Search

Background Bursectomy, the total resection of the bursa omentalis, is a standard procedure in gastrectomy for resectable gastric cancer. A phase III trial (JCOG1001) comparing bursectomy and omentectomy alone was terminated early at the interim analysis. The final results of the updated analysis after a minimum follow-up of 5 years are reported here. Methods Patients with histologically proven adenocarcinoma of the stomach (cT3–T4a) were randomized (1 : 1) during surgery to bursectomy or omentectomy-alone groups and then underwent D2 gastrectomy. The primary endpoint was overall survival, analysed on an intention-to-treat basis. Results A total of 1204 patients (602 bursectomy and 602 omentectomy alone) were enrolled between June 2010 and March 2015. The bursectomy group had a significantly higher incidence of Clavien–Dindo grade III–IV intra-abdominal abscess than the omentectomy-alone group (5.5 versus 2.5 per cent respectively; P = 0.008). The updated 5-year overall survival rates were 74.9 (95 per cent c.i. 71.2 to 78.2) per cent in the bursectomy group and 76.5 (72.8 to 79.7) per cent in the omentectomy-alone group; the adjusted HR for death in the bursectomy group was 1.03 (95 per cent c.i. 0.83 to 1.27) (1-sided P = 0.598). Bursectomy did not decrease peritoneal recurrence (12.1 versus 12.3 per cent respectively; P = 1.000). In a multivariable analysis, old age (above 65 years), tumour located in the lower third or posterior wall of the stomach, macroscopic type 3/5, total gastrectomy, and cT4a were independent predictors of poor overall survival, but omentectomy alone was not. Conclusion In D2 gastrectomy, bursectomy is not recommended as a standard procedure for cT3–T4a gastric cancer. Registration number: UMIN000003688 (https://www.umin.ac.jp/ctr/).

To compare irinotecan-alone, paclitaxel-alone, and each combination chemotherapy with S-1 in patients with advanced gastric cancer (AGC) that is refractory to S-1 or S-1 plus cisplatin (SP). Patients with AGC after first-line chemotherapy with S-1 or SP, or patients during adjuvant chemotherapy or within 26 weeks after adjuvant chemotherapy completion with S-1 with confirmed disease progression were eligible. Patients were randomly divided into four groups based on treatment: irinotecan-alone (irinotecan; 150 mg/m2, day 1, q14 days), paclitaxel-alone (paclitaxel; 80 mg/m2, days 1, 8, 15, q28 days), S-1 plus irinotecan (irinotecan; 80 mg/m2, days 1, 15, S-1; 80 mg/m2, days 1–21, q35 days), and S-1 plus paclitaxel (paclitaxel; 50 mg/m2, day1, 8, S-1; 80 mg/m2, days 1–14, q21 days). The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS), response rate, and safety. From July 2008 to March 2012, 127 patients were enrolled. No difference in median OS was observed in the irinotecan vs. paclitaxel groups or in the monotherapy groups vs. the S-1 combination therapy groups. Median PFS was longer in the paclitaxel group compared with the irinotecan group (4.1 vs. 3.6 months, p = 0.035), although no difference was observed when comparing monotherapy vs. S-1 combination. The most common grade 3 to 4 hematological adverse events were neutropenia with no difference in incidence rate across the treatment groups. There was no difference in OS between irinotecan and paclitaxel no in OS prolongation of S-1 combination therapy in second-line chemotherapy.

BACKGROUND Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0-14 years) and adults (aged 15-99 years) diagnosed with a haematological malignancy during 2000-14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0-24 years). METHODS We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0-14 years), adolescents (15-19 years), and young adults (20-24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. FINDINGS 164 563 young people were included in this analysis: 121 328 (73·7%) children, 22 963 (14·0%) adolescents, and 20 272 (12·3%) young adults. In 2010-14, the most common subtypes were lymphoid leukaemia (28 205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010-14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000-14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. INTERPRETATION This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group. FUNDING Children with Cancer UK, the Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, US National Cancer Institute, and the American Cancer Society.

After D2 gastrectomy for advanced gastric cancer, patients with a high drainage fluid amylase level (d-AMY) on the first postoperative day (1POD) have an especially high risk of severe abdominal infectious complications (AICs), which could be fatal. On the hypothesis that prolonged antibiotic administration could reduce the incidence of severe AICs, we conducted a randomized phase II study to evaluate the optimal treatment duration of prophylactic antibiotics for patients who underwent D2 gastrectomy and had elevated d-AMY on 1POD. Patients whose d-AMY was >3000 IU/L on 1POD after D2 gastrectomy for gastric cancer were randomly assigned to normal prophylactic antibiotic treatment given only on the day of surgery (Group A) or to prolonged antibiotic treatment given for 1 week after surgery (Group B). The primary endpoint was the incidence of severe AICs (Clavien–Dindo grade IIIa or higher). This trial was registered as UMIN000012152. This study was started in December 2013 and stopped in February 2019 because of poor patient accrual. Finally, 35 and 37 patients were assigned to groups A and B, respectively. The incidences of AICs were 22.9% (eight of 35) in group A and 13.5% (five of 37) in group B. One-sided P value of the Fisher exact test was 0.234. No adverse reactions to antibiotic prophylaxis were observed in any of the patients. Prolonged prophylactic antibiotic administration had a marginal benefit in preventing grade III or higher AICs and caused no treatment-related morbidities.

Background Proximal gastrectomy (PG) has become an increasingly preferred procedure for early cancer in the upper third of the stomach, owing to reportedly superior quality of life (QOL) after PG when compared with total gastrectomy. However, various methods of reconstruction have currently been proposed. We compared the postoperative QOL among the three different reconstruction methods after PG using the Postgastrectomy Syndrome Assessment Scale-45 (PGSAS-45) questionnaire. Methods Post Gastrectomy Syndrome Assessment Study (PGSAS), a nationwide multi-institutional survey, was conducted to evaluate QOL using the PGSAS-45 among various types of gastrectomy. Of the 2,368 eligible data from the PGSAS survey, data from 193 patients who underwent PG were retrieved and used in the current study. The PGSAS-45 consists of 45 items including 22 original gastrectomy specific items in addition to the SF-8 and GSRS. These were consolidated into 19 main outcome measures pertaining postgastrectomy symptoms, amount of food ingested, quality of ingestion, work, and level of satisfaction for daily work, and the three reconstruction methods (n = 193; 115 esophago-gastrostomy [PGEG], 34 jejunal interposition [PGJI], and 44 jejunal pouch interposition [PGJPI]) were compared using PGSAS-45. Results Size of the remnant stomach was significantly larger in PGEG, and significantly smaller in PGJI and PGJPI (P P = 0.047–0.076). Conclusion PGJPI appears to be the most favorable of the three reconstruction methods after PG especially when the size of remnant stomach is rather small. Trial registration number UMIN-CTR #000002116 entitled as “A study to observe correlation between resection and reconstruction procedures employed for gastric neoplasms and development of postgastrectomy syndrome”

