INTRODUCTION: This study aimed to evaluate the efficacy of perioperative dysphagia rehabilitation in older adult patients diagnosed with gastric cancer who underwent gastrectomy. MATERIALS AND METHODS: This retrospective study included 149 patients over 80 years who underwent gastrectomies between January 2000 and December 2020. The patients were divided into two groups based on the intervention of the dysphagia rehabilitation team (DRT group: n = 101) and the non-intervention control group (C group: n = 48). Inverse probability weighting (IPW) analysis was used to reduce bias caused by potential confounding. RESULTS: The incidence of overall complications was significantly lower in the DRT group (odds ratio [OR]; 0.27[0.08-0.93]), among which the incidence of postoperative pneumonia (OR; 0.07[0.01-0.43]) and aspiration pneumonia (OR; 0.05[0.01-0.44] was significantly reduced. Ten patients developed postoperative pneumonia; seven were in the C group, and three were in DRT group. Sixty percent of these patients had preoperative comorbidities related to the respiratory system. Regarding the time of onset of aspiration pneumonia, two patterns were observed: onset within a short period after surgery and onset after the start of eating. In contrast, five patients underwent preoperative dysphagia rehabilitation in the DRT group. Among them, postoperative aspiration pneumonia was prevented in four patients, and the others were prevented from severe pneumonitis by the intervention of the dysphagia rehabilitation team. DISCUSSION: Perioperative intervention in dysphagia rehabilitation is not only associated with reduced postoperative pneumonia but also creates awareness in the medical staff and promotes careful observation of swallowing in patients, thereby controlling the incidence of postoperative pneumonia. The perioperative intervention of the dysphagia rehabilitation team is useful for older adult patients with gastric cancer.

We aimed to determine the frequency and prognosis of supraclavicular (#104) lymph node (LN) metastasis compared with other LN stations in patients with advanced thoracic esophageal cancer and to identify risk factors for metastasis to delineate the indications for three-field lymphadenectomy (3FL). The study cohort of 567 eligible patients with esophageal cancer had undergone subtotal esophagectomy from 2003 to 2020. LN metastasis was defined as pathologically proven metastasis or positron emission tomography-positive LNs. The efficacy index (EI), calculated from the frequency of LN metastases and survival rates, was used as prognostic value of each LN station dissection for patient survival. Risk factors for #104 LN metastasis were determined by multivariable logistic regression. The frequency of #104 LN metastasis was 11.6% overall, 31.7% in upper and 8.3% in middle/lower third lesion. Neoadjuvant chemotherapy was administered to 71% of patients and chemo-radiation to 11%. The 5-year overall survival was 45.8%. The EI for #104 LNs (5.3) was similar to that for #101 LNs. Risk factors were age < 65 years, upper third lesion, clinical N2-3, #101/106rec LN metastasis and poorly differentiated carcinoma. The 5-year overall survival of patients with middle/lower lesions was 38% (EI 3.1), similar to that for #101 and #8/9/11 LNs. The prognosis of patients with #104 LN metastases is similar to that of patients with metastases in other regional LN stations. Therefore, we recommend 3FL exclusively for patients at a high risk of #104 LN metastasis due to the overall metastatic rate not being high.

BACKGROUND: While a neoadjuvant chemotherapy regimen using docetaxel, cisplatin, and 5-fluorouracil (NAC-DCF) is considered the standard treatment for locally advanced esophageal cancer (EC) in Japan, a reliable marker for early prediction of treatment efficacy remains unclear. We investigated the utility of the tumor response after a first course of NAC-DCF as a post-surgery survival predictor in patients with EC. METHODS: We enrolled 150 consecutive patients who underwent NAC-DCF followed by surgery for EC between September 2009 and January 2019. The initial tumor reduction (ITR), defined as the percentage decrease in the shorter diameter of the tumor after the first course of NAC-DCF, was evaluated using computed tomography. We analyzed the relationship between ITR, clinicopathological parameters, and survival. RESULTS: The median ITR was 21.07% (range -11.45 to 50.13%). The optimal cut-off value for ITR for predicting prognosis was 10% (hazard ratio [HR] 3.30, 95% confidence interval [CI] 1.98-5.51), based on univariate logistic regression analyses for recurrence-free survival (RFS). Compared with patients with ITR <10%, patients with ITR ≥10% showed a significantly higher proportion of ypM0 (80.0% vs. 92.5%) and responders in terms of overall clinical response (50.0% vs. 80.8%). Multivariate analysis for RFS revealed that ypN2-3 (HR 2.78, 95% CI 1.67-4.62), non-response in terms of overall clinical response (HR 1.87, 95% CI 1.10-3.18), and ITR <10% (HR 2.48, 95% CI 1.42-4.32) were independent prognostic factors. CONCLUSIONS: Tumor response after the first course of NAC-DCF may be a good predictor of survival in patients with EC who underwent NAC-DCF plus surgery.

