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.

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 AND IMPORTANCE: Laparoscopic wedge resection has been widely performed for gastric gastrointestinal stromal tumors (GISTs). However, because GISTs in the esophagogastric junction (EGJ) are prone to deformity and postoperative functional disorders, laparoscopic resection is technically very difficult and rarely reported. Herein, we report a case of a GIST in the EGJ successfully treated by laparoscopic intragastric surgery (IGS). CASE PRESENTATION: A 58-year-old man with a GIST, which was intragastric growth type, 2.5 cm in diameter, located in the EGJ, and confirmed by upper gastrointestinal endoscope and endoscopic ultrasound-guided fine needle aspiration biopsy. We successfully performed IGS and the patient was discharged without complications. CLINICAL DISCUSSION: Using laparoscopic wedge resection by exogastric approach, it is problematic to resect a gastric SMT located at the EGJ because of the difficulty in viewing the surgical field and additional concerns of deformation of the EGJ. We suppose IGS as a suitable method for such tumors. CONCLUSION: Laparoscopic IGS for gastric GIST was useful in terms of safety and convenience even though the tumor was in the ECJ.

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: 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: 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.

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.

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.

Diazoxide is a benzothiadiazine that can be effective in managing hypoglycemia in frail patients with surgical risk. We report here a case of insulinoma effectively treated with diazoxide, as our report will be helpful for similar cases.

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.

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.

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 68-year-old man was scheduled for mediastinal tumor resection. Aortic invasion was unclear on preoperative computed tomography. Transesophageal echocardiography showed a smooth endothelial border, but the tumor was contiguous with the distal arch, and the adventitial border was unclear. After median sternotomy, the tumor was found to be adherent to the aorta. An endovascular stent graft was placed in the distal arch to protect the aorta, but excessive bleeding occurred from the aortic defect on tumor removal. This case shows that massive hemorrhage can occur during the resection of an aorta-invading tumor despite the use of an endovascular stent graft.

Vigorous explosive eruptions that produce continuous high eruption plumes (Plinian eruptions) are generally assumed to tap a magma reservoir. The 1914 Plinian eruption at the Sakurajima volcano located on the Aira caldera rim is one such case, where the main magma reservoir was assumed to be located approximately 10 km beneath the caldera. However, we report that estimated magma storage depths immediately prior to the eruption were much shallower (0.9–3.2 km) on the basis of pressure at which volatiles within the phenocryst melt inclusions and plagioclase rims were finally equilibrated. The same is observed for two historic Plinian eruptions in 1471 and 1779. This depth is even shallower than the shallowest magma reservoir estimated from the pressure source for geodetic deformation during recent Vulcanian explosions (4 km beneath the crater). We propose that the magmas were fed from a thick conduit pre-charged from deeper reservoirs. The ground subsidence observed after 1914 within the Aira caldera may have been caused by conduit recharge following the eruption. Voluminous conduit recharge could be key to forecasting the next possible large eruption at the Sakurajima volcano.

BACKGROUND: We carried out a phase II trial to evaluate the feasibility and efficacy of neoadjuvant chemotherapy comprising a single intraperitoneal administration of paclitaxel, followed by intravenous administrations of paclitaxel and cisplatin with S-1 for clinical stage III gastric cancer. METHODS: Patients with potentially resectable gastric cancer were eligible. A laparoscopic survey was performed to confirm CY0 and P0. Intraperitoneal paclitaxel (60 mg/m 2 ) was administered, followed by systemic chemotherapy. Surgery was performed after two cycles of chemotherapy. The primary endpoint was the response rate of chemotherapy. Secondary endpoints were adverse events, pathological response rate, and overall survival rate. RESULTS: Twenty patients were enrolled. Planned cycles were completed in all patients. Grade 3/4 leukopenia and grade 3/4 neutropenia were observed in four (20%) and seven (35%) patients, respectively. The overall response rate was 70% (partial response: 14, stable disease: 5, progressive disease: 1). All patients underwent R0 gastrectomy with D2 lymph-node dissection, with no surgery-related deaths. The pathological response rate was 65% (13 of 20). The 3- and 5-year overall survival rates were 90.0% and 77.1%, respectively. CONCLUSIONS: Neoadjuvant chemotherapy including intraperitoneal paclitaxel followed by sequential intravenous paclitaxel and cisplatin with S-1 for resectable advanced gastric cancer is feasible and effective.