This phase II study assessed the efficacy of capecitabine plus cisplatin in patients with advanced gastric cancer refractory to adjuvant S-1.This single-arm, open-label, multicenter, phase II study was conducted by Tohoku Clinical Oncology Research and Education Society (T-CORE) in Japan. Patients aged ≥20 years with advanced HER2-negative gastric cancer that was refractory to S-1 were enrolled. Patients received 80 mg/mIn total, 21 patients were enrolled from seven hospitals. The median patient age was 63 years. Nineteen patients received the protocol treatment. Median PFS was 3.7 months [90% confidence interval (CI)=2.7-5.6 months], which did not reach the predefined threshold of 4.0 months. ORR was 5.9% (95%CI=0.0-17.1%). Median OS was 11.9 months (95% CI 6.3-19.4 months). Febrile neutropenia was observed in 5.3% of patients. The most frequently observed grade 3 non-hematologic toxicities were nausea (15.8%) and hyponatremia (15.8%).The addition of a fluoropyrimidine to a platinum agent after adjuvant therapy is not suitable for gastric cancer.

Gastric cancer with extensive lymph node metastasis is commonly regarded as unresectable, while preoperative chemotherapy followed by gastrectomy has been tested since 2000 in JCOG (JCOG0001 and JCOG0405). The survivals were quite different between the trials despite the similar eligibility criteria. The aim of this study was to investigate if survival is still better in JCOG0405 after adjusting baseline factors and if there is any subset of patients who benefit more from either treatment. Eligibility criteria for both trials included histologically proven gastric adenocarcinoma; bulky nodal involvement around the celiac artery and its major branches (bulky N) and/or para-aortic lymph node (PAN); cM0 (except PAN); negative lavage cytology; not linitis plastica type; PS of 0 or 1. Patients received two or three cycles of preoperative chemotherapy of irinotecan plus cisplatin in JCOG0001, or S-1 plus cisplatin in JCOG0405, followed by D3 gastrectomy. Multivariable analysis for overall survival adjusting baseline and treatment factors was performed with the Cox regression model. After adjusting baseline factors, S-1 plus cisplatin was superior to irinotecan plus cisplatin for overall survival (HR = 0.39: 95% CI 0.22–0.67). The 5-year overall survival was poor for patients with bulky N+/PAN+ (19.2%) compared with bulky N+/PAN− (50.7%) or bulky N−/PAN+ (43.5%). S-1 plus cisplatin was shown to be a favorable preoperative treatment for gastric cancer with extensive lymph node metastasis by multivariable analysis, while poor prognosis in patients having both bulky N+ and PAN+ may necessitate further treatment improvement.

Summary Background Postoperative adjuvant chemotherapy with S-1 for 1 year (corresponding to eight courses) is standard care for stage II gastric cancer. Whether the duration of S-1 could be shortened to 6 months (corresponding to four courses) without worsening survival is unclear. The aim of this study was to investigate the non-inferiority of four courses of S-1 compared with eight courses of S-1 for patients with stage II gastric cancer. Methods We did a phase 3, open-label, randomised controlled, non-inferiority trial at 59 hospitals in Japan. Patients aged 20–80 years with stage II adenocarcinoma of the stomach were randomly assigned (1:1) to eight courses or four courses of S-1. Randomisation was done by the Japan Clinical Oncology Group Data Center website, using a minimisation method with a random component using institution, stage (IIA vs IIB), age ( vs ≥70 years), and mode of operation (open gastrectomy with bursectomy vs open gastrectomy without bursectomy vs laparoscopic gastrectomy) as adjustment factors. One course was 80 mg/day per m 2 of S-1 administered for 4 weeks followed by a rest for 2 weeks. The primary endpoint was relapse-free survival, analysed by intention to treat, with a non-inferiority margin for the hazard ratio (HR) set at 1·37. This study is registered at UMIN-Clinical Trial Registry, number UMIN000007306. Findings Between Feb 16, 2012, and March 19, 2017, 590 patients were enrolled (295 per group). 528 (89%) patients were analysed at the first planned interim analysis in March, 2017, at which time the point estimate of HR for the four-course group compared with the eight-course group was 2·52 (95% CI 1·11–5·77), which exceeded 1·37 and met the prespecified criteria for early termination. Predictive probability for showing non-inferiority at the final analysis was calculated to be 2·9%. The study was stopped for futility. Updated 3-year relapse-free survival analysed in May, 2017, was 93·1% (95% CI 87·8–96·1) for the eight-course group and 89·8% (84·2–93·5) for the four-course group (HR 1·84, 95% CI 0·93–3·63). The most common grade 3–4 adverse event was neutropenia, observed in 46 (16%) patients in the eight-course group and 51 (17%) patients in the four-course group. Interpretation S-1 for 1 year should remain as standard adjuvant chemotherapy for stage II gastric cancer. Funding Japan Agency for Medical Research and Development; the Ministry of Health, Labour and Welfare of Japan; the National Cancer Center Research and Development Fund, Japan.

Background In the ABSOLUTE trial, weekly nanoparticle albumin-bound paclitaxel (w-nab-PTX) showed non-inferiority to weekly solvent-based paclitaxel (w-sb-PTX) for overall survival (OS). Thus, w-nab-PTX might be an option for second-line chemotherapy in advanced gastric cancer (AGC). However, predictive factors for efficacies of these agents have not been evaluated. Methods Patients previously enrolled in the ABSOLUTE trial were divided into apparent peritoneal metastasis group (PM group) and no apparent peritoneal metastasis group (no PM group) based on baseline imaging evaluated by RECIST ver. 1.1 criteria and amount of ascites. OS, progression-free survival, and overall response rate were compared between two arms in each group. Results This study included 240 and 243 patients in the w-nab-PTX and w-sb-PTX arms, respectively. In the PM group, the w-nab-PTX arm (n = 88) had longer OS than the w-sb-PTX arm (n = 103), and median survival time (MST) of 9.9 and 8.7 months [hazard ratio (HR) 0.63; 95% CI 0.45–0.88; P = 0.0060], respectively. In the no PM group, the w-nab-PTX arm (n = 140) had shorter OS than the w-sb-PTX arm (n = 152), and MST of 11.6 and 15.7 months (HR 1.40; 95% CI 1.06–1.86; P = 0.0180), respectively. After adjusting for prognostic factors, the HR for OS in the w-nab-PTX arm versus the w-sb-PTX arm was 0.59 (95% CI 0.42–0.83; P = 0.0023; PM group) and 1.34 (95% CI 1.01–1.78; P = 0.0414; no PM group), with significant interaction between treatment efficacy and presence of peritoneal metastasis (P = 0.0003). Conclusions The presence of apparent peritoneal metastasis might be a predictive factor for selecting w-nab-PTX for pretreated AGC patients. Trial registration number JapicCTI-132059.