症例は89歳,女性.直腸癌(cT3N0M0,cStageIIa)に対し,ロボット支援Hartmann手術を施行した.術後6日目にイレウスを発症し,左上腹部にゴルフボール大の隆起を認めたため,単純CTを施行したところ左上腹部の8mmポートサイト腹壁に小腸の嵌入を認め,ポートサイトヘルニアと診断した.用手還納できず,同日緊急手術を施行した.左上腹部のポート創を開創したところ,嵌入した小腸とヘルニア門を同定した.小腸の色調は良好であったため,小腸を腹腔内に還納し,創部は0-PDS(PDS II:ZB776,ETHICON)で筋膜と腹膜を縫合閉鎖した.術後経過は良好で,術後11日目に退院となった.ポートサイトヘルニアは腹腔鏡手術特有の合併症であるが,ロボット支援手術における8mmダビンチポートサイトを閉鎖すべきかについての明確なエビデンスはない.今回,ロボット支援Hartmann手術後に8mmポートサイトヘルニアを発症した症例を経験したので報告する.(著者抄録)

症例は89歳,女性.直腸癌(cT3N0M0,cStageIIa)に対し,ロボット支援Hartmann手術を施行した.術後6日目にイレウスを発症し,左上腹部にゴルフボール大の隆起を認めたため,単純CTを施行したところ左上腹部の8mmポートサイト腹壁に小腸の嵌入を認め,ポートサイトヘルニアと診断した.用手還納できず,同日緊急手術を施行した.左上腹部のポート創を開創したところ,嵌入した小腸とヘルニア門を同定した.小腸の色調は良好であったため,小腸を腹腔内に還納し,創部は0-PDS(PDS II:ZB776,ETHICON)で筋膜と腹膜を縫合閉鎖した.術後経過は良好で,術後11日目に退院となった.ポートサイトヘルニアは腹腔鏡手術特有の合併症であるが,ロボット支援手術における8mmダビンチポートサイトを閉鎖すべきかについての明確なエビデンスはない.今回,ロボット支援Hartmann手術後に8mmポートサイトヘルニアを発症した症例を経験したので報告する.(著者抄録)

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.

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.

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.

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.

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.

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.

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.

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.

INTRODUCTION: Cirrhosis is a significant determinant of postoperative morbidity and mortality. Patients with severe liver cirrhosis are substantially contraindicated for surgical treatment of inguinal hernia because of the substantial recurrence rate and high postoperative morbidity and mortality. However, hernia with incarceration and strangulation, which could become life-threatening, should be repaired urgently even for patients with severe liver cirrhosis. No clear surgical guidelines have been established regarding the treatment strategy for inguinal hernia in patients with cirrhosis. PRESENTATION OF CASE: A 62-year-old man with a history of chronic C-type liver cirrhosis (Child-Pugh classification C) and hepatocellular carcinoma was referred to us for surgical treatment of an irreducible right inguinal hernia. An abdominal computed tomography (CT) scan revealed that the small intestine had herniated into the scrotum and severe abdominal wall varicose veins due to liver cirrhosis. We performed a hybrid method that combines examination laparoscopy and Lichtenstein's technique to observe the abdominal cavity and to avoid the risks due to severe varicosis of the inferior epigastric vein. DISCUSSION: There have been some reports of inguinal hernia with cirrhosis and ascites, but no reports of incarcerated inguinal hernia with abdominal wall varicose veins. In the present case, we chose a laparoscopic approach to observe the abdominal cavity to confirm intestinal necrosis. Hybrid surgery using laparoscopy and Lichtenstein's technique for incarcerated inguinal hernia could be performed safely. CONCLUSION: Hybrid surgery using laparoscopy and Lichtenstein's technique may be an effective method for patients with incarcerated inguinal hernia with end-stage cirrhosis and severe abdominal varicosis.

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.

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.

＜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.

＜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.

