Search

While proximal gastrectomy is being performed increasingly frequently for the treatment of gastric cancer, a standard reconstruction method to obtain optimal postoperative quality of life (QOL) still remains to be established. We modified the original esophagogastrostomy technique by introducing an additional posterolateral fundoplication (PLF) technique to minimize the risk of reflux esophagitis in patients undergoing proximal gastrectomy. The aim of this study was to clarify the clinical benefit of PLF.A retrospective analysis of the database was conducted to evaluate the effects of PLF. The data were compared between 44 patients in whom PLF was performed (PLF group) and 17 patients in whom conventional esophagogastrostomy without PLF was performed (C group). A number of incidence of postoperative reflux esophagitis and symptoms were assessed by findings of endoscopic examination and the PGSAS-45 questionnaire, respectively.The incidence of grade B or worse esophagitis after surgery was significantly lower in the PLF group than in the C group (0% vs. 58.8%, P 0.01). The score for the esophageal reflux subscale, as the main outcome measure of PGSAS-45, was significantly better in the PLF group (PLF: 1.5 vs C: 2.4, P 0.01). Cohen's d value was 1.75, which suggested a rather large effect size. Postoperative benign anastomotic stricture was encountered in 10 cases (22.7%) of the PLF group and 4 cases (23.5%) of the C group, all of whom were successfully treated by brief endoscopic mechanical dilatation.PLF is an expedient procedure for reconstruction after proximal gastrectomy.

To investigate the postoperative quality of life (QOL) in patients with proximal gastric cancer (PGC) or esophago-gastric junction cancer, a nationwide multi-institutional study (PGSAS NEXT trial) was conducted.Patients who had undergone radical resection more than 6 months previously were enrolled from 70 Japanese institutions between July 2018 and June 2020. The Postgastrectomy Syndrome Assessment Scale (PGSAS)-45 questionnaire was distributed to eligible patients, and responses were collected by mail. The main outcome measures of the PGSAS-45 were then calculated and compared.Questionnaires were retrieved from 1950 participants, and data from 300 patients who had undergone a proximal gastrectomy (PG) with esophagogastrostomy for PGC were analyzed. The mean esophageal reflux subscale value was 1.9 among the 276 patients who underwent an anti-reflux procedure, which was significantly better than the mean value (2.6) for the 21 patients who did not undergo an anti-reflux procedure (p = 0.002). The esophageal reflux subscale values were also compared among 3 major anti-reflux procedures: the double-flap technique (N = 153), the pseudo-fornix and/or His angle formation (N = 67), and fundoplication (N = 44); no statistically significant differences were observed.An anti-reflux procedure during esophagogastrostomy after PG for PGC is necessary to improve postoperative esophageal reflux symptoms, regardless of the type of procedure.The PGSAS NEXT study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; registration number: 000032221).

Ramucirumab (RAM) plus paclitaxel (PTX) therapy has shown promising results as a standard second-line treatment for advanced gastric cancer patients. Recently, combined docetaxel (DOC) plus S-1 (DS) therapy could be regarded as the new standard adjuvant chemotherapy for patients with curatively resected stage III gastric cancer. However, the efficacy and safety of RAM plus PTX therapy in patients treated previously with DOC-containing therapy remains unclear. This study assessed the clinical outcomes of RAM plus PTX therapy in advanced gastric cancer patients with or without a previous history of treatment with a DOC-containing regimen. In a series of 107 consecutive patients enrolled for this study, the median PFS and OS were 4.2 and 6.2 months, respectively. Fifty-five patients had a history of prior therapy with DOC and 52 did not. There was no significant difference between with and without DOC groups in the ORR (22.2% vs. 23.5%), PFS (4.2 vs. 5.3 months), or OS (7.2 vs. 6.4 months). In a comparison taking into account the interval from the DOC-containing therapy to the RAM plus PTX therapy, the number of treatment courses was significantly smaller and the PFS significantly shorter in the patient group with an interval of ≤ 6 months (median, 2 vs 4.5 courses, P = 0.033; 3.4 months vs. 5.1 months, P = 0.043). RAM plus PTX therapy in patients with advanced gastric cancer is effective even in patients who have previously received DOC-containing chemotherapy, especially if the interval is > 6 months.

