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Background: Large type 3 (diameter ≥ 8 cm) and type 4 gastric cancers have been arbitrarily combined in Japan as a single entity. However, whether these two types are oncologically similar remain unclear. This study aimed to clarify this issue., Methods: In this retrospective study, we analyzed a database of 3,575 patients from nine institutions who underwent gastrectomy between 2010 and 2014. Using propensity scores to balance significant variables, we compared prognoses and tumor recurrences., Results: Of patients with clinical T3/T4 who underwent R0 resection, 75 and 73 had large type 3 and 4 tumors, respectively. Patients with type 4 tumors had significantly lower overall survival rates than those of patients with large type 3 tumors (hazard ratio [HR] 1.77; 95% confidence interval [CI] 1.14-2.74). However, among the large type 3 tumors, a remarkable difference in prognosis was observed between the differentiated and undifferentiated histological types. A comparison was made between large type 3 with undifferentiated phenotype and type 4, each with 39 patients after propensity score matching. Outcomes in both groups were similar in terms of overall survival (HR 1.28; 95% CI 0.73-2.25) and relapse-free survival (HR 1.34; 95% CI 0.80-2.27). No statistically significant differences were observed in the incidence of peritoneal recurrence (35.9% vs. 46.1%, P = 0.36) and lymph node recurrence (25.6% vs. 12.8%, P = 0.15)., Conclusions: Large type 3 tumors with undifferentiated phenotype and type 4 tumors were oncologically similar. This subgroup could be considered as a new entity for future clinical trials., (© 2024. The Author(s).)

Background: The significance of reinforcement of the duodenal stump with seromuscular sutures and the effectiveness of reinforced staplers in preventing duodenal stump leakage remain unclear. We aimed to explore the importance of duodenal stump reinforcement and determine the optimal reinforcement method for preventing duodenal stump leakage., Methods: This retrospective cohort study was conducted between January 1, 2012 and December 31, 2021, with data analyzed between December 1, 2022 and September 30, 2023. This multicenter study across 57 institutes in Japan included 16,475 patients with gastric cancer who underwent radical gastrectomies. Elective open or minimally invasive (laparoscopic or robotic) gastrectomy was performed in patients with gastric cancer., Results: Duodenal stump leakage occurred in 153 (0.93%) of 16,475 patients. The proportions of males, patients aged ≥ 75 years, and ≥ pN1 were higher in patients with duodenal stump leakage than in those without duodenal stump leakage. The incidence of duodenal stump leakage was significantly lower in the group treated with reinforcement by seromuscular sutures or using reinforced stapler than in the group without reinforcement (0.72% vs. 1.19%, p = 0.002). Duodenal stump leakage incidence was also significantly lower in high-volume institutions than in low-volume institutions (0.70% vs. 1.65%, p = 0.047). The rate of duodenal stump leakage-related mortality was 7.8% (12/153). In the multivariate analysis, preoperative asthma and duodenal invasion were identified as independent preoperative risk factors for duodenal stump leakage-related mortality., Conclusions: The duodenal stump should be reinforced to prevent duodenal stump leakage after radical gastrectomy in patients with gastric cancer., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Background: Clinical findings and postoperative follow-up data on remnant gastric cancer (RGC) are limited due to its rarity. Additionally, the preoperative staging, radical surgery, and managing recurrence in RGC present significant clinical challenges., Methods: We analyzed the clinicopathological findings, adjuvant chemotherapy, and patterns of postoperative recurrence of 313 consecutive patients who underwent curative surgery for RGC at 17 Japanese institutions. This study investigated the optimal management of RGC and the impact of adjuvant chemotherapy (AC) on recurrence-free survival (RFS)., Results: Pathological stages I, II, and III were observed in 55.9% (N = 175), 24.9% (N = 78), and 19.2% (N = 60) of the patients, respectively. The overall concordance rate between clinical and pathological T staging was 58.3%, with a clinical T4 sensitivity of 41.4% for diagnosing pathological T4. During the median follow-up period of 4.6 years, disease recurrence occurred in 24.3% of patients. Most recurrences (over 80%) occurred within 2.5 years, and 96.1% within 5 years after RGC surgery. Peritoneal recurrence was the most common in patients with advanced RGC, accounting for 14.1% in stage II and 28.3% in stage III. Multivariable regression analysis showed that AC was significantly associated with a longer RFS, with a hazard ratio of 0.45 (95% confidence interval: 0.26-0.76)., Conclusions: Our study underscores the importance of early detection, accurate preoperative staging, and postoperative surveillance in managing advanced RGC cases. Despite some limitations, our findings indicate that AC may provide survival benefits comparable to those seen in primary gastric cancer., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Purpose: This study investigated the prognostic value of the geriatric nutritional risk index (GNRI) in patients undergoing curative gastrectomy for remnant gastric cancer (RGC)., Methods: This multicenter retrospective study included 105 patients with RGC of ≥ 65 years of age who underwent curative gastrectomy at 10 institutions in Japan between January 2000 and December 2016. Postoperative complications, overall survival (OS), and disease-specific survival (DSS) were analyzed., Results: Receiver operating curve analyses indicated that the optimal cutoff value of the GNRI for OS was 95.4. Patients were categorized into high and low GNRI groups based on the optimal GNRI cutoff value. The GNRI was significantly correlated with body mass index (p < 0.001), amount of bleeding (p = 0.021), Clavien-Dindo grade 5 postoperative complications (p = 0.040), death caused by primary disease (p = 0.010), and death caused by other diseases (p = 0.002). The OS and DSS were significantly worse in the low GNRI group. A low GNRI and T3 or deeper tumor invasion were independent prognostic factors for OS and DSS., Conclusions: The GNRI is a promising predictor of both short- and long-term outcomes in older patients with RGC., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

As novel biomarkers for gastroenteropancreatic neuroendocrine tumors (GEPNET) are in demand, we aimed to validate the clinical value of the NETest in Japanese patients. Between 2021 and 2023, blood and clinical data were collected from patients with GEPNET. Among 35 patients (median age: 59 [49-66] years), 27 cases originated from the pancreas and eight from the gastrointestinal tract. Of 69 samples sent to the laboratory, 56 (81.2%) underwent NETest. The diagnostic sensitivity was 97.1%. Among three patients who underwent R0 resection and four treated with peptide receptor radionuclide therapy, the changes in NETest scores closely correlated with disease progression. The NETest demonstrated high diagnostic efficacy and accurate therapeutic monitoring capabilities in a Japanese population.