In Japan, S-1 adjuvant chemotherapy for 1 year is the standard of care for the treatment of stage II and III patients under 80 years old with gastric cancer after curative operation. However, the feasibility of S-1 chemotherapy in patients over 80 years old has not yet been elucidated. To clarify the current treatment situation and feasibility of S-1 treatment in patients over 80 years old, a questionnaire survey of the patients treated from January 2011 to December 2012 was conducted at 58 member institutions of the Stomach Cancer Study Group of the JCOG (Japan Clinical Oncology Group). Gastrectomy was performed in 15,573 patients of all ages, and 1,660 (10.7%) patients were over 80 years of age. Of these elderly patients, 661 (4.2%) were diagnosed as stage II and III. While S-1 adjuvant chemotherapy was recommended to 248 (37.5%) of the stageII/III patients, only 99 (15.0%) of them actually received S-1. Interestingly, the creatinine clearance rate was between 30 and 80 mL/min in 87 (87.9%) of the patients suggesting that S-1 dose modification should be considered. Moreover, S-1 compliance was poor in patients with more than 15% body weight loss. In general practice, surgery alone can be regarded as the standard of care for stage II and III gastric cancer patients over 80 years old. The feasibility and efficacy of S-1 adjuvant chemotherapy should be elucidated in a randomized control trial considering the vulnerabilities of the elderly.

Background and objectives Limited information exists regarding beneficial effects of Helicobacter pylori. To examine the effect in advanced gastric cancer, we compared survival for patients treated with surgery-only or adjuvant chemotherapy on the basis of H. pylori infection status. Methods A cohort of 491 patients who underwent R0 resection for locally advanced gastric cancer between 2000 and 2009 at 12 institutions in northern Japan was included. H. pylori infection status, was assessed from paraffin-embedded formalin-fixed samples. Overall survival (OS) and disease-free survival (DFS) in surgery-only (Surgery) and adjuvant chemotherapy (S-1) groups were analyzed. A propensity score matching was employed to correct for confounding factors by indication. Results H. pylori infection was positive in 175 patients and negative in 316 patients. H. pylori-positive patients showed significantly better survival than H. pylori-negative patients in both OS (hazard ratio [HR] 0.593, 95% confidence interval [CI] 0.417-0.843; P = 0.003]) and DFS (HR 0.679, 95%CI 0.492-0.937; P = 0.018). Propensity score matching further confirmed that S-1 was virtually only effective when tumors were H. pylori-positive. Conclusions The favorable outcome of H. pylori-positive patients implies that the host immune system is modulated by H. pylori enhancing the chemotherapeutic efficacy.

BACKGROUND Postoperative adjuvant chemotherapy is not indicated for T1N1M0/T2N0M0/T3N0M0 gastric cancer. However, approximately 10% to 30% of these patients experience recurrence and metastasis. METHODS Among 658 patients with gastric cancer who received gastrectomy with curative intent, 130 T1N1M0/T2N0M0 and 73 T3N0M0 patients were enrolled. Overall survival (OS) and relapse-free survival (RFS) were analyzed based on TP53 codon 72 polymorphisms Arg/Arg, Arg/Pro, and Pro/Pro. The hazard ratio (HR) for each subgroup was compared by TP53 codon 72 polymorphisms. RESULTS Of the 189 patients for whom polymorphism analysis results were available, the 5- and 10-year OS was 84.9% and 65.1%, respectively. The 5- and 10-year RFS was 81.8% and 65.4%, respectively. When the study cohort was divided into two groups according to polymorphism status (ie, "Arg/Arg and Arg/Pro" vs Pro/Pro), both the OS (HR, 2.799; 95% confidence interval [CI], 1.071-7.315; P = .036) and RFS (HR, 2.639; 95% CI, 1.025-6.794; P = .044) of the Pro/Pro group were significantly lower than those for the Arg/Arg and Arg/Pro groups across the entire observation period. CONCLUSIONS The TP53 codon 72 Pro/Pro polymorphism may isolate a relatively high-risk patient group in T1N1M0/T2N0M0/T3N0M0 gastric cancer.

No confirmatory randomized controlled trials (RCTs) have evaluated the efficacy of laparoscopy-assisted distal gastrectomy (LADG) compared with open distal gastrectomy (ODG). We performed an RCT to confirm that LADG is not inferior to ODG in efficacy. We conducted a multi-institutional RCT. Eligibility criteria included histologically proven gastric adenocarcinoma in the middle or lower third of the stomach, clinical stage I tumor. Patients were preoperatively randomized to ODG or LADG. This study is now in the follow-up stage. The primary endpoint is relapse-free survival (RFS) and the primary analysis is planned in 2018. Here, we compared the surgical outcomes of the two groups. This trial was registered at the UMIN Clinical Trials Registry as UMIN000003319. Between March 2010 and November 2013, 921 patients (LADG 462, ODG 459) were enrolled from 33 institutions. Operative time was longer in LADG than in ODG (median 278 vs. 194 min, p

TPS4646 Background: Standard surgery for resectable advanced gastric cancer is D2 (standardized extended lymph node dissection) gastrectomy with omentectomy. The reason why omentectomy has been performed is as follows; (1) principal surgery for gastrointestinal cancers is en-block resection of mesothelium including regional lymph nodes. Omentum is a part of the mesothelium of the stomach. (2) Cancer cells implanted into the peritoneal cavity aggregated in the milky-spot of the omentum and formed peritoneal dissemination in an animal model. (3) By special staining, micrometastasis detected in the omentum. There is some arguments for this theory. (1) no prospective study showed survival benefit of omentectomy as compared with omentum preservation. (2) anatomically, milky-spot is found not only in the omentum but also in other mesothelium or Douglas pouch. (3) JCOG1001 phase III study showed no survival benefit of bursectomy against non-bursectomy although bursa is a part of mesothelium of the stomach. (4) Anti-immunity is accelerated by antigen presentation by macrophage in the milky-spot of the omentum. Preservation of the omentum may have several benefits; (1) decrease in blood loss and operation time, (2) preservation of physical function by omentum such as reaction to peritonitis and prevention of adhesion, and (3) overcoming difficulties in laparoscopic omentectomy and avoidance of organ injury during surgery. Methods: The study is multicenter randomized phase III trial designed to confirm non-inferiority of omentum preservation to omentectomy for resectable advanced gastric cancer. Patients aged 20-79 years, histologically proven gastric adenocarcinoma, clinical subserosal/serosal invasion, and expected R0 (curative) resection are randomly assigned (1:1) during surgery to either omentum preservation or omentectomy. Total or distal gastrectomy with D2 dissection is performed in both arms. Laparoscopic gastrectomy is not allowed. Intraoperative photographs of the dissected field are centrally reviewed for all patients for quality control. The primary endpoint is relapse-free survival (RFS) and the secondary endpoints are overall survival, blood loss, operation time, and adverse events. Sample size was set at 1050 considering expected 3-year RFS of 77% in both arms with non-inferiority margin of 5%, one-sided alpha of 5%, and power of 80%. Planned accrual and follow up period are 6.5 years and 3 years respectively. The trial was activated in March 2019, and 177 patients are enrolled as of January 2020. Clinical trial information: UMIN000036253 .