INTRODUCTION AND IMPORTANCE: We describe the case of a patients with a diaphragmatic hernia associated with radiofrequency ablation for hepatocellular carcinoma who was treated by laparoscopic repair. CASE PRESENTATION: An 82-years-old man with history of HCC with hepatitis C virus-related liver cirrhosis (Child-Pugh B). The patient was treated RFA to HCC for segment 4, 5, 6, 8. After 16 months from latest RFA for segment 8, the patient was admitted to our hospital because of mild dyspnea. Computed tomography revealed a diaphragmatic herniation of bowel loops into the right thoracic cavity. The patients electively underwent laparoscopic repair of the diaphragmatic hernia. The patient was discharged from hospital without any post-operative complications. CLINICAL DISCUSSION: The only treatment to diaphragmatic hernia is surgery, but liver cirrhosis patients limits this possibility. For the surgical treatment of patients with severe cirrhosis, the operation should be carefully assessed. We believe that a laparoscopic approach should be used for repairing diaphragmatic hernia. In the present case, we considered that a laparoscopic approach was safer and more feasible than open laparotomy. CONCLUSION: Diaphragmatic hernia is a rare late-onset complication associated with RFA for HCC. And patients with HCC often have severe liver dysfunction and cirrhosis. A laparoscopic approach is safe and minimally invasive for sever cirrhosis patients.

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.

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.

＜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.

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.

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.

The effectiveness of endovascular aneurysm repair (EVAR) has been proven, but anatomical limitations, including narrow access route, may obstruct procedure of EVAR and cause serious complications. Parallel placement of Excluder legs (W. L. Gore & Associates, Inc., Newark, DE, USA) was established to treat patients with type IIIb endoleak or those with a narrow aorta, who could not be treated using a standard main body. In this report, we applied this technique in two patients with aortoiliac aneurysms with occlusive lesion.

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.

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.

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.

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)

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)

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)

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.

A 71-year-old man with a history of hypertension, diabetes mellitus, and cerebral infarction was admitted to our hospital with dysphagia. Gastroduodenoscopy, thoracoabdominal CT, and PET-CT findings showed type 2 advanced esophageal cancer( squamous cell carcinoma)with upper mediastinal and cervical lymph node(LN)metastasis: cT3N2M1(LYM #104L), cStage Ⅳ. Two courses of neoadjuvant UDONchemotherapy containing 5-FU(640mg/m / 2, days 1-5), docetaxel(28mg/m2, days 1 and 15), and nedaplatin(72mg/m2, day 1)were administered every 4 weeks. UDONtherapy caused grade(Gr)3 febrile neutropenia, Gr 2 diarrhea, and Gr 1 thrombopenia; the tumor and LNs partially responded to the therapy. After 2 courses of UDONtherapy, esophagectomy with right thoracotomy, 3-field LNdissection, and reconstruction of the gastric tube were performed. The postoperative course was almost uneventful besides recurrent nerve palsy, aspiration, pneumonia, and delirium, and the patient was discharged 60 days after surgery. The pathological diagnosis was ypT0N0M0, ypStage 0, and the histological response of the primary tumor and LNs were evaluated as Gr 3. Neoadjuvant UDON therapy is feasible for elderly patients with advanced esophageal cancer and renal failure or comorbidities, for whom CDDP could not be administered. We are planning a clinical trial to assess the effectiveness of neoadjuvant UDONtherapy.

The usefulness of intraperitoneal(IP)chemotherapy for gastric cancer with intraperitoneal metastasis has been examined in some clinical trials. We report a case of intestinal perforation caused by a catheter for IP ports. A 75-year-old man had undergone IP therapy for type 4 gastric cancer. After IP therapy, he underwent total gastrectomy. He had no recurrence for 3 years. He complained of high fever and abdominal pain more than 1 week ago. Based on contrast-enhanced CT, we diagnosed him with peritonitis by intestinal perforation due to the catheter, and on the same day, we removed the catheter and performed intraperitoneal drainage by emergent laparotomy. The tube penetrated the ileum 20 cm from the ileocecal portion. We resected the ileocecal area and damaged intestinal tract and removed the subcutaneous IP port. He was discharged on the 25th postoperative day. IP ports should be removed after the completion of IP chemotherapy because the incidence of perforation by IP ports was reported as 0 to 3.5%in a previous report.

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.

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.

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.

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.