Purposes: The present study evaluated the impact of clinical guidelines for gastric cancer surgery on surgeons' choice of procedure in real-world practice. We focused on the 2014 guideline revision recommending laparoscopic surgery and the evidence concerning splenectomy for prophylactic lymphadenectomy reported in 2015 using the National Clinical Database, which is the most comprehensive database in Japan., Methods: We investigated the monthly percentages of laparoscopic distal gastrectomies performed for stage I gastric cancer (LDG%) and splenectomies performed during total gastrectomy for advanced cancer (TGS%) between 2014 and 2017. We evaluated the descriptive statistics of the time-series changes in the LDG%, TGS%, and annual trends of outcomes., Results: In total, 124,787 patients were enrolled. The mean LDG% and TGS% were 69.8% and 9.2%, respectively. The LDG% and TGS% were 66.4% and 16.7%, respectively, in January 2014 and 73.1% and 5.9%, respectively, in December 2017. LDG% consistently increased, and TGS% showed a consistent downward trend throughout the observation period. There was no significant change in this trend after the publication of the guideline recommendations or clinical trial results., Conclusion: No significant changes in surgical procedures were observed after publication of the guidelines or results of clinical trials., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background and Aims: Evidence for endoscopic resection (ER) in elderly patients with early gastric cancer (EGC) is limited. We assessed its clinical outcomes and explored new indications and curability criteria., Methods: We analyzed data from a Japanese multicenter, prospective cohort study. Patients aged ≥75 years with EGC treated with ER were included. We classified eCuraC-2 (corresponding to noncurative ER, defined in the Japanese gastric cancer treatment guidelines) into elderly-high (>10% estimated metastatic risk) and elderly-low (EL-L) (≤10% estimated metastatic risk)., Results: In total, 3371 patients with 3821 EGCs were included; endoscopic submucosal dissection was the prominent treatment choice. Among them, 3586 lesions met the guidelines' ER indications, and 235 did not. The proportions of en bloc and R0 resections and perforations were 98.9%, 94.4%, and 0.8%, respectively, in EGCs within the indications. In EGCs beyond the indications, they were 99.5%, 85.4%, and 5.9%, respectively, for lesions diagnosed as ≤3 cm and 96.0%, 64.0%, and 18.0%, respectively, for those >3 cm. Curative ER and EL-L were observed in 83.6% and 6.2% of lesions within the indications, respectively, and in 44.2% and 16.8% of lesions <3 cm beyond the indications, respectively. The 5-year cumulative gastric cancer death rates after curative ER and elderly-high were 0.3% (95% confidence interval [CI], 0.2-0.6) and 3.5% (95% CI, 2.0-5.7), respectively. After EL-L, the rate was 0.9% (95% CI, 0.2-3.5) even without subsequent treatment., Conclusions: The usefulness of endoscopic submucosal dissection for elderly EGC patients was confirmed by their clinical outcomes. Lesions of ≤3 cm and EL-L emerged as new ER indication and curability criteria, respectively. (Clinical trial registration number: UMIN000005871.)., Competing Interests: Disclosure All authors disclosed no financial relationships. This study was supported by a grant for Clinical Cancer Research from the Japanese Ministry of Health, Labor, and Welfare (H21-022); a grant from Daiwa Securities Health Foundation (H24-16); and grants for the National Cancer Center Research and Development from the Japanese Ministry of Health, Labor, and Welfare (25-A-12, 28-K-1, 29-A-13, and 2021-A-18)., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objectives: Early gastric cancer endoscopic resection (ER) is prominent in Japan. However, evidence regarding ER of gastric submucosal tumors (SMT) is limited. This prospective multicenter phase II study investigated the efficacy and safety of endoscopic full-thickness resection (EFTR) for gastric SMT., Methods: Endoscopic full-thickness resection indication for gastric SMT was 11-30 mm, histologically proven or clinically suspicious (irregular margin, increasing size, or internal heterogeneity) gastrointestinal stromal tumors (GIST), with no ulceration and intraluminal growth type. The primary end-point was the complete ER (ER0) rate, with a sample size of 42., Results: We enrolled 46 patients with 46 lesions between September 2020 and May 2023 at seven Japanese institutions. The mean ± SD (range) endoscopic tumor size was 18.8 ± 4.5 (11-28) mm. The tumor resection and defect closure times were 54 ± 26 (22-125) min and 33 ± 28 (12-186) min, respectively. A 100% ER0 was achieved in all 46 patients. The EFTR procedure was accomplished in all patients without surgical intervention. One patient had delayed perforation and was managed endoscopically. GIST accounted for 76% (n = 35) of the cases. R0, R1, and RX rates were 33 (77%), 3 (6.5%), and 7 (15%), respectively., Conclusion: Endoscopic full-thickness resection for gastric SMT of 11-30 mm is efficacious. It warrants further validation in a large-scale cohort study to determine the long-term outcome of this treatment for patients with gastric GIST., (© 2023 Japan Gastroenterological Endoscopy Society.)

Background: Chemotherapy consisting of 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel is the standard perioperative treatment for resectable esophageal adenocarcinoma and esophagogastric junctional adenocarcinoma (EGJ-AC) in Western countries. Meanwhile, preoperative chemotherapy consisting of docetaxel, cisplatin, and 5-fluorouracil (DCF) has been developed for esophageal squamous cell carcinoma in Japan. However, there are few reports on the safety and efficacy of preoperative DCF for resectable EGJ-AC in the Japanese population., Methods: Patients with histologically confirmed resectable EGJ-AC who received preoperative DCF (docetaxel 70 mg/m 2 and cisplatin 70 mg/m 2 on day 1 and continuous infusion of 5-fluorouracil 750 mg/m 2 /day on days 1-5 every 3 weeks with a maximum of three cycles) between January 2015 and April 2020 were retrospectively evaluated. We assessed the rates of completion of ≥ 2 courses of DCF and R0 resection, histopathological response, progression-free survival (PFS), overall survival (OS), and adverse events., Results: Thirty-two patients were included. Median follow-up was 28.7 (range, 5.2-70.8) months and median age was 63 (range, 42-80) years. Twenty-one patients (66%) had a performance status of 0. The proportions of clinical stage IIA/IIB/III/IVA/IVB disease were 3%/0%/44%/44%/9%, respectively. The treatment completion rate was 84%. A histopathological response of grade 1a/1b/2/3 was obtained in 58%/26%/13%/3% of cases. Median PFS was 40.7 months (95% confidence interval 11.8-NA). Median OS was not reached (80.8% at 3 years). Grade ≥ 3 adverse events were observed in 63% of cases (neutropenia, 44%; febrile neutropenia, 13%). No treatment-related deaths occurred., Conclusions: Preoperative DCF for resectable EGJ-AC was well tolerated and has promising efficacy., (© 2024. The Author(s).)

Background: This study examined temporal shifts in adjuvant therapy patterns in Japanese patients with resectable gastric cancer (GC) and treatment patterns of first-line and subsequent therapy among those with recurrent disease., Methods: This retrospective analysis of hospital-based administrative claims data (April 1, 2008 to March 31, 2022) included adults (aged ≥ 20 years) with GC who started adjuvant therapy on or after October 1, 2008 (adjuvant cohort) and patients in the adjuvant cohort with disease recurrence (recurrent cohort), further defined by the time to recurrence (≤ 180 or > 180 days after adjuvant therapy)., Results: In the adjuvant cohort (n = 17,062), the most common regimen during October 2008-May 2016 was tegafur/gimeracil/oteracil potassium (S-1; 95.7%). As new standard adjuvant regimen options were established, adjuvant S-1 use decreased to 65.0% and fluoropyrimidine plus oxaliplatin or docetaxel plus S-1 use increased to 15.0% and 20.0%, respectively, in September 2019-March 2022. In the recurrent cohort with no history of trastuzumab/trastuzumab deruxtecan treatment (n = 1257), the most common first-line regimens were paclitaxel plus ramucirumab (34.0%), capecitabine plus oxaliplatin (CapeOX; 17.0%), and nab-paclitaxel plus ramucirumab (10.1%) in patients with early recurrence, and S-1 plus oxaliplatin (26.3%), S-1 plus cisplatin (15.3%), CapeOX (14.0%), S-1 (13.2%), and paclitaxel plus ramucirumab (10.8%) in those with late recurrence., Conclusions: This study demonstrated temporal shifts in adjuvant treatment patterns that followed the establishment of novel regimens, and confirmed that post-recurrent treatment patterns were consistent with the Japanese Gastric Cancer Association guideline recommendations., (© 2024. The Author(s).)

