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Background/aim: Biomarkers indicating sensitivity to poly ADP-ribose polymerase (PARP) inhibitors have not yet been identified in gastric cancer. PARP inhibitors target homologous recombination deficiency (HRD); however, homologous recombination (HR) induces complex changes in gene expression, which makes it difficult to identify reliable biomarkers. In this study, we identified a multi-gene expression signature as a marker of PARP inhibitor sensitivity in gastric cancer., Materials and Methods: Seven gastric cancer cell lines were evaluated for susceptibility to PARP inhibitors using a growth inhibition assay. Gene expression profiling (GEP) was used to identify differentially expressed genes between PARP inhibitor-sensitive and -resistant cell lines. The resulting gene set was subjected to cluster analysis using tumor samples from 250 patients who underwent gastrectomy for primary gastroesophageal junction and gastric adenocarcinoma. HRD was defined as a truncating mutation in one or more of 22 HR-related genes and HRD scores were calculated using whole-exome sequencing data., Results: In the growth inhibition assays, the HGC27 and HSC39 cell lines were sensitive to the PARP inhibitors, olaparib, and rucaparib, and were significantly correlated with the GEP results. Seven (2.8%) patients harbored truncating mutations in HR-related genes. A gene expression signature based on the top 100 high and low differentially expressed genes between sensitive and resistant cell lines revealed a patient cluster with a high prevalence of HR-related gene mutations and high HRD scores., Conclusion: The 100-gene expression signature identified in this study may serve as a valuable predictive biomarker for PARP inhibitor sensitivity in gastric cancer., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Chemotherapy is the mainstay treatment for liver metastasis from gastric cancer. However, some retrospective studies and meta-analyses have indicated the efficacy of hepatectomy, which is an aggressive treatment option. However, the optimal selection criteria for hepatectomy and the role of perioperative chemotherapy remain unclear. Therefore, a meta-analysis of studies on hepatectomy was performed to assess the impact of various factors on overall survival (OS). A systematic review was conducted in accordance with the PRISMA criteria using studies published until 2022. The primary outcome was the hazard ratio (HR) for OS. Comparisons were made between hepatectomy and nonhepatectomy, solitary and multiple metastases, synchronous and metachronous metastases, treatment with and without neoadjuvant chemotherapy, and treatment with and without adjuvant chemotherapy. A total of 50 studies involving 1966 patients who underwent hepatectomy were included in the analysis. The meta-analysis showed a 5-year OS rate of 25 %. A meta-analysis comparing hepatectomy with nonhepatectomy showed an HR of 0.2 for hepatectomy. A meta-analysis comparing solitary and multiple metastases showed a trend toward better OS in patients with solitary metastases (odds ratio [OR]: 0.35). A meta-analysis comparing synchronous and metachronous metastases showed favorable OS for patients with metachronous metastases (OR: 0.66). A meta-analysis comparing neoadjuvant chemotherapy with no neoadjuvant chemotherapy showed no difference in OS. In contrast, a meta-analysis comparing adjuvant chemotherapy with no adjuvant chemotherapy showed better OS for adjuvant chemotherapy (OR: 0.39). This retrospective study indicates that hepatectomy may benefit patients with liver metastases from gastric cancer, particularly those with solitary and metachronous metastases., Competing Interests: Declaration of competing interest M.T. has received research grants from Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Bristol Myers Squib Japan K.K., Yakult Honsha Co., Ltd., Takeda Pharmaceutical Co., Ltd., Eli Lilly Japan, Pfizer Japan Inc., Daiichi Sankyo Ltd., Johnson and Johnson K.K., Medtronic Japan Co., Ltd., Intuitive Japan Inc., and Olympus Co., Ltd., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Gastric cancer is a common malignancy with a high incidence in East Asia. Gastric resection ranges from endoscopic resection to open total gastrectomy. However, nationwide data are lacking., Methods: This observational study analyzed data from the publicly accessible National Database of Health Insurance Claims and Specific Health Checkups, which includes most national health insurance claims data in Japan. Trends in the types of resection performed for malignant gastric tumors between 2014 and 2021, patients' age and sex distributions, and regional disparities were investigated., Results: The annual number of resections was highest in 2015 (109,000) and lowest in 2020 (90,000) after the COVID-19 pandemic. The proportion of endoscopic resections increased from 47% in 2014 to 57% in 2021 while that of total gastrectomies decreased from 17 to 10%. In 2021, 70% of patients who underwent resection were men. That year, 83.8% of all patients who underwent any type of gastric resection and 87.1% of those who underwent endoscopic submucosal dissection were aged ≥ 65 years. The annual incidence of gastric resection per million population was highest in Tottori (n = 1236) and lowest in Okinawa (n = 251). The proportion of endoscopic resections was highest in Miyagi (66%) and lowest in Aichi (45%) and that of open surgery was highest in Aomori (36%) and lowest in Wakayama (5%)., Conclusions: Gastric malignancy is increasingly treated by endoscopic submucosal dissection rather than open total gastrectomy. However, regional disparities remain in resection type. Standardization of treatment and a more even distribution of specialists are needed., (© 2024. The Author(s).)