4型胃がん(スキルス胃がん)のなかに、「診断困難な症例」が少なからず存在する。内視鏡検査で粘膜面から異常が指摘できないもの、内視鏡では"太い襞"がありスキルス胃がんであるが、生検でがん組織が得られない場合である。患者は85歳、男性。太い雛壁がありスキルス胃がんと診断されたが、生検でがん組織が得られず当院に紹介された。狭窄があるため、開腹による精査と治療を説明し実施した。開腹により適切な診断ができ、本人の希望どおりに手術(胃全摘)を行った。術後化学療法なしに1年生存中である。スキルス胃がんは内視鏡生検の結果だけに頼らず試験開腹まで行って早期に診断を付け、治療を開始すべきである。(著者抄録)

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)

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)

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)

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)

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)

食道入口部に及ぶ頸部食道癌を化学放射線療法(CRT)と術式の工夫によって、quality of life(QOL)と根治性を両立し得た喉頭温存手術の1例を報告する。症例は58歳、男性。腫瘍は食道入口部から胸骨切痕の高さまで及ぶT3頸部食道癌で、左右101リンパ節に転移を認めた。まずCRT(5-FU+CDDP+30Gy)で腫瘍を縮小させ、切離断端の腫瘍陰性を確保した。手術においては切離断端距離を最大限確保するため、両側輪状咽頭筋、下咽頭収縮筋下端を切離し、輪状軟骨上縁の高さでの食道を切離した。また、術後の誤嚥対策として、術後に瘢痕拘縮して喉頭挙上運動に拮抗作用を呈する舌骨下筋群を胸骨付着部で切離した。再建は遊離空腸で行った。病理結果は扁平上皮癌、ypT2、INFb、ly0、v0、PM0(10mm)、ypN0、ypStage IIAであった。術後4日目に抜管し、右反回神経麻痺を認めたが誤嚥はなく経過し、嚥下リハビリに時間を要したものの経口摂取は良好で、術後71日目に退院した。その後は社会復帰し、術後5年間再発なく経過した。(著者抄録)

Some of scirrhous gastric cancer are difficult to diagnose on the surface view or to take correct biopsy specimen.A 85-yearold man with dysphagia was diagnosed scirrhous gastric cancer endoscopically, but could not be taken a biopsy specimen showing cancer.We informed cases of scirrhous gastric cancer difficult to take correct biopsy specimen and recommended surgical operation to take correct specimen and to start a treatment.Patient underwent total gastrectomy after cancer diagnosis( P0CY0cT4aN0).He can eat more food and survive longer than 1 year without any chemotherapies.Scirrhous gastric cancer needs early diagnosis and treatment to improve patient prognosis.

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.

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)

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.

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.

The patient was a 58-year-old man suffering from dysphagia. He was diagnosed with T3 cervicalesophagealcancer that invaded the posterior hypopharyngealwal lwith lymph node metastasis. The patient received neoadjuvant chemoradiotherapy (30 Gy with CDDP/5-FU), followed by larynx-preserving surgery(LPS)for cervicalesophagealcancer. Two techniques for successfulLPS consist of the dissections of cricopharyngealmuscl e and the inferior pharyngealsphincter, and the complete division of the bilateral infrahyoid muscles attached to the sternum(CDBIMS). The former technique of releasing the esophagus from the trachea at the cricoid cartilage level results in the extension of the oral surgical margin. The latter technique is expected to prevent postoperative aspiration pneumonia, as the lack of flexibility of scarred infrahyoid muscles is regarded as one of the major causes of dysfunction in swallowing. Free jejunum was transferred for cervical reconstruction. Pathological examination indicated degenerated squamous cell carcinoma(ypT2, INF b, ly0, v0, PM0, ypN0, ypStage II A). Although the patient had recurrent nerve palsy, he could eat meals without aspiration. He returned to normal life after discharge from the hospital. Five years after surgery, no recurrence had been observed.

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.

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)

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.

膵頭十二指腸切除術後の膵液瘻の重症化を防ぐためには感染に対する早期の対策と制御が重要である。今回、PD術後早期におけるドレーン排液の監視培養の結果とPFの重症化との関連を検討した。対象は2011年9月から2015年9月までに当院でPDを施行した35例で、感染徴候の有無にかかわらず、術後第1病日(POD1)、POD3に留置されている各ドレーン排液の培養を行った。POD1で10例(28.6%)、POD3で新たに4例を加えた14例(40.0%)で細菌が検出された。いずれも腸管由来と考えられる菌であり、Enterococcus属の頻度が最も高かった。多変量解析ではPOD3までの菌の検出は、Grade B/CのPFへ進展する独立した危険因子であった。術後早期のドレーン排液培養は、PFの重症化の予測因子となることが示唆された。(著者抄録)

Owing to the advances in diagnosis and treatment, it is imperative to develop a multidisciplinary approach for the management of cancer patients. In our cancer center, multidisciplinary organ-based tumor units have been organized for team medical care. These units consist of cancer specialists from multiple departments including medical oncology, surgery, radiology, histopathology, and nursing. Members of each unit regularly conduct meetings to discuss diagnostic and therapeutic aspects, as well as to report the progress of cancer patients. Co-operation with the counseling and support center, utilization of the computerized medical record system, and using brochures for advertisement, all play important roles in adequate management of multidisciplinary organ-based tumor units.