Background and Aim: Changes in the number of surgeries for gastric cancer during the coronavirus disease 2019 (COVID-19) pandemic have been reported, but data are insufficient to understand the impact at the national level. This study aimed to determine the impact of the COVID-19 pandemic on gastric surgery in Japan., Methods: Insurance claims data registered from January 2015 to January 2021 were used. Changes in the number of endoscopic resections and gastrectomies for gastric cancer were estimated using an interrupted time-series analysis., Results: The number of endoscopic resections significantly decreased in July 2020 (-1565; 95% confidence interval [CI]: -2022, -1108) and January 2021 (-539; 95% CI: -970, -109), and the number of laparoscopic surgeries significantly decreased in July 2020 (-795; 95% CI: -1097, -492), October 2020 (-313; 95% CI: -606, -19), and January 2021 (-507; 95% CI: -935, -78). Meanwhile, the number of open gastrectomies remained unchanged, and the number of robot-assisted gastrectomies steadily increased since their coverage by public health insurance in April 2018., Conclusions: The decreased number of endoscopic resections and laparoscopic surgeries in Japan suggests a decline in early-stage gastric cancer diagnosis, likely due to the suspension of gastric cancer screening and diagnostic testing during the pandemic. Meanwhile, the number of open and robot-assisted gastrectomies remained unchanged and increased, respectively, indicating that these applications were not affected by the pandemic-related medical crisis. These findings highlight that procedures for cancer diagnosis, including screening, should still be provided during pandemics., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Purpose: The relationship between board certification, clinical guideline implementation, and quality of gastric cancer surgery remains unclear., Methods: A web-based questionnaire survey was administered to departments registered in the National Clinical Database (NCD) of Japan between October 2014 and January 2015. Quality indicators (QIs) based on the Donabedian model were evaluated. Structural QIs (e.g., affiliations with academic societies and board certifications) and process QIs (adherence to clinical practice guidelines for gastric cancer) were assessed using risk-adjusted odds ratios (AORs) for surgical mortality. Multivariable logistic regression models with a generalized estimating equation were used., Results: A total of 835 departments performing 40,992 distal gastrectomies and 806 departments performing 19,618 total gastrectomies responded. Some certified institutions and physicians showed significant associations, with lower AORs for surgical mortality. Important process QIs included pre- and postoperative abdominal CT scanning, endoscopic resection based on progression, curative resection with D2 dissection for advanced gastric cancer, laparoscopic surgery, and HER2 testing for patients with unresectable recurrent gastric cancer., Conclusions: Multiple structural and process QIs are associated with surgical mortality after gastrectomy in Japan. Measuring and visualizing QIs may enhance healthcare improvements., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: For patients with gastric cancer, a well-balanced treatment that considers both oncological aspects and surgical risk is demanded. This study aimed to explore the optimal extent of lymph node dissection (LND) for patients with gastric cancer according to surgical risk, stratified by the risk calculator system produced by the Japan National Clinical Database (NCD)., Patients and Methods: We retrospectively evaluated 187 patients who underwent radical gastrectomy for gastric cancer. Using the median predicted anastomotic leak rate obtained by the NCD risk calculator as the cutoff value, we classified 97 and 90 patients as having high and low risks, respectively., Results: In low-risk patients, although limited LND reduced the postoperative intraabdominal infectious complications (IAIC), multivariate analysis revealed standard LND as an independent prognostic factor that improved Relapse-free survival (RFS). In high-risk patients, the rates of postoperative IAIC and RFS were similar between standard and limited LND. Pancreatic fistula was not observed in the limited dissection group., Conclusion: Limited LND might be the optimal treatment strategy for patients with gastric cancer with high surgical risk., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Background: This randomized phase II study explored the superiority of trastuzumab plus S-1 plus cisplatin (SP) over SP alone as neoadjuvant chemotherapy (NAC) for HER2-positive resectable gastric cancer with extensive lymph node metastasis., Methods: Eligible patients with HER2-positive gastric or esophagogastric junction cancer and extensive lymph node metastasis were randomized to receive three or four courses of preoperative chemotherapy with SP (arm A) or SP plus trastuzumab (arm B). Following gastrectomy, adjuvant chemotherapy with S-1 was administered for 1 year in both arms. The primary endpoint was overall survival, and the sample size was 130 patients in total. The trial is registered with the Japan Registry of Clinical Trials, jRCTs031180006., Results: This report elucidates the early endpoints, including pathological findings and safety. The study was terminated early due to slow patient accruals. In total, 46 patients were allocated to arm A (n = 22) and arm B (n = 24). NAC was completed in 20 patients (91%) in arm A and 23 patients (96%) in arm B, with similar incidences of grade 3-4 hematological and non-hematological adverse events. Objective response rates were 50% in arm A and 84% in arm B (p = 0·065). %R0 resection rates were 91% and 92%, and pathological response rates (≥ grade 1b in Japanese classification) were 23% and 50% (p = 0·072) in resected patients, respectively., Conclusions: Trastuzumab can be safely added to platinum-containing doublet chemotherapy as NAC, and it has the potential to contribute to higher antitumor activity against locally advanced, HER2-positive gastric or esophagogastric junction cancer with extensive nodal metastasis., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Purpose: Various basic and clinical studies have investigated the association between the types of anesthetic agents and prognosis. However, the results have varied among studies and remain controversial. In the present study, we aimed to investigate whether the risk of all-cause mortality differs between inhaled or intravenous anesthetics in patients with gastric cancer undergoing gastrectomy., Methods: Using a Japanese nationwide insurance claims database, we analyzed patients who underwent gastrectomy under general anesthesia for gastric cancer between January 2005 and September 2019. Postoperative outcomes were compared between two groups: those who received inhaled anesthetics (Sevoflurane, Isoflurane, or Desflurane) and those who received intravenous anesthetics (propofol), using a multivariable Cox proportional hazards model. The primary outcome was overall survival., Results: Among 2671 eligible patients, 2105 were in the inhaled anesthetic group, and 566 were in the intravenous anesthetic group. The median (interquartile range) age was 58 (51-63) years, and 1979 (74.1%) were men. The median follow-up period was 795 days. We identified 56 (2.7%) and 16 (2.8%) deaths during the follow-up period in the inhaled and intravenous anesthetic use groups, respectively. There was no difference in postoperative overall survival between the two groups (hazard ratio, 0.97; 95% confidence interval, 0.56-1.70; P = 0.93)., Conclusions: We found no significant difference in the postoperative risks of overall survival between inhaled and intravenous anesthesia in patients with gastric cancer undergoing gastrectomy., (© 2023. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Introduction: We investigated the factors associated with synchronous multiple early gastric cancers and determined their localization., Methods: We analyzed 8,191 patients who underwent endoscopic submucosal dissection for early gastric cancers at 33 hospitals in Japan from November 2013 to October 2016. Background factors were compared between single-lesion (n = 7,221) and synchronous multi-lesion cases (n = 970) using univariate and multivariate analyses. We extracted cases with two synchronous lesions (n = 832) and evaluated their localization., Results: Significant independent risk factors for synchronous multiple early gastric cancer were older age (≥75 years old) (odds ratio [OR] = 1.257), male sex (OR = 1.385), severe mucosal atrophy (OR = 1.400), tumor localization in the middle (OR = 1.362) or lower region (OR = 1.404), and submucosal invasion (OR = 1.528 [SM1], 1.488 [SM2]). Depressed macroscopic type (OR = 0.679) and pure undifferentiated histology OR = 0.334) were more common in single early gastric cancers. When one lesion was in the upper region, the other was more frequently located in the lesser curvature of the middle region. When one lesion was in the middle region, the other was more frequently located in the middle region or the lesser curvature of the lower region. When one lesion was in the lower region, the other was more frequently located in the lesser curvature of the middle region or the lower region., Conclusion: Factors associated with synchronous multiple early gastric cancer included older age, male sex, severe mucosal atrophy, tumor localization in the middle or lower region, and tumor submucosal invasion. Our findings provide useful information regarding specific areas that should be examined carefully when one lesion is detected., (© 2024 S. Karger AG, Basel.)

Introduction: Despite the increasing performance of laparoscopic proximal gastrectomy (LPG) for proximal gastric cancer and esophagogastric junction cancer, the benefit of LPG over laparoscopic total gastrectomy (LTG) remains to be established. Therefore, this study was conducted to compare postoperative outcomes between LPG and LTG., Methods: Data from 141 patients who underwent LPG or LTG for gastric neoplasm with curative intent between 2016 and 2022 were retrospectively reviewed. Clinicopathological findings, body weight changes, and serological nutritional markers during the postoperative course were evaluated., Results: LPG and LTG were performed in 78 patients and 63 patients, respectively. Patients' characteristics did not differ; however, tumor stages in patients who underwent LTG were more advanced than those who underwent LPG. The mean (± standard deviation) weight loss rate after 1 year was -13.5 (±6.9)% and -18.7 (±6.6)% for LPG and LTG, respectively (p < .01). LTG (OR: 3.326, p < .01), pT disease (OR: 3.000, p = .01), pN disease (OR: 2.708, p = .02), and postoperative chemotherapy (OR: 2.488, p = .05) were correlated with severe weight loss (16% or more) 1 year after surgery, then multivariate analysis identified LTG as an independent factor (p = .01). The mean (± standard deviation) serum total protein level of LPG was significantly higher than that of LTG at 3 months (6.8 ± 0.5 vs. 6.6 ± 0.4 g/dL, p = .02) and 1 year (6.9 ± 0.4 vs. 6.7 ± 0.5 g/dL, p = .01) postoperatively. No difference was observed in postoperative serum hemoglobin and albumin levels., Conclusion: LPG more improved postoperative weight loss than LTG., (© 2023 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Background: Surgical procedures for proximal gastric cancer remain a highly debated topic. Total gastrectomy (TG) is widely accepted as a standard radical surgery. However, subtotal esophagectomy, proximal gastrectomy (PG) or even subtotal gastrectomy, when a small upper portion of the stomach can technically be preserved, are alternatives in current clinical practice., Methods: Using a cohort of the PGSAS NEXT trial, consisting of 1909 patients responding to a questionnaire sent to 70 institutions between July 2018 and December 2019, gastrectomy type, reconstruction method, and furthermore the remnant stomach size and the anti-reflux procedures for PG were evaluated., Results: TG was the procedure most commonly performed (63.0%), followed by PG (33.4%). Roux-en-Y was preferentially employed following TG irrespective of esophageal tumor invasion, while jejunal pouch was adopted in 8.5% of cases with an abdominal esophageal stump. Esophagogastrostomy was most commonly selected after PG, followed by the double-tract method. The former was preferentially employed for larger remnant stomachs (≧3/4), while being used slightly less often for tumors with as compared to those without esophageal invasion in cases with a remnant stomach 2/3 the size of the original stomach. Application of the double-tract method gradually increased as the remnant stomach size decreased. Anti-reflux procedures following esophagogastrostomy varied markedly., Conclusions: TG is the mainstream and PG remains an alternative in current Japanese clinical practice for proximal gastric cancer. Remnant stomach size and esophageal stump location appear to influence the choice of reconstruction method following PG., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2022 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Oligometastases are generally defined as a small number of metastases(2-3 or less)in 1 or 2 organs. Oligometastases are rare in gastric cancer because they are often associated with peritoneal dissemination, but gastric cancer patients experience a relatively high incidence of para-aortic lymph node and liver metastases in particular. The Sixth Edition of the Japanese Gastric Cancer Treatment Guidelines weakly recommends surgical resection after medical therapy for a small number of para-aortic lymph node metastases confined to No. 16a2/b1 and a single liver metastasis in the absence of other non-curative resection factors. In Japan, the common treatment strategy is surgical resection after drug therapy, often with the addition of adjuvant chemotherapy after surgery as well. Preoperative drug therapy is generally administered for 3-4 months. Surgical resection has been shown to be relatively safe in experienced centers. Prospective clinical trials are underway in Japan and overseas to establish a higher level of evidence.