Background: Microsatellite instability-high (MSI-H) tumors are distinct molecular subtypes in gastric cancer. However, a few studies have comprehensively reported the molecular features of MSI-H tumors and their prognostic factors in locally advanced gastric cancer. This study aimed to clarify the molecular features and prognostic factors of locally advanced MSI-H gastric cancer., Methods: This study included 499 patients with locally advanced gastric cancer who underwent radical gastrectomy. We evaluated the MSI status and compared with previously published whole-exome sequencing, panel sequencing, and gene expression profiling data. Clinicopathological characteristics and molecular profiles were compared between patients with MSI-H and microsatellite stable (MSS) gastric cancer. A subgroup analysis of survival was performed in patients with MSI-H gastric cancer., Results: MSI-H tumors were detected in 79 of 499 patients (15.8%). MSI-H tumors were associated with an increased tumor mutational burden, MLH1 downregulation, CD274 (PD-L1) upregulation, and enrichment of cell cycle pathways. Among patients with MSI-H gastric cancer, the disease-specific survival (DSS) tended to be better in the surgery plus tegafur, gimeracil, and oteracil potassium (S-1) adjuvant chemotherapy group than in the surgery alone group, especially for stage III patients. Furthermore, DSS was better in the T cell-inflamed gene expression signature-high group, and it tended to be worse in the non-solid type poorly differentiated adenocarcinoma group., Conclusions: The molecular features and prognostic factors of locally advanced MSI-H gastric cancer were clarified. S-1 adjuvant chemotherapy appears to be beneficial, and the T cell-inflamed gene expression signature and histopathological type are prognostic factors in MSI-H tumors., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Background & Aims: Preoperative sarcopenia in gastric cancer is associated with increased postoperative complications and reduced long-term survival. However, the association between postoperative sarcopenia and long-term outcomes remains unclear. Therefore, this study aims to clarify the association between sarcopenia after gastrectomy for gastric cancer and survival outcomes., Methods: This retrospective study included 1512 patients aged ≥65 who underwent curative gastric resection for clinical stage I-III primary gastric cancer during 2008-2018. Sarcopenia was assessed preoperatively by measuring arm muscle area and grip strength, which was repeated 1 month after surgery. We compared the clinical characteristics, surgical treatments, and long-term outcomes between the postoperative normal and sarcopenia groups., Results: Sarcopenia was observed in 173 and 305 patients pre- and postoperatively, respectively. Factors increasing the risk of postoperative sarcopenia included age of ≥75, lower preoperative body mass index, diabetes, and clinical stage II/III gastric cancer. Patients with postoperative sarcopenia after surgery had a significantly lower overall survival rate (hazard ratio [HR] 2.596, p < 0.001). Furthermore, postoperative sarcopenia was linked to decreased overall survival in patients with (HR 2.813, p = 0.002) and without (HR 1.925, p < 0.001) preoperative sarcopenia. Cumulative incidence showed significantly higher rates of deaths due to gastric cancer (HR 1.928, p < 0.001) and other causes (HR 2.736, p < 0.001) in the postoperative sarcopenia group., Conclusions: Postoperative sarcopenia in gastric cancer is linked to an increased risk of death due to cancer and other causes, underscoring the importance of perioperative sarcopenia management strategies., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: Inflammatory myofibroblastic tumor (IMT) of the stomach is an uncommon mesenchymal neoplasm. We present a case of gastric submucosal tumor (SMT) where the final diagnosis was IMT., Case Presentation: A 69-year-old man presented with a 24-mm SMT on the posterior wall of the middle third of the stomach that was detected by screening upper gastrointestinal endoscopy. Abdominal contrast-enhanced computed tomography showed that the tumor was well-enhanced. Although endoscopic ultrasonography-guided biopsy was performed, the histological diagnosis was not confirmed preoperatively. Since the tumor was clinically suspected to be a gastrointestinal stromal tumor, we performed gastric wedge resection by laparoscopic-endoscopic cooperative surgery. Pathologically, proliferative spindle cells with a positive reaction for smooth muscle actin, negativity for c-kit, desmin, s-100, CD34, STAT-6, β-catenin and anaplastic lymphoma kinase 1 were identified. Hence, the tumor was finally diagnosed as an IMT originating from the stomach., Conclusions: When an SMT of the stomach is identified, the possibility of gastric IMT should be considered., (© 2024. The Author(s).)