ACTH-independent Cushing's syndrome (CS) is mainly caused by cortisol-secreting adrenocortical tumours. It is well known that secondary adrenal insufficiency occurs after surgical resection of these tumours. In this regard, impaired adrenocortical function is likely induced by atrophy of the residual adrenal tissue as a result of chronic suppression by the low ACTH levels of the hypercortisolism state. Therefore, we considered the prevention of adrenal atrophy as a method for preventing postoperative adrenal insufficiency. On the basis of these findings, we hypothesized that the use of a glucocorticoid receptor (GR) antagonist before surgery in ACTH-independent CS would rapidly activate the hypothalamic-pituitary-adrenal (HPA) axis and residual adrenal function. We thus examined adrenal function in a dexamethasone- (DEX-) induced CS rat model with or without mifepristone (MIF). In this study, MIF-treated rats had elevated plasma ACTH levels and increased adrenal weights. In addition, we confirmed that there were fewer atrophic changes, as measured by the pathological findings and mRNA expression levels of corticosterone synthase CYP11B1 in the adrenal glands, in MIF-treated rats. These results indicate that MIF treatment prevents the suppression of the HPA axis and the atrophy of the residual adrenal tissue. Therefore, our study suggests that preoperative GR antagonist administration may improve residual adrenal function and prevent postoperative adrenal insufficiency in ACTH-independent CS.

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: 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.

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.

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.

切除困難な局所進行食道癌cT4(大動脈)も化学療法(ChT)/化学放射線療法(CRT)の進歩に伴い治癒切除率が向上し、より精度の高い深達度診断が求められている。我々は通常の仰臥位CTでのcT4診断(Picus角(PA)≧90度)に加え、重力差を利用した腹臥位CTとの比較による動的評価法を考案し、その有用性を検討した。対象は初診時仰臥位造影CTでcT3以深の食道癌22例(cT3/T4=17/5)35測定、全例ChT/CRTを先行し18例で手術を施行。腫瘍-大動脈壁間距離(T-A D)とPAを仰/腹CTで測定し、最終深達度(fT4=R1、2、fT3.5=R0 and著明な瘢痕化(+)、fT3=R0 and瘢痕化(-)、非手術例はEUS所見)と比較した。全35測定の平均後縦隔前後径(下縦隔)は仰/腹の順に12.3/26.0mmで、PA<60度(21測定)の平均T-A DとPAは3.0/4.4mm、23.2/16度と腹臥位で距離は延長し角度は縮小した(p<0.05)。治療前PA≧60度の10例はfT3/T3.5/T4=5/2/3。fT3は腹臥位で全例PAは減少しT-A Dも3/5例で延長、fT3.5はいずれかが不変、fT4は両方不変であった。以上より、仰/腹CTにおけるT-A D/PAの比較はT3(両方変化)、T3.5(いずれか不変)、T4(両方不変)を鑑別できる可能性が示唆された。(著者抄録)

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)

症例は71歳の男性で,HER2陽性4型胃癌に対し審査腹腔鏡検査を施行した.SE N1 M1 P1 CY1 Stage IVにてtrastuzumabを含む化学療法を行った.再度審査腹腔鏡検査で腹膜播種消失を確認後,胃全摘(D2),脾摘術を施行した.病理組織診はpor SM N0 M0 P0 CY0 Stage IAで,術後にS-1+trastuzumabを投与した.術後8ヵ月より嘔気が出現し,CEA上昇を認めた.胸腹部造影CTで再発所見はなかった.意識レベルの低下で近医に緊急入院となった.頭部造影MRIで小脳,中脳,右側側頭葉内側の軟膜に異常濃染を認めた.感染所見はなく感染性髄膜炎は否定的で,経過より髄膜癌腫症と診断するも発症12病日に死亡した.胃癌の髄膜癌腫症はまれで極めて予後不良である.症状も多彩で診断に苦慮することが多い.脳症状・神経症状を認めた場合は髄膜癌腫症を念頭に精査する必要があると考えられた.(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.