がん診療においては診断・治療の発展に伴い、多科・多職種で運営されるチーム医療体系が求められている。当院のがんセンターでは「臓器別腫瘍ユニット」という多科・多職種で構成された臓器別チーム医療を実践している。運営の核となっているのは定期的に開催しているユニットカンファレンスであり、診療にかかわる各科・職種が参加し、診断・治療方針の決定や診断経過や治療経過の報告を行っている。また、がん相談支援センターとの連携、電子カルテの活用、パンフレットを用いた患者への臓器別腫瘍ユニット診療体制であることの広報なども、臓器別腫瘍ユニット運営の工夫としてあげられる。(著者抄録)

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)

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.

Granulomatous mastitis (GM) is a rare chronic inflammatory breast condition with unknown etiology. There is still no generally accepted optimal treatment for GM. Corticosteroid treatment and/or wide excision is most commonly reported in the literature. Incision and drainage or limited excision alone has little benefit because of a strong tendency of recurrence. Corticosteroids also have a high failure rate and possible side effects. In the current series, we treated GM patients without corticosteroids, except for one patient. We also devised multidirectional deep drainage for advanced and complicated abscesses, which are characteristic of GM. This retrospective study included 13 women who met the required histologic criteria of GM. The mean age of the patients was 41 years. All of the patients were premenopausal. Six patients had breast-fed in the last 5 years. Five patients were under medication with antidepressants. A total of 11 patients developed abscesses during the clinical course, and the abscesses penetrated the retromammary space in 4 patients. We treated 2 of these 4 patients with multidirectional deep drainage and obtained complete remission in 5 and 6.5 months, respectively. These times were much shorter than those in the other 2 patients. The time to resolution in 11 patients was 4 to 28 months. This overall outcome was comparable with that of corticosteroid treatment reported in the literature. Because the natural history of GM is thought to be self-limiting, close observation and minimally required drainage of abscesses without corticosteroid administration remain the treatment modality of choice.

POU5F1B (POU domain class 5 transcription factor 1B), a processed pseudogene that is highly homologous to OCT4, was recently shown to be transcribed in cancer cells, but its clinical relevance and biological function have remained unclear. We now show that POU5F1B, which is located adjacent to MYC on human chromosome 8q24, is frequently amplified in gastric cancer (GC) cell lines. POU5F1B, but not OCT4, was also found to be expressed at a high level in GC cell lines and clinical specimens. In addition, the DNA copy number and mRNA abundance for POU5F1B showed a positive correlation in both cancer cell lines and GC specimens. Overexpression of POU5F1B in GC cells promoted colony formation in vitro as well as both tumorigenicity and tumor growth in vivo, and these effects were enhanced in the additional presence of MYC overexpression. Furthermore, knockdown of POU5F1B expression with a short hairpin RNA confirmed a role for the endogenous pseudogene in the promotion of cancer cell growth in vitro and tumor growth in vivo. POU5F1B overexpression induced upregulation of various growth factors in GC cells as well as exhibited mitogenic, angiogenic and antiapoptotic effects in GC xenografts. Finally, amplification of POU5F1B was detected in 17 (12%) of 145 cases of GC and was a significant predictor of poor prognosis in patients with stage IV disease. In conclusion, we found that the POU5F1B pseudogene is amplified and expressed at a high level in, as well as confers an aggressive phenotype on, GC, and that POU5F1B amplification is associated with a poor prognosis in GC patients.

ストーマ旁ヘルニアは主要なストーマ関連合併症の一つである。ストーマ旁ヘルニアに対する修復術は、従来の方法(筋膜縫合術、ストーマ再造設術)では再発率が高い。最近ではメッシュを使用した方法が中心となっているが、なお再発リスクと感染リスクの問題が存在する。腹腔鏡下修復術(Sugarbaker法)は、再発率と感染リスクを軽減し、また低侵襲である優れた方法である。双孔式ストーマでは挙上腸管の直線化を行う工夫が必要となるが、今後のストーマ旁ヘルニアに対する修復術の第一選択となりえる術式である。(著者抄録)

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.