Background: Colorectal cancer (CRC) is the most common cancer that coincides with gastric cancer (GC). Although the usefulness of total colonoscopy (TCS) as a CRC screening tool has been reported in preoperative patients with GC, the long-term outcome of patients with synchronous CRC (SCRC) remains unclear. This study aims to clarify the significance of preoperative screening TCS for GC in terms of survival outcomes., Patients and Methods: We included 796 patients who underwent preoperative screening TCS for GC. The risk factors, clinicopathological features, and survival outcome of SCRC were examined. Furthermore, the cost-effectiveness was evaluated from the perspective of improving the rates of mortality caused by CRC., Results: SCRC was observed in 43 patients (5.4%). Endoscopic treatment for SCRC was performed on 30 patients. In total, 15 patients underwent surgical resection, including 2 patients requiring additional surgery after endoscopic treatment. Regarding pathological stages, 25 patients had stage 0, 12 patients had stage I, 5 patients had stage II, and 1 patient had stage IIIB disease. The cumulative mortality rates were as follows: GC-related deaths, 12.6%; deaths from cancers other than CRC, 1%; deaths from other causes, 5.5%. No deaths were attributed to SCRC. Comparing the patients who did not undergo TCS, an incremental cost-effectiveness ratio analysis suggested that a screening cost of 5.86 million yen was required to prevent one CRC death., Conclusions: Curative treatment was possible in all patients with SCRC. No deaths were attributed to SCRC, suggesting that screening TCS for GC is effective., (© 2023. Society of Surgical Oncology.)

Gastric neuroendocrine carcinoma (G-NEC) usually has NEC and adenocarcinoma components and is considered to have a common origin in gastric adenocarcinoma because common pathogenic mutations are shared. However, G-NEC without adenocarcinoma also exists, and it may have a different mechanism of tumorigenesis. We aimed to elucidate the tumorigenesis of G-NEC by focusing on the proportion of NEC components. Thirteen patients with G-NEC were included in this study. Comprehensive genetic analysis using whole-exome sequencing was performed. G-NEC without an adenocarcinoma component was defined as pure NEC. TP53 was detected as the most frequent gene mutation (85% of the patients), independent of classification. RB1, KMT2C, LTBP1, and RYR2 mutations were identified in two of three pure NEC patients but were not detected in other G-NEC patients. Pure NEC has different somatic mutation profile than other NECs. This study provides insights into the mechanism of tumorigenesis in G-NEC., Competing Interests: Declaration of competing interest MT reports receiving personal fees from Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, BMS, Yakult Honsha, Takeda Pharmaceutical, Eli Lilly Japan, Pfizer Japan, Daiichi Sankyo, Johnson and Johnson, Medtronic Japan, Intuitive Japan, and Olympus outside the submitted work. EB reports receiving personal fees from Johnson and Johnson, Medtronic Japan, Intuitive Japan, and Kaken Pharmaceutical outside the submitted work. The other authors declare no conflicts of interest., (Copyright © 2023 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Patients with poorly cohesive gastric carcinoma (PCC) are known to have poor survival. However, detailed molecular biology of PCC has not been elucidated, except for mutations in CDH1 and RHOA. Additionally, the molecular profiles of signet-ring cell carcinoma (SRC) have not been fully investigated. We aimed to investigate the association between molecular profiles and survival in PCC and PCC subtypes., Methods: The present study included 455 patients with gastric adenocarcinoma underwent radical gastrectomy. Whole-exome sequencing and gene expression profiling were conducted. Patients were classified according to the WHO classification as PCC or non-PCC, with PCC being further classified into SRC, combined, and PCC not-otherwise-specified (NOS). Clinicopathological factors and survival were compared with molecular profiles., Results: Of the patients, 159 were classified with PCC, while 296 were classified with non-PCC. Among PCC, 44 were classified with SRC, 64 with combined, and 51 with PCC-NOS. Mutations in CDH1 and RHOA were