Background: Proficiency of the operating surgeon is one of the most critical factors potentially associated with reductions in complications and surgery-related mortality. With video-rating systems having shown potential for assessing laparoscopic surgeons' proficiency, the Endoscopic Surgical Skill Qualification System (ESSQS) was developed by the Japan Society for Endoscopic Surgery to subjectively assess the proficiency of laparoscopic surgeons by rating applicants' non-edited case videos. We conducted a study to evaluate how ESSQS skill-qualified (SQ) surgeon involvement influences short-term outcomes of laparoscopic gastrectomy performed for gastric cancer., Methods: Data from the National Clinical Database regarding laparoscopic distal and total gastrectomy performed for gastric cancer between January 2016 and December 2018 were analyzed. Operative mortality, defined as 30-day mortality or 90-day in-hospital mortality, and anastomotic leakage rates were compared per involvement vs. non-involvement of an SQ surgeon. Outcomes were also compared per involvement of a gastrectomy-, colectomy-, or cholecystectomy-qualified surgeon. The association between the area of qualification and operative mortality/anastomotic leakage was also analyzed with a generalized estimating equation logistic regression model used to account for patient-level risk factors and institutional differences., Results: Of 104,093 laparoscopic distal gastrectomies, 52,143 were suitable for inclusion in the study; 30,366 (58.2%) were performed by an SQ surgeon. Of 43,978 laparoscopic total gastrectomies, 10,326 were suitable for inclusion; 6501 (63.0%) were performed by an SQ surgeon. Gastrectomy-qualified surgeons outperformed non-SQ surgeons in terms of both operative mortality and anastomotic leakage. They also outperformed cholecystectomy- and colectomy-qualified surgeons in terms of operative mortality or anastomotic leakage in distal and total gastrectomy, respectively., Conclusion: The ESSQS appears to discriminate laparoscopic surgeons who can be expected to achieve significantly improved gastrectomy outcomes., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The frequency of lymph node metastases per lymph node site in early gastric cancer has not been well clarified from the data based on prospective studies. This exploratory analysis aimed to determine the frequency and location of lymph node metastases in clinical T1 gastric cancer using the data from JCOG0912 to investigate the validity of the extent of standard lymph node dissection defined in Japanese guidelines., Methods: This analysis included 815 patients with clinical T1 gastric cancer. The proportion of pathological metastasis was identified for each lymph node site per tumor location (middle third and lower third) and four equal parts of the gastric circumference. The secondary aim was identification of the risk factor for lymph node metastasis., Results: Eighty-nine patients (10.9%) had pathologically positive lymph node metastases. Although the overall frequency of metastases was low (0.3-5.4%), metastases were widely located in each lymph node sites when primary lesion was in the middle third of the stomach. No. 4sb and 9 showed no metastasis when primary lesion was in the lower third of the stomach. Lymph node dissection of metastatic nodes resulted in a 5-year survival in more than 50% of patients. A tumor greater than 3 cm and a T1b tumor were associated with lymph node metastasis., Conclusions: This supplementary analysis demonstrated that nodal metastasis from early gastric cancer is widely and disorderly not depending on the location. Thus, systematic lymph node dissection is necessary to cure the early gastric cancer., (© 2023. Japanese Society of Gastroenterology.)

Objectives: The effectiveness and impact of any treatment on patients' physical functions, especially in older patients, should be closely considered. This study aimed to evaluate activities of daily living (ADLs) after oncological surgery in patients with gastrointestinal and hepatobiliary-pancreatic cancers by age groups in Japan., Design: Retrospective observational study using health services utilisation data from 1 January 2015 to 31 December 2016., Setting: Data for patients with gastrointestinal and hepatobiliary-pancreatic cancers diagnosed in 2015 from 431 hospitals nationwide in Japan., Participants: Patients who underwent endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR) and laparoscopic or open surgery were included., Outcome Measures: The proportion of ADL decline at discharge, death and unexpected readmission within 6 weeks postsurgery was calculated by age groups (40-74, 75-79 and ≥80 years)., Results: Data for 68 032 patients were analysed. The difference in the proportion of ADL decline after ESD/EMR between patients aged ≥80 years and <75 years was marginal (0.8%-2.5%), whereas that after laparoscopic (4.8%-5.9%) or open surgery (4.6%-9.4%) was large, except for pancreatic cancer (3.0%). Among patients with gastric cancer who underwent laparoscopic or open surgery, the proportion of unexpected readmission tended to be higher in patients aged ≥80 years than in the remaining younger patients (laparoscopic surgery 4.8% vs 2.3% (p=0.001); open surgery 7.3% vs 4.4% (p<0.001)). The postoperative mortality rate was <3% (<10 cases) across all ages and cancer types., Conclusions: In ESD/EMR, postoperative ADL decline was almost the same between older and younger patients. Laparoscopic or open surgery is associated with increased rates of ADL decline in older patients, especially in those aged ≥80 years. The potential decline in ADLs should be carefully considered preoperatively to best maintain the patient's quality of life postsurgery., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The guidelines recommend additional gastrectomy after noncurative endoscopic resection for early gastric cancers (EGCs). However, no additional treatment might be acceptable in some patients aged ≥ 85 years. We aimed to identify this patient group using the data in a highly aged area., Methods: We enrolled patients aged ≥ 85 years after noncurative endoscopic resection for EGCs at 30 institutions of the Tohoku district in Japan between 2002 and 2017. Treatment selection and prognosis after noncurative endoscopic resection were investigated. Fourteen candidates were evaluated using the Cox model to identify risk factors for poor overall survival (OS) in patients with no additional treatment., Results: Of 1065 patients aged ≥ 85 years, 143 underwent noncurative endoscopic resection. Despite the guidelines' recommendation, 88.8% of them underwent no additional treatment. The 5-year OS rates in those with additional gastrectomy and those with no additional treatment were 63.1 and 65.2%, respectively. Multivariate analysis showed independent risk factors for poor OS in patients with no additional treatment were the high-risk category in the eCura system (hazard ratio [HR], 2.91), Charlson comorbidity index (CCI) ≥ 3 (HR, 2.78), and male (HR, 2.04). In patients with no additional treatment, nongastric cancer-specific survival was low (69.0% in 5 years), whereas disease-specific survival rates were very high in the low- and intermediate-risk categories of the eCura system (100.0 and 97.1%, respectively, in 5 years)., Conclusions: No additional treatment may be acceptable in the low- and intermediate-risk categories of the eCura system in patients aged ≥ 85 years with noncurative endoscopic resection for EGCs., (© 2023. Japanese Society of Gastroenterology.)