＜ポイント＞pT3,pN2,鎖骨上リンパ節陽性例,ly+,v+であったものが,再発高リスク群であり,また再発の70%が術後1年内に確認され,88%が2年内に確認された.リンパ節再発が最も多く,次に血行性再発が多い.また血行性転移の内訳は肺が33%,肝が30%,次いで骨が17%を占めた.寛解,長期生存できる可能性があるのは,頸部および縦隔のリンパ節や肺の1〜2個の転移再発であり,可能ならば積極的に切除を検討する.(著者抄録)

A 58-year-old woman was diagnosed with scirrhous gastric cancer suspected because of lymphangitis carcinomatosa. She was treated with 10 courses of S-1+CDDP chemotherapy. After 3 years and 6 months, CR was obtained and she underwent curative total gastrectomy with D2 lymph node dissection plus resection of the spleen and transverse colon. The pathological results of the resected specimen were tub2>por, pT1a, N1 (No.7), M0, CY0, P0, and HER2 (3+). After surgical treatment, supraclavicular lymph node metastasis occurred, and the patient underwent trastuzumab+capecitabine therapy, which resulted in CR for 1 year and 6 months. Thus, for unresectable scirrhous gastric cancer, multidisciplinary therapy such as longterm chemotherapy including trastuzumab and surgery is useful.

症例は58歳、女性。癌性リンパ管症を伴うスキルス胃癌に対し、S-1+CDDP化学療法10コース施行しCRを得た。3年6ヵ月後に根治切除施行。切除標本の病理結果はtub2>por、pT1a、N1(No.7)、M0、CY0、P0、HER2(3+)であった。その後、鎖骨上窩リンパ節再発を来し、trastuzumab+capecitabine併用化学療法施行。1年6ヵ月、画像上病巣は認めていない。切除不能スキルス胃癌に対しても長期にわたる化学療法、手術治療など集学的治療が有用であると考えられた。(著者抄録)

We report 2 rare cases of afferent loop syndrome caused by obstruction at the jejuno-jejunostomy site in the Roux-en-Y loop after total gastrectomy, which was successfully treated by endoscopic balloon dilatation of the anastomotic stenosis. Case 1: A 62-year-old woman presented with malaise and lower abdominal distension 6 months after laparoscopy-assisted total gastrectomy with Roux-en-Y reconstruction. She was diagnosed with afferent loop syndrome; CT imaging indicated marked dilatation of the afferent loop, with membranous obstruction at the jejuno-jejunostomy site in the Roux-en-Y loop. Although almost complete occlusion was noted at the jejuno-jejunostomy site, the obstruction was successfully relieved by endoscopic balloon dilation using TandemTM XL Triple Lumen ERCP Cannula (Boston Scientific)®. Case 2: A 70-year-old man presented with malaise and lower abdominal distension 3 years after laparoscopy-assisted total gastrectomy with Roux-en-Y reconstruction. He was diagnosed with afferent loop syndrome; CT imaging indicated complete obstruction at the jejuno-jejunostomy site in the Roux-en-Y loop. As in case 1, the obstruction was successfully treated by endoscopic balloon dilatation of the occluded anastomosis.