A 67-year-old man was diagnosed with esophageal cancer. Computed tomography(CT)revealed multiple sites of bilateral mediastinal lymph node swelling. Serum levels of soluble interleukin-2 receptor(sIL-2R)were elevated; however, serum levels of angiotensin-converting enzyme(ACE)were normal. Thus, we could not confirm a diagnosis of sarcoidosis. Esophagectomy with neck lymph node dissection was performed. The resected specimen, comprising the mediastinal lymph nodes, showed noncaseating epithelioid cell granuloma; this supported the diagnosis of sarcoidosis. Cases of sarcoidosis associated with esophageal cancer are rare. It is difficult to distinguish between metastasis and sarcoid-like reactions from swollen lymph nodes using preoperative CT or positron emission tomography(PET). It is possible to differentiate lymph node metastasis from its sarcoid reaction it the patient received.

A 67-year-old man was referred to our hospital because of fever and discomfort of the throat. Gastrointestinal endoscopy revealed hematoma at the middle thoracic esophagus. Computed tomography revealed posterior mediastinal hematoma extending the descending aorta. Bacillus was detected in the blood culture. Aortoesophageal fistula with an infected thoracic aortic aneurysm rupture was diagnosed. First, thoracic endovascular aortic repair (TEVAR) was performed. Resection of the thoracic esophagus and omentopexy was conducted 15 days after TEVAR. Esophageal reconstruction using a gastric tube was performed 43 days after esophagectomy. He has been doing well since then.

Summary Background The role of bursectomy, in which the peritoneal lining covering the pancreas and the anterior plane of the transverse mesocolon are dissected, has long been controversial for preventing peritoneal metastasis. We investigated the survival benefit of bursectomy in patients with resectable gastric cancer. Methods This phase 3, open-label, randomised controlled trial was done at 57 hospitals in Japan. Patients aged 20–80 years who had cT3(SS)–cT4a(SE) histologically proven gastric adenocarcinoma with an Eastern Cooperative Oncology Group performance status of 0 or 1 and body-mass index less than 30 kg/m 2 and who did not have distant metastasis or bulky lymph nodes were randomly assigned (1:1) during surgery to receive omentectomy alone (non-bursectomy) or bursectomy. Randomisation was done by telephone or website to the Japan Clinical Oncology Group Data Center and used a minimisation method with a random component to adjust for institution, cT status (T3 vs T4a), and type of gastrectomy (distal vs total). Both groups had total or distal gastrectomy with D2 lymphadenectomy. The primary endpoint was overall survival, analysed in the intention-to-treat population. The study is registered with UMIN-CTR, number UMIN000003688. Findings Between June 1, 2010, and March 30, 2015, 1503 patients were enrolled based on preoperative inclusion and exclusion criteria. Intraoperative inclusion and exclusion criteria were met in 1204 patients, of which 602 were allocated to the non-bursectomy group and 602 were allocated to the bursectomy group. At the planned second interim analysis on Sept 17, 2016, the JCOG Data and Safety Monitoring Committee independently reviewed the results and recommended their early publication on the basis of futility because overall survival was lower in the bursectomy group than the non-bursectomy group, and because the predictive probability of overall survival being significantly higher in bursectomy than non-bursectomy patients at the final analysis was only 12·7%. 5-year overall survival was 76·7% (95% CI 72·0–80·6) in the non-bursectomy group and 76·9% (72·6–80·7) in the bursectomy group (hazard ratio 1·05, 95% CI 0·81–1·37, one-sided p=0·65). 64 (11%) of 601 in the non-bursectomy group and 77 (13%) of 600 patients in the bursectomy group had grade 3–4 operative morbidity. Pancreatic fistula was significantly more common in the bursectomy group than in the non-bursectomy group (29 [5%] vs 15 [2%]; p=0·032). Six deaths occurred either in hospital or within 1 month of surgery: five in the non-bursectomy group and one in the bursectomy group. Interpretation Bursectomy did not provide a survival advantage over non-bursectomy. D2 dissection with omentectomy alone should be done as a standard surgery for resectable cT3–T4a gastric cancer. Funding Japan Agency for Medical Research and Development, the Ministry of Health, Labour and Welfare of Japan, and the National Cancer Centre Research and Development Fund.

