Research 10 (16) 5558 - 5565 1078-0432 2004/08 [Refereed]
     
    Purpose: Esophageal squamous cell carcinoma (ESCC) frequently shows a poor prognosis because of the occurrence of systemic metastasis, mainly via lymphatic vessels. Valosin-containing protein (VCP) has been shown to be associated with antiapoptotic function and metastasis via activation of the nuclear factor-κB signaling pathway. In the present study, we examined the association of VCP with the recurrence and prognosis of ESCC. Experimental Design: VCP expression in 156 ESCC patients [139 males and 17 females age range, 38-82 (median, 60) years] was analyzed by immunohistochemistry. Staining intensity in tumor cells was categorized as weaker (level 1) or equal to or stronger (level 2) than that in endothelial cells. The correlation of VCP expression between the mRNA and protein levels was examined in 12 patients. Results: Fifty-seven (37.3%) cases showed level 1 and 96 (62.7%) level 2 VCP expression. Quantitative reverse transcription-PCR analysis revealed greater VCP mRNA expression in level 2 (n = 6) than level 1 cases (n = 6 P < 0.05). ESCC with level 2 expression showed higher rates of lymph node metastasis (P < 0.01) and deep tumor invasion (P < 0.01), and poorer disease-free and overall survival rates (P < 0.001 for both analyses) than ESCC with level 1 expression. Multivariate analysis revealed that VCP expression level is an independent prognosticator for disease-free and overall survival. Furthermore, VCP level was an indicator for disease-free survival in the early (pT 1) and the advanced (pT2-pT4) stage groups. Conclusion: This study demonstrated the prognostic significance of VCP expression in ESCC.
  • 三吉 範克; 小川 稔; 瀧口 修司; 藤原 義之; 安田 卓司; 矢野 雅彦; 門田 守人
    外科 (株)南江堂 66 (8) 963 - 966 0016-593X 2004/08 
    食道癌術後に発生した胃管癌に対し,治癒切除し得た2例(症例1:69歳男,症例2:59歳男)を報告した.症例1は60歳時に食道癌のため右開胸開腹食道亜全摘,胸骨後胃管再建術を受けていた.上部消化管内視鏡検査で再建胃管の体中部に病変を認め,再建胃管に発生したtype 0-IIc胃癌の診断で胃管亜全摘術,有茎空腸間置術を行った.病理検査では深達度mp,組織型INFβ,Ly1,V0,リンパ節転移なしであった.症例2は約6年前に食道癌のため食道亜全摘,胸骨後管再建術を受けていた.上部消化管内視鏡検査で再建胃管下部に陥凹性病変を認め,group V(tub 1),深達度Mの診断で腹腔鏡下胃内手術を行った.病理検査では深達度m,組織型INFα,Ly0,V0,断端(-)であった.食道癌術後のフォローアップに際しては,転移再発のみならず,胃管癌の発生も念頭に置くべきであると思われた
  • 三吉 範克; 藤原 義之; 瀧口 修司; 宮田 博志; 安田 卓司; 矢野 雅彦; 門田 守人
    日本消化器外科学会雑誌 (一社)日本消化器外科学会 37 (5) 500 - 505 0386-9768 2004/05 
    症例1:50歳男.開腹手術後より両側の下腿外側から足背にかけて知覚異常,知覚過敏ならびに足の背屈力低下所見から両側腓骨神経麻痺と診断された.ビタミンB12を投与し理学療法を行い,1ヵ月後,足関節の背屈困難も殆ど消失し退院となった.症例2:46歳男.開腹手術直後より両上肢の知覚および運動麻痺所見から,両側腕神経叢麻痺と診断された.ステロイド,ビタミンB12を投与し,理学療法,星状神経節ブロックを行った結果,術後6ヵ月で全治した
  • Makari Y; Fujiwara Y; Yasuda T; Takiguchi S; Kimura Y; Yano M; Monden M
    Gan to kagaku ryoho. Cancer & chemotherapy 31 (4) 609 - 611 0385-0684 2004/04 [Refereed]
     
    Chemotherapy with TS-1 has recently become the first-line chemotherapy for recurrent and unresectable gastric cancer in Japan. Therefore, the establishment of a second-line chemotherapy is needed for cases that show resistance and aberrant effect to TS-1. In this study, 7 patients were treated with weekly administrations of paclitaxel after TS-1 treatment. We assessed the therapeutic effect and feasibility of chemotherapy with weekly administration of paclitaxel. Our results showed that weekly administration of paclitaxel could be a promising regimen as a second-line chemotherapy after TS-1.
  • Norikatsu Miyoshi; Yoshiyuki Fujiwara; Shuji Takiguchi; Hiroshi Miyata; Takushi Yasuda; Masahiko Yano; Morito Monden
    Japanese Journal of Gastroenterological Surgery Japanese Society of Gastroenterological Surgery 37 (5) 500 - 505 0386-9768 2004 [Refereed]
     
    We report 2 cases of transient peroneal nerve palsy and brachial plexus palsy after surgical resection for gastric cancer. Case 1: A 50-year-old man undergoing pancreatoduodenectomy for advanced gastric cancer of the spine reported numbness and weakness in both feet on the day after surgery. The administration of Vitamin B12 and physical rehabilitation were successful and he was discharged a month after surgery without any neurological deficits. Case 2: A 46-year-old man undergoing distal gastrectomy for gastric cancer of the spine with both arms abducted at 90° reported weakness in both arms on the day after surgery. The administration of steroids and vitamin B12, nerve block of the stellate ganglion, and physical rehabilitation were conducted and, 3 months after the surgery, he returned to work free of any deficits. The peroneal nerve palsy and brachial plexus palsy after abdominal surgery are very rare and few reports have been published. Intra operative overstretching and suppression of the nerves is assumed to be the main cause of palsy, suggesting the need to pay greater attention to the surgical position of patients during surgery.
  • Hirofumi Ikushima; Toshirou Nishida; Kiyoshi Takeda; Toshinori Ito; Takushi Yasuda; Masahiko Yano; Shizuo Akira; Hikaru Matsuda
    Surgery Mosby Inc. 135 (4) 376 - 385 0039-6060 2004 [Refereed]
     
    Background. Toll-like receptors (TLR) that recognize microbial pathogens play a critical role in innate immunity however, their expression and function after surgery remain unknown. The aim of this study was to examine TLR2 and TLR4 expression on monocytes and their responses to each agonist after surgical insults. Methods. Blood samples were obtained from 83 patients who underwent gastrointestinal surgery. TLR2, TLR4, and inducible nitric oxide synthase expressions on peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry. Macrophage-activating lipopeptide-2 or lipopolysaccharide-induced tumor necrosis factor-α and interleukin-6 production was measured by enzyme-linked immunosorbent assay. Results. TLR2 and TLR4 decreased and showed the lowest values on the postoperative days 3 and I, respectively. Macrophage-activating lipopeptide-2-stimulated tumor necrosis factor-α and interleukin-6 production was decreased immediately after the operation (P < .05), increased to a maximum value on postoperative day 1, and then decreased gradually. Lipopolysaccharide-stimulated tumor necrosis factor-α production was also suppressed immediately (P < .05) after operation then showed a gradual increase to maximum values on postoperative day 3. Inducible nitric oxide synthase in cultured PBMC that was obtained immediately after operation was upregulated (P < .05). Conclusion. Expressions of TLR2 and TLR4 were downregulated by operation, and agonist-induced cytokine production was suppressed transiently and soon increased through the activation of PBMC. The present study may offer new insights for postoperative modulation of innate immunity under surgical stress.
  • S. Takiguchi; M. Sekimoto; Y. Fujiwara; T. Yasuda; M. Yano; M. Hori; T. Murakami; H. Nakamura; M. Monden
    Surgical Endoscopy and Other Interventional Techniques 18 (1) 106 - 110 0930-2794 2004/01 [Refereed]
     
    Background: Laparoscopic extended lymph node dissection for gastric cancer is difficult to perform because it requires dissection with preservation of vessels. Therefore, an intraoperative navigation system for the angioarchitecture would be helpful. Recent enhanced volume-rendering computed tomography (CT) can produce clear intraluminal three-dimensional (3D) images. This advanced radiological technology can provide 3D angiographic images reconstructed in the same view as would be observed from a laparoscope inserted into the abdominal cavity. We report our experience with laparoscopic gastrectomy with radical lymph node dissection using this advanced radiological technology. Methods: 3D CT angiographic images from the celiac axis to the proper hepatic artery were reconstructed in two ways preoperatively. The first was only 3D angiographic images that were reconstructed as the laparoscopic view (LapView 3D CT angiography). The second was LapView 3D CT angiography with images of the body of the pancreas, which was more useful for intraoperative navigation in comprehensing anatomy. Two monitors were placed over the shoulder of the patient during surgery. One monitor, which was controlled by the image mixer, projected the laparoscopic images with picture in picture of 3D CT angiographic images. The surgeon performed the surgery with reference to this monitor during lymph node dissection. Results: 3D angiographic CT clearly showed all vessels of interest in laparoscopic lymph node dissection for gastric cancer in 10 cases. The anatomy of vessels appeared as if looking beyond visible surface. LapView 3D CT angiography was useful for laparoscopic navigation surgery.
  • Takaaki Ishii; Yoshiyuki Fujiwara; Satoru Ohnaka; Toshinori Hayashi; Hirokazu Taniguchi; Shuji Takiguchi; Takushi Yasuda; Masahiko Yano; Morito Monden
    Annals of Surgical Oncology 11 (8) 778 - 785 1068-9265 2004 [Refereed]
     
    Background: Detection of cancer micrometastases is required for improvement of cancer therapy. The aim of this study was to establish a rapid and practical genetic assay to detect micrometastasis in gastric cancer and to assess its clinical significance with respect to prognosis. Methods: A novel RNA amplification system with transcription-reverse transcription concerted reaction (TRC) was introduced for quantitative detection of cancer-specific carcinoembryonic antigen messenger RNA. The sensitivity and quantitative aspects of the assay were assessed with the full-length carcinoembryonic antigen messenger RNA, a gastric cancer cell line (MKN-45), and metastatic lymph nodes obtained from patients with gastric cancer. Peritoneal lavage fluid specimens that were collected from gastric cancer surgery were subjected to the assay, and the clinical significance of the results was examined for prediction of recurrence and survival. Results: The quantification, sensitivity, and reproducibility of the assay with the TRC reaction were equal to those of quantitative reverse transcriptase-polymerase chain reaction with LightCycler. The most important advantages of the assay were its simplicity and rapidity. Molecular diagnosis of peritoneal lavage fluid by the TRC reaction significantly correlated with depth of invasion, peritoneal metastasis, clinical stage, overall survival, and peritoneal recurrence-free survival. Conclusions: Molecular diagnosis of peritoneal lavage fluid with the TRC reaction could be a useful prognostic indicator for peritoneal recurrence and survival. Because the TRC reaction is more rapid and simpler than reverse transcriptase-polymerase chain reaction as a format for detecting RNA sequences, it may enhance the genetic diagnosis of cancer micrometastasis and may improve cancer therapy. Published by Lippincott Williams & Wilkins © 2004 The Society of Surgical Oncology, Inc.
  • T Mori; Y Fujiwara; Y Sugita; T Azama; T Ishii; K Taniguchi; K Yamazaki; S Takiguchi; T Yasuda; M Yano; M Monden
    ANNALS OF SURGICAL ONCOLOGY LIPPINCOTT WILLIAMS & WILKINS 11 (1) 14 - 20 1068-9265 2004/01 [Refereed]
     
    Background: In advanced gastric cancer, peritoneal recurrence is the main cause of death after curative surgical resection. The aim of this report was to describe a novel approach for quantitative genetic diagnosis using peritoneal lavage for the identification of patients at high risk for peritoneal recurrence and for evaluation of the clinical response to intraperitoneal chemotherapy in advanced gastric cancer. Methods: Nineteen patients with advanced gastric cancer who underwent staging laparoscopy and intraperitoneal chemotherapy before surgical resection or systemic chemotherapy between June 1999 and September 2001 were enrolled in this study. All peritoneal lavage specimens, collected at both staging laparoscopy and gastrectomy, were subjected to real-time quantitative genetic diagnosis. Results: The reverse transcriptase polymerase chain reaction (RT-PCR) values decreased in 8 cases, stabilized as negative in 5, and increased in 6 during therapy. Patients whose RT-PCR values diminished and were ultimately negative survived except for one, and all but one patient whose values increased during treatment died of recurrence. Conclusions: Quantitative evaluation of genetic changes can provide accurate, useful information on the effects of preoperative intra-abdominal chemotherapy and overall prognosis for patients with advanced gastric cancer.
  • Y Sugita; Y Fujiwara; H Taniguchi; T Mori; T Ishii; H Niwa; Y Okada; S Takiguchi; T Yasuda; M Yano; M Monden
    INTERNATIONAL JOURNAL OF ONCOLOGY PROFESSOR D A SPANDIDOS 23 (5) 1419 - 1423 1019-6439 2003/11 [Refereed]
     
    We developed a quantitative multiple-marker RTPCR assay for sensitive detection of free cancer cells in the peritoneal cavity and examined the significance of this molecular diagnostic technique for detection and prediction of peritoneal dissemination in patients with gastric cancer. Preoperative peritoneal lavage fluid samples obtained from 129 patients with gastric cancer were subjected to RT-PCR assay with primers specific for carcinoembryonic antigen (CEA) and cytokeratin-20 (CK-20), and conventional cytological examination with Papanicolaou staining. The multi-marker RT-PCR assay was positive in 59 of 129 (46%) gastric cancer patients, whereas conventional cytology was positive in only 9 of 129 (7%) patients. Thirty-two of 129 (22%) patients suffered disease recurrence after surgery. Twenty-one of these patients were confirmed to have had peritoneal recurrence. Although conventional cytology was positive on peritoneal washes in only 9 patients, the RT-PCR assay was positive in 20 of these 21 patients. Furthermore, in cases with negative cytology, patients with PCR-positive findings in peritoneal lavage fluid had a significantly poorer prognosis than those with negative PCR, mainly because of peritoneal recurrence. Our results suggest that the multiplex RT-PCR assay for CEA and CK-20 was highly sensitive for detection and might be useful for prediction of peritoneal dissemination in gastric cancer.
  • K Kishi; Y Doki; M Yano; T Yasuda; Y Fujiwara; S Takiguchi; S Kim; Higuchi, I; M Monden
    CLINICAL CANCER RESEARCH AMER ASSOC CANCER RESEARCH 9 (12) 4368 - 4375 1078-0432 2003/10 [Refereed]
     
    Purpose: Loss of function or expression of the mismatch repair gene MLH1 has been implicated in experimentally acquired resistance to cisplatin (CDDP) and other anticancer agents. The clinical significance of MLH1 expression was evaluated in advanced thoracic squamous cell carcinoma of the esophagus (ESCC) treated by neoadjuvant chemotherapy. Experimental Design: We investigated MLH1 and P53 expression by immunohistochemistry in the surgical specimens of 107 patients who had undergone preoperative chemotherapy using CDDP along with 5-FU and ADM. These findings were correlated with the clinical outcome for this treatment. Biopsy samples before chemotherapy in 20 of these patients, and another 43 surgical specimens without chemotherapy, were also examined as control samples. Results: In surgical specimens of ESCC, low MLH1 expression was not frequent without chemotherapy, whereas it was commonly observed after chemotherapy (14 versus 37%, P = 0.0057). Comparison between samples before and after chemotherapy revealed that MLH1 expression was unchanged during chemotherapy in 12 of 20 patients (60%) but was from high to low in 8 of 20 patients (40%). In the surgical specimen after neoadjuvant chemotherapy, MLH1 expression was not correlated with any clinicopathological factors, including the response to chemotherapy. However, low MLH1 showed poorer prognosis than high MLH1 (5-year survival 40.6 versus 19.3%, P = 0.0393), and in multivariate analysis, MLH1 was an independent prognostic factor for this multimodal treatment, following lymph node metastasis and clinical response to chemotherapy. Positive p53 expression, which was not affected by chemotherapy, was weakly associated with a poor response and clinical outcome, although this trend was not significant. Conclusions: In advanced ESCC, expression of MLH1 is reduced during CDDP-based chemotherapy, and this may partly account for poor postoperative survival.
  • Fujiwara Y; Taniguchi H; Kimura Y; Takiguchi S; Yasuda T; Yano M; Monden M
    Gan to kagaku ryoho. Cancer & chemotherapy 30 (11) 1614 - 1617 0385-0684 2003/10 [Refereed]
     
    Forty-eight patients with serosa-invaded advanced gastric cancer were administered to pre-operative intra-peritoneal chemotherapy to prevent peritoneal recurrence. There were no severe adverse effects from the intra-peritoneal chemotherapy. Of these patients, 2 showed malignant ileus shortly after intra-peritoneal chemotherapy and gastrectomy, and needed laparotomy because of dilatation of duodenum stump and liver dysfunction. The intestines and mesothelium showed diffuse thickness and hardness. We report the clinicopathological features of these cases and therapeutic limitation of intra-peritoneal chemotherapy.
  • Yasuda T; Yano M; Takiguchi S; Kimura Y; Fujiwara Y; Monden M
    Gan to kagaku ryoho. Cancer & chemotherapy 30 (11) 1737 - 1740 0385-0684 2003/10 [Refereed]
     
    We report the response of our new regimen of chemoradiotherapy for advanced esophageal carcinoma. The patient was a 66-year-old man who had double primary esophageal carcinomas: type o-IIc tumor of the cervical esophagus from the esophageal inlet to 23 cm from incisors and a 9 cm length type 3 tumor of the middle to lower thoracic esophagus with a 2 cm diameter cardiac lymph node metastasis. Since he completely rejected surgical treatment, new definitive chemoradiotherapy with 2 courses of FAP chemotherapy (cisplatin 50 mg/m2 and adriamycin 20 mg/m2 on day 1 and 5-FU 700 mg/day from day 1 to 5 continuously) concurrent with a split course of radiotherapy to a total dose of 60 Gy in 30 fractions was devised and administered. The treatment was completed and there was no severe toxicity except grade 3 leukocytopenia. Just after treatment, cervical tumor and cardiac lymph node reached complete response but stenosis and wall thickness remained in the thoracic tumor. Soon after, however, these findings improved and, at present 1 year later, complete response has continued. Our new regimen of chemoradiotherapy concurrent with FAP chemotherapy seems to be effective and promising for advanced esophageal carcinoma.
  • S Takiguchi; M Sekimoto; Y Fujiwara; T Yasuda; M Yano; M Monden
    SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES SPRINGER-VERLAG 17 (8) 0930-2794 2003/08 [Refereed]
     
    As a result of the recent improvement of the prognosis of esophageal cancer, the reporting frequency of gastric tube cancer following esophageal cancer has increased. Gastric tube total resection following median sternotomy, a highly invasive surgical procedure, is applied to the cases of advanced gastric tube cancer, whereas endoscopic mucosal resection is selected for the cases of early gastric tube cancer. If endoscopic mucosal resection is not applicable for some reason, partial or total resection of the gastric tube following median sternotomy has been selected. We applied laparoscopic intragastric surgery to such a case: The patient, a 59-year-old man with esophageal cancer, had undergone subtotal esophagectomy followed by gastric tube reconstruction through the retrosternal route 6 years before. Since endoscopy revealed early gastric cancer in the body of the stomach, we tried to perform mucosal resection but failed because of anastomotic stenosis. However, we successfully performed intragastric surgery, in which a camera and forceps were inserted directly into the gastric tube. Thus, laparoscopic intragastric surgery is a useful technique in cases to which endoscopic mucosal resection is not applicable.
  • Shinji Yamamoto; Yasuhiko Tomita; Yoshihiko Hoshida; Shuji Takiguchi; Yoshiyuki Fujiwara; Takushi Yasuda; Masahiko Yano; Shoji Nakamori; Masato Sakon; Morito Monden; Katsuyuki Aozasa
    Journal of Clinical Oncology 21 (13) 2537 - 2544 0732-183X 2003/07 [Refereed]
     
    Purpose: Valosin-containing protein (VCP also known as p97) was shown to be associated with antiapoptotic function and metastasis via activation of nuclear factor kappa-B signaling pathway. In this study, association of VCP expression with recurrence of gastric carcinoma (GC), in which lymphatic vessels are the main route of spread, was examined. Patients and Methods: VCP expression in 330 patients with GC (242 males and 88 females) with ages ranging from 26 to 81 years (median, 60 years) was analyzed by immunohistochemistry, in which staining intensity in tumor cells was categorized as weaker (level 1) or equal to or stronger (level 2) than that in endothelial cells. Results: Ninety-four (28.7%) patient cases showed level 1 and 233 patient cases (71.3%) showed level 2 VCP expression. Patients with level 2 expression showed higher rates of large tumor size (P < .0001), undifferentiated histologic subtype (P < .05), presence of vascular and lymphatic invasion (P < .0001 for both), presence of lymph node metastasis (P < .0001), deep tumor invasion (P < .0001), and poorer disease-free and overall survivals (P < .0001 for both) compared with those with level 1 VCP expression. Multivariate analysis revealed VCP expression level as an independent prognosticator for disease-free and overall survival. VCP level was an indicator for disease-free and overall survival in the early (pT1 P < .01 and P < .05, respectively) and advanced (pT2-4 P < .05 for both) group of pathologic tumor-node-metastasis system classification. Conclusion: The prognostic significance of VCP expression level in GC was demonstrated. © 2003 by American Society of Clinical Oncology.
  • Naomi Urano; Yoshiyuki Fujiwara; Seiichi Hasegawa; Yasuo Miyoshi; Shinzaburo Noguchi; Shuji Takiguchi; Takushi Yasuda; Masahiko Yano; Morito Monden
    Gastric Cancer 6 (2) 108 - 112 1436-3291 2003 [Refereed]
     
    Background. Effective chemotherapy for advanced gastric cancer is yet to be established. Taxanes, novel anticancer drugs which bind to beta-tubulin and prevent disruption of microtubules, are newly approved and promising agents for advanced and recurrent gastric cancer. To predict the chemoresistance to a taxan in gastric cancer, we examined the genetic mutations of the beta-tubulin gene. Methods. Fifty pairs of gastric tumor and normal mucosa tissues were obtained from operations and the genomic DNA was extracted from each specimen. The four exons of the beta-tubulin gene were amplified for DNA mutations by single-strand conformation polymorphism (SSCP) methods and sequencing analysis. Results. Nine (18%) of 50 patients with gastric cancer had two kinds of silent variations of the beta-tubulin gene in exon 4. Three kinds of intronic variations were detected in exons 1, 2, and 3. However, no genetic alterations that would change the beta-tubulin protein structure were detected in any of the 50 gastric tumors. Conclusion. Our findings indicate that mutations of the beta-tubulin gene, which might be a contraindication for chemotherapy based on taxans, were very rare events in gastric cancer.
  • T Mori; Y Fujiwara; M Yano; S Tamura; T Yasuda; S Takiguchi; M Monden
    ONCOLOGY KARGER 64 (2) 176 - 182 0030-2414 2003 [Refereed]
     
    Objective: Recent clinical trials have suggested that oral administration of a new anti-cancer agent, S-1, seems a promising therapy for advanced gastric cancer. In this study, we assessed the efficacy of S-1 against peritoneal dissemination of gastric cancer in a newly developed animal model and investigated the efficacy of S-1 from a pharmacokinetic angle. Methods: Human gastric cancer cells (MKN-45) were injected into the peritoneal cavity of nude mice. The cancer cells were transduced using an enhanced green fluorescent protein (EGFP)-expressing plasmid vector, enabling micrometastatic foci to be accurately assessed with a high level of detection sensitivity. To investigate pharmacokinetics, the concentration of 5-FU was determined in tumor, peritoneum and plasma. Results: Fourteen and 21 days after intraperitoneal injection, a significant difference in the number of fluorescent foci was observed between the control group and the S-1 group (p = 0.02 and p = 0.0024, respectively. The therapeutic effect of S-1 was significantly greater than that of 5-FU. Furthermore, S-1 treatment greatly improved the survival time and cachexia. The area under the curve of 5-FU in tumor was higher than in the peritoneum and plasma. Conclusion: Oral S-1 is a promising chemotherapy for peritoneal dissemination of gastric cancer. Copyright (C) 2003 S. Karger AG, Basel.
  • Shuji Takiguchi; Mitsugu Sekimoto; Yasuhiro Miyake; Yoshiyuki Fujiwara; Takushi Yasuda; Shigeyuki Tamura; Masahiko Yano; Eiji Taniguchi; Shuichi Ohashi; Morito Monden
    Surgery Today 33 (5) 371 - 374 0941-1291 2003 [Refereed]
     
    The development of more sophisticated instruments has enabled advanced laparoscopic surgery. We recently devised a totally laparoscopic method of performing Billroth-I hand-sewn anastomosis and established this technique in an animal training model. This report presents the case of a 50-year-old man in whom totally laparoscopic distal gastrectomy was successfully performed for gastric cancer, using the hand-sewn Billroth-I anastomotic technique. The patient was admitted with gastric cancer in the angle of the stomach and underwent laparoscopic distal gastrectomy with radical lymph node dissection. After the resected specimen was extracted through the small incision, a Billroth-I anastomosis was performed laparoscopically by the hand-sewn technique using the Albert-Leinbert method. The patient was discharged on the seventh postoperative day without any intra- or postoperative complications. Laparoscopic hand-sewn anastomosis was performed safely and allowed for quick recovery and good cosmesis in this patient.
  • Takuji Mori; Yoshiyuki Fujiwara; Masahiko Yano; Shigeyuki Tamura; Takushi Yasuda; Shuji Takiguchi; Morito Monden
    Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 6 Suppl 1 (1) 13 - 8 1436-3291 2003 [Refereed]
     