はじめに:われわれは極めてまれなY脚吻合部のほぼ完全閉塞よる輸入脚症候群に対し、侵襲の少ない内視鏡的バルーン拡張術にて狭窄を解除し得た2症例を経験したので報告する。症例1:62歳、女性。腹腔鏡補助下胃全摘、Roux-en-Y再建施行後6ヵ月目で全身倦怠と下腹部の膨満感出現、CTで輸入脚の著明な拡張変化を認め、輸入脚症候群と診断した。Y脚吻合部はほぼ完全狭窄の状態であったが、透明キャップとタンデムXL ERCPカニューレ(Boston Scientific)を用いて内視鏡的バルーン拡張術を完遂し得た。症例2:70歳、男性。腹腔鏡補助下胃全摘施行後3年目で軽度全身倦怠と易疲労、下腹部の膨満が出現、採血結果は特に異常を認めなかったが、CTで輸入脚の著明な拡張を認め、輸入脚症候群と診断した。Y脚吻合部完全狭窄であったが同様に透明キャップとタンデムカニューレを用いて内視鏡的バルーン拡張術を完遂し得た。まとめ:本疾患は迅速な対応が求められる場合が多いが、治療方法はできる限り低侵襲なものを選択すべきである。内視鏡的処置はその一つとして試みるべき手技と考える。(著者抄録)

Background Postoperative pneumonia is the most common complication after esophagectomy and is closely associated with swallowing dysfunction and silent aspiration. Silent aspiration in the elderly is associated with decreased secretion of substance P (SP), which controls the swallowing and cough reflexes. The majority of patients with esophageal cancer are elderly. We hypothesized that surgical stress would decrease SP secretion, thereby increasing the risk of postoperative aspiration after esophagectomy, and prospectively investigated. Methods Thirty patients with esophageal cancer scheduled to undergo esophagectomy were enrolled in the study. Plasma and salivary SP concentrations and cough reflex sensitivity were measured before surgery and on postoperative days 2 and 7 to examine the association with postoperative aspiration. Results Postoperative silent aspiration was observed in 6 patients, 4 of whom developed pneumonia. Plasma SP concentration did not change significantly during the perioperative period. Salivary SP concentration and cough reflex sensitivity could not be measured in nearly one-third of patients because of postoperative dry mouth and unwillingness of patients to undergo measurement, respectively; thus, these perioperative changes could not be assessed. Preoperative plasma and salivary SP concentrations had a significant association with postoperative aspiration on univariate analysis and multivariate logistic regression analysis using variables selected by stepwise forward selection identified preoperative plasma SP concentration as the only significant risk factor for postoperative aspiration (p = 0.023). Conclusion Definitive results supporting our hypothesis could not be obtained. However, multivariate analysis suggested that decreased preoperative plasma SP concentration is likely associated with postoperative silent aspiration after esophagectomy.

頸部食道癌に対し、喉頭温存を重視した治療戦略として、導入化学放射線療法の中間判定による治療選択と、次のような術式工夫を行い、良好な成績が得られているので報告した。1)喉頭温存手術の適応を拡大するため、輪状咽頭筋と下咽頭収縮筋下端を輪状軟骨付着部で切離することにより、輪状軟骨上縁までの食道剥離を可能とする。2)術後嚥下障害を回避するため、手術のさい舌骨上筋群には皮弁剥離操作をしないことで瘢痕を予防し、舌骨下筋群を胸骨付着部で全切離することで喉頭下方牽引力を取り除き、温存した舌骨上筋群で喉頭を挙上させることにより安全性を確保する。3)移植空腸を長めに採取し、犠牲腸管余剰腸間膜で気管全体を被覆し、死腔を埋めて気管を保護し感染を防ぐことにより気管壊死を予防する。4)再建腸管は緊張をもって直線的に再建することで通過性を良くし、誤嚥を予防する。