remarkably more frequent in PCC than in non-PCC. PCC had worse overall survival (OS) and disease-specific survival (DSS) compared to non-PCC. For PCC, the SRC group had good OS and DSS, whereas PCC-NOS classification with CDH1 mutations was associated with extremely poor survival. In the PCC-NOS and combined groups, patients with mutations in the extracellular domain 1 of CDH1 had poor survival., Conclusions: Our findings suggest that PCC has poorer survival than non-PCC. Accumulation of CDH1 and RHOA mutations are unique profiles in PCC. Among PCC, CDH1 mutations may play a crucial role in the survival of non-SRC PCC., (© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Background: Small intestine carcinoma (SIC) cases in Japan have recently been treated with chemotherapy according to colorectal carcinoma classification, while papilla of Vater carcinoma (PVC) cases according to cholangiocarcinoma (CHC) classification. However, few research reports support the molecular genetic validity of these therapeutic choices., Patients and Methods: Here, we investigated the clinicopathological and molecular genetic factors of SIC and PVC. We used the data from the Japanese version of The Cancer Genome Atlas. Additionally, molecular genetic data on gastric adenocarcinoma (GAD), colorectal adenocarcinoma (CRAD), pancreatic ductal adenocarcinoma (PDAC), and CHC were also referred to., Results: This study consisted of tumor samples from 12 patients of SIC and three patients of PVC treated from January 2014 to March 2019. Among them, six patients had pancreatic invasion. t-Distributed stochastic neighbor embedding analysis showed that the gene expression pattern of SIC was similar not only to those of GAD and CRAD, but also to that of PDAC in the pancreatic invasion patients. In addition, PVC resembled the GAD, CRAD, and PDAC, rather than the CHC. The molecular genetic characteristics of the six patients with pancreatic invasion were: one had high microsatellite instability, two had a TP53 driver mutation, and three had tumor mutation burden values <1 mutation/Mb with no driver mutation., Conclusions: In this study, the extensive gene expression profiling of organ carcinomas newly suggests that SIC or PVC may resemble GAD, CRAD, and PDAC. In addition, the data demonstrate that pancreatic invasive patients may be classified into several subtypes using molecular genetic factors., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Gastrointestinal stromal tumors (GIST) with KIT exon 11 deletions involving in codons 557-558 ( KIT Δ557-558) exhibit higher proliferation rates and shorter disease-free survival times compared with GISTs with other KIT exon 11 mutations. We analyzed 30 GIST cases and observed genomic instability and global DNA hypomethylation only in high-risk malignant GISTs with KIT Δ557-558. Whole-genome sequencing revealed that the high-risk malignant GISTs with KIT Δ557-558 (12 cases) had more structural variations (SV), single-nucleotide variants, and insertions and deletions compared with the low-risk, less malignant GISTs with KIT Δ557-558 (six cases) and the high-risk (six cases) or low-risk (6 cases) GISTs with other KIT exon 11 mutations. The malignant GISTs with KIT Δ557-558 showed higher frequency and significance in copy number (CN) reduction on chromosome arms 9p and 22q, and 50% of them had LOH or CN-dependent expression reduction in CDKN2A . In addition, SVs with driver potential were detected in 75% of them, in which AKT3 and MGMT were recurrently identified. Genome-wide DNA methylation and gene expression analyses showed global intergenic DNA hypomethylation, SNAI2 upregulation, and higher expression signatures, including p53 inactivation and chromosomal instability, as characteristics of malignant GISTs with KIT Δ557-558 that distinguished them from other GISTs. These genomic and epigenomic profiling results revealed that KIT Δ557-558 mutations are associated with increased genomic instability in malignant GISTs., Significance: We present genomic and epigenomic insights into the malignant progression of GISTs with KIT exon 11 deletions involving in 557-558, demonstrating their unique chromosomal instability and global intergenic DNA hypomethylation., (© 2023 The Authors; Published by the American Association for Cancer Research.)