    BACKGROUND: Favorable results have been reported for the novel oral anticancer agent S-1 (TS-1) in clinical studies of advanced gastric cancer with peritoneal dissemination. In the present study we assessed its pharmacokinetics, inhibitory effects, and effect on survival time in an animal model. METHODS: A model of peritoneal dissemination was created by intraperitoneally implanting 4-week-old female BALBc nu/nu mice with the human gastric cancer cell line MKN-45 after transfection with a fluorescent protein-expressing vector. Pharmacokinetics were investigated by measuring intratumor, peritoneal lining, and blood concentrations after the administration of S-1 and fluorouracil (5-FU). The effect of S-1 on survival time was also assessed, by administration once daily to seven animals per group, starting on day 7 after implantation, and survival time was compared with that of an untreated control group. The inhibitory effect of S-1 on peritoneal dissemination was evaluated by killing mice at the start of administration, and 1 and 3 weeks after the start of administration, and examining them for the presence of peritoneal dissemination under a fluorescence stereomicroscope. RESULTS: Maintenance of high 5-FU concentrations in the intraperitoneal tumors was confirmed in the S-1 group, and survival time was prolonged without any decrease in oral food intake or body weight. CONCLUSION: Assessment in a model of peritoneal dissemination of gastric cancer showed that the novel oral anticancer agent S-1 was effective against peritoneal dissemination, and that it improved the survival rate.
  • CDDP+S-FU+AUM併用化学放射線療法にてCRが得られた腹部リンパ節転移陽性の多発進行食道癌の例
    癌と化学療法 30 (11) 1737 - 1740 2003
  • 食道癌における3領域リンパ節郭清
    日本臨床 61 (8) 395 - 399 2003
  • Fujiwara Y; Tamura S; Yoshioka S; Okada Y; Takiguchi S; Yano M; Yasuda T; Monden M
    Gan to kagaku ryoho. Cancer & chemotherapy 29 (13) 2555 - 2559 0385-0684 2002/12 [Refereed]
     
    The importance of chemotherapy in the treatment of gastric cancer has increased after the appearance of more effective new agents such as TS-1. Therefore, the development of second line chemotherapy following TS-1 administration is needed urgently. Recently, we treated three cases of advanced and recurrent gastric cancers, using paclitaxel after TS-1 treatment. We herein describe these cases and discuss the therapeutic effect of paclitaxel and drug-related side effects in these patients.
  • Fujiwara Y; Takiguchi S; Mori T; Yasuda T; Yano M; Monden M
    Gan to kagaku ryoho. Cancer & chemotherapy 29 (12) 2279 - 2281 0385-0684 2002/11 [Refereed]
     
    In this study, intra-peritoneal chemotherapy was performed for advanced gastric cancer with serosal invasion. We assessed the efficacy of the chemotherapy using quantitative genetic diagnosis with peritoneal lavages collected before and after chemotherapy at staging laparoscopy and/or gastrectomy. Cases in which genetic diagnosis of peritoneal lavages showed negative results, or changed from positive to negative after chemotherapy, had a good prognosis. On the other hand, cases in which genetic diagnosis showed positive results after chemotherapy had worse prognosis. Intra-peritoneal chemotherapy may be indicated for patients with a positive genetic diagnosis only and cases becoming negative as a result of this therapy may have a better prognosis.
  • S Yoshioka; Y Fujiwara; Y Sugita; Y Okada; M Yano; S Tamura; T Yasuda; S Takiguchi; H Shiozaki; M Monden
    SURGERY MOSBY, INC 132 (1) 34 - 40 0039-6060 2002/07 [Refereed]
     
    Background. New molecular techniques have been designed to detect cancer micrometastases that are otherwise missed by conventional histologic examination. The aim of this study was to establish a sensitive and rapid genetic assay to detect lymph node micrometastasis and to assess its usefulness clinically for cervical lymphadenectomy in esophageal cancer.. We have recently shown that metastasis in the lymph node chain along the recurrent laryngeal nerves (rec LNs) is a predictor Of cervical node metastasis in esophageal cancer. In our retrospective study, the positive rate Of cervical lymph node metastasis with rec LNs metastasis was 51.6%, and the rate without rec LNs metastasis was 11.6%. There was a significant difference in both positive rates (P = .0002). Methods. Rec LNs obtained from 50 patients with esophageal cancer were assessed prospectively by intra-operative histopathologic examination (HE) and genetic analysis. The latter involved a real-lime quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) system with multiple markers, carcinoembryonic antigen, squamous cell carcinoma, and melanoma antigen-3, whose messenger RNAs are highly and frequently expressed in esophageal cancers. Cervical lymphadenectomy was subsequently performed in a subset of these patients. Results. Ten of 50 patients (20%) were scored as node positive by HE, and 24 patients (48%) were scored positive by genetic diagnosis, including 9 HE-positive cases. Genetic diagnosis of rec LNs accurately predicted all 9 cases with cervical lymph node metastasis and 2 cases with cervical lymph node recurrence, whereas HE missed 2 cases with cervical lymph node metastasis and 2 cases with cervical lymph node recurrence. Conclusions. Our real-time rapid RT-PCR assay can improve the sensitivity of HE for detection of lymph node metastasis and might be potentially useful for intraoperative genetic diagnosis for subsequent cervical lymphadenectomy in esophageal cancer surgery.
  • K Kishi; Y Doki; H Miyata; M Yano; T Yasuda; M Monden
    BRITISH JOURNAL OF SURGERY JOHN WILEY & SONS LTD 89 (5) 597 - 603 0007-1323 2002/05 [Refereed]
     
    Background: The sensitivity of cancer cells to chemotherapy and radiation therapy depends on various biological properties. This study investigated the expression of p53, CDC25B and metallothionein (MT), and evaluated their clinical significance in chemoradiation therapy (CRT) for oesophageal squamous cell carcinoma. Methods: The expression of p53, CDC25B and MT was evaluated by immunohistochemistry using biopsy specimens taken before CRT for 77 patients with oesophageal squamous cell carcinoma, and correlated with the pathological effects of CRT and survival. Results: p53-positive tumours and MT-positive tumours had a poor response to CRT, whereas tumours with strong CDC25B expression were associated with a good response. When each patient was scored for the presence of the three biological factors, there was a strong correlation between the sensitivity score and the pathological effect of CRT (P < 0.001), and a (non-significant) difference in the 5-year survival rate between patients with a high score and those with a low score (67 versus 34 per cent respectively; P = 0.12). Conclusions: The combined evaluation of p53, CDC25B and MT may help to identify patients with advanced oesophageal squamous cell carcinoma who will benefit from preoperative CRT.
  • Mori T; Fujiwara Y; Takiguchi S; Yasuda T; Tamura S; Yano M; Monden M
    Nihon Geka Gakkai zasshi 103 (5) 448 - 448 0301-4894 2002/05 [Refereed]
  • 頚部食道癌に対する積極的咽頭温存術式
    塩﨑 均; 安田卓司; 矢野雅彦; 田村茂行; 門田守人
    手術 56 (3) 335 - 342 2002/03
  • 塩﨑 均; 矢野雅彦; 田村茂行; 安田卓司; 藤原義之
    臨床外科 56 (11) 13 - 18 2001/10
  • Y Okada; Y Fujiwara; H Yamamoto; Y Sugita; T Yasuda; Y Doki; S Tamura; M Yano; H Shiozaki; N Matsuura; M Monden
    CANCER JOHN WILEY & SONS INC 92 (8) 2056 - 2064 0008-543X 2001/10 [Refereed]
     
    Background, Some patients with gastric carcinoma experience local disease recurrence despite undergoing curative resection of the tumor and regional lymph nodes (LNs), suggesting the presence of occult micrometastases. To evaluate the presence of gastric carcinoma micrometastasis in patients with otherwise histologically negative LNs, the authors established and tested a multiple-marker reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Methods. The authors assessed 435 LNs from 28 patients with gastric carcinoma who underwent gastrectomy with lymphadenectomy using the multiple-marker RT-PCR assay in addition to histologic examination. Carcinoembryonic antigen (CFA), cytokeratin-20 (CK-20), and MAGE-3 gene markers were used in this assay. LNs were scored positive for metastasis if at least one marker was positive. The presence of LN micrometastases also was verified by immunohistochemistry in histologically negative and RT-PCR positive LNs. Results. Sixty-nine of 435 LNs (16%) were positive for CEA (12%), CK-20 (10%), or MAGE-3 (5%). None of 16 control LNs obtained from disease free patients was positive by RT-PCR assay. Of 414 histologically negative LNs, 50 LN's (12%) were scored as positive for metastasis by the assay. Of 26 patients who underwent curative resection, the disease stage was upgraded in 10 patients by genetic diagnosis (from Stage LA to Stage IB in 5 patients, from Stage IB to Stage IIIA in 2 patients, from Stage IB to Stage IV in 1 patient, from Stage IB to Stage II in 1 patient, and from Stage II to Stage IIIB in 1 patient). In the latter 10 patients, immunohistochemistry identified LN micrometastases in 4 patients. Two patients with micrometastasis by genetic diagnosis had recurrent disease within 1 year. Conclusions. The current results indicate that the multiple-marker RT-PCR assay is a useful tool for the detection of micrometastases in regional LNs in patients with gastric carcinoma and may improve the staging system of gastric carcinoma for these patients. Cancer 2001;92:2056-64. (C) 2001 American Cancer Society.
  • Nishioka K; Doki Y; Shiozaki H; Yamamoto H; Tamura S; Yasuda T; Fujiwara Y; Yano M; Miyata H; Kishi K; Nakagawa H; Shamma A; Monden M. Clinical; significance of CD; and CD; expression i; squamous cell carcinomas of; the oesophagus; Br J; Canc
    Br J Cancer CHURCHILL LIVINGSTONE 85 (3) 412 - 421 0007-0920 2001/08 
    CDC25A, CDC25B and CDC25C belong to a family of protein phosphatases which activate the cyclin-dependent kinase at different points of the cell cycle. According to accumulating evidence, CDC25A and CDC25B seem to possess oncogenic properties. We have analysed these expressions by immunohistochemistry, western blot and RT-PCR in a series of 100 patients with squamous cell carcinoma of the oesophagus. When compared with non-cancerous cells, CDC25A and CDC25B were strongly expressed in the cytoplasm of cancer cells, with positive (+) classification in 46% (46 cases) and 48% (48 cases), respectively. There was no significant correlation between CDC25A and CDC25B expression, nor was there any association with the expression of other cell cycle-regulating molecules, including cyclin D1, Rb, p16(INK4), p27(kiP1) and PCNA (proliferating cell nuclear antigen). CDC25A (+), as well as CDC25B (+), was more frequently found in patients with deeper tumour invasion and lymph node metastasis, while tumour size was correlated only with CDC25A expression. Postoperative survival was significantly poorer for CDC25A (+) patients than CDC25A (-) patients, but was not affected by the CDC25B status. Nuclear localization of CDC25A was observed in 51 cases (51%), regardless of its cytoplasmic expression, and was not associated with clinico-pathological factors or prognosis. Multivariate analysis revealed only the CDC25A status to be an independent significant prognostic factor among these biological and clinico-pathological factors. CDC25A but not CDC25B may be a new prognostic factor for squamous cell carcinoma of the oesophagus. Thus, regulation of the G1 checkpoint in the cell cycle may be important in oesophageal carcinogenesis, which may also involve many other oncogenes. (C) 2001 Cancer Research Campaign.
  • Hiroshi Miyata; Yuichiro Doki; Hirofumi Yamamoto; Kentaro Kishi; Hiroyoshi Takemoto; Yoshiyuki Fujiwara; Takushi Yasuda; Masahiko Yano; Masatoshi Inoue; Hitoshi Shiozaki; I. Bernard Weinstein; Morito Monden
    Cancer Research 61 (7) 3188 - 3193 0008-5472 2001/04 [Refereed]
     
    CDC25B phosphatase plays a key role in controlling G2-M progression by dephosphorylating two inhibitory residues of CDC2 and also has been suggested to have an oncogenic property. In this study, we investigated the effect of CDC25B overexpression on radiation-induced G2-M arrest and radiation sensitivity in esophageal cancer cells. TE8-CDC25B, in which CDC25B was overexpressed under an inducible system, was more radiosensitive than the vector control (TE8-neo) in a clonogenic survival assay. Without radiation, CDC25B overexpression had little effect on cell cycle fractions or growth rate. After 10-Gy radiation, TE8-CDC25B showed decreased G2-M arrest and increased apoptosis, whereas TE8-neo displayed prolonged G2-M arrest and less apoptosis. During this period, there were no differences in the protein amounts of CDC2 and cyclin B1 between the two cell lines. However, more CDC25B expression, which was reduced immediately by radiation, was sustained in TE8-CDC25B than in TE8-neo. Moreover, induction of tyrosine phosphorylation of CDC2 and reduction of CDC2 kinase activity after irradiation was less significant in TE8-CDC25B than in TE8-neo. These results indicate that cancer cells that overexpress CDC25B override G2-M arrest by retaining CDC2 kinase activity and undergo apoptosis after radiation. This may point to an effective approach toward improving radiotherapy outcomes of various cancers.
  • Yuichiro Doki; Toshiyuki Kabuto; Osamu Ishikawa; Hiroaki Ohigashi; Yo Sasaki; Terumasa Yamada; Masahiro Hiratsuka; Isao Miyashiro; Masao Kameyama; Kohei Murata; Shingi Imaoka; Takushi Yasuda; Akihiko Nakaizumi; Akemi Takenaka
    Surgery Mosby Inc. 130 (5) 792 - 797 0039-6060 2001 [Refereed]
     
    Background. Operative manipulation occasionally exfoliates and spreads cancer cells in the surgical field, and it is a matter of concern whether the exfoliated cancer cells actually affect the patient's prognosis and sites of cancer recurrence. Methods. In 240 patients with esophageal cancers, lavage cytology (LC) of the right pleural cavity was performed before and after esophageal resection combined with regional lymphadenectomy. The cytologic results were compared with the pathologic factors associated with cancer extension, postoperative survival, and cause of surgical failure. Results. Only 3 patients (1.3%) were LC positive before resection. Of the 237 LC-negative patients, LC was also negative after resection in 215 patients (90.7%) (LC-/-), but LC became positive after resection in 22 patients (9.3 %) (LC-/+). The 3-year survival rate was 0% in the LC-/+ group versus 65% in the LC-/- group, and the median survival rates were 10.9 months and 25.0 months, respectively (P < .0001). Multivariate analysis revealed that LC-/+ was an independent prognostic factor (P = .0331), along with nodal involvement and depth of cancer invasion. However, there were no significant differences in the sites of cancer recurrence between the 2 groups. Only 1 patient was found to develop the first recurrence in the pleural cavity. The LC-/+ group had a higher incidence of bulky lymph-node metastasis (P = .0009). Conclusions. Pleural LC after resection of esophageal cancer seems to be a prognostic indicator of overall recurrence, but not necessarily in the pleural cavity. Patients with a positive LC after resection may benefit most by effective systemic adjuvant chemotherapy.
  • H Shiozaki; M Yano; T Tsujinaka; M Inoue; S Tamura; Y Doki; T Yasuda; Y Fujiwara; M Monden
    DISEASES OF THE ESOPHAGUS BLACKWELL PUBLISHING ASIA 14 (3-4) 191 - 196 1120-8694 2001 [Refereed]
     
    This study examined whether recurrent nerve chain node metastasis serves as an indicative factor for cervical lymph node dissection in thoracic esophageal cancer. The association of recurrent nerve chain lymph node metastasis and cervical node metastasis was analyzed for 91 patients with thoracic esophageal cancer who had undergone three-field lymph node dissection. In patients with upper thoracic esophageal cancer, the incidence of cervical lymph node metastasis was similar regardless of recurrent nerve chain node metastasis. On the other hand, in patients with middle or lower esophageal cancer, the incidence was significantly higher in recurrent nerve-positive (16/31, 51.6%) than in recurrent nerve-negative (5/43, 11.6%) patients. The prognosis of patients with recurrent nerve chain node metastasis was significantly better in the three-field dissection group than in the two-field dissection group, while in patients with no recurrent nerve chain node metastasis, survival was similar between the two groups. In conclusion, cervical lymphadenectomy can be omitted for recurrent nerve chain node-negative patients with middle and lower thoracic esophageal cancer.
  • T Utsunomiya; Y Doki; H Takemoto; H Shiozaki; M Yano; M Sekimoto; S Tamura; T Yasuda; Y Fujiwara; M Monden
    ONCOLOGY KARGER 61 (3) 226 - 233 0030-2414 2001 [Refereed]
     
    Objective: Beta-catenin activates transcription by TCF/LEF and has been regarded as an oncogene in a wide range of malignant tumors. Among various molecules regulated by beta-catenin/Tcf, cyclin D1 is the most likely candidate for stimulation of the oncogenic pathway. The association between beta-catenin and cyclin D1 was investigated using clinical samples from, colorectal cancers. Methods:The expression of beta-catenin and cyclin D1 was investigated by immunohistochemical analyses of samples from 70 patients with colorectal cancers. In 28 of the fresh tumor samples, beta-catenin; protein was separated into soluble and insoluble fractions and quantitatively correlated with cyclin D1 protein by Western blot analysis. Results: Compared with noncancerous epithelium, beta-catenin and! cyclin D1 were overexpressed (+) in 35 (50%) and 30 Gases (43%), respectively. Cyclin, D1 (+) was observed in 74% (26/35) of beta-catenin (+) cases, but only in 11% (4/35) of the beta-catenin (-) cases. Thus, there was a strong association between the expression of beta-catenin and that of cyclin D1 (p<0.001). In the Western blot analysis, the amount of cyclin D1 correlated well with beta-catenin expression in the soluble fraction (p=0.0016), but not with beta-catenin in the insoluble fraction or with E-cadherin expression. Beta-catenin (-)/cyclin D1 (-) cases displayed less tumor invasion than the remaining cases. However, there were no significant differences in lymph node metastasis or other clinicopathological findings. Conclusion: Our results indicate that beta-catenin overexpression in the cytoplasm may promote malignant transformation by triggering cyclin D1 expression in colorectal cancers. Copyright (C) 2001 S. Karger AG, Basel.
  • 児玉 憲; 東山 聖彦; 横内 秀起; 高見 康二; 安田 卓司; 甲 利幸; 櫻井 温; 高見 宏; 小林 亨
    胸部外科 (株)南江堂 53 (9) 721 - 725 0021-5252 2000/08 
    悪性腫瘍の際の,心・大血管合併切除時の呼吸循環補助手段としての経皮的心肺補助(PCPS)の有用性と適応を中心に報告した.最近の知見から,左房合併切除時の補助手段として,本法使用,心室細動下に行うのが最も安全かつ合理的と考えられる
  • Takehiro Utsunomiya; Yuichiro Doki; Hiroyoshi Takemoto; Hitoshi Shiozaki; Masahiko Yano; Masatoshi Inoue; Takushi Yasuda; Yoshiyuki Fujiwara; Morito Monden
    Gastric Cancer Springer Japan 3 (4) 193 - 201 1436-3291 2000 [Refereed]
     
    Background. Beta-catenin plays two distinct roles, in intercellular adhesion by E-cadherin, and in transcriptional activation via TCF/LEF. Theoretically, the former role is tumor-suppressive, while the latter is oncogenic. We investigated the involvement of beta-catenin in the histogenesis and clinical outcome of gastric cancers. Methods. The expression pattern of beta-catenin was evaluated in stomach and lymph nodes from 82 patients with gastric cancer by immunohistochemistry and Western blot. Its association with E-cadherin expression and clinicopathological factors, including histological type and postoperative survival, was examined. Results. Beta-catenin expression was classified into two patterns, normal (23.2% 19 patients) and disordered (76.8% 63 patients), the latter being subclassified as overexpressed (7.3% 6 patients) and reduced (69.5% 57 patients). A disordered beta-catenin expression pattern was significantly correlated with diffuse type adenocarcinoma and deep tumor infiltration (P = 0.0154), but was not associated with lymph node metastasis (P = 0.7877). E-cadherin was always expressed at the cell membrane, and disordered beta-catenin expression was significantly associated with reduced E-cadherin expression (P < 0.0001). On univariate analysis, the beta-catenin pattern, as well as depth of invasion and lymph node metastasis, was associated with postoperative prognosis however, only lymph node metastasis was an independent prognostic factor on multivariate analysis. Interestingly, different disordered patterns of beta-catenin expression, both overexpressed and reduced, were associated with E-cadherin reduction and poorer postoperative survival. Conclusion. Although disordered patterns of beta-catenin expression varied in gastric cancers, they were consistently associated with cancer progression.
  • 大動脈浸潤胸部食道癌に対する大動脈合併切除術
    手術 54 (4) 503 - 511 2000
  • Hiroshi Furukawa; Masahiro Hiratsuka; Shingi Imaoka; Osamu Ishikawa; Toshiyuki Kabuto; Yo Sasaki; Masao Kameyama; Hiroaki Ohigashi; Hiroshi Nakano; Takushi Yasuda; Kohei Murata
    Annals of Surgical Oncology Lippincott Williams and Wilkins 6 (2) 166 - 170 1068-9265 1999 [Refereed]
     
    Background: Endoscopic resection for treatment of early gastric cancer (EGC) is widely performed. Recently, however, surgeons began performing a limited operation for EGC when endoscopic resection was not indicated. This report discusses the surgical technique and the results of the limited operation, which is generally referred to as 'segmental resection' (SR). Methods: Since 1990, a total of 50 patients with intramucosal invasive EGC of the middle stomach underwent SR. The procedure included a limited gastrectomy, limited lymph node dissection, and preservation of the vagal nerve. We examined the surgical risk, postoperative complications, and patient survival rates and compared the results for the SR-treated patients (group A) with results for patients with EGC who underwent subtotal gastrectomy and systemic lymph node dissection (group B). Results: Blood loss was less in group A (239 ± 180 ml) than in group B (342 ± 176 ml) (P < .05). The incidence of postoperative complications was also lower in group A (2.0%) than in group B (14.0%) (P < .05). The incidence of postoperative cholelithiasis was lower in group A (4.0%) than in group B (18.0%) (P < .05). All patients in both groups are alive without recurrence. Conclusions: Compared with distal gastrectomy, SR for EGC of the middle stomach decreased the surgical risk and postoperative complications without increasing the recurrence rate.
  • T Yasuda; T Yasuda; Y Ohmachi; M Katsuki; M Yokoyama; A Murata; M Monden; K Matsubara
    JOURNAL OF BIOLOGICAL CHEMISTRY AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 273 (51) 34413 - 34421 0021-9258 1998/12 [Refereed]
     
    The human pancreatic secretory trypsin inhibitor (PSTI) genes introduced into mice are specifically expressed in pancreas. The 1.0 kilobase pairs of PSTI 5'-flanking sequence directed preferential expression of a linked reporter chloramphenicol acetyltransferase, which was active in a PSTI-expressing pancreatic cell line (AR42j) but not in a PSTI-nonexpressing fibroblast cell line (XC). Two positively acting elements were found, Region I (-161/-116) and Region PI (-103/-74), as defined by transfection and binding assays with ARA2j cells. Region II is sufficient for the pancreas-specific expression, but the presence of both Regions I and II is needed for the maximum activity. Sequence studies also revealed that these two elements differ from the previously identified recognition sequence for pancreas transcription factor 1 (PTF1), When the same set of experiments was done with XC cells, one negatively acting element was identified, Region IV(-154/-137), Interestingly, Regions I and IV share a core sequence (-149/ -139), CAATCAATAAC. These results suggest that this novel element regulates the human PSTI gene expression positively in pancreatic cells but negatively in nonpancreatic cells.
  • T Yasuda; T Yasuda; Y Ohmachi; M Katsuki; M Yokoyama; A Murata; M Monden; K Matsubara
    JOURNAL OF BIOLOGICAL CHEMISTRY AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 273 (51) 34413 - 34421 0021-9258 1998/12 
    The human pancreatic secretory trypsin inhibitor (PSTI) genes introduced into mice are specifically expressed in pancreas. The 1.0 kilobase pairs of PSTI 5'-flanking sequence directed preferential expression of a linked reporter chloramphenicol acetyltransferase, which was active in a PSTI-expressing pancreatic cell line (AR42j) but not in a PSTI-nonexpressing fibroblast cell line (XC). Two positively acting elements were found, Region I (-161/-116) and Region PI (-103/-74), as defined by transfection and binding assays with ARA2j cells. Region II is sufficient for the pancreas-specific expression, but the presence of both Regions I and II is needed for the maximum activity. Sequence studies also revealed that these two elements differ from the previously identified recognition sequence for pancreas transcription factor 1 (PTF1), When the same set of experiments was done with XC cells, one negatively acting element was identified, Region IV(-154/-137), Interestingly, Regions I and IV share a core sequence (-149/ -139), CAATCAATAAC. These results suggest that this novel element regulates the human PSTI gene expression positively in pancreatic cells but negatively in nonpancreatic cells.
  • Hiroshi Furukawa; Masahiro Hiratsuka; Shingi Imaoka; Osamu Ishikawa; Toshiyuki Kabuto; Yo Sasaki; Masao Kameyama; Hiroaki Ohigashi; Hiroshi Nakano; Takushi Yasuda
    Annals of Surgical Oncology 5 (4) 338 - 341 1068-9265 1998/06 [Refereed]
     
    Background: Because there are some difficulties with the diagnosis of invasion or the endoscopic resection technique, almost all gastric tumors are resected surgically. Surgeons now are performing a limited operation for early gastric cancer of the upper stomach (EGCUS) without lymph node metastasis. This paper discusses and evaluates the surgical technique and the results of the limited operation for EGCUS. Patients and Methods: Since 1988, a total of 34 patients with EGCUS, diagnosed as intramucosal invasion, have undergone a limited operation-fundectomy-which includes a limited proximal gastrectomy, a limited lymph node dissection, and a procedure preserving the vagal nerve. The surgical risk, postoperative complications, and survival rates of the fundectomy patients (group A) were compared with those of patients undergoing a total gastrectomy for EGCUS (group B). Results: Blood loss was lower in group A (300 ± 193 mL) than in group B (555 ± 316 mL) (P < .05). The incidence of postoperative pancreatic fistula also was lower in group A (0%) than in group B (15.0%) (P < .05). All patients in both groups (except one who died of a cerebral infarction) are alive without recurrence. Conclusion: Compared to the results of a total gastrectomy, performance of a limited fundectomy for EGCUS decreased surgical risk and postoperative complications without decreasing the survival rate.
  • Yo Sasaki; Shingi Imaoka; Hiroshi Nakano; Osamu Ishikawa; Hiroaki Ohigashi; Takushi Yasuda; Shoji Nakamori; Masao Kameyama; Masahiro Hiratsuka; Toshiyuki Kabuto; Hiroshi Furukawa; Hiroshi Kasugai; Atsuo Inoue; Makoto Fujita; Etsuo Inoue
    Journal of Hepato-Biliary-Pancreatic Surgery Springer Japan 5 (1) 14 - 17 0944-1166 1998 [Refereed]
     