Purpose: A research subgroup was established by the Japanese Society of Gastroenterological Surgery to improve the health care quality in the Chushikoku area of Western Japan., Methods: The records of four surgical procedures were extracted from the Japanese National Clinical Database and analyzed retrospectively to establish the association between hospital characteristics, defined using a combination of hospital case-volume and patients' hospital travel distance, and the incidences of perioperative complications of ≥ Grade 3 of the Clavien-Dindo classification after gastroenterological surgery., Results: This study analyzed 11,515 cases of distal gastrectomy for gastric cancer, 4,705 cases of total gastrectomy for gastric cancer, 4,996 cases of right hemicolectomy for colon cancer, and 5,243 cases of lower anterior resection for rectal cancer, with composite outcome incidences of 5.6%, 10.2%, 5.5%, and 10.7%, respectively. After adjusting for patient characteristics and surgical procedures, no association was identified between the hospital category and surgical outcomes., Conclusion: The findings of our study of the Chushikoku region did not provide positive support for the consolidation and centralization of hospitals, based solely on hospital case volume. Our grouping was unique in that we included patient travel distance in the analysis, but further investigations from other perspectives are needed., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

There are still remarkable discrepancies in chemotherapy for gastric cancer between the Asia and West. Frequency, pathophysiology, treatment details, and outcomes of gastric cancer vary greatly depending on racial and regional differences. For example, in Japan, endoscopic mucosal resection/dissection is widely used for the diagnosis of early gastric cancer. Surgical outcomes are better in Japan than in the West, and the degree of lymph node dissection tends to be lower in the West. It is important to note that there are differences in the various backgrounds surrounding gastric cancer in the geographical regions. This paper describes the current status and future prospects of chemotherapy strategies in the field of gastric cancer chemotherapy, where new agents have been introduced successively in recent years, in Asia and the West, including background differences such as frequency and pathological conditions.

The sixth edition of the Japanese Gastric Cancer Treatment Guidelines was completed in July 2021, incorporating new evidence that emerged after publication of the previous edition. It consists of a text-based "Treatments" part and a "Clinical Questions" part including recommendations and explanations for clinical questions. The treatments parts include a comprehensive description regarding surgery, endoscopic resection and chemotherapy for gastric cancer. The clinical question part is based on the literature search and evaluation by an independent systematic review team. Consequently, not only evidence for each therapeutic recommendation was clearly shown, but it also identified the research fields that require further evaluation to provide appropriate recommendations., (© 2022. The Author(s).)

Background: Gastrojejunostomy (GJ) is a surgical option for malignant gastric outlet obstruction (mGOO). Confronting an aging society, the demand to treat elderly cancer patients with unresectable malignancies is increasing; however, the benefit of GJ to the very elderly (≥ 80 years of age) has never been investigated., Methods: This multicenter, retrospective review included 108 patients who had undergone GJ for mGOO from two medical centers in Japan, one of the most long-lived countries. Patients were divided into two groups, with 80 years of age as the cut-off. Various factors, including surgical complications and patient survival, were compared., Results: GJ in the very elderly (aged ≥ 80 years) was associated with a higher incidence of surgical complications (p = 0.049), such as delayed gastric emptying (DGE; p < 0.001), aspiration pneumonia (p = 0.029), and consequent mortality (p = 0.016). Age ≥80 years was also identified as an independent predictor of DGE (odds ratio 6.444, p = 0.005) and survival after GJ (hazard ratio 7.767, p = 0.016). In particular, the median survival time after GJ in the population aged ≥80 years with gastric cancer was only < 2 months. About the surgical procedure, antiperistaltic anastomosis with partial stomach partitioning (PSP) yielded the lowest occurrence rate of DGE (3.4%) and aspiration pneumonia (1.7%)., Conclusions: GJ does not seem to be the optimal choice for very elderly patients, particularly those with gastric cancer. If performed, antiperistaltic anastomosis with PSP should be employed to reduce the surgical complications., (© 2022. Society of Surgical Oncology.)

Background: Although double tract reconstruction after proximal gastrectomy (PGDT) is commonly performed for proximal gastric or esophagogastric junction cancer, the impact of the procedure on postoperative quality of life (QOL) has not been clarified. We aimed to clarify the optimal PGDT procedure in terms of postoperative QOL., Methods: Postoperative QOL was analyzed in 172 patients who underwent PGDT for proximal gastric cancer and were enrolled in the PGSAS-NEXT study, a multicenter cross-sectional study in Japan (UMIN000032221), in relation to the remnant stomach size, length of interposed jejunum between the esophagojejunostomy (E-J) and jejunogastrostomy (J-G), and size of the J-G., Results: The remnant stomach size was approximately one-third in 13, half in 97, and two-thirds in 60 patients. Dissatisfaction scores for symptoms, diet, work, and daily life subscales were lower in patients with a larger stomach (p < 0.05). These patients also scored better in terms of weight loss (- 13.5%, - 14.0%, and - 11.2%, respectively) and amount of food ingested per meal (52%, 62%, and 66%). The length of the interposed jejunum was ≤ 10 cm in 62 and ≥ 11 cm in 97 patients. Weight loss (- 11.3% and - 13.8%) and dissatisfaction scores were better in the ≤ 10 cm group (p < 0.05). J-G size was ≤ 5 cm in 27 and ≥ 6 cm in 135 patients. The amount of food ingested (56%, 64%) and dissatisfaction scores were better in the > 6 cm group (p < 0.05)., Conclusions: Larger remnant stomach, shorter length of interposed jejunum, and longer J-G might contribute to better postoperative QOL after PGDT., (© 2022. The Society for Surgery of the Alimentary Tract.)

Background: Information on whether there is a relationship between hospital volume and bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is limited. This study aimed to compare the bleeding rates after ESD for EGC according to the hospital volume., Methods: Patients who underwent ESD for EGC at 33 institutions in Japan between November 2013 and October 2016 were included in this multicenter retrospective study. Hospital volume was categorized into three groups, based on the average annual number of ESD procedures: low- and medium-volume group (LMVG), high-volume group (HVG), and very high-volume group (VHVG). The bleeding rate after ESD for EGC was compared between the three hospital volume groups after propensity score matching., Results: A total of 10,320 patients, including 2797 patients in the LMVG, 4646 patients in the HVG, and 2877 patients in the VHVG, were identified. Propensity score matching yielded 2002 patients in each hospital volume group, with an improved balance of confounding variables between the three groups. The bleeding rates in the LMVG, HVG, and VHVG were 4.3%, 3.7%, and 4.9%, respectively, and no significant difference was noted between the three groups., Conclusions: The bleeding rate after ESD for EGC did not differ between hospitals in Japan. The finding indicated that ESD for EGC is equally feasible across Japanese hospitals of different volumes regarding bleeding after ESD., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Robotic gastrectomy (RG) has increased since being covered by universal health insurance in 2018. However, to ensure patient safety the operating surgeon and facility must meet specific requirements. We aimed to determine whether RG has been safely implemented under the requirements for universal health insurance in Japan., Methods: Data of consecutive patients with primary gastric cancer who underwent minimally invasive total or distal gastrectomy-performed by a surgeon certified by the Japan Society for Endoscopic Surgery (JSES) endoscopic surgical skill qualification system (ESSQS) between October 2018 and December 2019-were extracted from the gastrointestinal surgery section of the National Clinical Database (NCD). The primary outcome was morbidity over Clavien-Dindo classification grade IIIa. Patient demographics and hospital volume were matched between RG and laparoscopic gastrectomy (LG) using propensity score-matched analysis (PSM), and the short-term outcomes of RG and LG were compared., Results: After PSM, 2671 patients who underwent RG and 2671 who underwent LG were retrieved (from a total of 9881), and the standardized difference of all the confounding factors reduced to 0.07 or less. Morbidity rates did not differ between the RG and LG patients (RG, 4.9% vs. LG, 3.9%; p = 0.084). No difference was observed in 30-day mortality (RG, 0.2% vs. LG, 0.1%; p = 0.754). The reoperation rate was greater following RG (RG, 2.2% vs. LG, 1.2%; p = 0.004); however, the duration of postoperative hospitalization was shorter (RG, 10 [8-13] days vs. LG, 11 [9-14] days; p < 0.001)., Conclusions: Insurance-covered RG has been safely implemented nationwide., (© 2021. The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Sleeve gastrectomy was covered by Japan's national health insurance as bariatric surgery for morbid obesity in 2014. There are a few cases of gastric bypass surgery, which is a different procedure. Given that the current incidence of gastric cancer in Japan is higher than that in the EU and US, the difficulty that gastric bypass surgery presents in examining the bypassed stomach necessitates a cautious approach to the indication of gastric bypass surgery in Japan. We present the case of a woman in her fifties who developed gastric cancer in the bypassed stomach 12 years after undergoing a laparoscopic Roux-en-Y gastric bypass. When a patient develops anemia and abdominal symptoms after bariatric surgery, the surgical procedure should be considered in the inspection.