Background: Postoperative adjuvant chemotherapy with S-1 for 1 year (corresponding to 8 courses) is a standard care for pathological stage II gastric cancer. It remains unclear whether duration of S-1 for 1 year could be shortened to 6 months (corresponding to 4 courses) without worsening the survival. Methods: We conducted a phase 3, open-label, randomized controlled non-inferiority trial at 59 hospitals in Japan. Patients with pathological stage II adenocarcinoma of the stomach were randomly assigned (1:1) to 4 courses S-1 or 8 courses S-1. 80 mg/m2/day of S-1 was administered for 4 weeks with a rest for 2 weeks as one course. Primary endpoint was relapse-free survival (RFS), analyzed by intension to treat. Total sample size was determined to be 1,000, expecting 3-year RFS of 85% with non-inferiority margin of hazard ratio (HR) of 1·37, one-sided alpha of 5% and 80% power. Findings: Between Feb 2012 and Mar 2017, 590 patients were enrolled (8-courses, 295; 4-courses, 295). Among them, 528 patients were analyzed at the first planned interim analysis in Mar 2017. The point estimate of HR of the 4- courses group compared with the 8-courses group was 2·52 (95% CI: 1·11- 5·77), which was greater than 1·37 and met the prespecified criteria for early termination, associated with predictive probability of 2·9% for showing non-inferiority at the final analysis. Updated 3-year RFS analyzed in May 2017 were 93·1% (95% CI 87·8%-96·1%) for the 8-courses group and 89·8% (95% CI 84·2%-93·5%) for the 4-courses group (HR 1·84, 95% CI 0·93-3·63). Interpretation: Postoperative S-1 adjuvant chemotherapy for p-stage II gastric cancer should be continued for 1 year. Clinical Trial Number: This study is registered at UMIN-CTR, number UMIN000007306. Funding Statement: Japan Agency for Medical Research and Development; the Ministry of Health, Labour and Welfare of Japan; the National Cancer Center Research and Development Fund. Declaration of Interests: TYo had received reports grants from Japan Agency for Medical Research and Development (AMED) during the conduct of the study, lecture fees from Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol, MSD, Daiichi Sankyo, Yakult Honsha, Takeda Pharmaceutical, Nippon Kayaku, Kaken Pharmaceutical, Abbott Japan, Medtronic, Johnson & Johnson, and Olympus, and grant supports from Taiho Pharmaceutical, Chugai Pharmaceutical, and Yakult Honsha outside the submitted work. JM had received grants from Ministry of Health, Labour and Welfare, Japan, grants from Japan Agency for Medical Research andÝevelopment (AMED) during the conduct of the study. KY had received grants, personal fees, and non-financial support from Taiho Pharm. Co. during the conduct of the study, grants, personal fees, and non-financial support from Sanofi, grants, personal fees, and non-financial support from Chugai Pharm. Co., Ltd., grants, personal fees, and non-financial support from Yakult Honsha Co., Ltd., grants, personal fees, and non-financial support from Eli Lilly Japan K.K., grants, personal fees, and non-financial support from Daiichi Sankyo Co., Ltd., grants, personal fees, and non-financial support from Merck Serono Co., Ltd., grants, personal fees, and non-financial support from Novartis Pharma, grants, personal fees, and non-financial support from EA Pharma Co., Ltd., grants, personal fees, and non-financial support from Johnson & Johnson K.K., grants, personal fees, and non-financial support from Covidien Japan, grants, personal fees, and non-financial support from Takeda Pharmaceutical Co., Ltd., grants, personal fees, and non-financial support from Ono Pharm. Co.,Ltd, grants and personal fees from Nippon Kayaku Co.,Ltd., grants and personal fees from Otsuka Pharma Co., Ltd., grants from Sumitomo Dainippon Pharma, grants from Bristol Myers Japan, grants from Tsumura, grants from Kyowa Hakko Kirin, grants from Astellas, grants from Toyama Chemical, grants from KCI, grants from Abbott Japan, grants from Asahi Kasei, personal fees from Olympus, personal fees from Terumo, personal fees from Denka, personal fees from MSD K.K., personal fees from Bayer Yakuhin, Ltd, outside the submitted work. SI had received grants from MSD, grants from Ono Pharmaceutical, personal fees from Chugai Pharmaceutical, personal fees from Otsuka Pharmaceutical Factory outside the submitted work. HK had received grants from Ministry of Health, Labour and Welfare, Japan, grants from Japan Agency for Medical Research and Ýevelopment (AMED) during the conduct of the study and personal fees from Johnson & Johnson outside the submitted work. HF had received grants from Ministry of Health, Labour and Welfare, Japan, grants from National Cancer Center, Japan during the conduct of the study, personal fees from Taiho Pharma, and personal fees from Chugai Pharmaceutical outside the submitted work. NB had received honorarium from Taiho, Ono, Chugai, Shionogi, Yakult, Bristol Myers Squibb, Eli Lilly, Merck Serono, and study grant from Taiho, Ono and Bristol Myers Squibb outside of the submitted work. TS had received personal fees from Taiho Pharma outside the submitted work. MS had received personal fees from Taiho Pharmaceutical during the conduct of the study. Ethics Approval Statement: This study was done in accordance with the international ethical recommendations stated in the Declaration of Helsinki, Japanese Ethical Guidelines for Clinical Research. All patients were required to provide written informed consent prior to enrollment.

4067 Background: Recently, the negative impact of postoperative complications on long-term survival outcomes has been reported in patients with gastric cancer. However, most are single center, retrospective studies with different definitions of postoperative complications. The objective of this study was to evaluate the impact of postoperative complications on long-term outcomes using the data of a multicenter randomized controlled trial (JCOG1001). Methods: This study included 1191 out of all 1204 patients enrolled in JCOG1001 which was aimed to confirm the superiority of bursectomy for patients with cT3/4a locally advanced gastric cancer. Complications were graded by Clavien-Dindo classification. The relationships between the grade (≥grade II or ≥grade III) or type (all or intraabdominal infectious (pancreatic fistula, anastomotic leakage, and intra-abdominal abscess.)) of complications and survival outcomes were evaluated. Results: The incidences of ≥grade II and ≥grade III all complications were 23.0% and 9.7%, and those of ≥grade II and ≥grade III intraabdominal infectious complications were 13.4% and 6.9%, respectively. The hazard ratios for overall survival (OS) of patients with ≥grade II and ≥grade III all complications and those of patients with ≥grade II and ≥grade III intraabdominal infectious complications were shown in Table. With whichever definition we adopted, postoperative complications were significantly associated with OS in both univariable and multivariable analysis. Conclusions: Postoperative complication was identified as an independent prognostic factor in patients with cT3/4a gastric cancer. Hazard ratios for overall survival by univariable and multivariable Cox proportional hazard model. Clinical trial information: UMIN000003688. [Table: see text]

Background and Objectives We conducted a phase II study to evaluate the safety and efficacy of preoperative chemotherapy with S-1 + cisplatin followed by gastrectomy in patients with linitis plastica (type 4) or large ulcero-invasive-type (type 3) gastric cancer. Methods Eligibility criteria included histologically proven adenocarcinoma of the stomach; clinically resectable gastric cancer of type 4 or type 3. Patients received two 28-day courses of preoperative chemotherapy of S-1 (80–120 mg/body, p.o., days 1–21) and cisplatin (CDDP; 60 mg/m2, i.v., day 8). Primary endpoints were completion of protocol treatment and incidence of treatment-related death (TRD). Results Among the 49 eligible patients with the median age of 61 years, 36 completed the protocol treatment comprising two courses of preoperative chemotherapy and R0/1 resection (73.5% completion, 80% CI, 63.7–81.7%). One TRD was observed during the first course of chemotherapy. Median survival and 3-year overall survival were 17.3 months and 24.5%, respectively. Conclusions Preoperative chemotherapy with S-1 + CDDP followed by gastrectomy is a safe and promising treatment for type 4 and large type 3 gastric cancers. Based on the results of this study, we are now conducting a phase III study (JCOG0501) to confirm the superiority of this treatment. J. Surg. Oncol. 2013;107:741–745. © 2013 Wiley Periodicals, Inc.

Background Neoadjuvant chemotherapy (NAC) followed by radical surgery is a promising strategy to improve survival of patients with stage III gastric cancer, but is associated with the risk of preoperative overdiagnosis by which patients with early disease may receive unnecessary intensive chemotherapy. Methods We assessed the validity of a preoperative diagnostic criterion in a prospective multicenter study. Patients with gastric cancer with a clinical diagnosis of T2/T3/T4, M0, except for diffuse large tumors and extensive bulky nodal disease, were eligible. Prospectively recorded clinical diagnoses (cT category, cN category) were compared with postoperative pathological diagnoses (pT category, pN category, and pathological stage). The primary endpoint was the proportion of pathological stage I tumors among those diagnosed as cT3/T4, which we expected to be 5% or less. Results Data from 1260 patients enrolled from 53 institutions were analyzed. The proportion of pathological stage I tumors in those with a diagnosis of cT3/T4 (primary endpoint) was 12.3%, which was much higher than the prespecified value. The positive predictive value and the sensitivity for pathological stage III tumors were 43.6% and 87.8% respectively. The sensitivity and specificity of contrast-enhanced CT for lymph node metastasis were 62.5% and 65.7% respectively. After exploring several diagnostic criteria, we propose, for future NAC trials in Japan, a diagnosis of "cT3/T4 with cN1/N2/N3," by which inclusion of pathological stage I tumors was reduced to 6.5%, although its sensitivity for pathological stage III tumors decreased to 64.5%. Conclusion Clinical diagnosis of T3/T4 tumors was not an optimal criterion to select patients for intensive NAC trials because more than 10% of patients with pathological stage I disease were included. We propose the criterion "cT3/T4 and cN1/N2/N3" instead.