    To determine the clinical and tumor stage of hepatocellular carcinoma (HCC) that is the best indication for surgery, the postoperative long-term outcomes of patients who underwent hepatic resection were examined retrospectively. Of 975 patients with HCC who underwent regional therapy, 384 patients (39%) received hepatic resection (HR), 534 (55%) had transcatheter arterial chemoembolization (TACE), and the remaining 57 (6%) received percutaneous ethanol injection (PEI) into the tumor. The criteria defined by liver Cancer Study Group of Japan was used for staging and liver functional reserve (i.e., clinical staging).1 In the 133 patients with stage I HCC, there were no significant differences among the survivals of the HR, TACE, and PEI groups. In the 314 patients with stage II HCC, the 5- and 7-year survival rates were 51% and 46% in the HR group, 23% and 10% in the TACE group, and 0% and 0% in the PEI group. The survival of the HR group was significantly better than the survivals of the TACE and PEI groups (P < 0.001). The 5- and 10-year survivals of the stage II HCC patients who had HR were 64% and 47% in the clinical stage I (i.e., good liver function) group, significantly better than the 5 and 10-year survivals (32% and 23%) in the clinical stage II (i.e., bad liver function) group (P < 0.0001). Patients with good liver function in stage II are expected to have better survival and are considered to be the most suitable for HR. © Springer-Verlag 1998.
  • Hiroshi Furukawa; Masahiro Hiratsuka; Takeshi Iwanaga; Shingi Imaoka; Osamu Ishikawa; Toshiyuki Kabuto; Yo Sasaki; Masao Kameyama; Hiroaki Ohigashi; Shoji Nakamori; Takushi Yasuda
    Annals of Surgical Oncology Lippincott Williams and Wilkins 4 (3) 209 - 214 1068-9265 1997 [Refereed]
     
    Background: The prognosis after surgical treatment for type 4 gastric cancer, including linitis plastica, remains poor. The most frequent recurrence mode is retroperitoneal involvement. To remove the tumor and microinvasion surrounding the stomach, extended surgery, left upper abdominal exenteration plus the Appleby's method (LUAE + Apl), has been performed for type 4 cancers since 1983. Patients and Methods: A total of 54 patients with type 4 cancer underwent extended surgery (LUAE + Apl) over the past 11 years. In the LUAE + Apl surgical procedure, the whole stomach, pancreas body and tail, spleen, gallbladder, transverse colon, and left adrenal were removed en bloc. The results of this treatment are reported and the most beneficial application of this procedure (group A) is evaluated and compared with findings in similar patients who underwent common surgery between 1973 and 1983 (group B). Results: As postoperative complications, pancreatic fistula (30% control 19%), liver dysfunction (15% 14%), anastomosis failure (6% 9%), and infection (4% 1%) were observed (NS). In group A, one patient died of liver dysfunction and another of multiple organ failure due to major pancreatic fistula. In stage III, the 5-year survival rate of group A (40%) was better than that of group B (20% p < 0.05). In stage IV, the 5-year survival rate of group A (5% 3% in group B) was not improved. Conclusion: LUAE + Apl improved the survival of patients with scirrhous cancer in stage III, but it was not effective for those in stage IV. To improve the survival of patients in stage IV, a new concept of treatment and supportive therapy needs to be used. Published by Lippincott-Raven Publishers © 1997 The Society of Surgical Oncology, Inc.
  • Osamu Ishikawa; Hiroaki Ohigashi; Hiroshi Nakano; Takushi Yasuda; Shoji Nakamori; Masahiro Hiratsuka; Masao Kameyama; Yo Sasaki; Toshiyuki Kabuto; Hiroshi Furukawa; Shingi Imaoka
    Japanese Journal of Gastroenterological Surgery Japanese Society of Gastroenterological Surgery 30 (10) 2049 - 2053 0386-9768 1997 [Refereed]
     
    We have improved the 5-year survival rate from 9% to 29% by extending the range of lymphatic and connective tissue clearance (D2a) in resection of pancreatic head cancer. When D2a was performed, the long-term survivors were obtained mainly from the groups in which the positive nodes were absent or limited in the pancreaticoduodenal regions. Among these two groups, 40% of patients had cancer extension at a microscopic levels (microinvasion), in the nerve plexi or connective tissues beyound the pancreatic confines. The 5-year survival rate was around 40% even in the patients who had microinvasion around the superior mesenteric artery, celiac artery and aorta. Whereas, the long-term survival would be scarecely expected when the patients had either positive nodes beyond the pancreaticoduodenal region or microinvasion around the hepatic artery or inferior pancreatic head. These data lead us to conclude that the D2a-procedure is recommended for the selected patients with pancreatic head cancer.
  • Shoji Nakamori; Masao Kameyama; Shingi Imaoka; Takushi Yasuda; Hiroshi Nakano; Hiroaki Ohigashi; Masahiro Hiratsuka; Yo Sasaki; Osamu Ishikawa; Toshiyuki Kabuto; Hiroshi Furukawa; Takeshi Iwanaga; Yuki Izumi; Tatsuro Irimura
    Japanese Journal of Gastroenterological Surgery Japanese Society of Gastroenterological Surgery 29 (4) 873 - 877 0386-9768 1996 [Refereed]
     
    Sialyl Lewis-X antigen (sLex) and sialy Lewis-a antigen (sLea) are expressed in colorectal carcinomas and were recently shown to be a ligand for endothelial adhesion molecule E-selectin. In order to determined whether expression of cell surface sLex and sLea is associated with the metastatic potential of human colorectal carcinoma (CRC), we examined sLex and sLea expression in tissue samples obtained from 159 CRC patients to investigate whether this antigen expression could serve as a prognostic parameter, and examined metastatic phenotypes in variant CRC cell lines for high and low cell surface levels of sLex (KM12HX and KM12LX, respectively). Clinical records showed that the disease-free survival rate for CRC patients with high levels of sLex was significantly poorer than for patients with low levels of this antigen. Cox's multivariate analysis revealed that the sLex expression level was one of the significant discriminants of recurrence in colorectal cancer patients. KM12HX showed a higher metastatic potential in nude mice and greater adhesive ability in vitro than KM12LX cells. This increased adhesiveness of KM12HX was inhibited by anti-E-selectin antibody, an inhibitor of carbohydrate synthesis, benzyl-N-acetyl-α-D-galactosaminide, and sialidase. These results suggest that sLex expression could be involved in colon cancer metastasis and that sLex might prove to be a potent marker of recurrence in CRC patients. Also, they suggest the possibility of regulation of the metastatic potential of CRC by inhibition of carbohydrate antigen synthesis.
  • Hiroshi Furukawa; Masahiro Hiratsuka; Takeshi Iwanaga; Shingi Imaoka; Osamu Ishikawa; Toshiyuki Kabuto; Yo Sasaki; Masao Kameyama; Hiroaki Ohigashi; Shoji Nakamori; Hiroshi Nakano; Takushi Yasuda
    the japanese journal of gastroenterological surgery 28 (10) 2111 - 2114 1348-9372 1995 [Refereed]
     
    The pathological characteristics, location of the lesions, lymph node metastasis and metachronous multiple lesions in 323 patietns with multifocal cancer were studied. In macroscopic findings, the protruded type and flat type were observed more frequently in multifocal cancer than in single cancer. Lesions were close to eachother in 77% of patients younger than 49 years, and they were apart from each other in 70% of patients older than 50 years. The incidence of lymph node metastasis for multifocal cancer (33.3%) was lower than that for single cancer (43.8%) (p< 0.05). Within 10 years after partial gastrectomy for cancer, 80% of remnant stomach cancers were detected in regions apart from the anastomosis, and more than 15 years after the first operation, 50% of them were detected in the region of anastomosis. Before a partial gastrectomy the stomach should be examined carefully to avoid leaving cancer. After gastrectomy, endoscopy should be performedto detect any metachronous multiple lesions. © 1995, The Japanese Society of Gastroenterological Surgery. All rights reserved.
  • 安田卓司
    癌と化学療法 22 (11) 2863 - 2866 1995
  • Yoshitaka Ohmachi; Atsuo Murata; Takushi Yasuda; Kazunori Kitagawa; Syuuji Yamamoto; Morito Monden; Takesada Mori; Nariaki Matsuura; Kenichi Matsubara
    Journal of Hepatology 21 (6) 1012 - 1016 0168-8278 1994 [Refereed]
     
    Pancreatic secretory trypsin inhibitor, an acute phase reactant protein, is expressed in the liver in response to inflammatory cytokines, especially in hepatocellular carcinoma. Northern blots of 25 dissected liver tissues from non-hepatitis, chronic hepatitis and cirrhosis patients revealed that 10 (40%) expressed pancreatic secretory trypsin inhibitor. The expression seemed to be closely associated with hepatitis B viral infection, since among the 11 hepatitis B virus-infected samples, nine (81%) were pancreatic secretory trypsin inhibitor-positive. In contrast, this augmented expression was absent in non-infected livers (0/5 0%), and rare in those infected with hepatitis C virus (1/9 11%). There was no significant correlation between the pancreatic secretory trypsin inhibitor expression in the liver and the serum level of glutamic pyruvic transaminase, the hepaplastin test, the 15-min retention rate of indocyanine green, or the histological findings of the liver tissues such as lymphocyte infiltration and pseudolobular formation. Furthermore, we identified an almost three-fold increase in the transactivation of pancreatic secretory trypsin inhibitor gene expression in HepG2 cells after transient transfection with HBV-DNA or the X gene in an expression vector. These results suggest that the induction of pancreatic secretory trypsin inhibitor gene expression in livers with chronic hepatitis and cirrhosis is directly affected by hepatitis B virus. © 1994 Journal of Hepatology.
  • Y OHMACHI; A MURATA; T YASUDA; T YASUDA; M MONDEN; T MORI; M OGAWA; K MATSUBARA
    INTERNATIONAL JOURNAL OF CANCER WILEY-LISS 55 (5) 728 - 734 0020-7136 1993/11 [Refereed]
     
    Twenty hepatocellular carcinomas (HCC) were analyzed by Northern blotting to test the expression of pancreatic secretory trypsin inhibitor (PSTI). This gene was expressed in all HCCs, but not in other tumors, including mammary, thyroid, pulmonary and ovarian cancers. Some gastric and colonic cancers weakly expressed PSTI. Among cell lines examined in a similar manner, PSTI was expressed in all of 4 derived from hepatoma. On the other hand, among 15 cell lines derived from cancers other than hepatoma, only 3, derived from pancreatic, colonic and gastric cancers, weakly expressed PSTI. A CAT assay using a deletion set of the 5' region from the cloned PSTI gene has shown that in hepatoma cell lines, the expression of this gene is dependent on the presence of 2 regulatory regions that include an IL-6 responsive element and an AP-I-binding site. However, in non-hepatoma cell lines, the 2 regulatory regions are not necessary for expression. The blood level of PSTI in 27 patients with HCC was significantly increased, and it was positively correlated with tumor size, suggesting that specific expression of PSTI in HCC causes this effect and that elevated blood level of PSTI without inflammation indicates the presence of HCC. (C) 1993 Wiley-Liss, Inc.
  • Yoshio Oka; Atsuo Murata; Junichi Nishijima; Tadashi Yasuda; Nobuaki Hiraoka; Yoshitaka Ohmachi; Kazunori Kitagawa; Takushi Yasuda; Hitoshi Toda; Nobuo Tanaka; Takesada Mori
    Cytokine 4 (4) 298 - 304 1043-4666 1992 [Refereed]
     
    We examined postoperative serial changes in the levels of serum interleukin 6 (IL-6), serum acute phase reactants (APRs) and plasma neutrophil elastase (NE) in patients with various cancers and reviewed these changes in patients who did, and did not, show postoperative complications. Serum IL-6 level was elevated after surgery, peaking on the first postoperative day. Elevation of serum APRs and plasma NE levels also followed. There was a significant correlation between the serum peak level of IL-6 and those of APRs and NE (P < 0.01). Moreover, there was a significant difference in the serum IL-6 level in patients with and without complications. The relationship between the serum IL-6 > 400 pg/ml and the incidence of postoperative complications was also marked. These results suggest that circulating IL-6 is a clinically useful marker for the earliest detection and prediction of postoperative complications. © 1992.
  • H. Nagano; Y. Sasaki; S. Imaoka; S. Masutani; I. Ohashi; O. Ishikawa; H. Oohigashi; T. Yasuda; H. Furukawa; I. Fukuda; T. Kabuto; M. Hiratsuka; M. Kameyama; H. Koyama; T. Iwanaga
    Japanese Journal of Cancer and Chemotherapy 17 (8) 1758 - 1762 0385-0684 1990 [Refereed]
  • Osamu Ishikawa; Shingo Ishiguro; Hiroaki Ohhigashi; Yo Sasaki; Takushi Yasuda; Shingi Imaoka; Takeshi Iwanaga; Akihiko Nakaizumi; Makoto Fujita; Akira Wada
    The American Journal of Gastroenterology 85 (5) 597 - 601 1572-0241 1990 [Refereed]
     
    A case of solid and papillary neoplasm of a mesocolonic ectopic pancreas in a 13‐yr‐old girl is presented. An 8‐cm, well‐encapsulated, and partly calcified tumor which protruded from the mesocolon was resected surgically. Histologically, the tumor showed either solid sheets or papillary arrangements (around the vascular core) of uniformly small cells with α1‐antitrypsin‐positive cytoplasm. Some of the tumor cells had zymogenlike granules, suggesting acinar cell differentiation. At the base of this tumor, small pancreatic tissues (islet, acinar, and ductular cells) were detected in the mesocolonic tissue. Incidences of both ectopic pancreas outside the gastrointestinal wall and solid and papillary neoplasm of the pancreas are rare, and this is the first case reported in the literature. Copyright © 1990, Wiley Blackwell. All rights reserved