Gastric cancer (GC) patients with peritoneal metastasis are defined as stage IV in the Japanese classification of GC. For patients with peritoneal metastasis limited to positive peritoneal lavage cytology (CY1) and/or localized peritoneal metastasis (P1a), gastrectomy followed by S1 monotherapy is one of the most widely accepted therapeutic strategy in Japan. This study investigated the efficacy of preoperative chemotherapy as initial treatment in GC patients with CY1 and/or P1a. We retrospectively reviewed GC patients diagnosed with CY1 and/or P1a at 34 institutions in Japan between 2008 and 2012. Selection criteria were: adenocarcinoma, no distant metastasis except CY1 or P1a, and no prior treatment. The subjects were divided into an Initial-Chemotherapy group and an Initial-Surgery group, according to the initial treatment. A total of 824 patients were collected and 713 eligible patients were identified for this study. As the initial treatment, 150 patients received chemotherapy (Initial-Cx), and 563 patients underwent surgery (Initial-Sx). Initial-Cx regimens were cisplatin plus S1/docetaxel plus cisplatin plus S1/others (n = 90/37/23). Both overall survival (OS) and progression-free survival (PFS) were similar between the Initial-Cx and Initial-Sx groups (median OS 24.8 and 24.0 months, HR 1.07, 95% CI 0.87–1.3; median PFS 14.9 and 13.9 months, HR 1.04, 95% CI 0.85–1.27). The 5-year OS rates were 22.3% in the Initial-Cx group and 21.5% in the Initial-Sx group. Although, the preoperative chemotherapy did not show a survival benefit for GC patients with CY1 and/or P1a, initial-Cx showed favorable survival in patients who converted to P0 and CY0.

Background The incidence of metachronous multiple gastric cancer (MMGC) after gastrectomy remains unclear. This study evaluated the incidences of MMGC according to specific gastrectomy types, including pylorus-preserving gastrectomy (PPG), proximal gastrectomy (PG), and function-preserving gastrectomy (FPG), which was categorized as segmental gastrectomy and local resection. Methods We conducted a questionnaire survey of the Japanese Society for Gastro-Surgical Pathophysiology members, who were asked to report their institutional numbers of radical gastrectomy cases for cancer between 2003 and 2012. The cases were categorized according to whether the remnant stomach’s status was followed for > 5 years, confirmation of MMGC, time to diagnosis, and treatment for MMGC. We calculated the “precise incidence” of MMGC by dividing the number of MMGC cases by the number of cases in which the status of remnant stomach was followed up for > 5 years. Results The responses identified 33,731 cases of gastrectomy. The precise incidences of MMGC were 2.35% after distal gastrectomy (DG), 3.01% after PPG, 6.28% after PG (p p p p Conclusions The incidence of MMGC was 2.4% after DG, and higher incidences were observed for larger stomach remnants. However, the proportion of cases in which MMGC could be treated using endoscopic submucosal dissection was significantly higher after PG and FPG than after DG.

Pylorus-preserving gastrectomy (PPG) is widely used for early gastric cancer located in the middle third of the stomach. The minimization of the extent of gastrectomy may increase the risk of metachronous multiple gastric cancer (MGC). We report the findings of a study that was conducted to evaluate the prevalence of MGC after PPG. The clinical data of 533 patients who underwent PPG for gastric cancer between 1993 and 2018 were reviewed. The clinicopathological characteristics at the time of the primary treatment that were predictive of the development of MGC were explored. The median (range) observation period was 112.4 (8.1–290.7) months. Metachronous MGC was diagnosed in 33 of the 533 patients. The cumulative 5-year and 10-year event rates were 3.3% and 6.2%, respectively. The patient gender, presence/absence of synchronous MGC and the macroscopic type of the primary gastric cancer were significantly associated with the risk of development of metachronous MGC. Multivariate analysis identified the presence of synchronous MGC (hazard ratio [HR]: 4.828, 95% confidence interval [CI]; 1.611–12.30, p = 0.004) and Type 0-IIa primary gastric cancer (HR 2.810, 95% CI; 1.113–7.090, p = 0.029) as independent factors associated with the risk of development of MGC. All the patients could be treated by surgical or endoscopic resection for the metachronous MGC. Recurrence was observed in one patient. There was quite a few incidence of development of metachronous MGC after PPG. Nevertheless, PPG remains reasonable treatment option, if adequate postoperative surveillance can be ensured.

Although several procedures for mechanical anastomosis have recently been reported, intracorporeal manually hand-sewn anastomosis for totally laparoscopic pylorus-preserving gastrectomy (TLPPG) is considered technically difficult. Here, we report a new technique for laparoscopic reconstruction using hand-sewn sutures.Together with a proper lymphadenectomy, the stomach was detached and resected using separate two-layer incisions, similar to the original laparotomy method. An approximately 5-cm antral cuff was left in place. The essential concept of this new method was to align the anastomotic site by rotating each clamped gastric stump. This allowed us to perform a secure, hand-sewn, two-layer anastomosis successfully. The short-term surgical outcome after TLPPG was retrospectively compared with that for patients who underwent a conventional laparoscopy-assisted procedure (LAPPG).Of the 20 consecutive patients who underwent pylorus-preserving gastrectomy in our department between 2014 and 2021, the first 8 patients and the subsequent 12 patients underwent LAPPG and TLPPG, respectively. The operation time was significantly longer in the TLPPG group (median, 302 vs. 269 min). The morbidity was comparable (8.3% in TLPPG vs. 12.5% in LAPPG). Postoperative delayed gastric emptying was only observed in one patient in the LAPPG group. TLPPG reduced the cost of the operation by reducing the number of linear stapler cartridges required.A purely hand-sewn gastrogastrostomy is safe, feasible, and cost-effective, and it omits the need for a mini-laparotomy in the upper abdomen.