Lymphocyte antigen 6 complex locus K (LY6K) has been identified as a tumor-associated antigen in lung cancers and esophageal squamous cell carcinomas. The immunogenicity of LY6K-177 peptide vaccine therapy has been demonstrated in patients with advanced esophageal cancer. This study extends this treatment to gastric cancer. LY6K expression in clinical samples obtained from gastric cancer patients was examined by immunochemistry. As a phase I clinical trial, the safety and immunogenicity of LY6K-177 peptide vaccine emulsified with Montanide ISA 51 was evaluated in six patients with unresectable advanced gastric cancer. LY6K-177 peptide (1 mg in 1 ml sterile saline) was emulsified with incomplete Freund's adjuvant (1 ml) and intracutaneously administered to the inguinal region or axilla. One treatment course comprised four vaccinations, performed weekly for the first and second treatment courses and biweekly for the third treatment course. LY6K expression was confirmed in 85 % of gastric cancer tissues. Induration and redness at the vaccination site (grade I), possibly a delayed-type hypersensitivity reaction, was observed in all patients; however, no systemic toxicology was identified in any patient throughout the observation period. Three of the six patients had stable disease, and a tumor contraction effect was observed in one patient. LY6K was expressed in 85 % of observed gastric cancers. Vaccination with LY6K-177 peptide/Montanide ISA 51 appeared to be tolerated by advanced gastric cancer patients, and moreover anticancer efficacy was suggested. This trial was registered with ClinicalTrial.gov (no. NCT00845611).

はじめに 近年の新規抗癌剤出現により、進行癌に対するいくつかの集学的治療が行われているが、その一つとして術前化学療法+手術の有用性が報告されている。今回我々は2型噴門部進行胃癌に対してTS-1/CDDPによる術前化学療法を施行した結果、病理組織学的にCRを得た症例を経験したので報告する。症例 67歳男性、健診にて胃病変を指摘され、近医にてGIF施行したところ噴門部後壁に2型胃癌認めたため当科紹介となった。経過 当初、画像診断で肝転移を伴う高度進行胃癌(T4aN1H1Stage IV)と診断してTS-1/CDDPの化学療法を3クール施行した。効果判定では主病変と所属リンパ節は著明に縮小したが、肝病変は治療効果を認めず、血管腫の可能性も出てきたため肝部分切除+胃全摘術を行った。摘出病理標本では原発巣、リンパ節ともに癌細胞は認めず、肝病変は硬化性血管腫であったため、pathological CRと判断した。術後経過は良好で、退院後adjuvant chemotherapyとしてTS-1内服を1年半施行、26ヵ月経過した現在、無再発にて経過観察中である。(著者抄録)

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.

[目的]高齢者胃切除症例に対する腹腔鏡下手術の安全性と有用性を検討した.[対象]当科で施行した80歳以上の胃切除症例を腹腔鏡群(Lap群)58例と開腹群(Open群)59例に分け,術中の呼吸変動と血圧変動,術後合併症などを検討した.[結果]術中血圧変動は両群間に有意差を認めず,術中のETCO2はLap群で若干の高値であったが,術後高炭酸ガス血症が遷延することはなかった.術後合併症はOpen群25.4%,Lap群13.8%で,最も割合の多かった呼吸器合併症はLap群5.2%,Open群8.5%であった.[結論]高齢者胃癌症例に対する腹腔鏡下手術は術後合併症,特に呼吸器合併症に対して有利と思われ,有用な治療法として筆者らは現在積極的に導入している.(著者抄録)

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.

Up-regulated gene in lung cancer 10 (URLC10), confirmed to be lymphocyte antigen 6 complex locus K and defined as an oncoantigen, has been identified as a tumor-associated antigen by systematic analysis of expression levels of thousands of genes in lung cancer tissues and esophageal squamous cell carcinoma tissues, which were compared with those of normal human tissues by use of cDNA microarray analysis. Human leukocyte antigen (HLA)-A*2402-positive dendritic cells pulsed with URLC10-derived epitope peptide induced CD8(+) cytotoxic T lymphocytes to exert specific cytotoxicity against the HLA-A*2402-positive URLC10-expressing esophageal carcinoma cell lines. In a phase I clinical trial we evaluated the safety and immunogenicity of a URLC10-177 peptide vaccine emulsified with Montanide ISA51 for patients with unresectable advanced esophageal cancer. One milligram of URLC10-177 peptide in 1 mL sterile saline was emulsified with 1 mL incomplete Freund's adjuvant and administered subcutaneously to the inguinal region or axilla of the patients. One course of treatment comprised four vaccinations, which were performed every week in the first and second treatment courses and subsequently every 2 weeks after the first vaccination in the third treatment course. Redness and induration of the skin were the only adverse events at the injection site and were believed to be a delayed-type hypersensitivity (DTH) reaction against the peptide vaccine. A URLC10-177-specific immune reaction in the enzyme-linked immunospot assay was detected in three of four DTH-positive patients (75 %) and in one of three DTH-negative patients (33 %). Furthermore, patients who had a DTH reaction seemed to survive longer than those who had no DTH reaction. URLC10-177 peptide/Montanide vaccine therapy was well tolerated and induced a URLC10-177 peptide-specific immune response. Therapeutic URLC10-177 peptide vaccination is expected to have clinical benefit in prolonging the survival of patients with unresectable advanced esophageal cancer.