Conference Activities & Talks

  • 完全鏡視下による簡便な手術食道残胃吻合法（Overlap変法を加えた偽穹窿部食道裂孔挿入法）  [Not invited]
    安田篤; 木村豊; 加藤寛章; 平木洋子; 岩間密; 白石治; 新海政幸; 安田卓司
    第31回日本内視鏡外科学会総会  2018/12
  • 逆流防止を考慮した安全で簡便な食道残胃吻合再建の治療成績  [Not invited]
    木村豊; 安田篤; 平木洋子; 加藤寛章; 岩間密; 白石治; 新海政幸; 今本治彦; 安田卓司
    第31回日本内視鏡外科学会総会  2018/12
  • 4食道癌に対する根治化学放射線療法後の積極的サルベージュ手術とその功罪  [Not invited]
    白石治; 加藤寛章; 岩間密; 平木洋子; 安田篤; 新海政幸; 木村豊; 今野元博; 安田卓司
    第80回日本臨床外科学会総会  2018/11
  • 開腹から完全鏡視下まで容易に導入できる改良型食道残胃吻合法  [Not invited]
    安田篤; 木村豊; 平木洋子; 加藤寛章; 岩間密; 白石治; 新海政幸; 今野元博; 安田卓司
    第80回日本臨床外科学会総会  2018/11
  • 簡便かつ容易な完全鏡視下手術食道残胃吻合法（Overlap変法を加えた菱形胃管作成＋偽穹窿部食道裂孔挿入法）  [Not invited]
    安田篤; 木村豊; 平木洋子; 加藤寛章; 岩間密; 白石治; 新海政幸; 今野元博; 安田卓司
    第48回胃外科・術後障害研究会  2018/11
  • 「当院における安全で簡便な完全鏡視下手術食道残胃吻合法（Overlap変法）  [Not invited]
    木村豊; 安田篤; 平木洋子; 加藤寛章; 岩間密; 白石治; 新海政幸; 今野元博; 今本治彦; 古河洋; 安田卓司
    第80回日本臨床外科学会総会  2018/11
  • 当院における噴門側胃切除術後の食道残胃吻合再建の成績  [Not invited]
    木村豊; 安田篤; 加藤寛章; 岩間密; 白石治; 平木洋子; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第48回胃外科・術後障害研究会  2018/11
  • 高用量CDDPの使用が困難な進行食道癌患者に対する術前化学療法の検討  [Not invited]
    木村豊; 白石治; 川上尚人; 植田勲人; 奥野達哉; 岩間密; 加藤寛章; 平木洋子; 安田篤; 新海政幸; 今野元博; 今本治彦; 中川和彦; 安田卓司
    第26回日本消化器関連学会週間JDDW  2018/11
  • 食道進行胃癌に対する術前治療後の腫瘍特異的ペプジドワクチンを用いた術後補助免疫療法の有用性  [Not invited]
    安田卓司; 白石治; 岩間密; 加藤寛章; 平木洋子; 安田篤; 新海政幸; 木村豊; 今野元博
    第80回日本臨床外科学会総会  2018/11
  • 進行食道癌における気管前106pre LN郭清手技のコツと安全性  [Not invited]
    安田卓司; 白石治; 岩間密; 加藤寛章; 平木洋子; 安田篤; 新海政幸; 木村豊; 今野元博
    第16回日本消化器外科学会大会JDDW  2018/11
  • 食道癌術後胃管再建における再建経路の比較―後縦隔経路と胸骨後経路―  [Not invited]
    山崎誠; 田中晃司; 杉村啓二郎; 牧野知紀; 白石治; 宮田博志; 木村豊; 安田卓司; 矢野雅彦; 森正樹; 土岐祐一郎
    第71回日本胸部外科学会定期学術集会  2018/11
  • 腎機能低下を伴う進行食道癌患者に対する安全な3剤併用術前化学療法（UDON療法）  [Not invited]
    木村豊; 白石治; 川上尚人; 奥野達哉; 岩間密; 加藤寛章; 平木洋子; 安田篤; 新海政幸; 今野元博; 中川和彦; 安田卓司
    第56回日本癌治療学会学術集会  2018/10
  • Efficacy of neoadjuvant chemotherapy on micrometastasis in lymph nodes for esophageal cancer patients in OGSG1003 trial  [Not invited]
    木村豊; 加藤寛章; 岩間密; 山崎誠; 矢野雅彦; 土岐祐一郎; 安田卓司
    第77回日本癌学会学術総会  2018/09
  • 胃癌腹膜転移に対する腹腔内化学療法における腹腔内アクセスポート関連合併症の報告  [Not invited]
    平木洋子; 今野元博; 加藤寛章; 岩間密; 白石治; 安田篤; 新海政幸; 木村豊; 今本治彦; 安田卓司
    第73回日本消化器外科学会総会  2018/07
  • 胸部食道癌に対する縦隔側からの101-106recリンパ節徹底郭清  [Not invited]
    白石治; 加藤寛章; 岩間密; 平木洋子; 安田篤; 新海政幸; 木村豊; 今野元博; 今本治彦; 安田卓司
    第73回日本消化器外科学会総会  2018/07
  • 開腹手技の継承により鏡視下手術への導入を容易にする改良型食道残胃吻合法  [Not invited]
    安田篤; 木村豊; 平木洋子; 加藤寛章; 岩間密; 白石治; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第73回日本消化器外科学会総会  2018/07
  • 胃癌腹膜播種に対するPTX腹腔内投与＋PCS全身化学療法による集学的治療の可能  [Not invited]
    新海政幸; 今野元博; 平木洋子; 加藤寛章; 岩間密; 白石治; 安田篤; 木村豊; 今本治彦; 安田卓司
    第73回日本消化器外科学会総会  2018/07
  • 進行食道癌患者に対するFU+dosetaxel+nedaplatin(UDON)療法による術前化学療法の検討  [Not invited]
    木村豊; 白石治; 川上尚人; 植田勲人; 奥野達哉; 岩間密; 加藤寛章; 平木洋子; 安田篤; 新海政幸; 今野元博; 今本治彦; 中川和彦; 安田卓司
    第16回日本臨床腫瘍学会学術集会  2018/07
  • 胃全摘術後の早期体重減少を制御するための取り組み  [Not invited]
    木村豊; 三上城太; 間狩洋一; 平木洋子; 加藤寛章; 岩間密; 白石治; 安田篤; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第55回日本外科代謝栄養学会学術集会  2018/07
  • 胃癌腹膜播種症例に対するcoversion surgeryの意義  [Not invited]
    今野元博; 加藤寛章; 岩間密; 白石治; 安田篤; 新海政幸; 木村豊; 今本治彦; 古河洋; 安田卓司
    第73回日本消化器外科学会総会  2018/07
  • 食道癌特異的ペプチドワクチンの術後補助療法の有用性に関する探索的単施設第2相臨床試験の最終報告  [Not invited]
    安田卓司; 錦 耕平; 白石 治; 岩間 密; 加藤寛章; 安田 篤; 新海政幸; 木村 豊; 今野元博; 中村祐輔
    第73回日本消化器外科学会総会  2018/07
  • 食道癌縦隔郭清の将来展望～根治性に基づいた柔軟なアプローチ法選択と拡大視の活用  [Not invited]
    安田卓司; 白石 治; 岩間 密; 加藤寛章; 平木洋子; 安田 篤; 新海政幸; 木村 豊; 今野元博
    第73回日本消化器外科学会総会  2018/07
  • スキルス胃がんが疑われた早期胃癌の切除例  [Not invited]
    中野博史; 古河洋; 中室誠; 近藤禎晃; 大久保遊平; 星本真弘; 太田善夫; 佐藤隆夫; 木村豊; 今野元博; 安田卓司
    第40回日本癌局所療法研究会  2018/06
  • 腹腔内化学療法用の腹腔内アクセスポートにより腸管穿通きたした1例  [Not invited]
    平木洋子; 今野元博; 木村豊; 加藤寛章; 岩間密; 白石治; 安田篤; 新海政幸; 今本治彦; 古河洋; 安田卓司
    第40回日本癌局所療法研究会  2018/06
  • 頸部食道癌、頸胸境界部癌に対する咽頭温存術における根治性確保、嚥下機能温存の工夫  [Not invited]
    加藤寛章; 白石治; 岩間密; 平木洋子; 安田篤; 新海政幸; 今野元博; 木村豊; 今本治彦; 安田卓司
    第72回日本食道学会学術集会  2018/06
  • 肝転移、傍大動脈リンパ節転移食道癌におけるコンバージョン手術の意義  [Not invited]
    白石治; 加藤寛章; 岩間密; 平木洋子; 安田篤; 新海政幸; 木村豊; 今野元博; 今本治彦; 安田卓司
    第72回日本食道学会学術集会  2018/06
  • 高齢の進行食道癌患者に対する3剤併用術前化学療法の検討  [Not invited]
    木村豊; 白石治; 川上尚人; 植田勲人; 加藤寛章; 岩間密; 安田篤; 新海政幸; 中川和彦; 安田卓司
    第72回日本食道学会学術集会  2018/06
  • 5-FU+docetaxel+nedaplatin併用術前化学療法が奏効した進行食道癌患者の1例  [Not invited]
    木村豊; 白石治; 川上尚人; 植田勲人; 奥野達哉; 平木洋子; 加藤寛章; 岩間密; 安田篤; 新海政幸; 今野元博; 今本治彦; 中川和彦; 安田卓司
    第40回日本癌局所療法研究会  2018/06
  • 胃癌学会・食道学会合同ワーキンググループの食道胃接合部癌リンパ節転移研究の報告  [Not invited]
    安田卓司; 黒川幸典; 竹内裕也; 峯真司; 寺島雅典; 吉田和弘; 大幸宏幸; 木村豊; 北川雄光; 土岐祐一郎
    第72回日本食道学会学術集会  2018/06
  • 頸部食道癌術後甲状腺転移に対して、甲状腺摘出術を施行した１例  [Not invited]
    中西智也; 加藤寛章; 白石治; 岩間密; 平木洋子; 安田篤; 新海政幸; 今野元博; 木村豊; 今本治彦; 安田卓司
    第118回日本外科学会定期学術集会  2018/04
  • 進行食道癌に対する術前化学療法のランダム化比較試験：ACFvsDCF(OGSG1003)におけるリンパ節転移制御効果  [Not invited]
    平木洋子; 今野元博; 加藤寛章; 岩間密; 白石治; 安田篤; 新海政幸; 木村豊; 今本治彦; 安田卓司
    第118回日本外科学会定期学術集会  2018/04
  • 当科での頸部食道切除後の遊離空腸再建～頸部合併症予防の工夫～  [Not invited]
    加藤寛章; 白石治; 岩間密; 平木洋子; 安田篤; 新海政幸; 今野元博; 木村豊; 今本治彦; 安田卓司
    第118回日本外科学会定期学術集会  2018/04
  • 食道-悪性-1」T4食道癌に対する根治化学放射線療法＋積極的サルベージュ手術  [Not invited]
    白石治; 加藤寛章; 岩間密; 平木洋子; 安田篤; 新海政幸; 今野元博; 木村豊; 今本治彦; 安田卓司
    第118回日本外科学会定期学術集会  2018/04
  • 高齢胃癌患者に対する周術期の嚥下リハビリテーション介入の有用性  [Not invited]
    安田篤; 木村豊; 平木洋子; 加藤寛章; 岩間密; 白石治; 新海政幸; 今野元博; 今本治彦; 古河洋; 安田卓司
    第118回日本外科学会定期学術集会  2018/04
  • 「P1進行胃癌に対するPTX腹腔内投与＋PCS全身化学療法による集学的治療の治療成績」  [Not invited]
    新海政幸; 今野元博; 平木洋子; 加藤寛章; 岩間密; 白石治; 安田篤; 木村豊; 今本治彦; 安田卓司
    第118回日本外科学会定期学術集会  2018/04
  • 消化吸収能を考慮した胃切除術後障害に対する対策  [Not invited]
    木村豊; 三上城太; 間狩洋一; 平木洋子; 加藤寛章; 岩間密; 白石治; 安田篤; 新海政幸; 今野元博; 今本治彦; 藤田淳也; 安田卓司
    第118回日本外科学会定期学術集会  2018/04
  • 切除可能進行癌に対する術前化学療法としてのDCFとACF療法の多施設共同ランダム化比較試験  [Not invited]
    山崎誠; 安田卓司; 矢野雅彦; 平尾素宏; 小林研二; 藤谷和正; 田村茂行; 木村豊; 宮田博志; 本告正明; 白石治; 牧野知紀; 佐藤太郎; 森正樹; 土岐祐一郎
    第118回日本外科学会定期学術集会  2018/04
  • 内視鏡的に止血困難な出血性進行胃癌に対する血管塞栓術  [Not invited]
    平木洋子; 木村豊; 間狩洋一; 三上城太; 栗生明博; 加藤寛章; 岩間密; 白石治; 安田篤; 新海政幸; 今野元博; 今本治彦; 藤田淳也; 安田卓司
    第90回日本胃癌学会総会  2018/03
  • 進行度（病理分類）Ⅰ,Ⅱ期胃癌患者の胃切除後の骨密度変化に関する前向きコホート研究（LOHAS Study）  [Not invited]
    加藤 寛章; 今野元博; 千葉康敬; 千葉佐知; 藤谷和正; 岩間密; 白石治; 安田篤; 新海政幸; 木村豊; 今本治彦; 古河洋; 吉田和弘; 伊木雅之; 安田卓司
    第90回日本胃癌学会総会  2018/03
  • 腹腔鏡下胃全摘と比較した腹腔鏡下噴門側胃切除(食道残胃吻合）のメリット（残胃を残す意義）  [Not invited]
    安田篤; 木村豊; 平木洋子; 加藤寛章; 岩間密; 白石治; 新海政幸; 今野元博; 今本治彦; 古河洋; 安田卓司
    第90回日本胃癌学会総会  2018/03
  • 進行再発胃癌に対するramucirumab療法における尿中蛋白／クレアチニン比測定の意義  [Not invited]
    木村 豊; 間狩 洋一; 三上 城太; 藤井 千賀; 平木 洋子; 加藤 寛章; 岩間 密; 白石 治; 安田 篤; 新海 政幸; 今野 元博; 今本 治彦; 藤田 淳也; 古河 洋; 安田 卓司
    第90回日本胃癌学会総会  2018/03
  • 進行再発胃癌におけるramucirumab投与前の尿中蛋白／クレアチニン比測定の意義  [Not invited]
    木村豊; 間狩洋一; 三上城太; 藤井千賀; 平木洋子; 加藤寛章; 岩間密; 白石治; 安田篤; 新海政幸; 今野元博; 今本治彦; 藤田淳也; 古河洋; 安田卓司
    第22回関西がんチーム医療研究会  2018/03
  • 臓器把持用クリップを活用した肥満患者に対する腹腔鏡下胃切除術の工夫．  [Not invited]
    木村 豊; 安田 篤; 加藤寛章; 岩間 密; 白石 治; 新海政幸; 今本治彦; 安田卓司
    第30回日本内視鏡外科学会総会  2017/12  京都
  • 高齢食道癌患者における術後肺炎と予後に関する検討．  [Not invited]
    木村 豊; 岩間 密; 白石 治; 平木洋子; 加藤寛章; 安田 篤; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第30回日本外科感染症学会総会  2017/11  東京
  • 胸部食道癌補助療法後の頸部郭清省略の選別の妥当性．  [Not invited]
    白石 治; 加藤寛章; 岩間 密; 平木洋子; 安田 篤; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第79回日本臨床外科学会総会  2017/11  東京
  • 胃切除術後症候群に対する膵酵素補充剤の有用性に関する検討．  [Not invited]
    木村 豊; 三上城太; 間狩洋一; 平木洋子; 加藤寛章; 岩間 密; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第79回日本臨床外科学会総会  2017/11  東京
  • 医師主導治験における食道亜全摘術評価の困難性．  [Not invited]
    宮崎安弘; 矢野雅彦; 安田卓司; 山崎 誠; 牧野知紀; 田中晃司; 宮田博志; 杉村啓二郎; 木村 豊; 黒川幸典; 高橋 剛; 森 正樹; 土岐祐一郎
    第79回日本臨床外科学会総会  2017/11  東京
  • 左側臥位食道切除術における安定した術野確保のための肺圧排固定器具の開発．  [Not invited]
    安田卓司; 白石 治; 岩間 密; 加藤寛章; 平木洋子; 安田 篤; 新海政幸; 今野元博; 木村 豊; 今本治彦
    第79回日本臨床外科学会総会  2017/11  東京
  • The effect of pancrelipase against diarrhea in patients after gastrectomy．  [Not invited]
    Kimura Y; Mikami J; Makari Y; Hiraki Y; Kato H; Iwama M; Shiraishi O; Yasuda A; Shinkai M; Imano M; Imamoto H; Fujita J; Yasuda T
    21st Asian Congress of Surgery  2017/11  東京
  • A newly modified esophagogastrostomy after proximal gastrectomy in our institution．  [Not invited]
    Yasuda A; Kimura Y; Hiraki Y; Kato H; Iwama M; Shiraishi O; Shinkai M; Imano M; Imamoto H; Yasuda T
    21st Asian Congress of Surgery  2017/11  東京
  • A Phase I/? Trial of Chemo-Radiotherapy for Resectable Type 4 or Large Type 3 Gastric Cancer．  [Not invited]
    Imano M; Furukawa H; Satoh T; Yasuda T
    日本放射線腫瘍学会 第30回学術大会 30th JASTRO  2017/11  大阪
  • Intramural Spread and Lymph Node Metastases Detected in the Mesorectum Distal to Carcinoma of the Rectum by the Clearing Method．  [Not invited]
    J Hida; H Ushijima; Y Yoshioka; K Daito; J Kawamura; K Ueda; T Tokoro; I Matsumoto; T Yasuda; K Okuno
    IASGO World Congress 2017  2017/11  フランス
  • 既治療に耐性の進行再発胃癌に対するramu-cirumab療法における蛋白尿に関する検討．  [Not invited]
    木村 豊; 間狩洋一; 三上城太; 平木洋子; 加藤寛章; 岩間 密; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 藤田淳也; 安田卓司
    第55回日本癌治療学会学術集会  2017/10  横浜
  • ｃT4食道癌の外科治療の限界と成績．  [Not invited]
    安田卓司; 白石 治; 岩間 密; 加藤寛章; 平木洋子; 安田 篤; 宮田博志; 新海政幸; 今野元博; 木村 豊; 矢野雅彦; 今本治彦
    第55回日本癌治療学会学術集会  2017/10  横浜
  • 食道癌特異的ペプチドワクチンの術後補助療法としての有用性と腫瘍微小環境との関連．  [Not invited]
    安田卓司; 錦 耕平; 白石 治; 岩間 密; 加藤寛章; 平木洋子; 安田 篤; 新海政幸; 今野元博; 木村 豊; 今本治彦; 奥野清隆; 中村祐輔
    第55回日本癌治療学会学術集会  2017/10  横浜
  • 良性潰瘍に対する胃切既往のある胸部食道癌における、腹部リンパ節転移状況の検討．  [Not invited]
    加藤寛章; 白石 治; 岩間 密; 平木洋子; 田中裕美子; 安田 篤; 新海政幸; 今野元博; 木村 豊; 今本治彦; 安田卓司
    第25回日本消化器関連学会週間（JDDW）  2017/10  福岡
  • 食道癌術後気管切開における甲状腺上アプローチの有用性．  [Not invited]
    安田卓司; 白石 治; 岩間 密; 加藤寛章; 平木洋子; 安田 篤; 新海政幸; 今野元博; 木村 豊; 今本治彦
    第25回日本消化器関連学会週間（JDDW）  2017/10  福岡
  • 進行再発胃癌に対するramucirumab使用例における蛋白尿の検討．  [Not invited]
    木村 豊; 間狩洋一; 三上城太; 平木洋子; 加藤寛章; 岩間 密; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 藤田淳也; 安田卓司
    第25回日本消化器関連学会週間（JDDW）  2017/10  福岡
  • 鏡視下手術の導入を考慮した当科における腹腔鏡補助下噴門側胃切除後食道残胃吻合法．  [Not invited]
    安田 篤; 木村 豊; 今本治彦; 平木洋子; 加藤寛章; 岩間 密; 白石 治; 新海政幸; 今野元博; 安田卓司
    近畿内視鏡外科研究会 第30回記念大会  2017/09  大阪
  • 高齢食道癌患者における術後の誤嚥・肺炎に関する検討．  [Not invited]
    木村 豊; 白石 治; 加藤寛章; 今本治彦; 安田卓司
    第70回日本胸部外科学会定期学術集会  2017/09  札幌
  • 高度進行胸部食道癌への外科的挑戦〜術前治療と拡大手術の意義と適応．  [Not invited]
    安田卓司; 白石 治; 加藤寛章; 宮田博志; 木村 豊; 矢野雅彦; 今本治彦
    第70回日本胸部外科学会定期学術集会  2017/09  札幌
  • 高齢食道癌患者における術後の誤嚥・肺炎に関する検討．  [Not invited]
    木村 豊; 白石 治; 加藤寛章; 今本治彦; 安田卓司
    第70回日本胸部外科学会定期学術集会  2017/09  札幌
  • 胸部食道癌に対する選択的3領域リンパ節郭清の妥当性．  [Not invited]
    白石 治; 加藤寛章; 木村 豊; 今本治彦; 安田卓司
    第70回日本胸部外科学会定期学術集会  2017/09  札幌
  • 進行食道癌に対する術前化学療法ランダム化比較試験FAP vs DCF（OGSG1003）におけるリンパ節微小転移制御効果．  [Not invited]
    平木洋子; 今野元博; 加藤寛章; 岩間 密; 白石 治; 安田 篤; 新海政幸; 木村 豊; 今本治彦; 安田卓司
    第26回日本がん転移学会学術集会・総会  2017/07  大阪
  • 高齢・胃切後胸部食道癌に対する嚥下機能温存と血行付加を考慮した新規縦隔横断胸骨後経路高位胸腔内吻合．  [Not invited]
    平木洋子; 白石 治; 岩間 密; 加藤寛章; 安田 篤; 新海政幸; 今野元博; 木村 豊; 今本治彦; 安田卓司
    第72回日本消化器外科学会  2017/07  石川
  • cT4 局所進行食道癌に対するSalvage 手術を前提とした導入化学放射線療法による治療戦略．  [Not invited]
    岩間 密; 白石 治; 加藤寛章; 平木洋子; 安田 篤; 新海政幸; 今野元博; 木村 豊; 今本治彦; 安田卓司
    第72回日本消化器外科学会  2017/07  石川
  • 胃切除術後早期の体重減少抑制を目指した取り組み．  [Not invited]
    木村 豊; 三上城太; 間狩洋一; 藤田淳也; 平木洋子; 安田 篤; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第72回日本消化器外科学会  2017/07  石川
  • 胃切既往のある胸部食道癌の腹部リンパ節転移の検討〜残胃全摘の省略は許容されるか〜．  [Not invited]
    加藤寛章; 白石 治; 岩間 密; 平木洋子; 安田 篤; 新海政幸; 今野元博; 木村 豊; 今本治彦; 安田卓司
    第72回日本消化器外科学会  2017/07  石川
  • 菱形残胃作成と食道裂孔挿入を付加した噴門側胃切除・食道残胃吻合法．  [Not invited]
    安田 篤; 新海政幸; 加藤寛章; 平木洋子; 岩間 密; 白石 治; 今野元博; 木村 豊; 今本治彦; 安田卓司
    第72回日本消化器外科学会  2017/07  石川
  • 安定した術野確保のための右肺圧排固定器具の開発と胸腔鏡拡大画像に基づく左側臥位縦隔リンパ節郭清手技．  [Not invited]
    安田卓司; 白石 治; 岩間 密; 加藤寛章; 平木洋子; 安田 篤; 新海政幸; 今野元博; 木村 豊; 今本治彦
    第72回日本消化器外科学会  2017/07  石川
  • リンパ節転移状況に基づく進行EGJ 腺癌に対するNAC+胸腹連続郭清．  [Not invited]
    白石 治; 平木洋子; 加藤寛章; 岩間 密; 安田 篤; 新海政幸; 木村 豊; 今野元博; 今本治彦; 安田卓司
    第72回日本消化器外科学会  2017/07  石川
  • CY(+) 進行胃癌に対するPTX 腹腔内投与+PCS 全身化学療法の有用性の検討．  [Not invited]
    新海政幸; 今野元博; 平木洋子; 加藤寛章; 岩間 密; 白石 治; 安田 篤; 木村 豊; 今本治彦; 安田卓司
    第72回日本消化器外科学会  2017/07  石川
  • 胸部食道癌における術後肺炎と縫合不全のリスク因子とその対策  [Not invited]
    白石 治; 錦 耕平; 岩間 密; 牧野知紀; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第69回日本消化器外科学会総会  2017/07  郡山
  • 食道癌術後の進行胃管癌に対して胃管分節切除術で切除できた1例．  [Not invited]
    幕谷悠介; 白石 治; 平木洋子; 田中裕美子; 加藤寛章; 岩間 密; 安田 篤; 新海政幸; 今野元博; 木村 豊; 今本治彦; 安田卓司
    第39回日本癌局所療法研究会  2017/06  京都
  • 巨大胃GISTに対して術前イマチニブ投与を行い、根治切除可能であった1例．  [Not invited]
    平木洋子; 加藤寛章; 安田 篤; 田中裕美子; 岩間 密; 白石 治; 新海政幸; 今野元博; 木村 豊; 今本治彦; 安田卓司
    第39回日本癌局所療法研究会  2017/06  京都
  • 集学的加療により咽頭温存とともにR0切除を得た胸部上部食道癌1切除例．  [Not invited]
    岩間 密; 白石 治; 加藤寛章; 平木洋子; 田中裕美子; 安田 篤; 新海政幸; 今野元博; 木村 豊; 今本治彦; 安田卓司
    第39回日本癌局所療法研究会  2017/06  京都
  • 食道入口部に及ぶ大型頸部食道癌に対し、喉頭温存手術を成し得た1例．  [Not invited]
    白石 治; 加藤寛章; 岩間 密; 平木洋子; 田中裕美子; 安田 篤; 新海政幸; 木村 豊; 今野元博; 今本治彦; 安田卓司
    第39回日本癌局所療法研究会  2017/06  京都
  • 胸部食道癌の術前化学療法にて腫瘍穿破寸前の状態に陥り、緊急手術を行った1例．  [Not invited]
    安田 篤; 木村 豊; 加藤寛章; 平木洋子; 田中裕美子; 岩間 密; 白石 治; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第39回日本癌局所療法研究会  2017/06  京都
  • 噴門部GISTに対する機能温存を配慮した腹腔鏡下胃内手術の有用性．  [Not invited]
    安田 篤; 木村 豊; 新海政幸; 平木洋子; 田中裕美子; 加藤寛章; 岩間 密; 白石 治; 今野元博; 今本治彦; 安田卓司
    第39回日本癌局所療法研究会  2017/06  京都
  • P0CY1胃癌に対するPTX腹腔内投与＋PCS3剤全身化学療法の治療成績．  [Not invited]
    新海政幸; 今野元博; 平木洋子; 加藤寛章; 岩間 密; 白石 治; 安田 篤; 今本治彦; 木村 豊; 古河 洋; 安田卓司
    第39回日本癌局所療法研究会  2017/06  京都
  • paclitaxel＋ramcirumab療法によりgrade3の蛋白尿をきたした再発胃癌の1例．  [Not invited]
    木村 豊; 間狩洋一; 三上城太; 平木洋子; 田中裕美子; 加藤寛章; 岩間 密; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 藤田淳也; 安田卓司
    第39回日本癌局所療法研究会  2017/06  京都
  • 内視鏡生検でがん細胞が検出できなかったスキルス胃癌の切除例．  [Not invited]
    古河 洋; 中室 誠; 中野博史; 近藤禎晃; 石川和男; 大久保遊平; 今野元博; 木村 豊; 安田卓司
    第39回日本癌局所療法研究会  2017/06  京都
  • 胃癌手術既往のある異時性重複食道癌における、腹腔内リンパ節転移の検討〜残胃温存は許容されるか？〜．  [Not invited]
    加藤寛章; 白石 治; 岩間 密; 平木洋子; 田中裕美子; 安田 篤; 新海政幸; 今野元博; 木村 豊; 今本治彦; 安田卓司
    第60回関西胸部外科学会学術集会  2017/06  大阪
  • 高齢者食道癌手術の対策と現状．  [Not invited]
    白石 治; 加藤寛章; 岩間 密; 平木洋子; 田中裕美子; 安田 篤; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第60回関西胸部外科学会学術集会  2017/06  大阪
  • 胃切除後の食道癌患者に対する新しい術式〜縦隔横断胸骨後経路高位胸腔内吻合〜．  [Not invited]
    木村 豊; 白石 治; 平木洋子; 岩間 密; 加藤寛章; 田中裕美子; 安田 篤; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第60回関西胸部外科学会学術集会  2017/06  大阪
  • Cancer peptide vaccine to suppress postoperative recurrence in esophageal SCC patients with induction of antigen-specific CD8+ T cell.  [Not invited]
    Yasuda T; Nishiki K; Yoshida K; Shiraishi O; Iwama M; Kato H; YasudaA; Shinkai M; Chiba Y; Okuno K; Nakamura Y
    ASCO2017  2017/06  シカゴ
  • 胃癌，頭頸部癌との重複食道癌に対する治療戦略．  [Not invited]
    加藤寛章; 白石 治; 岩間 密; 平木洋子; 安田 篤; 新海政幸; 今野元博; 木村 豊; 今本治彦; 安田卓司
    第71回日本食道学会学術集会  2017/06  軽井沢
  • 当科におけるSalvage手術の安全性と有効性に関する検討．  [Not invited]
    岩間 密; 白石 治; 加藤寛章; 平木洋子; 安田 篤; 新海政幸; 今野元博; 木村 豊; 今本治彦; 安田卓司
    第71回日本食道学会学術集会  2017/06  軽井沢
  • Survival and Quality of Life after Pelvic Exenteration for Locally aAdvanced Colorectal Cancer.  [Not invited]
    J Hida; Yoshioka; H Ushijima, Y; K Daito; J Kawamura; K Ueda; T Tokoro; I Matsumoto; T Yasuda; K Okuno