Background The time interval between initial partial gastrectomy and diagnosis of cancer in the remnant stomach reportedly differs according to the reconstruction procedure used in the initial gastrectomy. However, factors correlated with the time interval from the initial surgery for gastric cancer to the detection of metachronous multiple gastric cancer (MMGC) remain unclear. This study was performed to evaluate the association between the type of initial gastrectomy or reconstruction procedure and the time interval from initial gastrectomy to detection of MMGC as well as the association between the type of initial gastrectomy and the procedure performed for MMGC. Methods A questionnaire survey on remnant stomach cancer was conducted by the Japanese Society for Gastro-Surgical Pathophysiology in 2018. Participating facilities were asked to indicate the number of patients who underwent surgery for MMGC between 2003 and 2017, in accordance with the time interval from the initial gastrectomy until treatment for MMGC by type of initial gastrectomy or reconstruction procedure. The number of patients who underwent each treatment procedure (completion total gastrectomy or partial gastrectomy) was also collected. Results Analyses were performed using data from 45 facilities. Gastrectomy for MMGC was performed in 1,234 patients during the period. Billroth-II and Roux-en Y accounted for 22.3% (103/462) and 1.3% (6/462), respectively, of patients who underwent surgery for MMGC ≥ 10 years from initial DG, while these patients accounted for 8.0% (23/286) and 21.7% (65/286), respectively, of patients who underwent surgery for MMGC within 5 years after initial DG. Likewise, the proportion of each reconstruction procedure differed by the time interval from initial proximal gastrectomy to treatment for MMGC. In terms of the treatments performed for MMGC, the proportion of patients who underwent partial gastrectomy increased in accordance with the size of the remnant stomach after the initial gastrectomy. Conclusions The types of gastrectomy or reconstruction procedures for initial gastrectomy differed significantly by time interval between the initial gastrectomy and treatment for MMGC, and their time trends were assumed to be a major cause of the differences. The proportion of patients who underwent completion total gastrectomy deceased as the size of the remnant stomach increased.

Gastric cancer (GC) patients with positive peritoneal lavage cytology (CY1) and/or localized peritoneum metastasis (P1a) are defined as stage IV in the 15th edition of the Japanese Classification of Gastric Cancer. In Japan, the most common treatment for patients with CY1 and/or P1a is gastrectomy followed by postoperative chemotherapy. Subjects in this multi-institutional retrospective study were GC patients with CY1 and/or P1a who received surgical resection that leaves no macroscopically visible disease. Patients were selected from 34 institutions in Japan between 2007 and 2012. Selection criteria included adenocarcinoma, no distant metastasis except CY1 and P1a, and no prior treatment for GC before surgery. Among 824 patients registered, 506 were identified as eligible, with a background of P0CY1, P1aCY0, or P1aCY1 (72.5%, 16.0%, and 11.5% of subjects, respectively). Sixty-two patients had not received postoperative chemotherapy (no-Cx), whereas 444 patients had received postoperative chemotherapy: S-1 monotherapy (S-1; n = 267, 52.7%), cisplatin plus S-1 (CS; n = 114, 22.5%), and others (n = 63, 12.6%). Overall survival (OS) was 29.5, 24.7, 25.4 and 9.9 months in the S-1, CS, ‘others’, and no-Cx groups, respectively [CS vs. S-1: hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.89–1.50; p = 0.275]. In multivariate analysis, OS was similar between the S-1 and CS groups (CS vs. S-1: HR 1.19, 95% CI 0.92–1.55; p = 0.18). Postoperative chemotherapy after gastrectomy that leaves no macroscopically visible disease may have some survival benefits for GC patients with CY1 and/or P1a. In contrast, S-1 plus cisplatin seems to have no additional benefit over S-1 treatment alone.