To clarify the role of splenectomy in total gastrectomy for proximal gastric cancer.Splenectomy in total gastrectomy is associated with increased operative morbidity and mortality, but its survival benefit is unclear. Previous randomized controlled trials were underpowered and inconclusive.We conducted a multiinstitutional randomized controlled trial. Proximal gastric adenocarcinoma of T2-4/N0-2/M0 not invading the greater curvature was eligible. During the operation, surgeons confirmed that R0 resection was possible with negative lavage cytology, and patients were randomly assigned to either splenectomy or spleen preservation. The primary endpoint was overall survival (OS) and the secondary endpoints were relapse-free survival, operative morbidity, operation time, and blood loss. The trial was designed to confirm noninferiority of spleen preservation to splenectomy in OS with a noninferiority margin of the hazard ratio as 1.21 and 1-sided alpha of 5%.Between June 2002 and March 2009, 505 patients (254 splenectomy, 251 spleen preservation) were enrolled from 36 institutions. Splenectomy was associated with higher morbidity and larger blood loss, but the operation time was similar. The 5-year survivals were 75.1% and 76.4% in the splenectomy and spleen preservation groups, respectively. The hazard ratio was 0.88 (90.7%, confidence interval 0.67-1.16) (1.21); thus, the noninferiority of spleen preservation was confirmed (P = 0.025).In total gastrectomy for proximal gastric cancer that does not invade the greater curvature, splenectomy should be avoided as it increases operative morbidity without improving survival.

A Phase III study was started in Japan to evaluate the non-inferiority of overall survival of laparoscopy-assisted distal gastrectomy with open distal gastrectomy in patients with clinical IA (T1N0) or IB [T1N1 or T2(MP)N0] gastric cancer. This study followed the previous Phase II study to confirm the safety of laparoscopy-assisted distal gastrectomy (JCOG0703) and began in March 2010. A total of 920 patients will be accrued from 33 institutions within 5 years. The primary endpoint is overall survival. The secondary endpoints are relapse-free survival, proportion of laparoscopy-assisted distal gastrectomy completion, proportion of conversion to open surgery, adverse events, short-term clinical outcomes, postoperative quality of life. Only a credentialed surgeon can be responsible for both open distal gastrectomy and laparoscopy-assisted distal gastrectomy.

We compared a monoclonal antibody (SV2-61γ) and a polyclonal antibody (Dako HercepTest) in immunohistochemical assessments of human epidermal growth factor receptor 2 (HER2) expression in 73 samples of advanced gastric cancer. Results were scored as 0 to 3+, and equivocal or discordant (SV2-61γ/Dako HercepTest = 0/2+, 0/3+, 1+/3+ or 2+/3+) cases were subjected to fluorescence in situ hybridization (FISH) analysis. The frequencies of HER2 scores of 2+ or 3+ were 15.1% (11/73) using SV2-61γ and 38.4% (28/73) using Dako HercepTest. All of the equivocal or discordant cases with a HER2 score of 3+ using Dako HercepTest exhibited amplification of the HER2 gene regardless of the HER2 score determined with SV2-61γ. The results of the HER2 tests differed according to the antibodies used for immunohistochemistry that preceded FISH analysis, being 15.1% (11/73) using SV2-61γ and 23.3% (17/73) using Dako HercepTest. Thus, therapeutic decisions might be markedly influenced by the selection of antibody used in the HER2 test.

141 Background: Neoadjuvant chemotherapy (NAC) with cisplatin plus S-1 (CS) followed by gastrectomy with D2 plus para-aortic lymph node (PAN) dissection is regarded as a standard treatment in Japan for advanced gastric cancer with bulky lymph node (BN) and/or PAN metastasis based on the results of JCOG0405. In JCOG1002, we added docetaxel to CS (DCS) to further improve the long-term outcome. However the primary endpoint, clinical response rate (RR), did not meet the expected level (Ito S, Gastric Cancer. 2017). Herein we report the long-term survival. Methods: Patients with BN and/or PAN metastasis received two or three cycles of DCS therapy (docetaxel at 40 mg/m2 and cisplatin at 60 mg/m2 on day 1, S-1 at 40 mg/m2 twice daily for 2 weeks, were administered every four weeks) followed by gastrectomy with D2 plus PAN dissection and postoperative S-1 for 1 year. Results: Between July 2011 and May 2013, 53 patients were enrolled. Clinically, 17.0% of patients had both PAN and BN metastasis, and remaining patients had either PAN (26.4%) or BN (56.6%) metastasis. The clinical response rate (RR) was 57.7 % as assessed by RECIST v1.0, and the R0 resection rate was 84.6%, which did not exceed those in JCOG0405 (64.7% and 82.3%, respectively). The pathological RR defined as residual tumor corresponding to less than one-third the size of the original tumor was 34.6% in 52 eligible patients, which was slightly higher than in JCOG0405 (28.6%). Among all eligible patients, 5-year overall survival was 54.9% (95% confidence interval 40.3–67.3%) at the date cut-off of May 2018. Among 44 eligible patients with R0 resection, 5-year progression-free survival was 47.7% (95% confidence interval 32.5–61.5%). These were similar to the results of JCOG0405 (52.8% and 50.0%). Twenty patients developed cancer recurrence. The most frequent site of recurrence was lymph nodes (50.0% of all recurrences). Conclusions: Adding docetaxel to CS in NAC for extensive lymph node metastasis did not improve not only short-term outcomes but also long-term survival. NAC with CS followed by D2 + PAN dissection and postoperative S-1 remains standard for patients with extensive nodal metastasis. Clinical trial information: UMIN000006069.

4024Background: Postoperative S-1 for 1 year (corresponding to 8 courses) is one of standard adjuvant chemotherapies for p-stage II gastric cancer. We reported 4-courses of S-1 was inferior to 8-co...