    52nd International Meeting of the European Society for Surgical Research (|ESSR)  2017/06  オランダ
  • 切除可能進行食道癌に対する術前DCF vs ACF療法多施設ランダム化比較第?相試験．  [Not invited]
    白石 治; 山崎 誠; 本告正明; 宮田博志; 牧野知紀; 木村 豊; 平尾素宏; 矢野雅彦; 土岐祐一郎; 安田卓司
    第71回日本食道学会学術集会  2017/06  軽井沢
  • 高齢食道癌患者に対する手術における誤嚥，肺炎の発症の低減を目指した治療選択．  [Not invited]
    木村 豊; 白石 治; 岩間 密; 加藤寛章; 平木洋子; 安田 篤; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第71回日本食道学会学術集会  2017/06  軽井沢
  • 食道癌RO切除困難症例への挑戦．  [Not invited]
    安田卓司; 白石 治; 岩間 密; 加藤寛章; 平木洋子; 田中裕美子; 安田 篤; 新海政幸; 今野元博; 木村 豊; 今本治彦
    第71回手術手技研究会  2017/05  名古屋
  • 頸部食道癌術後2年目発症の気管食道瘻に対し、遊離前腕皮弁による瘻孔閉鎖・気管孔再形成が有用であった1例．  [Not invited]
    加藤寛章; 白石 治; 岩間 密; 平木洋子; 田中裕美子; 安田 篤; 新海政幸; 今野元博; 木村 豊; 今本治彦; 安田卓司
    第71回手術手技研究会  2017/05  名古屋
  • 食道癌手術において捻転イレウスを回避できる腹腔鏡下空腸瘻増設術．  [Not invited]
    白石 治; 加藤寛章; 岩間 密; 平木洋子; 田中裕美子; 安田 篤; 新海政幸; 木村 豊; 今野元博; 今本治彦; 安田卓司
    第71回手術手技研究会  2017/05  名古屋
  • 胃切除術の既往のある高齢胸部食道癌患者に対する縦隔横断胸骨後経路高位胸腔内吻合．  [Not invited]
    木村 豊; 白石 治; 平木洋子; 岩間 密; 加藤寛章; 田中裕美子; 安田 篤; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第71回手術手技研究会  2017/05  名古屋
  • 胸部食道癌根治術後再発とその治療戦略―再び根治を目指して―．  [Not invited]
    加藤寛章; 白石 治; 岩間 密; 平木洋子; 田中裕美子; 安田 篤; 新海政幸; 今野元博; 木村 豊; 今本治彦; 安田卓司
    第117回日本外科学会定期学術集会  2017/04  横浜
  • 噴門側胃切除・食道残胃吻合における食道胃逆流防止の工夫．  [Not invited]
    安田 篤; 平木洋子; 田中裕美子; 加藤寛章; 岩間 密; 白石 治; 新海政幸; 今野元博; 今本治彦; 木村 豊; 古河 洋; 安田卓司; 奥野清隆
    第117回日本外科学会定期学術集会  2017/04  横浜
  • 腹腔鏡下にD2郭清を伴う腹腔鏡下胃切除術を安全に行うための工夫．  [Not invited]
    木村 豊; 三上城太; 間狩洋一; 藤田淳也; 平木洋子; 田中裕美子; 加藤寛章; 岩間 密; 白石 治; 安田 篤; 新海政幸; 今野元博; 古河 洋; 今本治彦; 安田卓司
    第117回日本外科学会定期学術集会  2017/04  横浜
  • 胸部食道癌手術における頸部郭清の合理化は可能か―Standard or Selective―．  [Not invited]
    安田卓司; 白石 治; 岩間 密; 加藤寛章; 平木洋子; 田中裕美子; 安田 篤; 新海政幸; 今野元博; 木村 豊; 今本治彦
    第117回日本外科学会定期学術集会  2017/04  横浜
  • 安全性を目指した胸部食道癌手術における再建術の工夫．  [Not invited]
    岩間 密; 加藤寛章; 白石 治; 平木洋子; 田中裕美子; 安田 篤; 新海政幸; 今野元博; 木村 豊; 今本治彦; 安田卓司
    第117回日本外科学会定期学術集会  2017/04  横浜
  • 切除可能進行胃癌に対する術前TS-1＋Cisplatin＋Paclitaxel併用療法（PCS療法）．  [Not invited]
    新海政幸; 今野元博; 平木洋子; 田中裕美子; 加藤寛章; 岩間 密; 白石 治; 安田 篤; 木村 豊; 今本治彦; 安田卓司
    第117回日本外科学会定期学術集会  2017/04  横浜
  • A study about gastric tube cancer after radical esophagectomy for thoracic esophageal cancer． 胸部食道癌術後胃管癌に関する検討．  [Not invited]
    岩間 密; 白石 治; 加藤寛章; 平木洋子; 田中裕美子; 安田 篤; 新海政幸; 今野元博; 木村 豊; 今本治彦; 安田卓司
    第89回日本胃癌学会総会  2017/03  広島
  • Feasibility of neoadjuvant chemoradiation therapy for resectable advanced gastric cancer． 根治切除可能な大型3型／4型胃癌に対する術前化学放射線療法の実現可能性．  [Not invited]
    白石 治; 田中裕美子; 加藤寛章; 岩間 密; 安田 篤; 新海政幸; 木村 豊; 今野元博; 今本治彦; 古河 洋; 塩? 均; 安田卓司
    第89回日本胃癌学会総会  2017/03  広島
  • Examination of Pylorus Preserving Gastrectomy in our institution． 当科での幽門保存胃切除術の検討．  [Not invited]
    安田 篤; 平木洋子; 田中裕美子; 加藤寛章; 岩間 密; 白石 治; 新海政幸; 古河 洋; 今野元博; 木村 豊; 今本治彦; 安田卓司; 奥野清隆
    第89回日本胃癌学会総会  2017/03  広島
  • The examination of factors affecting body weight loss in patients after total gastrectomy． 胃全摘術後早期の体重減少に影響を及ぼす因子に関する検討．  [Not invited]
    木村 豊; 三上城太; 間狩洋一; 藤田淳也; 平木洋子; 加藤寛章; 岩間 密; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第89回日本胃癌学会総会  2017/03  広島
  • Neoadjuvant combination chemotherapy with S-1, CDDP and PTX for resectable advanced gastric cancer． 切除可能進行胃癌に対する術前PCS療法．  [Not invited]
    新海政幸; 今野元博; 平木洋子; 田中裕美子; 加藤寛章; 岩間 密; 白石 治; 安田 篤; 木村 豊; 今本治彦; 安田卓司
    第89回日本胃癌学会総会  2017/03  広島
  • Phase ? study of ip paclitaxel plus S-1/iv paclitaxel in GC pts．with positive peritoneal cytology． 腹腔内洗浄細胞診陽性症例に対するパクリタキセル腹腔内投与＋S-1／パクリタキセル静脈投与法の第?相臨床試験．  [Not invited]
    今野元博; 石神浩徳; 梨本 篤; 藪崎 裕; 今本治彦; 山下裕玄; 岸健太郎; 小寺泰弘; 上之園芳一; 藤原義之; 秀村晃生; 田村茂行; 福島亮治; 山口博紀; 北山丈二
    第89回日本胃癌学会総会  2017/03  広島
  • 内視鏡的に止血困難な出血性進行胃癌に対する血管塞栓術に関する検討．  [Not invited]
    平木洋子; 木村 豊; 藤田淳也; 安田卓司
    日本消化器病学会近畿支部第106回例会  2017/02  大阪
  • 症例頃のリスク軽減の工夫による根治的リンパ節郭清を共な食道癌外科治療戦略．  [Not invited]
    安田卓司; 白石 治; 岩間 密; 加藤寛章; 田中裕美子; 平木洋子; 安田 篤; 新海政幸; 今野元博; 木村 豊; 今本治彦
    第78回日本臨床外科学会総会  2016/11  東京
  • 75歳以上の根治切除可能な4型・大型3型胃癌に対する術前化学放射線療法の試み．  [Not invited]
    曽我部俊介; 田中裕美子; 岩間 密; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第116回日本外科学会  2016  大阪
  • 胃癌術後5年目に発症した脾転移の1切除例．  [Not invited]
    田中裕美子; 平木洋子; 加藤寛章; 岩間 密; 白石 治; 安田 篤; 新海政幸; 木村 豊; 今野元博; 今本治彦; 安田卓司
    第78回日本臨床外科学会総会  2016  東京
  • 高齢者幽門側胃切除後の呼吸器合併症に対する嚥下リハビリ介入の効果に対する検討．  [Not invited]
    田中裕美子; 安田 篤; 加藤寛章; 岩間 密; 白石 治; 新海政幸; 木村 豊; 今野元博; 今本治彦; 安田卓司
    第46回胃外科・術後障害研究会  2016  鳥取
  • Barrett 食道癌と乳頭部癌に対し一期的切除をしえた同時性重複癌の1 例．  [Not invited]
    田中裕美子; 曽我部俊介; 加藤寛章; 岩間 密; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第71 回日本消化器外科学会総会  2016  徳島
  • 腹臥位での重力差とCT値による客観評価での新しい進行食道癌大動脈浸潤評価の有用性．  [Not invited]
    田中裕美子; 白石 治; 熊野正士; 曽我部俊介; 岩間 密; 安田 篤; 新海政幸; 今野元博; 今本治彦; 村上卓道; 安田卓司
    第70回日本食道学会学術集会  2016  東京
  • 仰臥位と腹臥位CTにおける重力差とCT値による客観評価を用いた新しい進行食道癌大動脈浸潤の評価の有用性．  [Not invited]
    田中裕美子; 白石 治; 熊野正士; 曽我部俊介; 岩間 密; 安田 篤; 新海政幸; 今野元博; 今本治彦; 村上卓道; 安田卓司
    第116回日本外科学会  2016  大阪
  • 輪状咽頭筋切開による咽頭温存食道切除・高位吻合の有用性．  [Not invited]
    加藤寛章; 田中裕美子; 岩間 密; 白石 治; 安田 篤; 新海政幸; 木村 豊; 今野元博; 今本治彦; 安田卓司
    第78回日本臨床外科学会総会  2016  東京
  • 当科における噴門側胃切除後食道残胃吻合（菱形残胃作成と食道裂孔挿入の意義）．  [Not invited]
    加藤寛章; 安田 篤; 田中裕美子; 岩間 密; 白石 治; 新海政幸; 木村 豊; 今野元博; 今本治彦; 安田卓司
    第46回胃外科・術後障害研究会  2016  鳥取
  • 食道切除後胃管再建術-縫合不全ゼロの追求-．  [Not invited]
    加藤寛章; 曽我部俊介; 田中裕美子; 岩間 密; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第71 回日本消化器外科学会総会  2016  徳島
  • 胸部食道癌手術における術後合併症予防の工夫．  [Not invited]
    岩間 密; 田中裕美子; 加藤寛章; 白石 治; 安田 篤; 新海政幸; 木村 豊; 今野元博; 今本治彦; 安田卓司
    第78回日本臨床外科学会総会  2016  東京
  • 胸部食道癌手術における術後合併症の予防策に関する検討．  [Not invited]
    岩間 密; 曽我部俊介; 田中裕美子; 加藤寛章; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第71回日本消化器外科学会総会  2016  徳島
  • サルベージ手術を前提とした導入化学放射線療法によるcT4局所進行食道癌治療戦略．  [Not invited]
    岩間 密; 曽我部俊介; 田中裕美子; 加藤寛章; 白石治; 安田篤; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第70回日本食道学会学術集会  2016  東京
  • 胸部食道癌における鎖骨上リンパ節転移の意義〜遠隔転移 or 領域内転移？  [Not invited]
    岩間 密; 曽我部俊介; 田中裕美子; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第116回日本外科学会  2016  大阪
  • 当院の胃切除後における食道切除後有茎空腸再建術の工夫．  [Not invited]
    白石 治; 田中裕美子; 加藤寛章; 岩間 密; 安田 篤; 新海政幸; 木村 豊; 今野元博; 今本治彦; 安田卓司
    第78回日本臨床外科学会総会  2016  東京
  • 高齢者胸部食道癌手術におけるリスク因子と対策．  [Not invited]
    白石 治; 田中裕美子; 加藤寛章; 岩間 密; 安田 篤; 新海政幸; 木村 豊; 今野元博; 今本治彦; 安田卓司
    第68回日本気管食道科学会  2016  東京
  • 局所進行食道癌に対する集学的治療の至適切除時期．  [Not invited]
    白石 治; 加藤寛章; 木村 豊; 今本治彦; 安田卓司
    第69回日本胸部外科学会定期学術集会  2016  岡山
  • 食道切除後の胃再建不能例における血管吻合を付加する挙上空腸再．  [Not invited]
    白石 治; 曽我部俊介; 加藤寛章; 岩間 密; 安田 篤; 新海政幸; 今野元博; 今本治彦; 奥野清隆; 安田卓司
    第71回日本消化器外科学会総会  2016  徳島
  • リンパ節転移状況に基づく至適郭清範囲“中下縦隔から腹腔動脈周囲までの連続的郭清”．  [Not invited]
    白石 治; 曽我部俊介; 田中裕美子; 加藤寛章; 岩間密; 安田篤; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第70回日本食道学会学術集会  2016  東京
  • 食道胃接合部癌のリンパ節転移・再発状況に基づく治療戦略及び中下縦隔から腹腔動脈周囲までの連続的郭清．  [Not invited]
    白石 治; 田中裕美子; 曽我部俊介; 岩間 密; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 塩? 均; 安田卓司
    第116回日本外科学会  2016  大阪
  • 噴門胃切除後の菱形残胃作成と偽穹窿部食道裂孔挿入による食道残胃吻合法．  [Not invited]
    安田 篤; 今本治彦; 田中裕美子; 加藤寛章; 岩間 密; 白石 治; 新海政幸; 木村 豊; 今野元博; 古河 洋; 安田卓司; 奥野清隆
    第29回日本内視鏡外科学会総会  2016  横浜
  • 高齢者に対する腹腔鏡補助下幽門側胃切除後の検討．  [Not invited]
    安田 篤; 今本治彦; 田中裕美子; 加藤寛章; 岩間 密; 白石 治; 新海政幸; 木村 豊; 今野元博; 安田卓司
    第46回胃外科・術後障害研究会  2016  鳥取
  • 当院におけるGIST に対する腹腔鏡手術の検討．  [Not invited]
    安田 篤; 今本治彦; 加藤寛章; 岩間 密; 白石 治; 新海政幸; 今野元博; 古河 洋; 安田卓司; 奥野清隆
    第71 回日本消化器外科学会総会  2016  徳島
  • 胃噴門側GISTに対する腹腔鏡下胃内手術．  [Not invited]
    安田 篤; 今本治彦; 曽我部俊介; 田中裕美子; 岩間 密; 白石 治; 新海政幸; 今野元博; 古河 洋; 安田卓司; 奥野清隆
    第116回日本外科学会  2016  大阪
  • 噴門側胃切除後の食道残胃吻合法（円錐状胃管作成＋食道裂孔挿入法）．  [Not invited]
    安田 篤; 今本治彦; 曽我部俊介; 田中裕美子; 岩間 密; 白石 治; 新海政幸; 今野元博; 古河 洋; 安田卓司; 奥野清隆
    第88回日本胃癌学会総会  2016  大分
  • 胃全摘後の栄養評価；CT画像による脂肪量と筋量の経時変化について．  [Not invited]
    安田 篤; 曽我部俊介; 田中裕美子; 岩間 密; 白石 治; 新海政幸; 今野元博; 古河 洋; 今本治彦; 安田卓司; 奥野清隆
    第88回日本胃癌学会総会  2016  大分
  • CY1胃癌に対するPTX腹腔内投与＋PCS全身化学療法の治療成績．  [Not invited]
    新海政幸; 今野元博; 平木洋子; 加藤寛章; 岩間密; 白石治; 安田篤; 木村豊; 今本治彦; 古河洋; 安田卓司
    第78回日本臨床外科学総会  2016  東京
  • 高度進行胃癌に対する放射線化学療法を用いた集学的治療．  [Not invited]
    新海政幸; 今野元博; 曽我部俊介; 田中裕美子; 加藤寛章; 岩間密; 安田篤; 今本治彦; 古河洋; 安田卓司
    第71回日本消化器外科学会総会  2016  徳島
  • 胸部食道癌根治術後における再発の現状と再発例に対する治療戦略．  [Not invited]
    新海政幸; 曽我部俊介; 田中裕美子; 加藤寛章; 岩間密; 白石治; 安田篤; 今野元博; 今本治彦; 安田卓司
    第70回日本食道学会学術集会  2016  東京
  • Ｐ１進行胃癌に対するPTX腹腔内投与＋PCS全身化学療法の治療成績．  [Not invited]
    新海政幸; 今野元博; 田中裕美子; 曽我部俊介; 岩間密; 白石治; 安田篤; 今本治彦; 古河洋; 安田卓司
    第88回日本胃癌学会総会  2016  大分
  • 腹腔鏡下胃切除術において出血を減少させるための工夫．  [Not invited]
    木村 豊; 三上城太; 間狩洋一; 藤田淳也; 平木洋子; 田中裕美子; 加藤寛章; 岩間 密; 白石 治; 安田 篤; 彭 英峰; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第29回日本内視鏡外科学会総会  2016  横浜
  • 当院における腹腔鏡下胃切除術の工夫―臓器把持用クリップの活用―．  [Not invited]
    木村 豊; 三上城太; 間狩洋一; 藤田淳也; 平木洋子; 田中裕美子; 加藤寛章; 岩間 密; 白石 治; 安田 篤; 新海政幸; 今野元博; 古河 洋; 今本治彦; 安田卓司
    第78回日本臨床外科学会総会  2016  東京
  • 進行再発胃癌に対するpaclitaxel+ramcirumab療法の検討．  [Not invited]
    木村豊; 間狩洋一; 三上城太; 藤田淳也; 神垣俊二; 池島あゆみ; 藤井千賀; 辻江正樹; 大里浩樹; 今本治彦; 安田卓司
    第54回日本癌治療学会学術集会  2016  横浜
  • 狭窄を伴う下咽頭癌術後の早期食道癌に対して経胃的逆行性にESDを施行した1例．  [Not invited]
    木村 豊; 黒野由莉; 三上城太; 天野浩司; 間狩洋一; 中田 健; 光藤大地; 北村信次; 山本為義; 辻江正樹; 大里浩樹; 安田卓司
    第70日本食道学会学術集会  2016  東京
  • 高度進行食道癌に対する至適集学的治療〜成績向上のための戦略と課題．  [Not invited]
    安田卓司; 白石 治; 加藤寛章; 木村 豊; 今本治彦
    第69回日本胸部外科学会定期学術集会  2016  岡山
  • 前治療後手術のpN(+)食道扁平上皮癌に対する術後補助ペプチドワクチン第２相試験．  [Not invited]
    安田卓司; 錦 耕平; 白石 治; 岩間 密; 加藤寛章; 田中裕美子; 安田 篤; 新海政幸; 今野元博; 今本治彦
    第70回日本食道学会学術集会  2016  東京
  • 切除可能進行食道癌に対する術前化学療法のランダム化比較試験（OGSG1003）．  [Not invited]
    杉村啓二郎; 宮田博志; 矢野雅彦; 山崎 誠; 牧野知紀; 安田卓司; 白石 治; 平尾素宏; 西川和宏; 山本和義; 藤谷和正; 本居正明; 森 正樹; 土岐祐一郎
    第116回日本外科学会  2016  大阪
  • Salvage縦隔気管瘻手術における気管血流温存と根治CRT後の気管食道瘻手術における術式の工夫．  [Not invited]
    安田卓司; 白石 治; 岩間 密; 曽我部俊介; 田中裕美子; 安田 篤; 新海政幸; 今野元博; 今本治彦
    第116回日本外科学会  2016  大阪
  • 腹腔鏡下造設空腸瘻のイレウス対策“カーテン法”．  [Not invited]
    白石 治; 田中裕美子; 曽我部俊介; 岩間 密; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第28回日本内視鏡外科学会  2015/12  大阪
  • 腹腔鏡補助下手術での噴門側胃切除・食道残胃吻合再建（胃管様作成＋食道裂孔挿入）．  [Not invited]
    安田 篤; 今本治彦; 曽我部俊介; 田中裕美子; 加藤寛章; 岩間 密; 白石 治; 新海政幸; 今野元博; 古河 洋; 安田卓司; 奥野清隆
    第28回日本内視鏡外科学会総会  2015/12  大阪
  • 食道癌術後再発に対する治療戦略．  [Not invited]
    曽我部俊介; 白石 治; 田中裕美子; 岩間 密; 安田 篤; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第77回日本臨床外科学会総会  2015/11  福岡
  • 胃癌腹膜播種症例におけるPTX単回腹腔内投与とTS-1+PTX+CDDPによる逐次全身化学療法の安全性と効果における検討．  [Not invited]
    田中裕美子; 今野元博; 曽我部俊介; 岩間 密; 白石 治; 安田 篤; 新海政幸; 今本治彦; 安田卓司
    第77回日本臨床外科学会総会  2015/11  福岡
  • 縫合不全0を目指した食道癌切除後再建法．  [Not invited]
    岩間 密; 曽我部俊介; 田中裕美子; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第77回日本臨床外科学会  2015/11  福岡
  • 縫合不全1％の食道癌術切除後胃管再建．  [Not invited]
    白石 治; 田中裕美子; 曽我部俊介; 岩間 密; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第77回日本臨床外科学会  2015/11  博多
  • 嚥下リハビリ介入の効果について臨床外科学会総会高齢者幽門側胃切除術後の呼吸器合併症に対する嚥下リハビリ介入の効果について．  [Not invited]
    安田 篤; 今本治彦; 曽我部俊介; 田中裕美子; 加藤寛章; 岩間 密; 白石 治; 新海政幸; 今野元博; 古河 洋; 安田卓司; 奥野清隆
    第77回日本臨床外科学会総会  2015/11  福岡
  • 大型3型、4型胃癌に対する放射線化学療法後の開腹手術の留意点．  [Not invited]
    新海政幸; 古河洋; 田中裕美子; 曽我部俊介; 岩間 密; 白石 治; 安田 篤; 今野元博; 今本治彦; 奥野清隆; 安田卓司
    第77回日本臨床外科学会総会  2015/11  福岡
  • 胃癌腹膜播種症例に対する外科的介入の意義．  [Not invited]
    今野元博; 岩間 密; 田中裕美子; 曽我部俊介; 白石 治; 安田 篤; 新海政幸; 今本治彦; 古河 洋; 安田卓司; 光冨徹哉; 竹山宜典; 奥野清隆
    第77回日本臨床外科学会総会  2015/11  福岡
  • 食道癌手術におけるoncologyに基づいた徹底覚醒と低侵襲手術の融合．  [Not invited]
    安田卓司; 白石 治; 岩間 密; 錦 耕平; 曽我部俊介; 田中由美子; 安田 篤; 新海政幸; 今野元博; 古河 洋; 今本治彦
    第77回日本臨床外科学会総会  2015/11  福岡
  • 進行胸部食道癌に対するPET診断に基づくNAC個別化選別と予後予測．  [Not invited]
    白石 治; 田中裕美子; 曽我部俊介; 岩間 密; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第68回日本胸部外科学会  2015/10  神戸
  • T4食道癌に対する根治的化学放射線療法後の積極的Salvage手術治療戦略  [Not invited]
    白石 治; 田中裕美子; 曽我部俊介; 岩間 密; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第23回JDDW  2015/10  東京
  • The choice of reconstruction route after esophagectomy.  [Not invited]
    安田卓司
    第68回日本胸部外科学会定期学術集会  2015/10  神戸
  • 局所と遠隔制御のバランスからみた進行食道癌に対する個別化治療戦略．  [Not invited]
    安田卓司
    第13回日本消化器外科学会大会  2015/10  東京
  • 頸部食道癌根治放射線治療後に喉頭温存をなし得た1切除例．  [Not invited]
    眞鍋弘暢; 岩間 密; 曽我部俊介; 田中裕美子; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    南大阪消化器外科懇談会  2015/09  大阪
  • 小開腹先行腹腔鏡補助下胃切除再建の有用性．  [Not invited]
    安田 篤; 今本治彦; 岩間 密; 白石 治; 新海政幸; 今野元博; 古河 洋; 安田卓司
    第28回日本小切開・鏡視外科学会  2015/09  福岡
  • 当科での胃体上部癌における腹腔鏡補助下噴門側胃切除と腹腔鏡補助下胃全摘術の比較検討．  [Not invited]
    今本治彦; 岩間 密; 白石 治; 新海政幸; 今野元博; 古河 洋; 安田卓司; 奥野清隆
    第28回近畿内視鏡外科研究会  2015/09  和歌山
  • 腐食性食道炎による頸部食道狭窄に対し、狭窄部切開・遊離空腸パッチ術を施行した１例．  [Not invited]
    曽我部俊介; 白石 治; 岩間 密; 錦 耕平; 田中裕美子; 安田 篤; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第69回日本食道学会学術集会  2015/07  横浜
  • Techniques and outcomes of the retrosternal gastric tube reconstruction after esophagectomy using the narrow gastric tube.  [Not invited]
    田中裕美子; 白石 治; 曽我部俊介; 岩間 密; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第70回日本消化器外科学会総会  2015/07  浜松
  • 胃癌腹膜播種に対し術前化学療法施行後根治手術をしえたが、術後8ヶ月目に脳転移・髄膜癌腫症をきたした1例．  [Not invited]
    田中裕美子; 曽我部俊介; 岩間 密; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第37回癌局所療法研究  2015/07  千葉
  • 腹臥位CTにおける腫瘍-大動脈間のCT値測定による進行食道癌大動脈浸潤の評価の有用性．  [Not invited]
    田中裕美子; 白石 治; 曽我部俊介; 岩間 密; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第69回日本食道学会学術集会  2015/07  横浜
  • 胃癌腹膜播種症例に対するPTX単回腹腔内投与およびTS-1+PTX+CDDPによる逐次全身化学療法の試み．  [Not invited]
    岩間 密; 今野元博; 白石 治; 安田 篤; 新海政幸; 今本治彦; 古河 洋; 安田卓司
    第70回日本消化器外科学会総会  2015/07  浜松
  • 胸部食道癌におけるFDG-PETによるpN予測、術前化学療法の適応とその効果予測．  [Not invited]
    岩間 密; 曽我部俊介; 田中裕美子; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第69回日本食道学会学術集会  2015/07  横浜
  • 縫合不全を回避する胃管再建の工夫と反回神経リンパ節郭清．  [Not invited]
    白石 治; 田中裕美子; 曽我部俊介; 岩間 密; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第70回日本消化器外科学会総会  2015/07  浜松
  • 縫合不全を回避する胃管再建の要点．  [Not invited]
    白石 治; 田中裕美子; 曽我部俊介; 岩間 密; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第69回日本食道学会学術集会  2015/07  横浜
  • 頸部食道癌の導入CRTによる治療戦略．  [Not invited]
    白石 治; 田中裕美子; 曽我部俊介; 岩間 密; 安田篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第69回日本食道学会学術集会  2015/07  横浜
  • 胃体上部早期癌に対する腹腔鏡補助下噴門側胃切除と胃全摘の比較検討．  [Not invited]
    安田 篤; 今本治彦; 里井俊平; 田中裕美子; 曽我部俊介; 岩間 密; 白石 治; 新海政幸; 今野元博; 古河 洋; 竹山宜典; 安田 卓司
    第70回日本消化器外科学会総会  2015/07  浜松
  • 高度進行胃癌に対する術前放射線化学療法．  [Not invited]
    新海政幸; 今野元博; 古河 洋; 安田 篤; 横川正樹; 西村恭昌; 黒川幸典; 辻中利政; 今本治彦; 安田卓司
    第70回日本消化器外科学会総会  2015/07  浜松
  • 頸部食道癌CRT後再々発に対し咽喉食摘、縦隔気管瘻造設(Grillo)を施行した1例．  [Not invited]
    新海政幸; 田中裕美子; 曽我部俊介; 錦 耕平; 岩間 密; 白石 治; 安田 篤; 今野元博; 今本治彦; 安田卓司
    第69回日本食道学会学術集会  2015/07  横浜
  • 食道癌サルベージ手術における安全性の確立とcT4に対する新たな治療戦略．  [Not invited]
    新海政幸; 田中裕美子; 曽我部俊介; 錦 耕平; 岩間 密; 白石 治; 安田 篤; 石川一樹; 西村恭昌; 安田卓司
    第69回日本食道学会学術集会  2015/07  横浜
  • 胃癌腹膜播種症例に対する外科的介入を併用した治療戦略の検討．  [Not invited]
    今野元博; 岩間 密; 白石 治; 安田 篤; 新海政幸; 今本治彦; 古河 洋; 安田卓司; 竹山宜典; 奥野清隆
    第70回日本消化器外科学会総会  2015/07  浜松
  • Oncology、外科的画像読影、確かな治療戦略に裏付けられた食道手術手技の伝承と教育．  [Not invited]
    安田卓司; 白石 治; 岩間 密; 錦 耕平; 曽我部俊介; 田中由美子; 安田 篤; 新海政幸; 今野元博; 今本治彦
    第58回関西胸部外科学会学術集会  2015/06  岡山
  • NearT4食道癌に対する50Gy以上の根治的化学放射線療法後の積極的Salvage手術治療戦略．  [Not invited]