Background: Clinical trials comparing laparoscopic gastrectomy (LG) versus traditional open gastrectomy (OG) have been planned, their surgical outcomes reported but their oncologic outcomes are still pending. Consequently, we have conducted this large-scale historical cohort study to provide relevant information rapidly to guide our current practice. Methods: Through a consensus meeting involving surgeons, biostatisticians, and epidemiologists, 30 variables of preoperative information possibly influencing surgeons’ choice between LG versus OG and potentially associating with outcomes were identified to enable rigorous estimation of propensity scores. A total of 4235 consecutive patients who underwent gastrectomy for gastric adenocarcinoma were identified and their relevant data were gathered from the participating hospitals. After propensity score matching, 1848 patients (924 each for LG and OG) were selected for comparison of long-term outcomes. Results: In the propensity-matched population, the 5-year overall survival was 96.3% [95% confidence interval (CI) 95.0–97.6] in the OG as compared with 97.1% (95% CI, 95.9–98.3) in LG. The number of all-cause death was 33/924 in the OG and 24/924 in the LG through the entire period, and the hazard ratio (LG/OG) for overall death was 0.75 (95% CI, 0.44–1.27; P = 0.290). The 3-year recurrence-free survival was 97.4% (95% CI, 96.4–98.5) in the OG and 97.7% (95% CI, 96.5–98.8) in the LG. The number of recurrence was 22/924 in the OG and 21/924 in the LG through the entire period, and the hazard ratio was 1.01 (95% CI, 0.55–1.84; P = 0.981). Conclusions: This observational study adjusted for all-known confounding factors seems to provide strong enough evidence to suggest that LG is oncologically comparable to OG for gastric cancer.

e16581 Background: Whereas radical resection for gastric cancer is only life-saving option, resulting host response have been suggested to trigger the outgrowth of previously disseminated foci at distant anatomical sites via alteration of anti-tumor immunity. The prognostic nutrition index (PNI) which was calculated as 10 × serum Alb concentration (g/dL) + 0.005 × peripheral total lymphocyte count (/µL) is a surrogate marker of inflammation related nutritional decline and the imbalance of T lymphocyte differentiation. The aim of study was to evaluate the impact of perioperative change of PNI. Methods: The medical record of 567 gastric cancer patients who matched with the following inclusion criteria, R0 resection between 2006 and 2018, no preoperative anticancer treatment, pStage IB-IIIC according to UICC TNM classification and no other organ cancer at surgery, was identified from the prospectively maintained database. The postoperative laboratory data was routinely evaluated at POD 1, 3, 7 and first visit after discharge (AD). The PNI was compared through the perioperative course. Then the predictive value of low PNI-AD which defined as PNI < 40 on the relapse free survival (RFS) after surgery was estimated by COX proportional hazards analysis. Results: The median value of PNI at base line, 1, 3, 7 POD and AD was 51.0, 35.9, 34.0, 38.3 and 48.2, respectively. The PNI as significantly decreased at 1, 3 and 7 POD. Though the PNI at AD had a proclivity to recover, which was still significantly lower than that at base line. During observation period after surgery, the recurrence was encountered in 80 patients. The 5-year RFS rate in patients of pStage IB (n = 164), II (n = 228) and III (n = 175) was 97.4%, 88.9% and 64.7%, respectively. The multivariate analysis identified female gender (HR: 1.715, 95%CI; 1.018-2.890, p = 0.04), pT3-4 (HR:3.620, 95%CI; 2.011-6.518, p < 0.01), pN1-3 (HR:2.741, 95%CI; 1.428-5.263, p = 0.02), vessel invasion (+) (HR:2.666, 95%CI; 1.681-4.229, p < 0.01), PNI-AD < 40 (HR:1.833, 95%CI; 1.002-3.352, p = 0.04) were independent predictors of recurrence. The low PNI-AD was significantly related to the recurrence in the population of pStage III, but not in pStage IB and II. Conclusions: The retardation of postoperative recovery of PNI might evoke the distant metastasis.

The prognosis for locally advanced gastric cancer (AGC) remains unsatisfactory, even with S-1 adjuvant chemotherapy. We investigated the efficacy of neoadjuvant chemotherapy consisting of docetaxel, cisplatin and S-1 (DCS).We retrospectively reviewed 59 patients who underwent neoadjuvant DCS therapy for clinical stage III tumors or serosa-positive tumors between January 2009 and December 2013 at Niigata Cancer Center Hospital. The patients received S-1 (40 mg/m(2) bid) on days 1-14, and docetaxel (35 mg/m(2)) and cisplatin (35 mg/m(2)) on days 1 and 15 every 4 weeks.Forty-three patients (72.9 %) received two courses of DCS therapy, while 16 patients (27.1 %) received one course of treatment. The clinical response rate of the primary tumor was 74.6 %, and the disease control rate was 100 %. A pathological response, defined as one-third or more of the affected tumor, was observed in 71.2 % of patients. The common grade 3/4 adverse events from chemotherapy were leucopenia (16.9 %), neutropenia (44.1 %), febrile neutropenia (8.5 %), anemia (10.2 %), anorexia (8.5 %) and nausea (6.8 %). Postoperative complications occurred in 11 patients (18.6 %). There was no treatment-related mortality or reoperation. The 3- and 5-year overall survival rates were 88 and 68.6 %, respectively. Clinical responders had a significantly higher survival rate than non-responders. Multivariate analysis identified clinical response as the only independent prognostic factor.Neoadjuvant DCS therapy demonstrated a very high clinical and pathological response rate with acceptable toxicities. Therefore, this therapy may improve the prognosis of locally AGC.