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)

Mucin glycoproteins from the gallbladder epithelium are thought to contribute to the matrix or nucleus of gallstones and other biomineralization systems. The involved acidic glycoproteins have been reported in bile and gallstones. In addition, osteopontin (Opn) is a noncollagenous acidic bone matrix glycoprotein that possesses calcium-binding properties. To investigate the role of Opn in pigment gallstone formation, the involvement of Opn in pigment gallstone formation was studied immunohistochemically in the gallbladder wall and in the stones. Staining for Opn was strongly positive in the epithelium of stone-laden gallbladders and in their stones. The stone-laden gallbladders were infiltrated by macrophages, which intensely stained for Opn. Sections of the pigment stones, under low magnification, showed a lamellar pattern of Opn immunolabeling and showed a reticular pattern under high magnification. Our results indicate that Opn, an acidic glycoprotein from the gallbladder epithelium, seems to be involved in lithiasis. Opn from macrophages and/or the epithelium seems to help form the matrix protein.

Osteopontin (OPN) is significantly overexpressed in a variety of malignancies. However, little is known concerning the significance of OPN expression in human cancers. Thus, the aim of this study was to determine the relationship between the degree of OPN expression, the proliferative activity of cancer cells, and the clinicopathological findings for surgically resected gastric cancer. We evaluated the immunohistochemical expression of OPN in 85 specimens of cancer. Additionally, we investigated a cancer cell proliferative index using an anti-MIB-1 antibody and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling staining. Levels of OPN expression in gastric cancers were classified into three groups. To compare the relationship between OPN expression and clinicopathological findings, the features of cancer lesions were classified using the TNM Classification of Malignant Tumors, 6th Edition. Immunohistochemical examination of OPN expression in gastric cancer revealed diffuse granular staining in the cytoplasm. High OPN expression was observed in 37 of 85 carcinomas. Strong OPN expression was significantly associated with a low apoptotic index, a high proliferative index, depth of invasion, lymphatic invasion, and venous invasion. Pathologically, intestinal type carcinoma showed strong expression of OPN. These data suggested that OPN may play an important role in the invasiveness and the progressive nature of gastric cancer.

症例は64歳,女性で右乳房腫瘤を主訴に当科外来を受診される.理学所見で右乳房A領域に弾性硬で可動性良好な腫瘤を触知し,マンモグラフィーおよびエコーでも右乳房A領域に1.0×1.5cmの腫瘤陰影を認め,生検目的にて腫瘤摘出を施行した.病理検査において乳腺原発のアポクリン癌と診断され,後日胸筋温存乳房切除術(児玉法)を追加施行した.乳腺アポクリン癌は浸潤癌特殊型に分類される比較的稀な疾患で,発育が緩慢でリンパ節転移もきたしにくい,生物学的悪性度の比較的低い癌である.また腫瘍径が小さく,stageの低いものが多く発見されることから,今後乳房温存術といった縮小手術の可能な症例がさらに増えていくものと考えられた.