A woman in her 50s was referred to our hospital with intestinal obstruction. Ten years prior, she had been treated for gastric cancer, pathologically confirmed as stage IIIA poorly differentiated adenocarcinoma with signet-ring cell carcinoma. Intraoperatively, a 4-cm hard white tumor was found in the mesoileum and around the ileum. Pathological examination revealed poorly differentiated adenocarcinoma with signet-ring cell carcinoma and infiltration and fibrosis. Late peritoneal recurrence of gastric carcinoma was diagnosed. Recurrence of gastric carcinoma more than 10 years after curative gastrectomy is extremely rare. A review of 30 cases reported in Japan revealed recurrence was more frequent in females (60%) and the mean age was around 50 years at the time of primary surgery. Poorly differentiated adenocarcinoma and/or signet-ring cell carcinoma was the primary gastric cancer in 82% of cases and bone metastasis was the most frequent site of recurrence.

Introduction: After curative gastrectomy followed by 1-year adjuvant S-1 monotherapy for pathological stage (pStage) II or III gastric cancer, some patients experience peritoneal, hematogenous, or lymph nodal recurrence. However, risk factors for each recurrence pattern despite completed adjuvant S-1 monotherapy remain unclear. The aim of this study was to determine which factors influence each recurrence type after curative gastrectomy followed by 1-year adjuvant S-1 monotherapy., Materials and Methods: A total of 380 patients with pStage II or III gastric cancer who completed 1-year adjuvant S-1 monotherapy after R0 gastrectomy between January 2008 and December 2013 were enrolled in this study. The risk factors that were associated with peritoneal, hematogenous, and lymph nodal recurrence were investigated by univariate and multivariate analyses., Results: Eighty (21.1%) of 380 patients developed recurrence. As the first site, peritoneal, hematogenous, and lymph nodal recurrence occurred in 42 (11.1%), 26 (6.8%), and 12 (3.2%) patients, respectively. In multivariate analysis, peritoneal metastasis was associated with signet ring cell carcinoma (P < 0.001), pT4 (P = 0.001), and pN3 (P < 0.001), while hematogenous recurrence was associated with pN3 (P = 0.019) and later initiation of S-1 (P = 0.013), and lymph nodal recurrence was associated with pN3 (P = 0.002)., Conclusion: The risk factors for peritoneal, hematogenous, and lymph nodal recurrence in pStage II or III gastric cancer patients who complete adjuvant S-1 monotherapy differ. This information may be helpful for daily surveillance of recurrence in post-operative and chemotherapeutic patients. Furthermore, it may be a useful reference to develop novel perioperative chemotherapy., Competing Interests: Declaration of competing interest Daisuke Takahari received honoraria for lecture fees from Eli Lilly, Bristol-Myers Squibb, Yakult and Chugai Pharmaceutical, and received research finding from Taiho Pharmaceutical and Ono Pharmaceutical; Kensei Yamaguchi received honoraria for lecture fees from Takeda Pharmaceutical Company Limited, Bayer, Daiichi-Sankyo, Sanofi, Dainippon-Sumitomo Pharma, MSD and Gilead and received research finding from Taiho Pharmaceutical, Eli Lilly, Ono Pharmaceutical, Bristol-Myers Squibb, Yakult and Chugai Pharmaceutical; Takeshi Sano received honoraria for lecture fees from Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, MSD and Eli Lilly., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

A 73‒year‒old man, living in the United States since 1985, visited the University of Minnesota Medical Center with a complaint of upper abdominal pain in December 2019. Gastroendoscopy revealed a depressed lesion in the U area of the stomach, and the biopsy results indicated a diagnosis of por/sig. On further examination, the condition was diagnosed as gastric cancer of cStage II/III. A gastrectomy procedure was planned after treatment with neoadjuvant chemotherapy(NAC). After 1 course of mFOLFOX6, the patient decided to undergo treatment in Japan. He travelled to Japan in February and visited our hospital. In March, he underwent total gastrectomy plus D2 dissection plus Roux‒en‒Y reconstruction. The final diagnosis was gastric cancer, U, Less, ypType 2, ypT3(ss), ypN1, sM0, yfStage IIB, and the therapeutic effect was Grade 2. DS therapy was started as adjuvant chemotherapy in April. After 8 courses, he returned to the United States. After moving to the United States, he personally imported S‒1 and continued adjuvant chemotherapy at the University of Minnesota Hospital. The guidelines in Japan do not recommend NAC. Given that Grade 2 therapeutic effect was obtained even with 1 course of the treatment, FOLFOX therapy could be effective as preoperative chemotherapy for advanced gastric cancer cases.

Purpose: The Endoscopic Surgical Skill Quantification System for qualified surgeons (QSs) was introduced in Japan to improve surgical outcomes. This study reviewed the surgical outcomes after initial experience performing laparoscopic distal gastrectomy (LDG) and evaluated the improvement in surgical outcomes following accreditation as a QS., Methods: Eighty-seven consecutive patients who underwent LDG for gastric cancer by a single surgeon were enrolled in this study. The cumulative sum method was used to analyze the learning curve for LDG. The surgical outcomes were evaluated according to the two phases of the learning curve (learning period vs. mastery period) and accreditation (non-QS period vs. QS period)., Results: The learning period for LDG was 48 cases. Accreditation was approved at the 67th case. The operation time and estimated blood loss were significantly reduced in the QS period compared to the non-QS period (230 vs. 270 min, p < 0.001; 20.5 vs. 59.8 ml, p = 0.024, respectively). Furthermore, the major complication rate was significantly lower in the QS period than in the non-QS period (0 vs. 10.6%, p = 0.044)., Conclusions: Experience performing approximately 50 cases is required to reach proficiency in LDG. After receiving accreditation as a QS, the surgical outcomes, including the complication rate, were improved., (© 2021. Springer Nature Singapore Pte Ltd.)

Global studies have been planned to achieve early approval of the new agent especially in cancer chemotherapy. On the other hand, it is important to consider the difference in efficacy among each region. As medical approval in Japan means reimbursement of medical cost, new drug is required to show its effectiveness in the medical situation in Japan, and the Japanese subgroup data is important. Especially in the gastric cancer field, where there is a large difference in survival time and surgical outcome between Japan and outside Japan need to consider Japanese domestic data. But characteristic of Japanese subgroup is the number of target patients is small, high censored case due to longer survival and the background factors are not even. So the interpretation of the data requires caution because of these robustness.