The aims of this study were to identify prognostic factors of patients with submucosa-invasive (T1b) gastric cancer and to verify the validity of adjuvant chemotherapy for this disease.We retrospectively examined the cases of 1,236 consecutive patients in our prospectively maintained database with T1b gastric cancer who underwent gastrectomy in 1995-2012. We used 11 clinicopathologic characteristics to identify prognostic factors by univariate and multivariate analyses. We compared the survival of the 160 node-positive T1b gastric cancer patients with that of 133 patients in the same database who had node-positive muscularis propria-invasive (T2) gastric cancer and had undergone gastrectomy without adjuvant chemotherapy during the same period, as a reference cohort.The 5-year overall survival rate was 91.4% for all 1,236 patients. Advanced age (hazard ratio [HR] 4.51; 95% confidence interval [CI] 3.26-6.24; P.01), male sex (HR 2.26; 95% CI 1.56-3.26; P.01), and the presence of lymph node metastasis (HR 1.89; 95% CI 1.33-2.70; P.01) were independent prognostic factors. The 5-year overall survival rates were 92.5% in node-negative patients, 84.5% in patients with 1 or 2 metastatic nodes, and 80.1% in patients with 3 or more metastatic nodes (P.01). The 5-year overall survival rates of the node-positive T1b and T2 gastric cancer patients were 83.6% and 81.2%, respectively (P = .73).The prognosis of node-positive T1b gastric cancer patients after curative gastrectomy was unsatisfactory. Adjuvant chemotherapy should be considered for these patients, especially those with 3 or more metastatic nodes.

A 59-year-old man was diagnosed with advanced thoracic esophageal cancer.He underwent neoadjuvant chemotherapy with cisplatin(CDDP), 5-fluorouracil(5-FU)(CF)followed by transthoracic esophagectomy with three-field lymphadenectomy. Histopathological examination revealed that the tumor was poorly differentiated squamous cell carcinoma invading the adventitia with 6 regional lymph node metastases.Four months after surgery, follow-up thoracic computed tomography (CT)showed multiple lung and mediastinal lymph node metastases.The patient's general condition was favorable, and he underwent systemic chemotherapy with docetaxel, CDDP, 5-FU(DCF).After 2 courses of DCF, chest CT revealed that the lung and mediastinal lymph node metastases had markedly decreased in size to the point of being unmeasurable.After receiving additional chemotherapy consisting of 2 courses of DCF and 8 courses of monthly docetaxel, the patient has been followed up without treatment.No tumor re-recurrence has occurred in the 6 years and 8 months since the first recurrence.In cases of recurrent or unresectable esophageal cancer, the rate of clinical response is reported to be higher for DCF than for CF. DCF is a tolerable regimen, even for postoperative patients, provided that monitoring is conducted for severe adverse events. In patients whose general conditions are favorable, DCF should be considered as a treatment option for recurrent esophageal cancer.

EGFR overexpression is a prognostic biomarker and is expected to be a predictive biomarker for anti-EGFR therapies in gastric cancer. However, few studies have reported the clinical impact of EGFR gene copy number (GCN) and its correlation with EGFR overexpression. We used dual in situ hybridization (DISH) to detect EGFR GCN and chromosome 7 centromere (CEN7) in a set of tissue microarrays representing 855 patients with gastric cancer. These data were compared with those of immunohistochemical (IHC) analysis of EGFR expression to evaluate prognostic value. EGFR GCN gain (≥2.5 EGFR signals per cell) was detected in 194 patients (22.7 %) and indicated poor prognosis. Among 194 patients, EGFR amplification (EGFR/CEN7 ≥ 2.0) was observed in 29 patients (14.9 %), which was almost identical to the IHC 3+ subgroup and worst prognostic subgroup. Patients with EGFR GCN gain but not amplification, including those exhibiting polysomy, also exhibited poorer prognosis than GCN non-gain patients and were distributed between IHC 0/1+ and 2+ subgroups. GCN gain was frequently observed in patients with more advanced disease, but served as an independent prognostic factor regardless of the pathological stage. EGFR GCN gain is a more accurate prognostic biomarker than EGFR overexpression in patients with gastric cancer.