AFP産生胃癌術後の門脈腫瘍栓を伴う肝転移再発に対して, 肝動注化学療法を施行し, 短期間に腫瘍栓および転移巣が縮小した後, 無再発で6年間経過している症例を経験した. 症例は71歳の女性で, 平成10年5月11日胃癌により幽門側胃切除術を施行した. 術前よりAFP高値で, 病理組織学的にもAFP産生胃癌と診断された. 術後約5か月後に肝転移再発が発見され, 門脈腫瘍栓を伴っていた. 切除不能と診断し, 肝動注化学療法を施行した. 約1か月で門脈腫瘍栓が消失した. すべての化学療法を中止して約4年経過した現在も門脈腫瘍栓は消失したままで, 転移巣は99%縮小し, 癌組織の消滅が推測された.

はじめに: 中下部胃癌に対してはD2郭清を伴う幽門側胃切除術 (distal gastrectomy; 以下, DG) が標準術式として確立しているが, 早期癌には縮小手術も行われている. その一つに幽門保存胃切除術 (pyrolus preserving gastrectomy;以下, PPG) があり, 当院でも採用してきたが, その評価は定まっていない. アンケートによるquality of life (以下, QOL) の調査や内視鏡検査所見を用いてPPGの評価を行った. 対象および方法: PPGを施行した胃癌71例 (PPG群) を対象とした. 予後, 術後合併症, 愁訴に対するアンケート調査, 残胃内視鏡所見について, DGが行われた症例 (DG群) を対照に用いて検討した. 結果: 5生率には差がなかった. 術後早期の残胃内食物停滞はPPG群14.1%, DG群3.4%でPPG群に多かった. アンケート調査の結果, 逆流があると答えた人がPPG群13.4%, DG群38.0%, 早期ダンピング症状はPPG群36.2%, DG群60.5%で, これらはPPG群で少なかった. 内視鏡所見はPPG群の69.2%に食物残渣を認め, DG群の32.5%より高頻度であった. 残胃炎はPPG群33.3%, DG群68.3%, 残胃内胆汁逆流はPPG群5.1%, DG群22.0%とPPG群に少なかった. 考察: PPGはダンピング症状や胆汁の逆流, それによる残胃炎が少ないが残胃内の食物残渣が多かった. しかし, アンケート調査では残渣に起因する症状に差はなく, PPGを行うことでQOLの向上が望めると考えられた.

Hepatoid adenocarcinoma of the stomach is a highly malignant neoplasm. Most gastric hepatoid adenocarcinomas coexist with tubular adenocarcinoma. However, the relationship between hepatoid adenocarcinoma and tubular adenocarcinoma is still unclear. In the present study, the characteristics of the coexistent tubular adenocarcinomas were determined by examining their profiles of mucin production. Subsequently, molecular pathological techniques were applied to determine the clonality of 15 mixed hepatoid and tubular adenocarcinomas of the stomach. Mucin analysis suggested that the coexistent tubular adenocarcinomas with hepatoid adenocarcinoma were of the intestinal type. The patterns of chromosome X inactivation were identical between the hepatoid adenocarcinoma component and tubular adenocarcinoma component in all of 3 informative female cases. Mutations in the p53 gene were found in 5 cases. The sequences were identical within both tumor components in all 5 cases. Microsatellite analysis indicated more than 3 common patterns of loss of heterozygosity in 8 cases. These observations strongly suggested that hepatoid adenocarcinomas were of identical origin to coexistent tubular adenocarcinomas.

91 Background: From the result of ACTS-GC study, adjuvant chemotherapy with S-1 for one year is standard therapy of gastric cancer in Japan. In this study, completion rate of pre-planned S-1 treatment was 65.8% and there is still room for improvement on this rate. Lafutidine is a H2 blocker and enhances submucosal blood flow via capsaicin-sensitive afferent neurons. Alleviating effect of lafutidine on toxicity of 5FU leading to discontinuation of adjuvant treatment could be expected. Methods: Patients with histologically confirmed stage II (excluding T1 cases), IIIA, or IIIB (Japanese Classification of Gastric Carcinoma 13th) who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive S-1 with lafutidine(L) or S-1 (S). All patients were given S-1 (40mg/m2) for 4 weeks with 2 weeks rest, repeated for 1 year after surgery. Patients of L group received lafutidine (20mg/day) every day for 1 year with S-1. The primary end point was treatment completion rate (TCR) of S-1. Definition of treatment completion was S-1 continuation for 1 year with over 70% planned dose. The secondary end points were toxicity (CTCAE v3.0) and relative total administration dose (RD) of S-1. Results: We randomly assigned 101 patients to the L group and 101 patients to the S group between February 2010 and December 2012 from 17 centers in Japan. After randomization, two patients were found to be ineligible in L group (the absence of cytologic examination of the peritoneal fluid, stageIB) and 1 in S group (allocation violation). TCR was 68.3% in the L group and 60.4% in the S group (p = 0.072, Cochran-Mantel-Haenzel test at a pre-specified one-sided significance level of 0.1). Adverse events of grade 3/4 excluding ineligible example was 30.0% in the L group, and 36.0% in the S group. Patients who require a dose reduction and/or delay of S-1 was 41.6% in the L group, and 51.5% in the S group. RD was 83.9% (range: 1.6-103.7) in the L group, and 84.0% (range: 1.7-103.8) in the S group. No any toxicity of lafutidine was observed. Conclusions: Lafutidine may increase a completion rate of adjuvant chemotherapy using S-1 within a 30% dose reduction for gastric cancer. This result need to be confirmed in double-blind placebo control study. Clinical trial information: UMIN000002703.

Human epidermal growth factor receptor 2 (HER2) is likely overexpressed and/or amplified in locally advanced gastric cancer with extensive (bulky N2 or paraaortic) lymph node metastasis, and patients may benefit from treatment with anti-HER2 antibodies. This study evaluated the frequency of HER2 overexpression and amplification in The Japanese Gastric Cancer Association (JGCA)-N3 and JGCA-bulky N2 tumors and the correlation between HER2 status and survival.HER2 status was assessed using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in tumor tissue samples from 89 patients with gastric adenocarcinoma enrolled in the phase II JCOG0001 and JCOG0405 trials. HER2 positivity was defined as IHC3+ or IHC2+ with confirmatory FISH results.Of the 89 tumor samples, 24 (27 %) showed HER2 positivity, including 16 scored as IHC3+ and 8 as IHC2+ and FISH positive. Multivariate analysis showed that the HER2 positivity rate was significantly higher in evaluable differentiated tumors than in undifferentiated tumors [18/44 (40.9 %) vs. 5/42 (11.9 %)]. Although the apparent OS curve of HER2 positive was superior to that of HER2 negative patients, HER2 status was not a statistically significant prognostic factor in multivariate analysis.The HER2 positivity rate was relatively high in patients with JGCA-bulky N2 and JGCA-N3 gastric adenocarcinoma, suggesting that HER2 evaluation is essential to select the therapeutic regimen for neoadjuvant chemotherapy for this group of patients.