Background and Aim: This study aimed to reveal the timing of bleeding and thromboembolism associated with endoscopic submucosal dissection (ESD) for early gastric cancer (EGC)., Methods: We retrospectively reviewed  10,320 patients who underwent ESD for EGC during November 2013-October 2016. We evaluated overall bleeding rates and their inter-group differences. Factors associated with early/late (cut-off 5 days) bleeding and thromboembolism frequency and its association with the intake of antithrombotic agents were investigated., Results: Overall, the post-ESD bleeding rate was 4.7% (489/10 320); the median time to post-ESD bleeding was 4 days. The post-ESD bleeding rates were 3.2%, 8.7%, 15.5%, and 29.9% in those not taking antithrombotic agents, those taking antiplatelet agents, those taking anticoagulants (ACs), and those taking antiplatelet agents and ACs. Warfarin (odds ratio [OR], 9.16), direct oral ACs (OR, 4.16), chronic kidney disease with hemodialysis (OR, 2.93), thienopyridine (OR, 2.25), aspirin (OR, 1.66), tumor size >30 mm (OR, 1.86), multiple tumors' resection (OR, 1.54), and tumor in the lower third of the stomach (OR, 1.40) were independent risk factors for early bleeding. The independent risk factors for late bleeding were direct oral ACs (OR, 7.42), chronic kidney disease with hemodialysis (OR, 4.99), warfarin (OR, 3.90), thienopyridine (OR, 3.09), liver cirrhosis (OR, 2.43), cilostazol (OR, 1.93), aspirin (OR, 1.92), ischemic heart disease (OR, 1.77), and male sex (OR, 1.65). There were three (0.03%) thromboembolic events (cerebral infarction = 2, transient ischemic attack = 1)., Conclusion: We revealed the timing of bleeding and risk factors for early/late bleeding and showed the thromboembolism frequency associated with ESD for EGC., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: As the aging of people in a society advances, the number of elderly patients older than 80 years in Japan with gastric cancer continues to increase. Although delayed ulcer bleeding is a major adverse event after endoscopic submucosal dissection (ESD), little is known about characteristic risk factors for bleeding in elderly patients undergoing ESD. This study aimed to evaluate risk factors for delayed bleeding after ESD for gastric cancer in elderly patients older than 80 years., Methods: We retrospectively evaluated the incidence of delayed bleeding after ESD in 10,320 patients with early-stage gastric cancer resected by ESD between November 2013 and January 2016 at 33 Japanese institutions and investigated risk factors for delayed bleeding in elderly patients older than 80 years., Results: The incidence of delayed bleeding in elderly patients older than 80 years was 5.7% (95% confidence interval [CI]: 4.6%-6.9%, 95/1,675), which was significantly higher than that in nonelderly (older than 20 years and younger than 80 years) patients (4.5%, 4.1%-5.0%, 393/8,645). Predictive factors for ESD-associated bleeding differed between nonelderly and elderly patients. On multivariate analysis of predictive factors at the time of treatment, risk factors in elderly patients were hemodialysis (odds ratio: 4.591, 95% CI: 2.056-10.248, P < 0.001) and warfarin use (odds ratio: 4.783, 95% CI: 1.689-13.540, P = 0.003)., Discussion: This multicenter study found that the incidence of delayed bleeding after ESD in Japanese patients older than 80 years was high, especially in patients receiving hemodialysis and taking warfarin. Management of ESD to prevent delayed bleeding requires particular care in patients older than 80 years., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background and Aims: A drawback of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is the development of metachronous gastric cancer (MGC). While MGC after ESD for differentiated-type (D-) EGC was well understood, little is known about MGC occurring after ESD for undifferentiated-type (UD-) EGC, because ESD had not been indicated. We evaluated the incidence and treatment outcomes of MGC after ESD of UD-EGC., Methods: This study is a post hoc analysis of JCOG1009/1010, a multicenter trial to evaluate the efficacy and safety of ESD for UD-EGC. The patients who underwent curative ESD of index solitary UD-EGC were analyzed. Surveillance endoscopy was performed biannually for the first 3 years and thereafter annually. We assessed the time to MGC occurrence after ESD, lesion characteristics, and treatment outcomes of MGC. Time to MGC occurrence was estimated by cumulative incidence function, with death and total gastrectomy as competing risks., Results: A total of 198 patients were included in this study. During a median follow-up period of 5.8 years, 4 patients (2%) developed MGC. Median time to MGC occurrence was 4.5 years (range: 3.1-5.4). Five-year cumulative incidence of MGC was 1.0% (95% CI: 0.2-3.3%). Two MGCs were histologically D-EGC, and the remaining two were UD-EGC. The median tumor size of MGCs was 1.0 cm (range: 0.7-1.7), and the depth of invasion (M/SM1/SM2) was 2/1/1, respectively. Three patients achieved curative resection with repeated ESD., Conclusions: MGC does not occur commonly after curative ESD of UD-EGC, and repeated ESD could contribute to stomach preservation., (© 2021. The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Two European phase III trials comparing D1 and D2 demonstrated that D2 did not improve the overall survival and was associated with a high mortality related to splenectomy. However, a long-term follow-up study showed that the gastric cancer-related death rate was significantly higher in D1 than D2. Based on these findings, the standard surgery in Europe became D2 without pancreatico-splenectomy to prevent mortality. In contrast, the JCOG9501 phase III comparing D2 and D2 plus para-aortic nodal dissection did not showed a survival efficacy of extended lymphadenectomy, but the mortality rate was quite low in both surgeries. Subsequently, the JCOG0110 phase III study comparing D2 and spleen-preserving D2 for upper gastric cancer not invading the greater curvature clearly showed the non-inferiority of spleen preservation. Thus, spleen-preserving D2 was made the standard surgery for these tumors in Japan. However, splenectomy is often selected for complete dissection of the splenic-hilar nodes, a frequent metastatic site for upper gastric tumors invading the greater curvature. Recently, an approach involving splenic hilar nodal dissection without splenectomy has been developed., (Copyright © 2021. Published by Elsevier Ltd.)

The prognosis of peritoneal carcinomatosis is poor. However, the emergence of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) as a treatment option has prolonged survival and it can even potentially cure patients with peritoneal carcinomatosis. Randomized controlled studies and other observational studies indicated that this combined therapy potentially improved the prognosis of patients with colon, gastric, and ovarian cancers with acceptable morbidity and mortality rates. Even in rarer diseases, such as pseudomyxoma peritonei and malignant peritoneal mesothelioma, CRS + HIPEC markedly improved the prognoses over those with conventional treatment. Based on the accumulated evidence, clinical guidelines recommend CRS + HIPEC for selected patients with peritoneal carcinomatosis. However, several issues still need to be overcome. A standard method for HIPEC has not yet been established. Furthermore, the criteria employed for patient selection need to be clarified to achieve real benefits. The peritoneal cancer index, chemo-sensitivity and several biological markers are considered to be key factors.

Although the incidence of gastric cancer has decreased because of the lower rate of Helicobacter pylori infection, it still accounts for a large number of deaths in Japan. Gastric cancer is mainly treated by resection, and the rate of radical resection is high in Japan because approximately 50% of cases are diagnosed at an early stage. Treatment advances have increased the number of endoscopic submucosal dissections, and development of laparoscopic surgery and robot-assisted surgery as minimally invasive approaches has yielded results similar to those of conventional surgeries, at least in the short term. Cases for which resection is contraindicated are treated with chemotherapy if performance status can be maintained. Although anticancer drugs are continuously under development, treatment outcomes remain unsatisfactory. As Japan becomes a super-aging society, the number of refractory cases is projected to increase. Therefore, evidence of any benefit for minimally invasive surgery and function-preserving surgery needs to be reported quickly. In this paper, we discuss gastric cancer treatment modalities recommended in the fifth edition of the gastric cancer treatment guidelines and describe recent research findings.

Background: The age-dependent survival impact of body mass index (BMI) remains to be fully addressed in patients with gastric carcinoma (GC). We investigated the prognostic impacts of BMI in elderly (≥70 years) and non-elderly patients undergoing surgery for GC., Methods: In total, 1168 GC patients were retrospectively reviewed. Patients were stratified into 3 groups according to BMI; low (<20), medium (20-25) and high (>25). The effects of BMI on overall survival (OS) and cancer-specific survival (CSS) were assessed using univariate and multivariate Cox hazards models., Results: There were 242 (20.7%), 685 (58.7%) and 241 (20.6%) patients in the low-, medium- and high-BMI groups, respectively. The number of patients with high BMI but decreased muscle mass was extremely small (n = 13, 1.1%). Patients in the low-BMI group exhibited significantly poorer OS than those in the high- and medium-BMI group (P < 0.001). Notably, BMI classification significantly demarcated OS and CSS curves (both P < 0.001) in non-elderly patients, while did not in elderly patients (OS; P = 0.07, CSS; P = 0.54). Furthermore, the survival discriminability by BMI was greater in pStage II/III disease (P = 0.006) than in pStage I disease (P = 0.047). Multivariable analysis focusing on patients with pStage II/III disease showed low BMI to be independently associated with poor OS and CSS only in the non-elderly population., Conclusions: BMI-based evaluation was useful for predicting survival and oncological outcomes in non-elderly but not in elderly GC patients, especially in those with advanced GC., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Pharmacologic prophylaxis such as enoxaparin for venous thromboembolism (VTE) is rarely used in Japan, even following abdominal cancer surgery, for which it is recommended in relevant guidelines (at least 7 days of use) along with mechanical prophylaxis with intermittent pneumatic compression. Reasons for enoxaparin's unpopularity include concerns over postoperative bleeding and its inconvenience in clinical practice. Here, we conducted a prospective clinical study of short-term (3 days) use of enoxaparin, which is considered to minimally impact postoperative management without increasing bleeding risk., Methods: Gastric cancer patients who underwent gastrectomy received enoxaparin for 3 days from postoperative day (POD) 1-4. The primary endpoint was the incidence of deep vein thrombosis (DVT), which was examined primarily via Doppler ultrasonography of the lower limbs between POD 8 and 14. The planned sample size was 70, which was calculated based on an estimated incidence rate of 9% and an upper limit of incidence rate of 20%, with alpha of 0.05 and beta of 0.2., Results: A total of 70 gastric cancer patients were enrolled, and ultimately, 68 patients received the protocol intervention and DVT evaluation. Sixty-seven patients completed 6 enoxaparin injections, but 1 patient did not complete the course due to abdominal bleeding after initiation. The incidence of DVT was 4.4% (3/68), and the 95% upper confidence interval was 12.2%, lower than the 20% threshold we set as the upper limit of DVT incidence. DVT was detected only in the peripheral veins of the lower extremities in all 3 affected patients. The incidence of bleeding-related complications, which were not severe, was 1.5% (1/68)., Conclusions: Short-term (3 days) use of enoxaparin was shown to be effective and safe for VTE prophylaxis, comparable to regular use (at least 7 days), in postoperative management of gastric cancer surgery., (Copyright © 2021 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Objectives: Epstein-Barr virus-associated gastric cancer (EBVGC) has been reported to be associated with a low risk for lymph node metastasis (LNM). However, the curative criteria for endoscopic submucosal dissection (ESD) for submucosal EBVGC (pT1b-EBVGC) remain unclear. Our study aimed to investigate the risk factors for LNM in pT1b-EBVGC., Methods: This was a retrospective multicenter study at five institutes in Japan. We reviewed medical records and extracted all pT1b-EBVGC cases that met the following criteria: (i) histologically proven submucosal gastric cancer; (ii) surgical or endoscopic resection between January 2000 and December 2016; and (iii) presence of Epstein-Barr virus (EBV) in tumor cells verified by EBV-encoded small RNA in situ hybridization (EBER-ISH). The association between clinicopathological factors and LNM were assessed using multivariable logistic regression analysis., Results: A total of 185 pT1b-EBVGC cases were included in the analysis. LNM was found in nine cases (4.9%). Multivariable logistic regression analysis demonstrated that lymphatic invasion (OR 9.1; 95% CI 2.1-46.1) and submucosal invasion ≥4000 μm (OR 9.2; 95% CI 1.3-110.3) were significant risk factors for LNM. When we focused on pT1b-EBVGC without lymphatic invasion and with submucosal invasion <2000 μm, the rate of LNM was 0% (0/96, 95% CI 0-3.8%)., Conclusions: Our findings indicated that lymphatic invasion and submucosal invasion ≥4000 μm were significant risk factors for LNM. ESD could be an appropriate option for pT1b-EBVGC without lymphatic invasion and with submucosal invasion <2000 μm., (© 2020 Japan Gastroenterological Endoscopy Society.)