Purpose Siewert type II esophagogastric junction adenocarcinoma (ADC) and squamous cell carcinoma (SCC) existing in the same area have distinct clinicopathological characteristics. The objective of this study was to examine differences in the surgical treatment and survival data, according to the histological subtype, in a single high-volume cancer center. Methods We retrospectively examined data from a total of 123 patients. Seventy-two patients with Siewert type II ADC and 51 patients with SCC in the same area. Results In terms of the clinicopathological factors, the SCC patients had more advanced stage disease and thoracotomy was more frequently performed than in the ADC patients. The 5-year overall survival (OS) rates did not differ significantly between SCC and ADC, regardless of whether or not mediastinal, splenic hilum and para-aortic lymph node dissection was performed. Based on the calculated index for the frequency of nodal metastasis and the five-year OS rate for involvement at each level, only node nos. 1, 2, 3 and 7 had a high index (>5) in both groups. The multivariate Cox regression analysis showed that only age (

A 76-year-old man was referred to our hospital for treatment of a submucosal tumor in the esophagus. The patient had a history of superficial esophageal cancer treated by endoscopic resection and radiation. Positron emission tomography showed intense localized uptake of fluorodeoxyglucose on the esophageal mass. Transthoracic esophagectomy and reconstruction with a gastric tube were performed. Histopathological examination revealed that the tumor consisted of a proliferation of atypical spindle cells with infiltration of many inflammatory cells. The spindle cells were positive for vimentin, alpha smooth muscle actin, and anaplastic lymphoma kinase immunostaining. The Ki-67 labeling index was 10–20 %. The tumor was finally diagnosed as inflammatory myofibroblastic tumor. Late phase inflammation caused by radiation potentially had an effect on the occurrence of the tumor in this case. For tumors of the irradiated esophagus, especially, careful pretreatment examination and treatment strategies with consideration of the radiation damage are important to obtaining a favorable outcome.

The ToGA trial demonstrated the beneficial effect of trastuzumab in gastric cancer patients with human epidermal growth factor receptor 2 (HER2)-overexpressing tumors. Therefore, evaluation of the relationship between HER2 expression and gastric cancer biology using a validated system has become an even more important task. Herein, we verified the correlation between HER2 overexpression in the tumor and the clinical course of gastric cancer patients.A total of 1,006 consecutive patients with gastric cancer who underwent surgery at the National Cancer Center Hospital East between January 2003 and July 2007 were examined using the tissue microarrays approach. HER2 expression was determined based on an immunohistochemistry score of 3+, or an immunohistochemistry score of 2+ plus HER2 gene amplification as detected by double-color fluorescent in situ hybridization. A retrospective review of the medical records was conducted to determine the correlation between the presence of HER2 overexpression and clinicopathological factors. Then, in 948 patients who had undergone curative resection, HER2 status was compared with the survival.HER2 overexpression was detected in 118 (11.7 %) patients. HER2 overexpression was correlated with age, gender, grade of differentiation, expanding growth pattern, and nodal status. In the survival analysis, HER2 overexpression was not found to be correlated with either disease-specific survival or recurrence-free survival.HER2 overexpression in the tumor was not identified as a significant prognostic factor in patients with operable gastric cancer. The HER2-targeted therapy may be beneficial in a proportion of cases.

This study aimed to clarify the oncological safety of pylorus-preserving gastrectomy (PPG) compared with conventional distal gastrectomy (DG). From three institutions specializing in cancer, the medical records for a cohort of 2898 consecutive patients who had undergone DG (n = 2208) or PPG (n = 690) for clinical stage I gastric cancer between January 2006 and December 2012 were analyzed. A propensity score for each patient was estimated on the basis of 38 preoperative clinical and tumor-related factors. After propensity score matching had been done, 1004 patients (502 DG patients, 502 PPG patients) were included in the analysis. The overall survival, relapse-free survival, and occurrence of secondary gastric cancer were then compared. The median observation period was 48.6 months (range 1–109.8 months). The 5-year overall survival rate was 98.4 % for the PPG group and 96.6 % for the DG group (hazard ratio 0.48, 95 % confidence interval 0.21–1.09, P = 0.07). The 3-year relapse-free survival rate was 99.5 % for the PPG group and 98.0 % for the DG group (hazard ratio 0.39, 95 % confidence interval 0.12–1.33, P = 0.12). Postoperative secondary gastric cancer was encountered in eight patients (1.6 %) in the PPG group and four patients (0.8 %) in the DG group. No significant differences in either overall survival, relapse-free survival, or the occurrence of secondary gastric cancer were observed between the two groups. Given the adequate estimation of the clinical tumor stage, the oncological safety of PPG for clinical T1N0 gastric cancer in the middle portion of the stomach was comparable to that of DG.