TPNと経腸栄養管理に対するbacterial translocationの比較検討を行い,TPN群ではMLNに腸内細菌であるE-coliとバクテロイデスを検出したのに対し,EN群では防止されていたことから,有用性を確認することができた.ラットTPNモデルで腸管免疫システムの一つであるIELs細胞数の減少,アポトーシス陽性細胞率の増加,IL-2産生量の減少,IL-2受容体発現率の減少,IFN-γ産生量増加および粘膜萎縮を認めた.対照的に経腸栄養モデルではこれらの改善を認めたことから,経腸栄養法の有用性を確認できた

栄養投与経路の違いによる腸管免疫防御機構への影響を,腸管上皮間リンパ球(IELs)機能面から検討し,bacterial translocation(BT)発生との関連をみた.7週齢ラットを中心静脈栄養(TPN群),経腸栄養(EN群)及び経口自由摂取(C群)で各々5日間栄養管理後,小腸粘膜形態学的変化,IELs細胞数,アポトーシス陽性細胞率,IL-2,IFN-γ産生能,IL-2 receptor(α)発現を測定,BTの指標として腸間膜リンパ節培養を行った.TPN群ではBT発生は高頻度で,粘膜萎縮と共にIELs細胞数減少,アポトーシス陽性細胞率の増加をみ,IL-2産生能,IL-2R発現率はいずれも低く,IFN-γ産生能は逆に亢進した.EN群ではC群と同等であった.TPNは物理的因子と共にIELs細胞数減少,機能低下を認め,BTを高頻度に引き起こし,経腸栄養は腸管免疫防御機構を維持し,BT発生を抑制した

食道癌術中の胸部操作終了後～標本摘出までの間に食道をカバーした袋内に貯留した液中の悪性細胞の有無を検討し、63例中3例（4.8％）で食道標本からの遊離癌細胞が陽性（2例：細胞診陽性、1例はセルブロックのみ陽性）であった。食道癌術中の胸部操作終了後～標本摘出までの間に食道から遊離癌細胞が漏出することをはじめて明らかにした。

食道癌術後は誤嚥のリスクが高く、重篤な肺炎に繋がる可能性からその予防は大きな課題である。嚥下運動機能障害による誤嚥は術式の改良やリハビリテーションによって改善されてきたが、嚥下反射の低下による誤嚥は未解決のままである。嚥下反射は脳の刺激で分泌されるサブスタンスP（SP）により制御されているので、術前血中SP値と無症候性脳梗塞および術前後の嚥下機能との関連を検討した。60歳以上の半数に認めると言われた無症候性脳梗塞は5%程度しか認めなかったが、血中SP低値の症例は術後の嚥下機能が悪く、誤嚥発症率は有意に高かった。以上より、血中SPの測定は術後の嚥下機能予測に有用である可能性が示唆された

本研究では、食道扁平上皮癌に対する化学療法、放射線化学療法の治療早期におけるp53-Ser46のリン酸化をバイオマーカーとした治療効果予測の有用性を検討し、実際に生検組織の検討でp53-Ser46のリン酸化の誘導を治療開始翌日の生検で初めて臨床的に確認したが、治療開始後早期のSer46リン酸化の有無と化学療法や化学放射線療法の治療効果との間には明らかな相関は認めなかった。CRが得られた症例の中にはp53 mutant/Ser-46リン酸化陰性例も認められており、今回の検討から化学療法や化学放射線療法に対する効果はp53によるアポトーシス経路のみでなく、他の要因も関わることが示唆された。

高齢者の誤嚥は、咳および嚥下反射を制御するサブスタンスP(SP)の分泌低下が原因である。そこで、高齢者に多く、術後に誤嚥のリスクの高い食道癌手術患者における術前後の血中SP値の推移を調べ、誤嚥発症との関連を検討した。術前後で有意な変動は見られなかったが、術前より低値を示す症例は有意に誤嚥を発症する率が高く(p=0.004)、術前血中SP低値(60pg/ml以下)の症例は術後誤嚥発症のハイリスク群と考えられた。