Background: When a patient has multiple tumors in different organs, it is very important to identify whether the tumors are multiple cancers or metastasis from one tumor in order to establish an optimal treatment strategy. However, it is difficult to obtain an accurate diagnosis from conventional diagnostic strategies, including immunohistochemistry. We report two patients with multiple tumors in which a somatic mutation comparison using next-generation sequencing (NGS) was useful for the diagnosis of a metastatic tumor., Case Presentations: Patient 1: A 64-year-old man was diagnosed with gastric and lung cancer. After radical chemoradiotherapy for lung cancer, gastrectomy was planned for gastric cancer. At gastrectomy, the patient underwent a multiple omics analysis for "Project HOPE". The gene mutational signature of the gastric tumor showed signature 4 of COSMIC mutational signature version 2, which was associated with smoking and has not been found in gastric cancer. To confirm that the gastric tumor was metastasis from lung cancer, we conducted a somatic mutation comparison of the two tumors with 409-gene panel sequencing, which revealed that 28 of 97 mutations in the lung tumor completely matched those of the gastric tumor. Based on these findings, the gastric tumor was diagnosed as metastasis from lung cancer. Patient 2: A 47-year-old woman underwent distal gastrectomy for gastric cancer. A colon tumor was detected 6 years after gastrectomy. The colon lesion was a submucosal tumor-like elevated tumor, and was suspected to be metastasis from gastric cancer. The patient underwent sigmoidectomy, and participated in "Project HOPE". The possibility of primary colon cancer could not be ruled out, and we conducted a somatic mutation comparison of the two tumors as we did with Patient 1. Panel sequencing revealed 11 mutations in the gastric tumors, 4 of which completely matched those of the colon tumor. The colon tumor was diagnosed as metastasis from gastric cancer., Conclusion: We reported two patients with multiple tumors in which a somatic mutation comparison using NGS was useful for the diagnosis of a metastatic tumor., (© 2022. The Author(s).)

Background: Gastric cancer surgery for obese patients is regarded as a technically challenging procedure. The morbidity after gastrectomy has been reported to be significantly higher in patients with high visceral fat area (VFA). Robotic gastrectomy (RG) is expected to be advantageous for complicated operations. However, whether RG is superior to conventional laparoscopic gastrectomy (LG) for patients with visceral fat obesity remains unclear. The present study aimed to clarify the impact of RG on the short- and long-term outcomes of patients with high VFAs., Methods: This study included 1306 patients with clinical stage I/II gastric cancer who underwent minimally invasive gastrectomy between January 2012 and December 2020. The patients were subclassified according to VFA. The short- and long-term outcomes of RG were compared with those of LG in two VFA categories., Results: This study included 394 (high-VFA, 151; low-VFA, 243) and 882 patients (high-VFA, 366; low-VFA, 516) in the RG and LG groups, respectively. RG was associated with a significantly longer operative time than LG (high-VFA, P < 0.001; low-VFA, P < 0.001). The incidence rates of overall and intra-abdominal infectious complications in the high-VFA patients were lower in the RG group than in the LG group (P = 0.019 and P = 0.048, respectively) but not significantly different from those in the low-VFA patients. In the multivariate analysis, LG was identified as the only independent risk factor of overall (odds ratio [OR] 3.281; P = 0.012) and intra-abdominal infectious complications (OR 3.462; P = 0.021) in the high-VFA patients. The overall survival of high-VFA patients was significantly better in the RG group than in the LG group (P = 0.045)., Conclusions: For patients with visceral fat obesity, RG appears to be advantageous to LG in terms of reducing the risk of complications and better long-term survival., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The robotic approach is especially promising for challenging surgeries, such as total gastrectomy. However, it remains unclear whether robotic total gastrectomy (RTG) is superior to conventional laparoscopic total gastrectomy (LTG). The present study aimed to clarify the impact of RTG on short- and long-term outcomes for patients with clinical stage I/IIA gastric cancer., Methods: This study included 98 patients with clinical stage I/IIA gastric