(Background/Aims: To evaluate the clinicopathological features and results of surgery for gastric cancer in elderly patients aged >80 years relative to those aged <79 years, and to recommend the appropriate surgical treatment for elderly patients. Methodology: A total of 332 patients with gastric cancer who underwent gastrectomy in our department between 2002 and 2012 were evaluated. Of these, 81 were aged >80 years (Group A) and 251 were aged <79 years (Group B). We compared surgical outcomes and survival in these two groups. Results: Postopeartive complications were associated with preoperative cormorbid disease(p<0.01). D2 and R0 resection was common in GroupB (p<0.01). Respiratory complications and hospital deaths were higher in Group A than in Group B. Overall survival (OS) was significantly lower in Group A than in Group B. Regarding Stage I disease, OS was significantly lower in Group A; however, cause-specific survival was similar between the two groups. Multivariate analysis showed that radicality and postoperative complications were independent prognostic factors for OS in elderly gastric cancer patients. Conclusion: These results indicate that postoperative respiratory complications and other causes of death worsened the prognosis of elderly. Preoperative accurate judgment of co-morbid disease, meticulous postoperative management and follow up might be improved survival of gastric cancer in elderly.

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. © 2008-2014 Impact Journals, LLC.

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.

The heparan sulfate sulfotransferase gene family catalyzes the transfer of sulfate groups to heparan sulfate and regulates various growth factor-receptor signaling pathways. However, the involvement of this gene family in cancer biology has not been elucidated. It was demonstrated that the heparan sulfate D-glucosaminyl 6-O-sulfotransferase-2 (HS6ST2) gene is overexpressed in colorectal cancer (CRC) and its clinical significance in patients with CRC was investigated. The mRNA levels of HS6ST2 in clinical CRC samples and various cancer cell lines were assessed using a microarray analysis and quantitative RT-PCR, respectively. An immunohistochemical (IHC) analysis of the HS6ST2 protein was performed using 102 surgical specimens of CRC. The correlations between the HS6ST2 expression status and clinicopathological characteristics were then evaluated. HS6ST2 mRNA was significantly overexpressed by 37-fold in CRC samples compared to paired colonic mucosa. High levels of HS6ST2 mRNA expression were also observed in colorectal, esophageal and lung cancer cell lines. The IHC analysis demonstrated that HS6ST2 was expressed in the cytoplasmic region of CRC cells, but not in normal colonic mucosal cells. Positive staining for HS6ST2 was detected in 40 patients (39.2%). There was no significant association between the clinicopathological characteristics and HS6ST2 expression. However, positive staining for HS6ST2 was associated with a poor survival (P=0.074, log-rank test). In conclusion, HS6ST2 was found to be overexpressed in CRC and its expression tended to be a poor prognostic factor, although the correlation was not significant. These findings indicate that HS6ST2 may be a novel cancer-related marker that may provide insight into the glycobiology of CRC.

Transcription factor Slug/SNAI2 (snail homolog 2) plays a key role in the induction of the epithelial mesenchymal transition in cancer cells; however, whether the overexpression of Slug mediates the malignant phenotype and alters drug sensitivity in lung cancer cells remains largely unclear. We investigated Slug focusing on its biological function and involvement in drug sensitivity in lung cancer cells. Stable Slug transfectants showed typical morphological changes compared with control cells. Slug overexpression did not change the cellular proliferations; however, migration activity and anchorage-independent growth activity with an antiapoptotic effect were increased. Interestingly, stable Slug overexpression increased drug sensitivity to tubulin-binding agents including vinorelbine, vincristine, and paclitaxel (5.8- to 8.9-fold increase) in several lung cancer cell lines but did not increase sensitivity to agents other than tubulin-binding agents. Real-time RT-PCR (polymerase chain reaction) and western blotting revealed that Slug overexpression downregulated the expression of beta III and beta IVa-tubulin, which is considered to be a major factor determining sensitivity to tubulin-binding agents. A luciferase reporter assay confirmed that Slug suppressed the promoter activity of beta IVa-tubulin at a transcriptional level. Slug overexpression enhanced tumor growth, whereas Slug overexpression increased drug sensitivity to vinorelbine with the downregulation of beta III and beta IV-tubulin in vivo. Immunohistochemistry of Slug with clinical lung cancer samples showed that Slug overexpression tended to be involved in response to tubulin-binding agents. In conclusion, our data indicate that Slug mediates an aggressive phenotype including enhanced migration activity, anoikis suppression, and tumor growth, but increases sensitivity to tubulin-binding agents via the downregulation of beta III and beta IVa-tubulin in lung cancer cells.

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 de1745 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.