    白石 治; 錦 耕平; 岩間 密; 牧野知紀; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 塩? 均; 奥野清隆; 安田卓司
    第115回日本外科学会定期学術集会  2015/04  名古屋
  • 放射線化学療法後の開腹胃切除における手術手技の工夫．  [Not invited]
    新海政幸; 古河 洋; 田中裕美子; 曽我部俊介; 錦 耕平; 牧野知紀; 岩間 密; 白石 治; 安田 篤; 今野元博; 今本治彦; 奥野清隆; 安田卓司
    第115回日本外科学会定期学術集会  2015/04  名古屋
  • 根治切除可能な漿膜浸潤を伴う胃癌に対する周術期化学療法（TS-1、パクリタキセル経静脈・腹腔内投与併用療法） 第?相試験．  [Not invited]
    今野元博; 石神浩徳; 藪崎 裕; 小林大介; 伊藤誠二; 上之園芳一; 上田修吾; 木村 豊; 山口博紀; 今本治彦; 梨本 篤; 古河 洋; 安田卓司; 竹吉 泉; 福島亮治; 小寺泰弘; 北山丈二
    第115回日本外科学会定期学術集会  2015/04  名古屋
  • 術前化学放射線療法にてpCRを得た大型3型胃癌の1切除例．  [Not invited]
    錦 耕平; 田中裕美子; 岩間 密; 曽我部俊介; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第87回日本胃癌学会総会  2015/03  広島
  • 残胃癌の治療戦略．  [Not invited]
    岩間 密; 曽我部俊介; 錦 耕平; 白石 治; 安田 篤; 新海政幸; 今本治彦; 古河洋; 安田卓司
    第87回日本胃癌学会総会  2015/03  広島
  • 食道胃接合部癌のリンパ節転移状況から導かれる治療方針．  [Not invited]
    白石 治; 田中裕美子; 曽我部俊介; 岩間 密; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 塩崎 均; 安田卓司
    第87回日本胃癌学会総会  2015/03  広島
  • 進行食道胃接合部癌に対する中下縦隔から腹腔動脈周囲までの連続的郭清．  [Not invited]
    白石 治; 田中裕美子; 曽我部俊介; 岩間 密; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 塩崎 均; 安田卓司
    第87回日本胃癌学会総会  2015/03  広島
  • 噴門側胃切除術の術後機能評価 当科における噴門側胃切除後食道残胃吻合の有用性について．  [Not invited]
    安田 篤; 今本治彦; 曽我部俊介; 錦 耕平; 岩間 密; 白石 治; 新海政幸; 今野元博; 古河 洋; 塩? 均; 安田卓司
    第87回日本胃癌学会総会  2015/03  広島
  • 腹腔鏡下噴門側胃切除術の再建手技 当科における腹腔鏡補助下噴門側胃切除・食道残胃吻合法について．  [Not invited]
    安田 篤; 今本治彦; 曽我部俊介; 錦 耕平; 岩間 密; 白石 治; 新海政幸; 今野元博; 古河 洋; 塩? 均; 安田卓司
    第87回日本胃癌学会総会  2015/03  広島
  • P1進行胃癌に対する集学的治療とその成績．  [Not invited]
    新海政幸; 今野元博; 田中裕美子; 曽我部俊介; 錦 耕平; 牧野知紀; 岩間 密; 白石 治; 安田 篤; 今本治彦; 古河 洋; 安田卓司
    第87回日本胃癌学会総会  2015/03  広島
  • 食道癌 診断・治療ガイドライン．  [Not invited]
    白石 治; 田中裕美子; 曽我部俊介; 岩間 密; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 塩崎 均; 安田卓司
    第16回関西がんチーム医療研究会  2015/02  大阪
  • 進行食道癌に対する個別化集学的治療．  [Not invited]
    白石 治; 田中裕美子; 曽我部俊介; 岩間 密; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 塩崎 均; 安田卓司
    第102回日本消化器病学会近畿支部  2015/02  京都
  • 胃癌腹膜播種に対し術前化学療法施行後根治手術をしえたが、術後8ヶ月目に脳転移・髄膜癌腫症をきたした1例．  [Not invited]
    田中裕美子; 曽我部俊介; 錦 耕平; 岩間 密; 牧野知紀; 白石 治; 新海政幸; 今野元博; 古河 洋; 安田卓司
    第196回近畿外科学会  2014/11  京都
  • 当院における食道表在癌の日本食道学会拡大内視鏡分類による深達度診断の検討．  [Not invited]
    朝隈 豊; 松井繁長; 南 知行; 山田光成; 田中梨絵; 足立哲平; 高山政樹; 峯 宏昌; 永井知行; 櫻井俊治; 樫田博史; 工藤正俊; 白石 治; 安田卓司
    第12回日本消化器外科学会大会  2014/10  神戸
  • cT3.5食道癌に対するnon split 50Gy導入化学放射線療法の安全性および有用性の検討．  [Not invited]
    牧野知紀; 曽我部俊介; 田中裕美子; 錦 耕平; 岩間 密; 白石 治; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第67回日本胸部外科学会定期学術集会  2014/10  福岡
  • 当科における幽門保存胃切除術の適応について.  [Not invited]
    安田 篤; 今本 治彦; 曽我部 俊介; 錦 耕平; 岩間 密; 白石 治; 新海 政幸; 今野 元博; 古河 洋; 安田 卓司; 奥野 清隆
    第27回日本内視鏡外科学会総会  2014/10  岩手
  • 徹底郭清と安全性を両立する食道癌Salvage surgeryにおける手術手技．  [Not invited]
    安田卓司; 白石 治; 牧野知紀; 岩間 密; 錦 耕平; 今本治彦
    第67回日本胸部外科学会定期学術集会  2014/10  福岡
  • 「症例検討（食道）」  [Not invited]
    安田卓司
    第12回日本消化器外科学会大会  2014/10  神戸
  • 肺葉外肺分画症を合併した横隔膜上食道憩室症の１例．  [Not invited]
    家根由典; 牧野知紀; 今本治彦; 曽我部俊介; 田中裕美子; 錦 耕平; 岩間 密; 白石 治; 新海政幸; 今野元博; 安田卓司
    第27回近畿内視鏡外科研究会  2014/09  神戸
  • 術前治療後のpN(+)食道扁平上皮癌に対する腫瘍特異的A-2402拘束性がんペプチドワクチンの第二相臨床試験と今後の展望．  [Not invited]
    安田卓司; 錦 耕平; 吉田浩二; 角田卓也; 中村祐輔; 奥野清隆
    第73回日本癌学会  2014/09  横浜
  • 術後縫合不全治療後に来した食物摂取障害に対して外科治療が有効であった1例（続報）．  [Not invited]
    石田興一郎; 坂口 聡; 庄野嘉治; 堀内哲也; 白石 治; 安田卓司
    第68回日本食道学会学術集会  2014/07  東京
  • 切除可能進行食道癌に対する術前化学療法のランダム化比較試験（ＯＧＳＧ1003）の短期成績．  [Not invited]
    本告正明; 矢野雅彦; 安田卓司; 平尾素宏; 宮田博志; 山崎 誠; 白石 治; 古河 洋; 土岐祐一郎
    第68回日本食道学会学術集会  2014/07  東京
  • 食道疣贅扁平上皮癌の2切除例  [Not invited]
    曽我部俊介; 田中裕美子; 錦 耕平; 岩間 密; 牧野知紀; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第68回日本食道学会学術集会  2014/07  東京
  • 当科における食道癌サルベージ手術の治療戦略の工夫と治療成績.  [Not invited]
    錦 耕平; 曽我部俊介; 岩間 密; 牧野知紀; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第69回日本消化器外科学会総会  2014/07  郡山
  • 食道癌術後における再建胃管癌8例の検討.  [Not invited]
    錦 耕平; 曽我部俊介; 岩間 密; 牧野知紀; 白石 治; 安田 篤; 新海政幸; 今野元博; 古河 洋; 今本治彦; 安田卓司
    第68回日本食道学会学術集会  2014/07  東京
  • リンパ節郭清効果からみた食道胃接合部癌における至適リンパ節郭清範囲および治療戦略の検討．  [Not invited]
    牧野知紀; 錦 耕平; 岩間 密; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第69回日本消化器外科学会総会  2014/07  郡山
  • 局所進行cT3.5食道癌に対するnon split 50GyCRT+切除の有用性．  [Not invited]
    牧野知紀; 曽我部俊介; 錦 耕平; 岩間 密; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 安田卓司
    第68回日本食道学会学術集会  2014/07  東京
  • 残胃癌に対する臨床病理学的検討.  [Not invited]
    岩間 密; 錦 耕平; 牧野知紀; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第69回日本消化器外科学会総会  2014/07  郡山
  • 106preおよび106tbLリンパ節転移の臨床学的意義．  [Not invited]
    岩間 密; 曽我部俊介; 錦 耕平; 牧野知紀; 白石 治; 安田 篤; 新海政幸; 今本治彦; 安田卓司
    第68回日本食道学会学術集会  2014/07  東京
  • 表層拡大型食道癌におけるリンパ節転移と予後―通常0-II型食道癌と相違―．  [Not invited]
    白石 治; 錦 耕平; 岩間 密; 牧野知紀; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第68回日本食道学会学術集会  2014/07  東京
  • 放射線化学療法後・高度化学療法後の開腹胃切除におけるD2リンパ節郭清の実際  [Not invited]
    新海政幸; 古河 洋; 錦 耕平; 牧野知紀; 岩間 密; 白石 治; 安田 篤; 今野元博; 今本治彦; 安田卓司
    第69回日本消化器外科総会  2014/07  郡山
  • 食道切除後の再建における安全な吻合法．  [Not invited]
    安田卓司; 白石 治; 牧野知紀; 岩間 密; 錦 耕平; 曽我部俊介; 安田 篤; 新海政幸; 今野元博; 今本治彦
    第69回日本消化器外科学会総会  2014/07  郡山
  • 化学療法にてCR後、局所再発に対し根治切除した胃癌の1例．  [Not invited]
    錦 耕平; 曽我部俊介; 岩間 密; 牧野知紀; 白石 治; 安田 篤; 新海政幸; 今野元博; 古河 洋; 今本治彦; 安田卓司
    第36回癌局所療法研究会  2014/06  大阪
  • 術食道癌術後乳糜腹水6例の検討．  [Not invited]
    錦 耕平; 曽我部俊介; 岩間 密; 牧野知紀; 白石 治; 安田 篤; 新海 政幸; 今野元博; 古河 洋; 今本治彦; 安田卓司
    第57回関西胸部外科学会学術集会  2014/06  大阪
  • cT4食道癌に対する導入化学放射線療法後の大動脈穿通に対して予防的大動脈ステント留置し一期的切除し得た１例．  [Not invited]
    牧野知紀; 白石 治; 錦 耕平; 岩間 密; 曽我部俊介; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第57回関西胸部外科学会学術集会  2014/06  大阪
  • 予防的頸部放射線照射後25年目に発生した胸部食道癌根治切除術後頸部食道癌の1切除例．  [Not invited]
    岩間 密; 白石 治; 牧野知紀; 曽我部俊介; 錦 耕平; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第57回関西胸部外科学会  2014/06  大阪
  • 胸腔内吻合及び血管吻合を同時に成し得る胸骨後→後縦隔横断経路による回結腸挙上再建．  [Not invited]
    白石 治; 村瀬貴昭; 曽我部俊介; 錦 耕平; 岩間 密; 牧野知紀; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 塩崎 均; 安田卓司
    第57回関西胸部外科学会  2014/06  大阪
  • 胃全摘後 Roux-Y 脚吻合部完全狭窄による輸入脚症候群の 2 症例.  [Not invited]
    安田 篤; 今本治彦; 曽我部俊介; 錦 耕平; 岩間 密; 牧野知紀; 白石 治; 新海政幸; 今野元博; 古河 洋; 奥野清隆; 安田卓司
    第36回日本癌局所療法研究会  2014/06  大阪
  • 切除困難食道癌手術における合併症予防対策と術中トラブルに対する対応．  [Not invited]
    安田卓司
    第57回関西胸部外科学会学術集会  2014/06  大阪
  • PET-N(-)切除可能進行胸部食道癌における術前化学療法.  [Not invited]
    錦 耕平; 白石 治; 岩間 密; 牧野知紀; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 塩? 均; 奥野清隆; 安田卓司
    第114回日本外科学会学術集会  2014/04  京都
  • Optimum surgical approach for esophago-gastric junction tumors based upon the metastatic status of mediastinal lymph node．  [Not invited]
    Tomoki Makino; Hiroaki Kato; Kohei Nishiki; Mitsuru Iwama; Osamu Shiraishi; Atsushi Yasuda; Masayuki Shinkai; Motohiro Imano; Haruhiko Imamoto; Hiroshi furukawa; Takushi Yasuda
    第114回日本外科学会定期学術集会  2014/04  京都
  • 進行食道癌に対するPET診断に基づくNAC至適個別化治療戦略．  [Not invited]
    白石 治; 錦 耕平; 岩間 密; 牧野知紀; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 塩? 均; 奥野清隆; 安田卓司
    第114回日本外科学会定期学術集会  2014/04  京都
  • 当科での噴門側胃切除後の食道残胃吻合法について.  [Not invited]
    安田 篤; 今本治彦; 曽我部俊介; 錦 耕平; 岩間 密; 牧野知紀; 白石 治; 新海政幸; 今野元博; 古河 洋; 奥野清隆; 安田卓司
    第114回日本外科学会総会  2014/04  京都
  • 術前化学療法が奏効した食道胃接合部癌の１切除例．  [Not invited]
    藤島一樹; 牧野知紀; 村瀬貴昭; 曽我部俊介; 錦 耕平; 岩間 密; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第54回南大阪消化器外科臨床懇話会  2014/03  大阪
  • 食道癌術後再建胃管癌6例の検討.  [Not invited]
    錦 耕平; 加藤寛章; 岩間 密; 牧野知紀; 白石 治; 安田 篤; 新海政幸; 今野元博; 古河 洋; 今本治彦; 安田卓司
    第86回日本胃癌学会学術集会  2014/03  横浜
  • 食道胃接合部癌における縦隔リンパ節状況からみた至適手術アプローチ法の検討．  [Not invited]
    牧野知紀; 加藤寛章; 錦 耕平; 岩間 密; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第86回日本胃癌学会総会  2014/03  横浜
  • 75歳以上根治切除可能4型・大型3型胃癌に対する術前TS-1併用化学放射線療法(SRT)の可能性．  [Not invited]
    岩間 密; 今野元博; 加藤寛章; 錦 耕平; 牧野知紀; 白石 治; 安田 篤; 新海政幸; 今本治彦; 古河 洋; 安田卓司
    第86回日本胃癌学会総会  2014/03  横浜
  • 進行食道胃接合部癌のリンパ節転移状況から導かれる至適術式．  [Not invited]
    白石 治; 加藤寛章; 錦 耕平; 岩間 密; 牧野知紀; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 塩崎 均; 安田卓司
    第86回日本胃癌学会総会  2014/03  横浜
  • ハイリスクである高齢者に対する幽門側胃切除術と腹腔鏡導入の意義.  [Not invited]
    安田 篤; 今本治彦; 曽我部俊介; 錦 耕平; 岩間 密; 牧野知紀; 白石 治; 新海政幸; 今野元博; 古河 洋; 奥野清隆; 安田卓司
    第86回日本胃癌学会総会  2014/03  横浜
  • 腹腔鏡補助下幽門側胃切除(LADG)の成績からみた適応拡大の可能性について.  [Not invited]
    安田 篤; 今本治彦; 曽我部俊介; 錦 耕平; 岩間 密; 牧野知紀; 白石 治; 新海政幸; 今野元博; 古河 洋; 奥野清隆; 安田卓司
    第86回日本胃癌学会総会  2014/03  横浜
  • CY1進行胃癌に対する治療戦略とその成績.  [Not invited]
    新海政幸; 今野元博; 村瀬貴昭; 曽我部俊介; 錦 耕平; 牧野知紀; 岩間 密; 白石 治; 安田 篤; 今本治彦; 奥野清隆; 古河 洋; 安田卓司
    第52回日本癌治療学会学術集会  2014/03  横浜
  • 放射線化学療法後・高度化学療法後の開腹手術  [Not invited]
    新海政幸; 古河 洋; 曽我部俊介; 加藤寛章; 錦 耕平; 牧野知紀; 岩間 密; 白石 治; 安田 篤; 今野元博; 今本治彦; 安田卓司
    第86回日本胃癌学会総会  2014/03  横浜
  • 根治切除可能な大型3型/4型胃癌に対する術前ＴＳ-1＋CDDP併用化学放射線療法 第?/?相臨床試験（OGSG1205）  [Not invited]
    今野元博; 古河 洋; 横川正樹; 西村恭昌; 黒川幸典; 佐藤太郎; 坂井大介; 今本治彦; 安田卓司; 辻中利政; 下川敏雄; 塩? 均
    第86回日本胃癌学会総会  2014/03  横浜
  • 術前治療後pN(+)食道癌に対するペプチドワクチンを用いた術後補助免疫療法  [Not invited]
    錦 耕平; 曽我部俊介; 奥野清隆; 安田卓司
    第26回日本バイオセラピー学会学術集会総会  2013/12  盛岡
  • 食道逆流に対する工夫を加えた噴門側胃切除後腹腔鏡補助下食道残胃吻合法  [Not invited]
    安田 篤; 今本 治彦; 加藤寛章; 錦 耕平; 岩間 密; 牧野 知紀; 白石 治; 新海政幸; 今野元博; 安田卓司; 古河 洋; 奥野清隆; 塩? 均
    第26回日本内視鏡外科学会  2013/11  福岡
  • 進行食道胃接合部癌の至適リンパ節郭清範囲と胸腹連続的切除  [Not invited]
    白石 治; 曽我部俊介; 錦 耕平; 岩間密; 牧野知紀; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 塩? 均; 奥野清隆; 安田卓司
    第75回日本臨床外科学会総会  2013/11  愛知
  • 食道癌周術期管理におけるチームアプローチの実際とその成績  [Not invited]
    新海政幸; 牛嶋北斗; 曽我部俊介; 加藤寛章; 錦 耕平; 岩間 密; 牧野知紀; 白石治; 安田 篤; 今野元博; 今本治彦; 古河 洋; 奥野清隆; 安田卓司
    第75回日本臨床外科学会総会  2013/11  愛知
  • T4進行食道癌に対する化学放射線療法後の大動脈壁への穿通に対し緊急大動脈ステント留置後に一期的切除術を施行し得た1例  [Not invited]
    牧野知紀; 加藤寛章; 錦 耕平; 岩間 密; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第75回日本臨床外科学会総会  2013/11  愛知
  • 頚胸境界部食道癌術後の気管孔狭窄に対し、遊離前腕皮弁にて気管孔再形成術を異時性胸部食道癌手術と同時に施行した1例  [Not invited]
    錦 耕平; 曽我部俊介; 加藤寛章; 岩間 密; 牧野知紀; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 奥野清隆; 安田卓司
    第75回日本臨床外科学会総会  2013/11  愛知
  • 当院における中心静脈穿刺に伴う深部静脈血栓症の現状  [Not invited]
    岩間 密; 保田知生; 白石 治; 武本昌子; 杉浦史哲; 錦 耕平; 安田卓司; 竹山宜典; 奥野清隆
    第75回日本臨床外科学会総会  2013/11  愛知
  • 胃癌胃全摘術後繰り返す縫合不全に難渋するもT-portion遊離皮弁により再建し得た1例  [Not invited]
    岩間 密; 曽我部俊介; 加藤寛章; 錦 耕平; 牧野知紀; 白石 治; 安田 篤; 彭 英峰; 新海政幸; 今野元博; 今本治彦; 古河 洋; 奥野清隆; 安田卓司
    第75回日本臨床外科学会総会  2013/11  愛知
  • 根治性と安全性を確保する胸部食道癌サルベージ手術対策  [Not invited]
    白石 治; 曽我部俊介; 錦 耕平; 岩間 密; 牧野知紀; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 塩? 均; 奥野清隆; 安田卓司
    第75回日本臨床外科学会総会  2013/11  愛知
  • 治療に難渋した特発性食道破裂の1例  [Not invited]
    曽我部俊介; 錦 耕平; 牧野知紀; 岩間 密; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 奥野清隆; 安田卓司
    第596回大阪外科集談会  2013/11  大阪
  • 食道疣贅扁平上皮癌の1切除例  [Not invited]
    松本正孝; 白石 治; 東 千尋; 錦 耕平; 岩間 密; 牧野知紀; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    第596回大阪外科集談会  2013/11  大阪
  • 食道原発悪性黒色腫に対して右開胸食道亜全摘胃管再建術を行った一例  [Not invited]
    西野将矢; 白石 治; 錦 耕平; 岩間密; 牧野知紀; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 塩? 均; 奥野清隆; 安田卓司
    第194回近畿外科学会  2013/11  大阪
  • 当科での噴門側胃切除後の食道残胃吻合法の検討  [Not invited]
    松本正孝; 今本治彦; 加藤寛章; 錦 耕平; 岩間 密; 牧野知紀; 白石 治; 安田 篤; 新海政幸; 今野元博; 古河 洋; 奥野清隆; 安田卓司
    第43回胃外科・術後障害研究会  2013/11  新潟
  • 80歳以上の超高齢者に対する幽門側胃切除の検討  [Not invited]
    安田 篤; 松本正孝; 今本治彦; 加藤寛章; 錦 耕平; 岩間 密; 牧野知紀; 白石 治; 新海政幸; 今野元博; 古河 洋; 奥野清隆; 安田卓司
    第43回胃外科・術後障害研究会  2013/11  新潟
  • 頸部食道癌に対する導入化学放射線療法と術式工夫による喉頭温存を重視した集学的治療戦略  [Not invited]
    白石 治; 安田卓司
    第65回日本気管食道科学会総会  2013/10  東京
  • 術前治療後のpN(+)食道癌に対する術後アジュバントペプチドワクチン第II相試験  [Not invited]
    安田卓司; 錦 耕平; 吉田浩二; 角田卓也; 新海政幸; 安田 篤; 白石 治; 岩間 密; 牧野知紀; 中村祐輔; 奥野清隆
    第51回癌治療学会学術集会  2013/10  京都
  • 術前治療後の病理学的リンパ節転移陽性食道癌に対する術後アジュバントペプチドワクチン第二相試験  [Not invited]
    安田卓司; 錦 耕平; 奥野清隆; 吉田浩二; 角田卓也; 中村祐輔
    第72回日本癌学会学術集会  2013/10  横浜
  • 食道胃接合部癌における縦隔リンパ節転移状況および術式選択の検討  [Not invited]
    牧野知紀; 安田卓司; 安田 篤; 白石 治; 岩間 密; 新海政幸; 今野元博; 今本治彦; 古河 洋; 塩? 均
    第68回日本消化器外科学会総会  2013/07  宮崎
  • リンパ節転移陽性食道癌に対する腫瘍特異的ペプチドワクチンを用いた術後補助免疫療法  [Not invited]
    錦 耕平; 安田卓司; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 奥野清隆; 塩? 均
    第68回日本消化器外科学会総会  2013/07  宮崎
  • 胸部食道癌手術における術後合併症（縫合不全・誤嚥性肺炎）の予防策とその治療効果に関する検討  [Not invited]
    岩間 密; 安田卓司; 曽我部俊介; 加藤寛章; 錦 耕平; 牧野知紀; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 奥野清隆; 塩? 均
    第68回日本消化器外科学会総会  2013/07  宮崎
  • 当科における噴門側胃切除後の食道残遺吻合再建の工夫  [Not invited]
    安田 篤; 今本治彦; 加藤寛章; 錦 耕平; 岩間 密; 牧野知紀; 白石 治; 新海政幸; 今野元博; 安田卓司; 古河 洋; 奥野清隆; 塩? 均
    第68回日本消化器外科学会総会  2013/07  宮崎
  • 治療成績からみた局所進行胸部食道癌に対する至適治療戦略  [Not invited]
    白石 治; 安田卓司; 加藤寛章; 錦 耕平; 岩間 密; 牧野知紀; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 奥野清隆; 塩? 均
    第68回日本消化器外科学会総会  2013/07  宮崎
  • 腹腔鏡補助下・腹腔鏡下(SILS)に切除した胃glomus腫瘍の2例  [Not invited]
    古川健太郎; 岩間 密; 西野将矢; 曽我部俊介; 加藤寛章; 錦 耕平; 牧野知紀; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 安田卓司
    南大阪消化器外科臨床懇話会  2013/07  大阪
  • 高齢者食道癌に対する外科治療成績と問題点  [Not invited]
    新海政幸; 安田卓司; 加藤寛章; 錦 耕平; 岩間 密; 牧野知紀; 白石 治; 安田 篤; 今野元博; 今本治彦; 古河 洋; 奥野清隆; 塩? 均
    第50回日本外科代謝栄養学会  2013/07  東京
  • リンパ節転移陽性食道癌に対する腫瘍特異的ペプチドワクチンを用いた術後補助免疫療法  [Not invited]
    錦 耕平; 安田卓司; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 奥野清隆; 塩? 均
    第67回日本食道学会学術集会  2013/06  大阪
  • FDG- PET-N(-)切除可能食道癌における予後予測に基づいた術前治療の個別化治療戦略  [Not invited]
    錦 耕平; 安田卓司; 新海政幸; 安田 篤; 白石 治; 牧野知紀; 岩間 密; 加藤寛章; 今野元博; 今本治彦; 古河 洋; 奥野清隆; 塩? 均
    第67回日本食道学会学術集会  2013/06  大阪
  • 食道癌術後合併症−縫合不全とその管理  [Not invited]
    安田卓司
    第67回日本食道学会学術集会  2013/06  大阪
  • 食道胃接合部癌における縦隔リンパ節転移状況および予後解析に基づいた外科治療戦略  [Not invited]
    牧野知紀; 安田卓司; 安田 篤; 白石 治; 岩間 密; 新海政幸; 今野元博; 今本治彦; 古河 洋; 塩? 均
    第67回日本食道学会学術集会  2013/06  大阪
  • 胸部食道扁平上皮癌pT1症例の転移・再発形式から見た至適治療戦略  [Not invited]
    岩間 密; 安田卓司; 加藤寛章; 錦 耕平; 牧野知紀; 白石 治; 安田 篤; 新海政幸; 今本治彦; 塩? 均
    第67回日本食道学会学術集会  2013/06  大阪
  • FDG-PETによるpNおよびpT予測に基づいた食道癌に対する術前化学療法の適応と効果予測  [Not invited]
    白石 治; 安田卓司; 牧野知紀; 岩間 密; 錦 耕平; 加藤寛章; 新海政幸; 今野元博; 今本治彦; 塩? 均
    第67回日本食道学会学術集会  2013/06  大阪
  • 局所制御および遠隔再発の予測に基づいた食道癌術前補助療法の個別化  [Not invited]
    白石 治; 安田卓司; 牧野知紀; 岩間 密; 錦 耕平; 加藤寛章; 新海政幸; 今野元博; 今本治彦; 塩? 均
    第67回日本食道学会学術集会  2013/06  大阪
  • 大型3型胃癌に対し術前放射線化学療法を施行し、良好な病理組織結果を得た1例の検討  [Not invited]
    安田 篤; 今野元博; 古河 洋; 加藤寛章; 錦 耕平; 牧野知紀; 岩間 密; 白石 治; 新海政幸; 安田卓司; 今本治彦; 奥野清隆; 塩? 均
    日本外科系連合学会  2013/06  東京
  • 進行食道癌に対する化学療法多回数施行後の外科切除症例における臨床効果とそのfeasibility  [Not invited]
    牧野知紀; 安田卓司; 白石 治; 田中裕美子; 加藤寛章; 錦 耕平; 岩間 密; 安田 篤; 新海正幸; 今野元博; 今本治彦; 古河 洋; 奥野清隆; 塩?均
    第113回日本外科学会定期学術集会  2013/04  福岡
  • 超高齢者に対する幽門側胃切除の安全性と根治性の検討  [Not invited]
    安田 篤; 今本治彦; 加藤寛章; 錦 耕平; 岩間 密; 牧野知紀; 白石 治; 新海政幸; 今野元博; 古河 洋; 奥野清隆; 安田卓司
    第113回日本外科学会定期学術集会  2013/04  福岡
  • 80歳以上の超高齢者に対する食道癌手術の検討  [Not invited]
    新海政幸; 安田卓司; 田中裕美子; 加藤寛章; 錦 耕平; 岩間 密; 牧野知紀; 白石 治; 安田 篤; 今野元博; 今本治彦; 古河 洋; 奥野清隆; 塩? 均
    第113回日本外科学会定期学術集会  2013/04  福岡
  • FDG-PETによる客観評価に基づく進行食道癌に対する集学的治療の個別化戦略  [Not invited]
    白石 治; 安田卓司; 加藤寛章; 錦 耕平; 岩間 密; 牧野知紀; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河 洋; 奥野清隆; 塩? 均
    第113回日本外科学会定期学術集会  2013/04  福岡
  • ＜経胸＞食道胃接合部癌に対する外科治療〜経胸の立場から  [Not invited]
    安田卓司; 安田 篤; 白石 治; 牧野知紀; 錦 耕平; 加籐寛章; 岩間 密; 新海政幸; 今野元博; 今本治彦; 古河 洋; 奥野清隆; 塩? 均
    第113回日本外科学会定期学術集会  2013/04  福岡