Multimodality therapy has been used in the management of gastric cancer associated with locoregional spread. However, the accurate clinical staging still remains to be established. The neutrophil/lymphocyte ratio (NLR) in the peripheral blood is reported to be an easily assessable prognostic factor in cancer patients. We evaluated the predictive significance of the NLR and other serological parameters in patients with wall-penetrating gastric cancer. Two hundred sixty-two patients who underwent gastric cancer surgery between 2002 and 2005 were identified retrospectively. Wall penetration was defined as wall invasion deeper than the muscularis propria (≥T2). Blood data were collected from routinely performed blood examinations before treatment and were analyzed with respect to T stage, nodal status, and histological features. A high NLR was defined as less than 3.2 based on ROC curve analysis, and the predictive value of a high NLR for T4 cancer was evaluated. Elevated levels of NLR (P = 0.004) and C-reactive protein (CRP) (P = 0.017) and the decrease in lymphocyte count (Lym, P = 0.032) and serum hemoglobin (Hb, P

109 Background: Peritoneal lavage cytology of class V and localized peritoneum metastasis of gastric cancer (GC) are defined as CY1 and P1 in the 14th edition of the Japanese Classification of GC. Because patients (pts) with CY1 and/or P1 have poor prognosis after resecting all macroscopically visible disease by standard surgical resection, post-operative chemotherapy (post-Cx) is commonly performed in the clinical practice in Japan. However, no standard chemotherapy has not been established. The aim of this study was to investigate the efficacy of post-Cx in patients with CY1 and/or P1. Methods: We retrospectively reviewed the GC pts who were diagnosed to have CY1 and/or P1 at 34 institutions participating in the Stomach Cancer Group of Japan Clinical Oncology Group between 2007 and 2012. Inclusion criteria were: PS 0-2, histology of adenocarcinoma, no distant metastasis other than CY1 or P1, no prior treatment for GC. The subject of this study was the patients who received surgery followed by post-Cx. Results: A total of 824 pts were collected from 34 institutions. Of the 506 eligible pts, 444 pts underwent standard gastrectomy followed by post-Cx: S-1 (n=267), S1 plus cisplatin (SP) (n=114) or others (n=63). 62 pts did not receive post-Cx (non-Cx). Median age for the S1/SP/Others/non-Cx group were 69/63/66/75. In the S-1 group, pts with P0CY1/P1CY0/P1CY1 were 197/44/26, and those were 81/21/12 in SP, 45/9/9 in Others, and 44/7/11 in non-Cx. Conclusions: Post-Cx may have survival benefit after surgery for GC with CY1 or P1, while there seems no additional benefit over S-1. [Table: see text]

We reported a case which developed obstructive cholangitis of the accessory bile duct 30 years after undergoing a cholecystectomy. A 78-year-old male patient was admitted to the emergency department, presenting with a fever of 40 degrees Celsius with chills and abdominal pain. The patient's past medical history included a cholecystectomy performed approximately 30 years ago. Contrast-enhanced computed tomography (CT) and magnetic resonance cholangio-pancreatography (MRCP) findings led to a diagnosis of obstructive cholangitis associated with jaundice due to the obstruction of the accessory bile duct. This was possibly attributable to a ligation of the accessory bile duct which was injured during cholecystectomy. The intraoperative findings showed confluence of the dilated intrahepatic bile duct and the common bile duct in the vicinity of the cystic duct which was already resected. The accessory bile duct was ligated and resected at the confluence followed by right hepatic lobectomy. A histopathological examination of the resected specimen showed the cord-like, occluded area of the stenosed accessory bile duct with no neoplastic lesions. It should be noted that inflammation may occur in the accessory bile duct associated with difficult differentiation if cholecystitis develops concurrently due to gallstone incarceration in the neck of the gallbladder. Therefore, drip infusion cholangiography-CT and MRCP are required preoperatively for the sufficient visualization of direction of the bile ducts, and endoscopic retrograde cholangiography should also be performed if no satisfactory results are obtained from these imaging tests. It is important to ensure that the direction of the bile ducts in the individual segments is always confirmed before performing a cholecystectomy.