Aim: Patients with scirrhous carcinoma of the gastrointestinal tract frequently develop peritoneal carcinomatosis particularly of the peritoneal extension type (PET), which has a bad prognosis. We developed a novel animal model, suitable for testing treatments for PET. Material and Methods: In order to develop the model, we scraped the entire peritoneum of Fischer 344 rats with sterile cotton swabs and injected 1x10(6) cells of the RCN-9 cell type into the peritoneal cavity. Results: In the novel experimental model, RCN-9 cells adhered only to the exposed basement membrane. The submesothelial layer and fibroblasts in the submesothelial layer grew and increased to a maximum at day 7, then decreased during late-phase peritoneal carcinomatosis. At day 14, RCN-9 cells coated the peritoneum in a manner similar to PET. Conclusion: We successfully established a novel animal model of peritoneal carcinomatosis that mimics clinicopathological features of PET. Fibroblasts in the submesothelial layer potentially play an important role in peritoneal carcinomatosis.

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)

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.

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.

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.

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.

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

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.

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)

A 27-year-old male developed a swelling in his right inguinal area, and was as having a right inguinal hernia. However, during surgery, only a lipoma was found ; there was no hernial sac. The lipoma was excised. A right inguinal swelling presented again 10 months later, and he was readmitted 14 months after the initial operation. A right inguinal hernia was diagnosed because the lesion enlarged on standing. An operation was done. A hernia sac was not found during surgery. A lipoma was found that protruded through the internal inguinal ring at the lateral aspect of the cold. It was resected. On pathology, a well-differentiated liposarcoma was diagnosed. Abdominal enhanced CT showed that the mass extended from the inferior pole of the right kidney to the inguinal area. A retroperitoneal liposarcoma was diagnosed ; it was removed. Retroperitoneal liposarcoma presenting as an inguinal swelling is rare. In fact, only 7 cases including the present case have been reported in Japan. We report a rare case of a liposarcoma presenting as an inguinal swelling.

64歳、男性。排便困難を主訴に近医を受診。大腸内視鏡検査で下部直腸癌と診断され、加療目的で当科紹介となった。肝転移を認めていたものの、腫瘍出血による貧血と狭窄症状コントロールの必要性を考慮し、開腹手術先攻の治療方針とした。術中所見は多発の肝転移を認めた。また、局所は小骨盤腔で側方リンパ節と一塊になっていた。この時点で局所の切除を断念し、S状結腸人工肛門造設とした。手術1ヵ月後より、まずは局所コントロールに主眼をおいてS-1併用放射線療法を施行した。S-1は120mg/day2週投薬1週休薬とした。放射線療法は2Gy/day5日照射2日休で合計60Gyの照射を行った。1ヵ月後のCTでPR inであった。さらに全身化学療法を行うため、CRT約1ヵ月後よりFOLFIRI療法を開始した。6コース後の画像診断でCRとなり、現在6ヵ月経過しているがCRを続行中である。手術不能直腸癌において、局所療法+全身療法により高い効果が得られる症例があることが示された。(著者抄録)

Preoperative chemotherapy is a promising strategy in patients with early-stage resectable non-small-cell lung cancer (NSCLC); optimal chemotherapy remains unclear. Clinical (c-) stage IB/II NSCLC patients were randomised to receive either two cycles of docetaxel (D)-cisplatin (P) combination chemotherapy (D 60 mg m(-2) and P 80 mg m(-2) on day 1) every 3-4 weeks or three cycles of D monotherapy (70 mg m(-2)) every 3 weeks. Thoracotomy was performed 4-5 weeks (DP) or 3-4 weeks (D) after chemotherapy. The primary end point was 1-year disease-free survival (DFS). From October 2002 to November 2003, 80 patients were randomised. Chemotherapy toxicities were mainly haematologic and well tolerated. There were two early postoperative deaths with DP (one intraoperative bleeding and one empyema). Pathologic complete response was observed in two DP patients. Docetaxel-cisplatin was superior to D in terms of response rate (45 vs 15%) and complete resection rate (95 vs 87%). Both DFS and overall survival were better in DP. Disease-free survival at 1, 2 and 4 years were 78, 65 and 57% with DP, and were 62, 44 and 36% with D, respectively. Preoperative DP was associated with encouraging resection rate and DFS data, and phase III trials for c-stage IB/II NSCLC are warranted.