The current standard surgical procedure for proximal gastric and gastroesophageal junction (P/GEJ) cancers with limited esophageal involvement is total gastrectomy (TG). TG is associated with impaired appetite and weight loss due to decreased levels of ghrelin (a "hunger hormone" secreted by the stomach) and with anemia due to intrinsic factor loss and vitamin B12 malabsorption. Theoretically, proximal gastrectomy (PG) with an anti-reflux technique such as double-tract reconstruction (DTR) can improve quality of life (QoL) by preserving gastric function.1 A recent Japanese prospective GEJ adenocarcinoma study reported a low incidence of lymph node metastases at peripyloric stations,2 indicating the oncological safety of PG for GEJ adenocarcinoma regardless of tumor stage. As a result, PG is increasingly performed in South Korea and Japan, although the QoL benefit of PG over TG remains unknown.3, 4 We have performed PG with DTR in select cases with satisfying short-term outcomes. In this video, we introduce our technique for robotic PG with DTR. The presented case is a 75-year-old woman with GEJ adenocarcinoma that showed an excellent response to preoperative chemoradiation therapy. The patient underwent robotic PG with DTR. Fluorescent sentinel lymphatic mapping was performed by injecting indocyanine green solution (total of 2 ml, at four quadrants around the tumor at submucosal space) via endoscopy at the beginning of the operation. It showed absence of sentinel lymphatic flow to peripyloric lymph nodes, which were thus considered safe to preserve. Pathologic examination confirmed a complete response. The patient's recovery was favorable, and she reported satisfaction with her QoL and good appetite, though some intermittent bloating after eating. PG with DTR has theoretical disadvantages including incomplete lymph node removal, which may result in recurrence; therefore, PG should be carefully performed for P/GEJ cancers with low risk of perigastric lymph node metastases, such as cT1 tumors or GEJ tumors with limited gastric involvement.2 In addition, delayed gastric emptying of the remnant stomach can cause upper gastrointestinal symptoms such as reflux and bloating. The QoL benefits of PG with DTR must be demonstrated before encouraging its use in the USA and other countries. International collaboration is warranted to test the benefits and safety of PG, and the effective use of sentinel lymphatic mapping, to standardize the surgical care of patients with P/GEJ cancers.

Background: Surveillance after curative surgery for gastric cancer is conventionally performed for 5 years. However, the appropriate follow-up period remains controversial., Methods: This study retrospectively compiled a clinicopathological database of patients who underwent curative gastrectomy between 1975 and 2010 at Toranomon Hospital and were reviewed until March 2020. Analyzing the follow-up rate and recurrence rate for each stage in each postoperative year, we set each follow-up endpoint when the subsequent recurrence rate fell below 1%., Results: A total of 5235 patients were eligible for inclusion in the study. The rate of patients followed up for 5 years was 90.3%. The rates of follow-up were 52.7% at 10 years, 38.3% at 15 years, and 10.3% at 20 years. Recurrence was confirmed in 850 patients in total (16.2%) and in 50 patients beyond 5 years. The adequate follow-up endpoints according to stage (with < 1% recurrence risk) were 2 years for stage IA, 4 years for IB, 6 years for IIA, 9 years for IIB, 7 years for IIIA, and 8 years for IV (curative). For stage IIIB and IIIC, the recurrence risk remained., Conclusions: The adequate surveillance duration of resected gastric cancer might be different in each stage. Although the follow-up duration for stage I disease could be reduced to less than 5 years, advanced gastric cancer such as stage III or IV disease has risk of recurrence beyond 5 years and therefore additional follow-up is required. These results could help decide the strategy for surveillance.

Background: The National Clinical Database (NCD) nationwide registry program of gastric cancer started in 2018. The purpose of this study was to report the treatment results of the NCD registry in the form of treatment results of the real world in Japan., Methods: Patients' characteristics, tumor features, treatments, and outcomes were collected using a web-based data entry system. We analyzed the initial NCD database for data on surgically treated gastric cancer patients in 2011., Results: A total of 30,257 patients with malignant gastric tumors were enrolled by the NCD registry program from 501 hospitals in all 47 prefectures. Of these, the status of data entry was not approved in 8.8% of the registered data, and follow-up information was missing in 1.2% of the approved cases. Excluding 1777 cases, which were not resected for primary gastric cancer, 25,306 resected cases included 44.4% of stomach surgeries recorded in the NCD. The 5 year survival rate of the resected cases was 71.3% and the operative mortality rate was 0.41%. The stage-specific 5 year survival rates were as follows: 89.6% for stage IA, 83.8% for stage IB, 77.3% for stage IIA, 69.1% for stage IIB, 58.7% for stage IIIA, 44.1% for stage IIIB, 30.1% for stage IIIC, and 13.4% for stage IV., Conclusions: The NCD gastric cancer registry program demonstrated validity for database construction. The gastric cancer registry is expected to become a nationwide registry with the dissemination of data entry system and method in the NCD.

Introduction: Laparoscopic surgery is a minimally invasive surgery; however, obstacles to its functional optimization remain. Surgical ports can accommodate only one instrument at a time so complex exchange manipulations are necessary during surgery which increases operation times and patient risk. We developed a new laparoscopic instrument that functions as both forceps and a suction tube, which renders intraoperative tool exchange unnecessary. This pilot study was undertaken to evaluate the safety and efficacy of this novel dual-function device in laparoscopic surgery for gastric cancer., Methods: This single-center pilot study assessed patient safety during and after laparoscopic distal gastrectomy for gastric cancer with the suction-forceps using intraoperative video and clinical follow-up, respectively. To evaluate instrument efficacy, we measured the time interval between the start of any bleeding and the start of aspiration ("suction access time") and compared this time with that of a conventional surgical setup., Results: In total 15 patients participated, with all procedures being successful. No excess tissue damage occurred during surgery. Suction access time was significantly shorter in cases of bleeding when the suction-tip forceps were used for aspiration (2.01 seconds) compared to an ordinary suction tube (12.5 seconds; P < .01)., Conclusion: These findings suggest that our new suction-tip forceps are a useful, safe, and efficacious operative tool. This surgical innovation may considerably simplify gastric laparoscopic surgery. This pilot study was registered with Japan Clinical Trial Registration on 22 June 2017 (registration number: UMIN000027879)., (© 2020 The Authors. Asian Journal of Endoscopic Surgery published by Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Gastric cancer (GC) is an aggressive tumor, which is usually diagnosed at an advanced stage and shows high mortality rates. Several GC classifications have been published, based on features such as tumor location, endoscopic features or microscopic architecture. However, TNM stage remains the mainstay of GC management and treatment. In the last years, technical advances have allowed us to investigate the biological heterogeneity of GC and develop new molecular classifications. This knowledge may enhance current classifications, and has the potential to refine GC management and aid in the identification of new molecular targets. In this literature review we have summarized the main findings in epidemiology, screening, classification systems and treatment of GC, focusing on the molecular alterations and new molecular classifications published in the last years., (Copyright © 2020 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)