  • 80歳以上の高齢者胃癌に対する幽門側胃切除術の検討  [Not invited]
    安田 篤; 今本治彦; 加藤寛章; 錦 耕平; 岩間 密; 牧野知紀; 白石 治; 新海政幸; 今野元博; 安田卓司; 古河 洋; 奥野清隆; 塩? 均
    第85回日本胃癌学会  2013/02  大阪
  • リンパ節陽性食道癌に対する腫瘍特異的ペプチドワクチンを用いた術後アジュバント療法  [Not invited]
    錦 耕平; 安田 卓司; 奥野 清隆; 塩? 均; 吉田 浩二; 角田 卓也; 中村 裕輔
    第25回日本バイオセラピー学会学術集会総会  2012/12  倉敷
  • 当科における進行胃癌に対する腹腔鏡補助下幽門側胃切除の妥当性の検討  [Not invited]
    安田 篤; 今本治彦; 加藤寛章; 錦 耕平; 岩間 密; 牧野知紀; 白石 治; 新海政幸; 安田卓司; 今野元博; 古河 洋; 奥野清隆; 塩? 均
    第25回日本内視鏡外科学会総会  2012/12  横浜
  • 術前治療後の病理学的リンパ節転移陽性食道癌に対する術後アジュバントペプチドワクチン第II相試験  [Not invited]
    安田卓司; 錦 耕平; 奥野清隆; 塩? 均; 吉田浩二; 角田卓也; 中村祐輔
    第25回日本バイオセラピィ学会学術集会  2012/12  倉敷
  • 胸腔内からの徹底郭清と反回神経リンパ節術中病理診による胸部食道癌 選択的 2 領域郭清  [Not invited]
    白石 治; 安田卓司; 加藤寛章; 錦 耕平; 岩間密; 安田 篤; 新海政幸; 今野元博; 今本治彦; 古河洋; 奥野清隆; 塩? 均
    第74回日本臨床外科学会総会  2012/11  東京
  • 噴門側胃切除における食道残胃吻合法と空腸間置法の比較  [Not invited]
    安田 篤; 今本治彦; 加藤寛章; 錦 耕平; 岩間 密; 牧野知紀; 白石 治; 新海政幸; 安田卓司; 今野元博; 古河 洋; 奥野清隆; 塩? 均
    第42回胃外科・術後障害研究会  2012/11  東京
  • 食道癌根治化学放射線療法後のSalvage手術の克服と安全性の確立  [Not invited]
    新海政幸; 安田卓司; 田中裕美子; 加藤寛章; 錦耕平; 岩間密; 白石治; 安田篤; 今野元博; 今本治彦; 奥野清隆; 古河洋; 塩?均
    第74回日本臨床外科学会総会  2012/11  東京
  • がんチーム医療におけるスピリチュアルケアの役割  [Not invited]
    古河 洋; 伊藤高章; 西村恭昌; 竹山宜典; 今本治彦; 安田卓司; 今野元博; 新海政幸; 原 聡; 奥野清隆; 千葉鐘子; 塩? 均
    第50回日本癌治療学会学術集会  2012/10  横浜
  • 食道扁平上皮癌におけるEGFR、HER2、FGFR2、METの遺伝子増幅  [Not invited]
    加藤寛章; 荒尾徳三; 林秀敏; 吉田修平; 永井知行; 松本和子; 藤田至彦; 木村英晴; 安田卓司; 奥野清隆; 塩崎均; 西尾和人
    第71回日本癌学会学術総会  2012/09  札幌
  • 噴門部胃粘膜下腫瘍（SMT）に対する腹腔鏡下胃内手術  [Not invited]
    安田 篤; 今本治彦; 加藤寛章; 錦 耕平; 岩間 密; 牧野知紀; 白石 治; 新海政幸; 安田卓司; 今野元博; 古河 洋; 奥野清隆; 塩? 均
    第6回TANKO式研究会  2012/08  札幌
  • 食道扁平上皮癌におけるEGFR-familyの遺伝子増幅と、EGFRの遺伝子変異  [Not invited]
    加藤寛章; 荒尾徳三; 松本和子; 藤田至彦; 木村英晴; 安田卓司; 奥野清隆; 塩崎均; 西尾和人
    第10回日本臨床腫瘍学会学術集会  2012/07  大阪
  • 外科手術成績向上をめざした胸部食道癌に対する積極的補助療法の個別化戦略  [Not invited]
    白石 治; 安田卓司; 加藤寛章; 錦 耕平; 安田 篤; 新海政幸; 今野元博; 今本治彦; 塩? 均
    第67回日本消化器外科学会総会  2012/07  富山
  • T4a胃癌に対するNAC(PTX腹腔内化学療法+逐次PTX+S-1による全身化学療法)の有用性  [Not invited]
    安田 篤; 今野元博; 今本治彦; 加藤寛章; 錦 耕平; 岩間 密; 白石 治; 新海政幸; 安田卓司; 古河 洋; 奥野清隆; 塩? 均
    第67回日本消化器外科学会総会  2012/07  富山
  • Salvage手術の克服とSalvage手術を前提としたcT4に対する新たな治療戦略  [Not invited]
    新海政幸; 安田卓司; 加藤寛章; 錦耕平; 白石治; 安田篤; 彭英峰; 今野元博; 今本治彦; 奥野清隆; 塩?均
    第67回日本消化器外科学会総会  2012/07  富山
  • リンパ節転移を伴う切除可能漿膜浸潤胃癌に対する術前補助化学療法としてのS-1+PTX+CDDP療法  [Not invited]
    今野 元博; 安田; 篤; 今本; 治彦; 新海; 政幸; 加藤; 寛章; 白石; 治; 安田; 卓司; 竹山; 宜典; 奥野; 清隆; 塩? 均
    第67回日本消化器外科学会総会  2012/07  富山
  • Salvage surgeryにおける根治性と安全性の確保  [Not invited]
    安田卓司; 塩? 均
    第67回日本消化器外科学会総会  2012/07  富山
  • 食道扁平上皮癌におけるEGFR-family (EGFR/HER2/HER3/HER4)の遺伝子異常  [Not invited]
    加藤寛章; 安田卓司; 荒尾徳三; 松本和子; 白石 治; 新海 政幸; 木村英晴; 奥野清隆; 西尾和人; 塩? 均
    第66回日本食道学会学術集会  2012/06  軽井沢
  • 食道扁平上皮癌におけるEGFR-familyの遺伝子増幅とEGFR遺伝子変異  [Not invited]
    加藤寛章; 荒尾徳三; 林秀敏; 吉田修平; 永井知行; 松本和子; 藤田至彦; 木村英晴; 安田卓司; 奥野清隆; 塩崎均; 西尾和人
    第16回日本がん分子標的治療学会学術集会  2012/06  北九州市
  • リンパ節陽性食道癌に対する腫瘍特異的ペプチドワクチンを用いた術後アジュバント療法  [Not invited]
    錦 耕平; 安田 卓司; 新海 政幸; 安田 篤; 白石 治; 加藤 寛章; 彭 英峰; 今野 元博; 今本 治彦; 塩? 均
    第66回日本食学会学術集会  2012/06  軽井沢
  • 切除可能食道癌におけるFDG-PETに基づいた個別化治療戦略  [Not invited]
    錦 耕平; 安田 卓司; 新海 政幸; 安田 篤; 白石 治; 加藤 寛章; 彭 英峰; 今野 元博; 今本 治彦; 塩? 均
    第66回日本食学会学術集会  2012/06  軽井沢
  • 傍大動脈リンパ節陽性食道癌に対し、免疫療法（ペプチドワクチン療法）を含めた集学的治療で長期生存が得られてる1例  [Not invited]
    錦 耕平; 安田 卓司; 加藤 寛章; 白石 治; 安田 篤; 新海 政幸; 今野 元博; 今本 治彦; 奥野 清隆; 塩? 均
    第55回関西胸部外科学会学術集会  2012/06  大阪
  • cT3.5食道癌に対する局所制御を重視した治療戦略“non split 50GyCRT+切除”  [Not invited]
    白石 治; 安田卓司; 加藤寛章; 錦 耕平; 安田 篤; 新海政幸; 今野元博; 今本治彦; 塩? 均
    第66回日本食道学会学術集会  2012/06  軽井沢
  • 喉頭温存と経口摂取を両立した腐食性食道炎の 2 手術例  [Not invited]
    白石 治; 安田卓司; 加藤寛章; 錦 耕平; 安田 篤; 新海政幸; 今野元博; 今本治彦; 塩? 均
    第55回関西胸部外科学会学術集会  2012/06  大阪
  • 食道癌周術期管理における当院でのチーム医療の取り組み  [Not invited]
    新海政幸; 安田卓司; 加藤寛章; 錦耕平; 白石治; 安田篤; 今野元博; 今本治彦; 塩?均
    第66回日本食道学会学術集会  2012/06  軽井沢
  • 術前治療後の瘢痕化食道癌手術における手術精度と機能性の追求  [Not invited]
    安田卓司; 新海政幸; 安田 篤; 白石 治; 錦 耕平; 加藤寛章; 今野元博; 今本治彦; 奥野 清隆; 塩? 均
    第66回日本食道学会学術集会  2012/06  軽井沢
  • 腹膜転移陽性胃癌症例に対する分子標的薬使用の可能性  [Not invited]
    彭 英峰; 今野元博; 加藤寛章; 錦 耕平; 岩間 密; 白石 治; 安田 篤; 新海政幸; 安田卓司; 今本治彦; 古河 洋; 塩? 均
    第112回日本外科学会学術集会  2012/04  千葉
  • 胸部食道癌PET診断に基づく術前化学療法の適応選別の合理性  [Not invited]
    白石 治; 安田卓司; 加藤寛章; 錦 耕平; 岩間 密; 安田 篤; 彭 英峰; 新海政幸; 今野元博; 今本治彦; 奥野清隆; 塩? 均
    第112回日本外科学会学術集会  2012/04  千葉
  • ラット後腹膜浸潤型腹膜播種モデルにおける中皮細胞と中皮下層の変化について  [Not invited]
    安田 篤; 今野元博; 今本治彦; 加藤寛章; 錦 耕平; 岩間 密; 白石 治; 新海政幸; 安田卓司; 古河 洋; 奥野清隆; 塩? 均
    第112回日本外科学会学術集会  2012/04  千葉
  • NonT4c-StageII,IIIにおける高齢者食道癌の治療戦略  [Not invited]
    新海政幸; 安田卓司; 井上啓介; 加藤寛章; 錦耕平; 白石治; 安田篤; 彭英峰; 今野元博; 今本治彦; 奥野清隆; 塩?均
    第112回日本外科学会定期学術集会  2012/04  千葉
  • 術前治療後の瘢痕化における食道癌手術のqualityの確保  [Not invited]
    安田卓司; 新海政幸; 彭 英峰; 安田 篤; 白石 治; 錦 耕平; 加藤寛章; 井上啓介; 今野元博; 今本治彦; 奥野 清隆; 塩? 均
    第112回日本外科学会定期学術集会  2012/04  千葉
  • 術前診断に難渋した胃粘膜下腫瘍の１切除例  [Not invited]
    鍵岡賛典; 岩間密; 田中裕美子; 加藤寛章; 錦耕平; 牧野知紀; 白石治; 安田篤; 新海政幸; 今野元博; 安田卓司; 今本治彦; 古河洋; 奥野清隆; 塩?均
    第192回近畿外科学会  2012/02  大阪
  • 噴門側胃切除における食道残胃吻合法と空腸間置法の比較検討  [Not invited]
    安田 篤; 今本治彦; 加藤寛章; 錦 耕平; 岩間 密; 白石 治; 新海政幸; 今野元博; 安田卓司; 奥野清隆; 塩? 均
    第84回日本胃癌学会総会  2012/02  大阪
  • 外科治療成績からみた食道癌に対する標準治療  [Not invited]
    安田卓司; 奥野清隆; 塩? 均
    第22回日本気管食道科学会認定気管食道科専門医大会  2012/02  東京
  • 胸部食道癌に対する術前補助療法の個別化  [Not invited]
    白石 治; 安田卓司; 加藤寛章; 錦 耕平; 安田 篤; 彭 英峰; 新海政幸; 今野元博; 今本治彦; 塩? 均
    第65回日本食道学会学術集会  2011  仙台
  • cT4胸部食道癌に対する局所制御に重点をおいた治療戦略  [Not invited]
    白石 治; 安田卓司; 加藤寛章; 錦 耕平; 中森康浩; 安田 篤; 彭 英峰; 新海政幸; 今野元博; 今本治彦; 奥野清隆; 塩? 均
    第111回日本外科学会定期学術総会  2011  東京
  • 胃管後縦隔経路再建後に縫合不全と膿胸を生じ、外科的治療にて治癒し得た1症例  [Not invited]
    安田 篤; 安田卓司; 加藤 寛章; 錦 耕平; 白石 治; 彭 英峰; 新海政幸; 今野元博; 今本治彦; 塩? 均
    第65回日本食道学会学術集会  2011  仙台
  • cT4を疑う局所進行食道癌に対するno split 50Gy 導入化学放射線療法+surgeryの治療成績  [Not invited]
    新海政幸; 安田卓司; 加藤寛章; 錦 耕平; 中森康浩; 白石 治; 安田 篤; 彭 英峰; 今野元博; 今本治彦; 奥野清隆; 塩? 均
    第65回日本食道学会学術集会  2011  仙台
  • 胸部食道癌に対する食道癌切除後早期再発死亡例の検討  [Not invited]
    新海政幸; 安田卓司; 錦耕平; 加藤寛章; 中森康浩; 白石治; 安田篤; 彭英峰; 今野元博; 今本治彦; 奥野清隆; 塩崎均
    第111回日本外科学会定期学術総会  2011  東京
  • 高度リンパ節転移を伴う進行食道胃接合部粘液癌に対しCisplatin/Capecitabine/Cetuximab投与後に根治切除術を施行した1例  [Not invited]
    加藤 寛章; 安田 卓司; 錦 耕平; 中森 康浩; 白石 治; 安田 篤; 彭 英峰; 新海 政幸; 今野 元博; 今本 治彦; 奥野 清隆; 塩? 均
    第66回日本消化器外科学会総会  2011  名古屋
  • 局所進行食道癌に対する50Gy no split 導入化学放射線療法による治療戦略  [Not invited]
    錦 耕平; 安田 卓司; 加藤 寛章; 中森 康浩; 白石 治; 安田 篤; 彭 英峰; 新海 政幸; 今野 元博; 今本 治彦; 奥野 清隆; 塩? 均
    第66回日本消化器外科学会総会  2011  名古屋
  • 心機能低下・肥満を合併した成人Bochdalek孔ヘルニアに対し経腹的にHALSで修復した1例  [Not invited]
    加藤 寛章; 今本 治彦; 錦 耕平; 白石 治; 安田 篤; 彭 英峰; 新海 政幸; 今野 元博; 安田 卓司; 奥野 清隆; 塩? 均
    第24回日本内視鏡外科学会総会  2011  大阪
  • 胸部食道癌根治切除後7年目の異時性直腸癌に対する術後補助化学療法中に認めた、再建胃管穿孔の1例  [Not invited]
    錦 耕平; 安田 卓司; 井上 啓介; 加藤 寛章; 中森 康浩; 白石 治; 安田 篤; 彭 英峰; 新海 政幸; 今野 元博; 今本 治彦; 奥野 清隆; 塩? 均
    第73回日本臨床外科学会総会  2011  東京
  • ハイリスク症例に対する胸部食道癌手術症例の検討  [Not invited]
    彭 英峰; 安田卓司; 中森康浩; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 奥野清隆; 塩? 均
    第66回日本消化器外科学会総会  2011  名古屋
  • 当科における幽門保存胃切除術の適応と有用性について  [Not invited]
    安田 篤; 今本治彦; 加藤 寛章; 錦 耕平; 白石 治; 彭 英峰; 新海政幸; 今野元博; 安田卓司; 塩? 均
    第73回日本臨床外科学会総会  2011  東京
  • 他臓器浸潤を疑う局所進行食道癌に対するno split 50Gy induction CRT+ surgeryの治療成績  [Not invited]
    新海政幸; 安田卓司; 井上啓介; 加藤寛章; 錦 耕平; 白石 治; 安田 篤; 彭 英峰; 今野元博; 今本治彦; 奥野清隆; 塩? 均
    第73回日本臨床外科学会総会  2011  東京
  • 合併症軽減を目指した食道癌胃管再建術における工夫  [Not invited]
    白石 治; 安田卓司; 加藤寛章; 錦 耕平; 安田 篤; 彭 英峰; 新海政幸; 今野元博; 今本治彦; 塩? 均
    第65回日本食道学会学術集会  2011  仙台
  • 縫合不全ゼロを目指した当科における胃管再建  [Not invited]
    白石 治; 安田卓司; 加藤寛章; 井上啓介; 錦 耕平; 安田 篤 彭 英峰; 新海政幸; 今野元博; 今本治彦; 奥野清隆; 塩? 均
    第73回日本臨床外科学会総会  2011  東京
  • 当科における胸部食道癌手術：胸骨後経路細径胃管再建術の工夫と治療成績  [Not invited]
    新海政幸; 安田卓司; 加藤寛章; 錦 耕平; 中森康浩; 白石 治; 安田 篤; 彭 英峰; 今野元博; 今本治彦; 奥野清隆; 塩? 均
    第66回日本消化器外科学会総会  2011  名古屋
  • 経口摂取不能P1胃癌症例に対するバイパス手術付加の意義について  [Not invited]
    安田 篤; 今野元博; 加藤 寛章; 中森康浩; 錦 耕平; 白石 治; 彭 英峰; 新海政幸; 安田卓司; 今本治彦; 塩? 均
    第83回日本胃癌学会総会  2011  三沢市
  • T4a胃癌に対するPTX腹腔内化学療法+逐次PTX+S-1による全身化学療法  [Not invited]
    彭 英峰; 安田卓司; 中森康浩; 白石 治; 安田 篤; 新海政幸; 今野元博; 今本治彦; 奥野清隆; 塩? 均
    第73回日本臨床外科学会  2011  東京
  • CY(+)胃癌に対するPTX腹腔内化学療法＋逐次PTX+S-1全身化学療法  [Not invited]
    彭 英峰; 今野元博; 今本治彦; 加藤寛章; 錦 耕平; 中森康浩; 白石 治; 安田 篤; 新海政幸; 安田卓司; 塩? 均
    第83回日本胃癌学会総会  2011  三沢市
  • 近畿大学医学部附属病院における外来化学療法の効率化と安全への取り組み  [Not invited]
    今野元博; 竹山宜典; 錦耕平; 井上啓介; 加藤寛章; 白石治; 安田篤; 彭英峰; 新海政幸; 安田卓司; 今本治彦; 奥野清隆; 塩?均
    第73回日本臨床外科学会総会  2011  東京
  • 食道がん治療戦略におけるFDG-PETの位置づけ  [Not invited]
    安田卓司; 奥野清隆; 塩? 均
    JDDW 2011 第9回日本消化器外科学会大会  2011  福岡
  • 当科における腹腔鏡補助下胃切除の適応拡大とその成績  [Not invited]
    安田 篤; 今本治彦; 加藤寛章; 錦 耕平; 白石 治; 彭 英峰; 新海政幸; 今野元博; 安田卓司; 塩? 均
    第24回日本内視鏡外科学会総会  2011  大阪
  • 高齢者胃癌症例に対する開腹手術と鏡視下手術の比較  [Not invited]
    安田 篤; 今本治彦; 加藤 寛章; 錦 耕平; 白石 治; 彭 英峰; 新海政幸; 今野元博; 安田卓司; 塩? 均
    第66回日本消化器外科学会総会  2011  名古屋
  • Paclitaxel腹腔内投与＋逐次全身化学療法のResponderである腹膜転移陽性症例に対する胃切除付加の意義  [Not invited]
    今野元博; 今本治彦; 新海政幸; 彭英峰; 安田篤; 白石治; 中森康浩; 錦耕平; 加藤寛章; 安田卓司; 竹山宜典; 奥野清隆; 塩?均
    第111回日本外科学会定期学術総会  2011  東京
  • 胸部食道癌に対する補助療法の個別化〜PET-N診断に基づく術前化学療法の適応選別〜  [Not invited]
    白石 治; 安田卓司; 中森康浩; 安田 篤; 彭 英峰; 新海政幸; 今野元博; 今本治彦; 奥野清隆; 塩? 均
    第66回日本消化器外科学会総会  2011  名古屋
  • リンパ節陽性食道癌に対する腫瘍特異的ペプチドワクチン術後アジュバント免疫療法  [Not invited]
    錦 耕平; 石川 原; 安田卓司; 奥野清隆; 塩? 均
    第23回日本バイオセラピィ学会  2010/12  大阪
  • 集学的治療にて根治切除しえた、転移リンパ節転移による気管 浸潤陽性をきたした胸部食道癌の一例  [Not invited]
    錦 耕平; 安田 卓司; 中森 康浩; 白石 治; 安田 篤; 彭 英峰; 新海 政幸; 今野 元博; 今本 治彦; 塩? 均
    第188回近畿外科学会  2010/11  大阪
  • 若手外科医でも根治性と機能温存を可能にするリンパ節領域廓 清のコツ  [Not invited]
    白石 治; 安田卓司; 加藤寛章; 錦 耕平; 中森康浩; 安田 篤; 彭 英峰; 新海政幸; 今野元博; 今本治彦; 奥野清隆; 塩? 均
    第188回近畿外科学会  2010/11  大阪
  • 当科における胃癌腹腔鏡手術の成績  [Not invited]
    安田 篤; 今本治彦; 加藤寛章; 錦 耕平; 白石 治; 彭 英峰; 新海政幸; 今野元博; 安田卓司; 塩? 均
    第72回日本臨床外科学会総会  2010/11  横浜
  • 胃管後縦隔経路再建後に縫合不全と膿胸を生じて対称的な転帰をたどった2症例の経験  [Not invited]
    彭 英峰; 安田 篤; 安田卓司; 加藤寛章; 錦 耕平; 中森康浩; 白石 治; 新海政幸; 今野元博; 今本治彦; 塩? 均
    第16回過大侵襲研究会  2010/11  大阪
  • 局所進行食道癌に対するno split 50Gy導入化学放射線療法＋adjuvant surgeryによる治療戦略  [Not invited]
    錦 耕平; 安田 卓司; 中森 康浩; 白石 治; 安田 篤; 彭 英峰; 新海 政幸; 今野 元博; 今本 治彦; 塩? 均
    第63回日本胸部外科学会定期学術集会  2010/10  大阪
  • 噴門部胃粘膜下腫瘍に対する腹腔鏡下胃内手術9例の経験とその成績  [Not invited]
    安田 篤; 今本治彦; 中森康浩; 白石 治; 彭 英峰; 新海政幸; 今野元博; 安田卓司; 塩? 均
    第23回日本内視鏡外科学会総会  2010/10  横浜
  • 当科でのP0Cy1胃癌症例に対する各治療方針の成績について  [Not invited]
    安田 篤; 今野元博; 加藤寛章; 中森康浩; 錦 耕平; 白石 治; 彭 英峰; 新海政幸; 安田 卓司; 今本治彦; 塩? 均
    第48回癌治療学会総会  2010/10  京都
  • 漿膜浸潤を伴う胃癌に対するPTX腹腔内化学療法+逐次PTX+S-1による全身化学療法  [Not invited]
    彭 英峰; 今野元博; 加藤寛章; 錦 耕平; 中森康浩; 白石 治; 安田 篤; 新海政幸; 安田卓司; 今本治彦; 塩? 均
    第48回日本癌治療学会  2010/10  京都
  • 腹膜転移陽性胃癌に対する単回腹腔内化学療法+全身化学療法の組織学的効果の検討  [Not invited]
    今野元博; 今本治彦; 安田卓司; 新海政幸; 彭 英峰; 安田 篤; 白石 治; 中森康浩; 錦 耕平; 加藤寛章; 奥野清隆; 塩? 均
    第48回日本癌治療学会学術集会  2010/10  京都
  • 有茎空腸皮下再建後の腹壁瘢痕ヘルニアに対するクーゲルパッチを用いた修復術の1症例  [Not invited]
    安田 篤; 安田卓司; 加藤寛章; 錦 耕平; 白石 治; 彭 英峰; 新海政幸; 今野元博; 今本治彦; 塩? 均
    第64回日本食道学会学術集会  2010/09  久留米
  • 食道癌の診断と治療に於けるPETの応用  [Not invited]
    白石 治; 安田卓司; 今本治彦; 今野元博; 新海政幸; 彭 英峰; 安田 篤; 岩間 密; 中森康浩; 塩? 均
    第64回日本食道学会  2010/08  久留米
  • 導入化学放射線療法の効果別による頸部食道癌喉頭温存治療戦略  [Not invited]
    白石 治; 安田卓司; 今本治彦; 今野元博; 新海政幸; 彭 英峰; 安田 篤; 岩間 密; 中森康浩; 塩? 均
    第64回日本食道学会  2010/08  久留米
  • エチレフリン・オクトレオチド併用療法にて保存的に治癒した乳糜腹水の3症例  [Not invited]
    中森康浩; 今本治彦; 安田卓司; 今野元博; 新海政幸; 彭 英峰; 安田 篤; 白石 治; 岩間 密; 塩? 均
    第65回日本消化器外科学会総会  2010/07  下関
  • 食道癌手術再建の工夫と実績  [Not invited]
    白石 治; 安田卓司; 今本治彦; 今野元博; 新海政幸; 彭 英峰; 安田 篤; 岩間 密; 中森康浩; 塩? 均
    第65回日本消化器外科学会総会  2010/07  下関
  • 臓器予備能が低下したハイリスク症例に対する内視鏡外科手術の有用性  [Not invited]
    安田 篤; 今本治彦; 村瀬貴昭; 加藤寛章; 岩間 密; 白石 治; 彭 英峰; 新海政幸; 今野元博; 安田卓司; 塩? 均
    第65回日本消化器外科学会総会  2010/07  下関
  • P0,CY1胃癌に対するネオアジュバントとしての腹腔内化学療法＋逐次全身化学療法  [Not invited]
    彭 英峰; 今野元博; 今本治彦; 加藤寛章; 錦 耕平; 中森康浩; 白石 治; 安田 篤; 新海政幸; 安田卓司; 塩? 均
    第65回日本消化器外科学会総会  2010/07  下関
  • 術前合併症を有する食道癌手術の治療成績  [Not invited]
    新海政幸; 安田卓司; 中森康浩; 岩間 密; 白石 治; 安田 篤; 彭 英峰; 今野元博; 重岡宏典; 今本治彦; 塩? 均
    第65回日本消化器外科学会総会  2010/07  下関
  • 腹膜播種陽性胃癌症例に対するAdditional therapyとしての外科治療  [Not invited]
    今野元博; 安田卓司; 今本治彦; 中森康浩; 岩間 密; 白石 治; 彭 英峰; 新海政幸; 塩? 均
    第65回日本消化器外科学会総会  2010/07  下関
  • 胸部食道癌に対する成績向上を目指した積極的補助療法  [Not invited]
    安田卓司; 今本治彦; 新海政幸; 彭 英峰; 安田 篤; 白石 治; 岩間 密; 今野元博; 重岡宏典; 塩? 均
    第65回日本消化器外科学会総会  2010/07  下関
  • 頸部食道癌術後の胸部下部食道癌に対する血行再建付加を考慮した縦隔横断経路（胸骨後→後縦隔）による回結腸再建の1例  [Not invited]
    白石 治; 安田卓司; 錦 耕平; 中森康浩; 安田 篤; 彭 英峰; 新海政幸; 今野元博; 今本治彦; 塩? 均
    第53回関西胸部外科学会  2010/06  名古屋
  • 胸部食道癌のリンパ節郭清  [Not invited]
    安田卓司; 今本治彦; 塩? 均
    第53回関西胸部外科学会  2010/06  名古屋
  • 術前治療後の食道癌手術手技における根治性と安全性の確保  [Not invited]
    安田卓司; 今本治彦; 塩? 均
    第64回手術手技研究会  2010/05  大阪
  • クエン酸誘発咳嗽反射閾値検査による食道癌術後誤嚥性肺炎のリスク評価  [Not invited]
    中森康浩; 安田卓司; 今本治彦; 今野元博; 新海政幸; 彭 英峰; 安田 篤; 白石 治; 岩間 密; 加藤寛章; 荒木麻利子; 塩? 均
    第110回日本外科学会  2010/04  名古屋
  • 腹膜播種に対する腹腔内投与の直接的効果と効果限界の検討（ラット腹膜播種モデルを用いて）  [Not invited]
    安田 篤; 今野元博; 加藤寛章; 中森康浩; 岩間 密; 白石 治; 彭 英峰; 新海政幸; 安田 卓司; 今本治彦; 塩? 均
    第110回日本外科学会定期学術集会  2010/04  名古屋
  • 腹膜播種陽性胃癌症例における外科切除の適応  [Not invited]
    今野元博; 安田卓司; 今本治彦; 新海政幸; 彭 英峰; 安田 篤; 白石 治; 岩間 密; 中森康浩; 加藤寛章; 荒木麻利子; 村瀬貴昭; 吉岡宏真; 塩? 均
    第110回日本外科学会定期学術集会  2010/04  名古屋
  • TS-1/CDDＰによる術前化学療法が著効し、組織学的ＣＲを得た進行胃癌の1例  [Not invited]
    村瀬貴昭; 安田 篤; 今野元博; 安田卓司; 今本治彦; 新海政幸; 彭 秀峰; 白石 治; 岩間 密; 中森康浩; 加藤寛章; 奥野清隆; 塩? 均
    第82回日本胃癌学会総会  2010/03  新潟
  • P0CY1胃癌に対する術前化学療法としての腹腔内化学療法＋全身化学療法  [Not invited]
    加藤寛章; 今野元博; 岩間 密; 中森康浩; 白石 治; 安田 篤; 彭 英峰; 新海政幸; 安田卓司; 今本治彦; 塩? 均
    第82回日本胃癌学会総会  2010/03  新潟
  • 当科における高齢者胃癌症例に対する腹腔鏡手術の有用性について  [Not invited]
    安田 篤; 今本治彦; 岩間 密; 白石 治; 彭 英峰; 新海政幸; 今野元博; 安田卓司; 塩? 均
    第82回日本胃癌学会総会  2010/03  新潟
  • 漿膜浸潤を伴う胃癌に対するPTX腹腔内化学療法+逐次TX+S-1による全身化学療法の安全性  [Not invited]
    彭 英峰; 今野元博; 村瀬貴昭; 加藤寛章; 中森康浩; 岩間 密; 白石 治; 安田 篤; 新海政幸; 安田卓司; 今本治彦; 塩? 均
    第82回日本胃癌学会  2010/03  新潟
  • 腹膜播種陽性胃癌症例における集学的治療  [Not invited]
    今野元博; 安田卓司; 今本治彦; 新海政幸; 彭 英峰; 安田 篤; 白石 治; 岩間 密; 中森康浩; 加藤寛章; 村瀬貴昭; 奥野清隆; 塩? 均
    第82回日本胃癌学会総会  2010/03  新潟
  • 食道癌におけるNeoadjuvant Therapy  [Not invited]
    安田 卓司; 今本 治彦; 塩﨑 均
    第182回近畿外科学会  2007/12  大阪  第182回近畿外科学会
  • 局所制御及び遠隔制御の意義と有用性からみたNon-T4 StageII/III進行胸部食道癌に対する至適治療  [Not invited]
    安田 卓司; 今本 治彦; 今野 元博; 平井 紀彦; 新海 政幸; 彭 英峰; 安田 篤; 白石 治; 武本 智樹; 清川 厚子; 中森 康浩; 塩﨑 均
    第69回日本臨床外科学会  2007/11  横浜  第69回日本臨床外科学会
  • 頸部食道癌に対する治療戦略～更なる根治性と機能性の向上を目指して～  [Not invited]
    安田 卓司; 今本 治彦; 今野 元博; 平井 紀彦; 新海 政幸; 彭 英峰; 安田 篤; 白石 治; 武本 智樹; 清川 厚子; 中森 康浩; 塩﨑 均
    第59回日本気管食道科学会  2007/11  前橋  第59回日本気管食道科学会
  • 食道癌に対する根治的化学放射線療法後のSalvage手術の意義と適応  [Not invited]
    安田 卓司; 新海 政幸; 平井 紀彦; 今野 元博; 彭 英峰; 安田 篤; 白石 治; 武本 智樹; 清川 厚子; 中森 康浩; 今本 治彦; 塩﨑 均
    第60回日本胸部外科学会  2007/10  仙台  第60回日本胸部外科学会
  • 胸部食道癌に対する3領域リンパ節郭清の意義  [Not invited]
    安田 卓司; 今本 治彦; 今野 元博; 平井 紀彦; 新海 政幸; 彭 英峰; 安田 篤; 武本 智樹; 清川 厚子; 塩﨑 均
    第62回日本消化器外科学会  2007/07  東京  第62回日本消化器外科学会
  • non-T4&N(+)StageII/III胸部食道癌に対する治療戦略 ～術前化学療法vs化学放射線療法  [Not invited]
    安田 卓司; 今本 治彦; 今野 元博; 平井 紀彦; 新海 政幸; 彭 英峰; 安田 篤; 武本 智樹; 清川 厚子; 塩﨑 均
    第61回日本食道学会  2007/06  横浜  第61回日本食道学会
  • 胸部食道癌縦隔徹底郭清における機能温存  [Not invited]
    安田 卓司; 今本 治彦; 今野 元博; 平井 紀彦; 川西 賢秀; 新海 政幸; 彭 英峰; 安田 篤; 武本 智樹; 清川 厚子; 錦 耕平; 塩﨑 均
    第107回日本外科学会  2007/04  大阪  第107回日本外科学会