ATX-s10-Na(II) is a novel second-generation photo-sensitizer for photodynamic therapy (PDT). PDT using ATX-s10 and diode laser (670 nm) induces an apoptotic response, inflammatory reaction, immune reaction and damage to the microvasculature. In particular, the vascular shut-down effect plays an important role in the anti-tumor activity of ATX-s10-PDT. It has been reported that PDT induces hypoxia and expression of the vascular endothelial growth factor (VEGF) via the hypoxia-inducible factor 1 (HIF1)-α pathway. We hypothesized that the expression of VEGF may cause tumor recurrence after PDT and exert unfavorable effect against the anti-tumor activity of ATX-s10-PDT. In this study, we showed by DNA microarray analysis in vitro that VEGF mRNA expression was induced 3 h after laser irradiation in ATX-s10-PDT. We compared the antitumor activity of ATX-s10-PDT against lung cancer cell lines SBC-3 and SBC-3/VEGF, the latter overexpressing VEGF there was no significant difference in the sensitivity to the PDT between the two cell lines as assessed by clonogenic assay. Furthermore, no statistically significant difference in the anti-tumor effect of PDT, as measured by tumor cures, was found between SBC-3 and SBC-3/VEGF tumors in female Balb/c-nu/nu nude mice in vivo. In conclusion, ATX-s10-PDT may prevent tumor recurrence despite induction of VEGF and promotion of tumor angiogenesis, which are known to enhance tumor proliferation and survival.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are involved in several RNA-related biological processes. We demonstrated hnRNP L as a candidate protein of DARP (duocarmycin-DNA adduct recognizing protein) by gel shift assay and amino acid sequencing. Stable transfectants of hnRNP L showed high sensitivity of the cells to the growth inhibitory effect of KW-2189, a duocarmycin derivative in vitro. Immunostaining of hnRNP L demonstrated differential intracellular localization of hnRNP L among human lung cancer cell lines. A transfection study using a series of deletion mutants of hnRNP L fused to indicated that the N-terminal portions of RRM(RNA recognition motif)I, RRM3 and RRM2 are involved in localization of hnRNP L. We identified sequences in these portions that have high homology with the sequences of known NLS (nuclear localization signal) and NES (nuclear export signal). hnRNP L is a factor that determines the sensitivities of cancer cells to the minor groove binder, and overexpression and differential intracellular localization of hnRNP L are involved in its function in lung cancer. © 2003 Wiley-Liss, Inc.

The differential expressions of hundreds of tightly transcriptionally controlled genes in freshly isolated human lung cancers and respective normal lung tissues were analyzed by the cDNA macroarray technique. Three lung cancer patients received pre-operative chemotherapy with cisplatin containing regimens. After chemotherapy, these patients underwent surgery, and poly (A)-RNA expressions of 588 genes in the samples prepared from the lung cancer and normal lung tissues were compared. These expressions of the 588 genes were demonstrated by spotting onto a filter. Histogram analysis of gene expression revealed the tumors to show commonly up-regulated expression of angiogenesis and invasion related genes and adhesion molecules such as fibroblast growth factor 3 (FGFR3), matrix metalloproteinase (MMP)15, 16 and 10, integrin β4, integrin α9, endonexin, and several types of collagens. Thus, post-chemotherapeutic tissues from lung cancer parents are characterized by remarkable up-regulation of molecules related to angiogenesis, invasion and adhesion. Tree view showed close clustering of angiogenesis related genes. Furthermore, when the angiogenesis related genes were selected and clustered, they were categorized into three groups depending upon gene expression profiles. These results suggest that angiogenesis related molecules are suitable candidates for target-based therapeutics and angiogenesis inhibitors are expected to be effective in lung cancer patients pretreated with chemotherapy.

Background: The number of N2 stations (single vs multiple N2 stations) is an important prognostic factor in patients with completely resected stage IIIA-N2 non-small cell lung cancer. However, the significance of both the N2 station(s) actually involved and the primary tumor location remains unclear. Methods: The database was built with the use of a questionnaire survey on the survival of patients with pathologic stage IIIA-N2 non-small cell lung cancer completely resected between January 1992 and December 1993. The survey was performed by the Japan Clinical Oncology Group as of July 1999. The data include information on the survival and N2 stations of 402 patients. Results: A, frequently metastasized single N2 station was the lower pretracheal station in primary tumors in the right upper lobe, the subaortic station in the left upper lobe, and the subcarinal station in the right middle or lower lobe and the left lower lobe. In multiple N2 stations, the frequency of metastasis of the N2 station observed in a single N2 station was as high as 72% to 89%, and one or two other frequently metastasized stations were added to each group. Regarding the survival of patients with a primary tumor in each lobe except for the left lower lobe, a single N2 station resulted in a significantly better survival than did multiple N2 stations. Furthermore, the overall survivals classified according to each primary site showed a significant difference among the four primary sites (P =.04). Conclusions: The primary tumors in each lobe showed a prevalence of N2 station(s). The number of N2 stations is a good prognosticator except in patients with a primary tumor in the left lower lobe. In addition, the site of a primary tumor itself is also considered to influence the survival of the patients.

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.

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.

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.

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.