PGE2 plays a key role in colon carcinogenesis. Evidence continues to accumulate that cyclooxygenase-2 (COX-2), an inducible COX isoform, represents a potential pharmacological target for the prevention and treatment of cancer, including tumors affecting the large bowels. Several mechanisms of COX-2 related tumor promotion have been identified. Some are dependent on PGE2 production (such as induction of cell proliferation, angiogenesis or local immunosuppression, inhibition of apoptosis, increase in cell motility). COX-2 expression has been demonstrated in epithelial cells of colorectal cancers and adenomas. Studies in experimental models of colon carcinogenesis show that selective COX-1 or COX-2 inhibitors reduce tumor formation and growth. Clinical studies have been initiated to determine the chemoprotective effects of selective COX-2 inhibitors in patients with familial adenomatous polyposis or sporadic adenoma. Possible cardiovascular effects will need to be taken into account in an assessment of the potential ability of any of these drugs to prevent neoplasia in the large bowel and other organs. Based on the fact that PGE2 is involved in almost all events concerning carcinogenesis, further examinations concerning mPGES-1, EP receptors, and 15-PGDH, should be promoted as a target for colon cancer prevention and therapeutics. Hence, detailed analyses are needed to clarify PGE2 related carcinogenesis.

A 66-year-old man was diagnosed with advanced type 2 gastric cancer and underwent total gastrectomy. The pathological diagnosis was T3N2H0P0CY0M0, stage ⅢB gastric cancer. Consequently, the patient received adjuvant S-1 therapy for 12 months. Thirty months after the operation, para-aortic lymph node recurrence was evident by computed tomography (CT). As a result, combination chemotherapy with paclitaxel, 5-fluorouracil, and cisplatin was initiated. However, after three courses of chemotherapy, abdominal CT showed progressive disease of the recurrent lymph node. Thereafter, radiotherapy at a total dose of 56 Gy was performed. After the radiotherapy treatment, abdominal CT demonstrated a remarkable reduction of the recurrent lymph node. The patient remains alive, with no signs of relapse, 70 months later. Therefore, this case suggests that radiotherapy may represent an effective treatment for localized remote lymph node recurrence of gastric cancer.

Objectives: Average human life expectancy is 82.6 years old in Japan. We report surgical treatment for extremely aged patients with gastric cancer. Methods: Between 1991 and 2011, 5330 gastric cancer patients were underwent gastrectomy in our hospital, and 78 patients (1.5%) were over 85 years old. The clinic-pathological findings in these patients were investigated retrospectively and compared with those in 4494 patients under 75 years old. Results: Median age was 86 (85-95) vs. 63 (19-75). The types of gastrectomy such as local/proximal/distal/total were 9/0/49/20 vs. 216/172/2983/1123. Preoperative morbidity rate was 73.1% vs. 23.2%. The ratio of extent nodal dissection was 30.8% vs. 53.5%. Postoperative morbidity/30-day mortality rate was 24.4%/1.3% vs. 15.3%/0.2%, especially pneumonia; brain infarction and urinary tract infection were more common in elderly group. Best supportive care is highly selected in case of recurrence in elderly group (66.7% vs. 11.9%). The overall 5-year survival rate of StageI/II/III/IV was 70.6/70.0/30.3/0% vs. 92.0/80.0/60.5/13.3%. The ratio of non-cancer death within 5 years after operation was 19.2% vs. 5.8%. Conclusion: Although the postoperative complications and non-gastric cancer death are high ratio, cautious operative procedure contributes to a good results and prognosis even in the extremely aged patients.

切除不能の膵・胆道癌患者に対する病状説明のinformed consent(IC)に際し,家族の関与を積極的に認めるICの有用性を評価し,今後の問題点も検討した.過去7年間に筆者(S.S)が病状説明を行った切除不能の膵・胆道癌89例を対象に,まず家族に対し患者本人に病状を正しく告知することの重要性と支援体制の確立を求めた.この結果,最終的に73人(82%)の患者に病状説明, 41人(46%)に予後の説明を行った.説明後のうつ状態からの回復は比較的早かったが,家族の支援が消極的であったり,キーパーソンが不在である場合は回復が遅れる傾向にあった.我が国では,未だ患者の自己決定権の意識が希薄で,患者自身が意志決定する際にも家族の支援が必要である.今後は,患者の意志を尊重するという考えを個人情報保護法とともに社会一般に啓蒙し,周知させていく努力が必要と考えられる.

We have studied the dehydration process of formic acid on a TiO2(110) surface by using first-principles theoretical calculations. Formic acid dissociatively adsorbs to form formate and hydroxyl. It turns out that simple decomposition processes of the formate on the stoichiometric surface are energetically unfavorable. The formation of H2O and O vacancies from two neighboring bridging hydroxyls is relatively easy and the activation barrier is calculated to be 114 kJ/mol. On the TiO2(110) surface with oxygen defect sites, formate adsorbs with one O at a defect site and with the other O on a five-fold Ti, forming a bridging configuration. Further decomposition of the formate occurs through a monodentate configuration with an activation barrier of 129 kJ/mol. We have also performed STM observation corresponding to the theoretical results. It was imaged that some formates were located along the oxygen row and at an intermediate position between the oxygen row and the Ti row at elevated temperatures at which re...