MISC

Industrial Property Rights

  • 特許6697193:圧排具    2020/04/28
    安田 卓司  学校法人近畿大学

Research Grants & Projects

  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    Date (from‐to) : 2022/04 -2027/03 
    Author : 安田 卓司; 今野 元博; 新海 政幸; 安田 篤; 白石 治; 加藤 寛章; 百瀬 洸太; 平木 洋子
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    Date (from‐to) : 2021/04 -2025/03 
    Author : 甲斐田 勇人; 石井 一成; 安田 卓司; 伊藤 彰彦; 細野 眞; 服部 聡; 河原 明彦
     
    本研究の目的は、術前化学療法を受ける進行食道癌患者対象に治療開始前FMISO PET/CTで治療効果予測が可能か病理学的評価を踏まえて検討することである。さらにFMISO集積で腫瘍内低酸素やPD-L1やCD8T細胞が発現する腫瘍免疫環境を予測可能か前向き研究で検討する。 科研費交付決定後に近畿大学医学部倫理委員会に研究計画書を提出し、一括申請を行った。倫理委員会で研究実施実施計画が承認された後に食道癌の病理組織標本に免疫染色行うための抗体やFMISOの薬剤合成にかかる消耗品の購入、FMISO PET/CTの検査が円滑に進められるように研究体制を整えた。倫理委員会承認後本研究を開始し、共同研究を行う上部消化管外科と密接に連携して、研究に参加可能な対象者を集め始めた。初年度は研究体制整備が主だった実績となった。 今年度は10症例程度を目標に予定していたが、医学部倫理委員会に申請する研究計画書の作成やその審査にかなり時間を要し、計画に遅れが生じた。次年度からは研究に該当する食道癌患者の収集を第一に努め、収集症例数をあげることである。また、食道癌の術前化学療法後、手術を行った患者の病理染色標本の染色および患者の経過観察に関して円滑に進めていけるように関係各所（近畿大学上部消化管外科、近畿大学病理学講座、久留米大学病院病理部病理診断科、大阪大学大学院医学系研究科情報統合医学講座医学統計学）との連携を再確認して、随時研究の打ち合わせの実施を行う。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2017/04 -2021/03 
    Author : Kato Hiroaki
     
    Malignant cells in the fluid that accumulated in the bag covering the esophagus between the end of the chest operation and the removal of the specimen during esophageal cancer surgery were studied. In three of 63 cases (4.8%), free cancer cells from the esophageal specimen were positive (two cases: positive cytology, one case only positive cell block). For the first time, it was found that free cancer cells leak from the esophagus between the end of chest manipulation and specimen removal during esophageal cancer surgery.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2015/04 -2020/03 
    Author : YASUDA Takushi
     
    Esophagectomy has a high risk of postoperative aspiration, which likely leads to severe pneumonia. Aspiration due to impaired swallowing movement has been improved by the refinement of surgical procedure and an intervention of swallowing rehabilitation, while aspiration due to decreased swallowing reflex remains a challenge. Swallowing reflex is regulated by substance P (SP) that is secreted by a stimulus of the brain. So, we investigated whether preoperative plasma SP value associated with subclinical cerebral infarction and pre- and post-operative swallowing function or not. Subclinical cerebral infarction reported to be observed in a half of the elderly aged over 60 years old was observed in only 5% of the study patients. However, the patients with low plasma SP level had postoperative swallowing dysfunction and showed a significantly high aspiration rate. Therefore, plasma SP value was suggested to be useful for predicting postoperative swallowing function.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2012/04 -2016/03 
    Author : YASUDA Takushi; IMAMOTO Haruhiko; IMANO Motohiro; SHINKAI Masayuki; YASUDA Atsushi; SHIRAISHI Osamu; IWAMA Mitsuru; KATO Hiroaki
     
    In this study, we examined the usefulness of induction of the phosphorylation of p53-Ser46 the next day after initiation of treatment as a biomarker of the prediction of treatment response of chemotherapy/chemoradiotherapy for esophageal squamous cell carcinoma. We confirmed the fact for the first time that the phosphorylation of p53-Ser-46 was induced by chemotherapy/chemoradiotherapy in the early stage of treatment. However, there was no significant correlation between the phosphorylation of p-53-Ser-46 and treatment response. Among cases obtained complete response to preoperative therapy, the cases with p-53 mutant and no induction of Ser-46 phosphorylation were involved, therefore, these results suggested that the effect on chemotherapy and chemoradiotherapy was caused not only by apoptosis thorough p53 pathway, but also by another pathway associating with other factors.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2009 -2011 
    Author : YASUDA Takushi; SHIOZAKI Hitoshi; IMAMOTO Haruhiko; IMANO Motohiro; SHINKAI Masayuki; PENG Ying-feng; YASUDA Atsushi; SHIRAISHI Osamu; NISHIKI Kouhei; KATO Hiroaki
     
    Aspiration of elderly patients is caused by decreased secretion of substance P(SP) that regulates cough and swallowing reflexes. We prospectively investigated the change of perioperative plasma SP concentration in patients with esophageal cancer undergoing esophagectomy and examined the association with development of aspiration. The plasma SP concentration did not show a significant change in the perioperative period. However, decreased preoperative SP concentration had a strong association with postoperative aspiration(p=0.004), suggesting that patients with decreased preoperative plasma SP concentration(60 pg/ml or less) might carry a higher risk of development of postoperative aspiration in patients after esophagectomy.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2006 -2007 
    Author : FUJIWARA Yoshiyuki; DOKI Yuichiro; YASUDA Takushi; TAKIGUCHI Syuji
     
    Novel molecular targeted therapy for peritoneal dissemination of gastric cancer was examined in this study. 1, The purpose of this study was to evaluate the efficacy of double-stranded decoy oligonucleotides targeting ets-1-binding cis elements for the suppression of ets-1 in treatment of a peritoneal dissemination model of gastric cancer. We have demonstrated that intra-peritoneal injection of ets-1 decoy inhibited the peritoneal dissemination of gastric cancer through suppression of tumor angiogenesis in a nude mice model. These results indicate that the decoy strategy for ets-1 can offer a promising therapy for patients with incurable peritoneal dissemination of gastric cancers. 2, The transcription factor nuclear factor-kB (NF-kB) plays important roles in tumor invasion, metastasis, and chemoresistance. Aberrant NF-kB expression correlates with aggressive tumor behavior and poor prognosis in patients with various malignancies. This study evaluated the sesquiterpene lactone parthenolide, an inhibitor of NF-kB, in the treatment of gastric cancer. Parthenolide significantly inhibited cell growth in three gastric cancer cell lines. It downregulated the phosphorylation of NF-kB, and acted synergistically with chemotherapeutic drugs, paclitaxel and cisplatin. In the peritoneal dissemination model, parthenolide as a single agent significantly suppressed the formation of disseminated nodules, and enhanced chemosensitivity to paclitaxel when used in combination. Furthermore, the combined parthenolide and paclitaxel therapy significantly prolonged survival. Parthenolide, a selective NF-□B inhibitor, seems to enhance the chemosensitivity of paclitaxel and cisplatin in the incurable peritoneal dissemination of gastric cancers.
  • 日本学術振興会：科学研究費助成事業 萌芽研究
    Date (from‐to) : 2006 -2007 
    Author : 土岐 祐一郎; 宮田 博志; 安田 卓司; 藤原 義之; 瀧口 修司
     
    消化器癌におけるオートファジーの意義について検討するためにオートファジー・マーカーとしてMicrotubule-associated protein 1 light chain 3 (LC3),の免疫染色を消化器癌で行った。対象は当科で切除を行った消化器癌163例(食道癌106例、胃癌38例、大腸癌19例)と前癌病変としての食道intraepithelial neoplasia 70例。食道癌においてはLC3発現と細胞増殖マーカーとしてのKi-67、低酸素マーカーとしてのCA-IXの発現との関係を調べた。LC3免疫染色の評価は陽性細胞数のfrequencyとintensityの総合評価をスコア化し高発現/低発現の2群に分けて検討を行った。LC3発現は正常組織ではみられず癌組織のcytoplasmのみに見られ、食道癌では53%、胃癌では58%、大腸癌では63%がLC3高発現であった。食道前癌病変から早期癌にかけてLC3スコアは増加したが、進行癌ではそれ以上の増加はなかった。またLC3とKi-67の関係ではLC3高発現を示す癌部分はKi-67陽性となる傾向があり、特に早期癌ではLC3発現とKi-67陽性率は相関した。一方、LC3とCA-IXの関係ではCA-IXが癌巣の中心部で染色されるのに対してLC3は癌巣の辺縁で染色され、早期癌、進行癌のいずれにおいても両者の染色性に相関はみられなかった。また食道癌におけるLC3発現と患者予後の間には関連はみられなかった。以上より、LC3は癌組織で高発現がみられオートファジーが亢進していると考えられた。特にオートファジーは癌進展の早期において重要な役割を果たすことが考えられた。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    Date (from‐to) : 2005 -2006 
    Author : DOKI Yuichiro; YASUDA Takushi; FUJIWARA Yoshiyuki; TAKIGUCHI Syuji; MIYATA Hiroshi
     
    We performed the Phase I clinical trial "Cancer vaccine with NY-ESO-1 protein against advanced esophageal cancer patients." 13 patients were entered, and advanced effects, immune responses and clinical responses by the reagent were observed. No severe advanced effect was observed. For NY-ESO-1 specific immune responses antibody and CD4, CD8 T cells were analyzed by ELISA and secretion assay of INF-gamma, respectively. Remarkable or local clinical responses were observed in 4 out of 13 patients and they showed both elevation of antibody titer and detectable induction of CD4 T cells. CD8 T cells were observed in most of patients. Epitopes of antibody, CD4 and CD8 T cells in NY-ESO-1 protein were analyzed and we identified high immunogenic lesion with about 70 amino acids long at the center of NY-ESO-1 protein sequence, which were easily and economically producible by the Peptide Synthesizer without use of E. Coli. Instead of whole protein, this high immnogenic 70-mer peptide is being synthesized for the "Cancer Vaccine with NY-ESO-1 Protein as Adjuvant Therapy after Surgical Treatment for esophageal cancer patients." For this trial, advanced esophageal cancer patients will be vaccinated as the adjuvant therapy after curative surgical treatment with pre-operative chemotherapy. We have already calculated the tumor-free survival rate of those 60 patients as a control. Performing the trial new control patients will be recruited accumulated on this control. We also plan to vaccine with overlapping serial short peptides from NY-ESO-1 sequence.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2005 -2006 
    Author : MIYATA Hiroshi; DOKI Yuichiro; YASUDA Takushi; FUJIWARA Yoshiyuki; TAKIGUICHI Syuji; KANGAWA Kenji
     
    1 In order to evaluate the effect of Ghrelin to proliferation of cancer cells, we performed MTT assay and counted the number of cancer cells after adding Ghrelin to culture medium of esophageal cancer cell lines (TE3,TE8) and gastric cancer cell lines (MKN-45,KATO-III), and found that Ghrelin did not affect proliferation of cancer cells. This result confirmed the safety of administering Ghrelin to patients with uppergastrointestinal cancers after surgery. 2 We administered Ghrelin to three healthy donors and also did saline as control to three healthy donors immediately after orally taking nutrition liquid (Racol), and examined Ghrelin, growth hormone and insulin levels in serum and blood glucose levels. We also examined gastric emptying function using breath test of measuring 13-C acetate. As a result, we found that serum growth hormone significantly increased as serum Ghrelin increased in Ghrelin group compared with control group and that serum insulin and blood glucose increased more immediately in Ghrelin group than control group. We also found that gastric emptying time shortened in Grhelin group. These results indicated that administrating Ghrelin to healthy donors facilitates gastric emptying function and glucose absorption. 3 After a phase II study of administrating Ghrelin to patients who undergo gastrectomy for gastric cancers was approved by the ethics committees at Osaka University Hospital, ten patients were enrolled in this study between August 2006 and March 2007. Ghrelin at a dose of 3μ g/kg were administrated to patients twice a day via drip infusion on days 5 to 15 after surgery, and we evaluated oral intake, intestinal motility, absorption function of small intestine and change of various blood sample data, such as growth hormone, albumin ghrelin and leptin. We plan to analyze patients data obtained from this study in detail.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2004 -2005 
    Author : FUJIWARA Yoshiyuki; TAKIGUCHI Shuji; MIYATA Hiroshi; YASUDA Takushi
     
    Detection of cancer micrometastases that are missed by conventional cytological and histopathological examination is required for improvement of cancer therapy. The aim of this study was to establish a rapid and practical genetic assay to detect micrometastasis in gastric cancer and to assess its clinical significance with respect to prognosis. A novel RNA amplification system with TRC reaction (transcription-reverse transcription concerted reaction) was introduced for quantitative detection of CEA (carcinoembryonic antigen) mRNA, which is widely used as a molecular marker for cancer micrometastasis. Peritoneal lavage fluid specimens and lymph nodes collected from cancer surgery were subjected to the assay, and the clinical significance of the results in prediction of recurrence and survival was examined. The quantification, sensitivity, and reproducibility of the assay using the TRC reaction were equal to those of quantitative RT-PCR with LightCycler^. The most important advantage of the assay was its simplicity and rapidity. Molecular diagnosis of peritoneal lavage fluid by the TRC reaction significantly correlated with depth of invasion, peritoneal metastasis, clinical stage, overall survival and peritoneal recurrence-free survival. Molecular diagnosis of peritoneal lavage fluid with the TRC reaction could be a useful prognostic indicator for peritoneal recurrence and survival. Because the TRC reaction is more rapid and simple than RT-PCR as a format for detecting RNA sequences, it may enhance the genetic diagnosis of cancer micrometastasis and may contribute to cancer therapy.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2004 -2005 
    Author : YASUDA Takushi; FUJIWARA Yoshiyuki; TAKIGUCHI Shuji; MIYATA Hiroshi
     
    (1)Development of positron probe for intra-operative application Apollomec corporation developed positron probe with two types of detectors, plastic scintillator for beta rays and BGO crystal for gamma rays. This probe counts as a real event only when both rays are detected simultaneously in order to reduce background level. (2)Committee on clinical application of radioisotope Our protocol in clinical application is planned to measure radioactivity by positron probe during operation after injection of ^<18>F-FDG in P3 room just before operation. Therefore, the influence to the human body of ^<18>F was evaluated in above-mentioned committee. As a result, the committee approved the usage of ^<18>F, because that half life is very short and the influence to the human body is very little. (3)Examination of injection time of ^<18>F-FDG As a matter of fact, to delay to start operation is needed to inject ^<18>F-FDG just before operation, because it takes a time to synthesize and purify ^<18>F-FDG. Therefore, we examined whether radioactivity of ^<18>F could be measured or not when ^<18>F-FDG was injected in the evening of the day before operation. The half life of ^<18>F is 109.8 minute. Theoretically, radioactivity is reduced to about 1/256, assuming to measure after 16 hours of injection. We measured radioactivity by gamma probe next morning in patients of esophageal squamous cell carcinoma with huge lymph node metastasis, however, its count was very subtle, so that this protocol of previous day injection was found not to be clinically applicable. Above all, the necessity of injection of ^<18>F-FDG just before operation was suggested to maintain diagnostic quality and accuracy by positron probe. Conclusion : A lot of issues to have to be resolved are still remained, however, FDG-guided surgery may be the promising new approach to have a potential as a breakthrough of quality of surgery.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2002 -2003 
    Author : FUJIWARA Yoshiyuki; YASUDA Takushi; YANO Masahiko; TAKIGUCHI Syuji; MONDEN Morito
     
    1, We have developed molecular diagnosis for micrometastasis in peritoneal lavage fluids of gastric cancer patients (Int.J.Oncol,2003). 2, We introduced pre-operative laparoscopy and molecular diagnosis with peritoneal lavage fluids for advanced gastric cancer. Pre-operative intra-operative chemotherapy was performed for serosa-invaded gastric cancer cases. These results showed that if molecular diagnosis changed from micrometastasis positive to negative, the prognosis of the patient was improved (Ann.Surg.Oncol,2004). 3, The pilot study of a new multidisciplinary therapy was performed for 60 cases with advanced gastric cancer. This study showed that pre-operative chemotherapy for high-risk patients of peritoneal recurrence was beneficial and the patients with molecular diagnosis (-) had a better prognosis. 4, In conclusion, the new multidisciplinary therapy combined with laparoscopy and molecular diagnosis will be effective for far-advanced gastric cancer patients.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2002 -2003 
    Author : YASUDA Takushi; TAKIGUCHI Shuji; FUJIWARA Yoshiyuki; YANO Masahiko
     
    (1) Prediction of the response to preoperative therapy by p53 status for patients with advanced esophageal squamous cell carcinoma (SCC). The presence or absence of mutation within exon 4 to 9 of p53 gene was analyzed with endoscopic biopsy sample before treatment using SSCP technique. Chemoradiotherapy was received in 67 patients, who were divided in 48 of wild type (WT) and 19 of mutant (MT). Grade 2 or more histological response was obtained in 31 of WT group (65%), to the contrary, in only 2 of MT group (11%). In 30 patients who underwent chemotherapy, WT and MT were observed in 21 and 9 patients, respectively. Clinically good responders were shown in 16 of WT group (76%) and only I of MT group (11%). (2) Response evaluation of neoadjuvant therapy by FDG-PET prediction of histological response. According to post treatment PET analysis, patients with or without FDG accumulation were classified in PET positive or PET negative. The maximum cross-sectional square area of residual tumor ranged from 0 to 32.6mm2 (average 10.0mm2) in PET negative group and from 66.0 to 676.0mm2 (average 287.7mm2) in PET positive group. The histological good response of grade 2 to 3 was obtained in 15 of PET negative patients (88%) and in only 2 of PET positive patients (12%). (3) Positive indication of salvage surgery. The 1-and 3-year overall survival rate were 93.3% and 81.7% in PET negative group compared with 67.8% and 40.7% in PET positive group. Conclusion: In multidisciplinary treatment for advanced esophageal SCC, the analysis of p53 status is useful to predict a treatment resistance and also FDG-PET may be the extremely useful modality to predict a histological response after neoadjuvant therapy. Post-treatment PET negative patient may be a good candidate for salvage surgery.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2001 -2002 
    Author : SEKIMOTO Mitsugu; IKENAGA Masakazu; YASUDA Takushi; YAMAMOTO Hirofumi
     
    In 2001, we developed cDNA microarray and investigated gene expression profile of colorectal cancer. First, we selected non-redundant 4600 genes among 30000 cDNA library clones from cancer, normal, and liver metastais samples, plus 170 colon cancer related genes in literature. After analysis of clinical samples, we identified 23 genes overexpressed in cancer samples two times more than normal mucosa and 36 decreased genes to a half lesser extent. Expression of selected genes was confirmed by RT-PCR (coincidence:93%), data form SAGE (N=12, coincidence:83%) or in literature (N=15). In 2002, we tested whether gene expression profile would predict liver when distinct samples of liver metastasis and found that the gene subsets successfully predicted liver metastasis in 85% cases. Now we are developing oligo-array for clinical application.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2001 -2002 
    Author : YANO Masahiko; YAMAMOTO Hirofumi; FUJIWARA Yoshiyuki; YASUDA Takushi
     
    This study investigated correlation between the lymph node metastasis, lymphatic invasion and the expression of several molecular markers which are reported to be associated with malignant potential of cancer cells. The markers which we measured in this study include cyclin D1, Rh, p16, p27 and PCNA as cell cycle regulator molecules, and E-cadherin, α- and β-catenin as intercellular adhesion molecules, Forty-three patients with superficial esophageal cancer who had had no prior chemotherapy and/or radiotherapy were enrolled in this study. Surgically resected samples were subjected to immunohistochemical analysis using antibodies against the above molecules. According to the tumor depth, the samples were classified into three groups; m1-m2 (group A): n=7, m3-sm1 (group B) n=9, and sm=2-3 (group C) n=27. For cyclin D1, strong expression was defined as abnormal expression, whereas for Rh, p16, p27, E-cadherin, α- and β-catenin, reduced expression was defined as abnormal one. For PCNA, percentage of positive cells was calculated. Lymph node metastasis was positive in 0% in A, 11% in B and 33% in C group, while lymphatic invasion was positive in 14% in A, 33% in B and 41% in C group. As regard with adhesion molecules, tumors with at least one abnormal expression were seen in 20% in A, 60% in B and 84% in C group, which increased in coincidence with the extent of tumor depth. However, it did not show correlation with lymph node metastasis. As regadr with cell cycle regulators, the only molecule that showed correlation with lymph node metastasis was cyclin D1. Eight out of 20 cases which showed strong cyclin D1 expression had lymph node metastasis, whereas only 2 out of 28 cases which showed weak expression had lymph node metastasis (p<0.05), On the other hand, 26 out of 28 cases which showed no lymphatic invasion had no lymph node metastasis, while 8 out of 15 cases which showed positive lymphatic invasion had lymph node metastasis (p<0.01). These suggest that combination of cyclin D1 and lymphatic invasion may help more accurate prediction of lymph node metastasis from superficial esophageal cncers. This study also investigated a risk factor for lymph node metastasis from colonic cancers using 123 superficial colonic cancer specimens. Tumor depth was defined acording to the distance from muscularis mucosa to the front of tumors as follows; sm1: 0-500μm, sm2: 500-1000μm , sm3: 1000-μm. Lymph node metastasis was seen in 0% in sm1, 2.0% in sm2 and 7.5% in sm3. The shortest distance of the tumors that had lymph node metastasis was 1200μm. Clinicopathological analysis revealed that the risk factor for lymph node metastasis was the distance from muscularis mucosa of more than 1200μm, lymphatic invasion, budding of the front of tumors and severe dysplasia. At present, correlation between these factors and molecular markers such as MMP7, MMP9, S100, Rho, cadherin, catenin, KI-67, apotosis marker.
  • Analysis of the usefulness of 18F-FDG PET in the judgement of response of neoadjuvant therapy for advanced esophageal carcinoma
    The Other Research Programs
    Date (from‐to) : 1999
  • 高度リンパ節転移陽性進行食道癌症的における術前FAP療法
    その他の研究制度
  • 進行食道癌の術前治療効果判定における18F-FDG-PETの有用性に関する研究
    その他の研究制度
  • Phase (]G0002[) study Phase (]G0002[) trial of 5-Fluorouracil, Adriamycin and Cisplatin patients of advanced esophageal carcinoma with multiple lymphnode metastasis
    The Other Research Programs

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