Billroth-I (BI) and Roux-en-Y (RY) are well-known reconstruction methods that are conducted following distal gastrectomy. However, the relative merits of these 2 methods are not well documented. The newly developed Postgastrectomy Syndrome Assessment Scale (PGSAS)-45 is an integrated questionnaire consisting of 45 items, including 8 items from the 8-Item Short-Form Health Survey (SF-8), 15 items from the Gastrointestinal Symptom Rating Scale, and 22 items selected by gastric surgeons. Postoperative QOL ratings were evaluated for each reconstruction method using PGSAS-45. The PGSAS-45 questionnaire was distributed to 2,922 patients who underwent gastrectomies at 52 medical institutions. Among the questionnaires distributed, 2520 (86 %) were retrieved and 2368 (81 %) met eligibility requirements. Statistical analyses were conducted to compare 1,384 of the eligible questionnaires, including responses from patients who underwent BI (n = 909) and RY (n = 475) procedures. BI procedures were associated with significantly longer postoperative periods, a significantly greater size of gastric remnants, and a higher frequency of laparoscopic approaches and celiac branch preservation. Postoperative QOL analysis indicated that BI procedures resulted in significantly lower postoperative weight loss and significantly higher esophageal reflux symptoms than RY procedures. There was no significant difference between the two groups on other outcome measures. Although weight loss was significantly lower following BI procedures, esophageal reflux symptoms were significantly higher. Either BI or RY procedures may be recommended based on the individual patient’s condition after distal gastrectomy. The newly developed QOL questionnaire, PGSAS-45 and changes in body weight proved useful for evaluation of QOL following gastrectomy.

We compared the results of immunohistochemical assessment of HER2 expression in 107 samples of advanced gastric cancer on using 3 currently used antibodies. Expression was scored as 0 to 3+, and equivocal or discordant cases were subjected to fluorescence in situ hybridization(FISH)analysis. HER2 scores of 2+or 3+were noted in 16.8% of cases(18/ 107)using SV2-61g, in 29.9% of cases(32/107)using Dako HercepTest, and in 34.6% of cases(37/107)using 4B5. The results of the HER2 test differed according to the antibodies used for immunohistochemistry preceding FISH analysis, and the HER2 positive rates after the FISH analysis were 14.0%(15/107)using SV2-61g, 19.6% (21/107)using Dako HercepTest, and 22.4% (24/107)using 4B5. Thus, therapeutic decisions might be considerably influenced by the antibody used for the HER2 test.

Pylorus-preserving gastrectomy (PPG) is sometimes performed as a function-preserving surgery for the treatment of early gastric cancer. The aim of this study was to use an integrated assessment scale for postgastrectomy syndrome to determine the appropriate indicators and optimal methods for PPG. The Postgastrectomy Syndrome Assessment Study (PGSAS) is a multicenter survey based on an integrated questionnaire (PGSAS-45) consisting of 45 items. Questionnaire responses were retrieved from a total of 2,520 patients, each of whom had undergone one of six different types of gastrectomy procedures; 313 responses from patients who had received PPG were analyzed here. The size of the proximal gastric remnant (less than one-quarter, about one-third, or more than one-half of the original size) significantly influenced the change in body weight, the scores for dissatisfaction at the meal, and dissatisfaction for daily life subscale (P = 0.030, P = 0.005, P = 0.034, respectively). The nausea score in patients who underwent hand-sewn anastomosis was significantly lower than in those who underwent anastomosis with a linear stapler (P = 0.006). The scores for diarrhea subscale, increased passage of stools, and sense of foods sticking differed significantly depending on the length of the preserved pyloric cuff (P = 0.047, P = 0.021, P = 0.046, respectively). The results suggest that preservation of a sufficient proximal gastric remnant is recommended when utilizing PPG as function-preserving surgery.

Liver metastases from gastric cancer are rarely indicated for surgery because they are often diagnosed as multiple nodules occupying both lobes and coexist with extrahepatic disease. A literature search identified no clinical trials on hepatectomy for this disease; only retrospective studies of a relatively small number of cases collected over more than a decade, mostly from a single institution, were found. Five-year survival rates from these reports ranged from 0 % to 37 %, and long-term survivors were observed among carefully selected case series. The most commonly reported prognostic factor was the number of metastatic nodules, and patients with a solitary metastasis tended to have superior outcome. Patients diagnosed to have a small number of metastatic nodules by modern imaging tools could be indicated for surgery. Because both intrahepatic and extrahepatic recurrences are common, patients are likely to benefit from perioperative adjuvant chemotherapy, although it is not possible at this time to specify which regimen is the most appropriate.

We compared a monoclonal antibody (SV2-61γ) and a polyclonal antibody (Dako HercepTest) in immunohistochemical assessments of human epidermal growth factor receptor 2 (HER2) expression in 73 samples of advanced gastric cancer. Results were scored as 0 to 3+, and equivocal or discordant (SV2-61γ/Dako HercepTest = 0/2+, 0/3+, 1+/3+ or 2+/3+) cases were subjected to fluorescence in situ hybridization (FISH) analysis. The frequencies of HER2 scores of 2+ or 3+ were 15.1% (11/73) using SV2-61γ and 38.4% (28/73) using Dako HercepTest. All of the equivocal or discordant cases with a HER2 score of 3+ using Dako HercepTest exhibited amplification of the HER2 gene regardless of the HER2 score determined with SV2-61γ. The results of the HER2 tests differed according to the antibodies used for immunohistochemistry that preceded FISH analysis, being 15.1% (11/73) using SV2-61γ and 23.3% (17/73) using Dako HercepTest. Thus, therapeutic decisions might be markedly influenced by the selection of antibody used in the HER2 test.

We conducted a phase II study to evaluate the safety and efficacy of preoperative chemotherapy with S-1 + cisplatin followed by gastrectomy in patients with linitis plastica (type 4) or large ulcero-invasive-type (type 3) gastric cancer.Eligibility criteria included histologically proven adenocarcinoma of the stomach; clinically resectable gastric cancer of type 4 or type 3. Patients received two 28-day courses of preoperative chemotherapy of S-1 (80-120 mg/body, p.o., days 1-21) and cisplatin (CDDP; 60 mg/m(2), i.v., day 8). Primary endpoints were completion of protocol treatment and incidence of treatment-related death (TRD).Among the 49 eligible patients with the median age of 61 years, 36 completed the protocol treatment comprising two courses of preoperative chemotherapy and R0/1 resection (73.5% completion, 80% CI, 63.7-81.7%). One TRD was observed during the first course of chemotherapy. Median survival and 3-year overall survival were 17.3 months and 24.5%, respectively.Preoperative chemotherapy with S-1 + CDDP followed by gastrectomy is a safe and promising treatment for type 4 and large type 3 gastric cancers. Based on the results of this study, we are now conducting a phase III study (JCOG0501) to confirm the superiority of this treatment.