cancer who underwent minimally invasive total gastrectomy from October 2013 to December 2020 at the Shizuoka Cancer Center. The short- and long-term outcomes of RTG were compared with those of LTG., Results: This study included 36 RTG and 58 LTG patients. RTG was associated with a significantly longer operative time than LTG (p = 0.023). All complications tended to be lower in the RTG group than in the LTG group (2.8% and 15.5%, respectively; p = 0.083). There were no patients with anastomotic leakage in the RTG group. The multivariate analysis identified LTG as the only independent risk factor for postoperative complications (odds ratio, 6.620; 95% confidence interval, 1.132-126.4; p = 0.034). The survival of the RTG and LTG groups was equivalent., Conclusions: RTG reduced the risk of complications compared to LTG. Patients treated using the two approaches showed equivalent survival., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: While paraaortic lymph node (PAN) dissection (PAND) has been found to be efficacious for patients with extensive lymph node metastasis (ELM) of locally advanced gastric cancer (LGC), the optimal indications for PAND remain to be elucidated. Thus, the prognostic factors among these patients were evaluated., Methods: A total of 35 patients with ELM of LGC who underwent gastrectomy with D2 and PAND between August 2008 and December 2019 were included and evaluated for long-term outcomes and prognostic factors., Results: Preoperative chemotherapy was administered to 33 patients [neoadjuvant chemotherapy (NAC), n = 26; palliative chemotherapy followed by conversion surgery, n = 7], none of whom suffered surgical mortality. The pathological analysis identified PAN metastasis in 11 patients (31.4%). The 5-year overall and relapse-free survival (RFS) survival were 66.4% and 52.6%, respectively. Locoregional recurrence was found in one patient. The multivariate analysis revealed that NAC (P = 0.011) and < 3 metastatic PANs on preoperative imaging (P = 0.017) were independently associated with RFS., Conclusion: D2 and PAND after NAC can be a promising approach for patients with ELM of LGC. In particular, patients with a limited number of metastatic PANs can be considered good candidates for PAND., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: Esophagogastroduodenoscopy (EGD) may contribute to early detection of secondary cancer in the upper gastrointestinal tract although the clinical relevance of follow-up after gastrectomy remains unclear. This study aimed to elucidate the effectiveness of follow-up EGD by investigating the incidence of secondary cancer in any part of the upper gastrointestinal tract., Methods: Data from 1438 patients who underwent curative partial gastrectomy for primary gastric cancer between 2008 and 2014 and follow-up EGD at least once during a 5-year follow-up period were retrospectively reviewed. Incidence rates of remnant gastric cancer, laryngeal cancer, and esophageal cancer detected after follow-up EGD were determined, and risk factors for secondary cancers were examined. The characteristics of clinicopathological diagnoses of secondary cancers were reviewed and compared according to the frequency of follow-up EGD., Results: The average annual frequency of EGD was 0.7, while the 5-year cumulative incidence rates of remnant gastric cancer and secondary laryngeal and esophageal cancers were 2.9% and 1.3%, respectively. Risk factors for remnant gastric cancer included heavy smoking, proximal gastrectomy, and tumor size ≥ 30 mm. All secondary cancers were resectable upon diagnosis, with endoscopically resectable cancer accounting for 81.0% of cases. Our results found a significantly higher proportion of endoscopically resectable cancers during regular follow-up than during infrequent follow-up., Conclusions: Follow-up EGD can be a useful modality for detecting secondary upper gastrointestinal tract cancer, likely leading to curative treatment for secondary cancer. Focusing on patients presenting with risk factors may increase the value of follow-up EGD after gastrectomy., (© 2022 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterology.)

Background: Gastric cancer (GC) has been classified based on molecular profiling like The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG), and attempts have been made to establish therapeutic strategies based on these classifications. However, it is difficult to predict the survival according to these classifications especially in radically resected patients. We aimed to establish a new molecular classification of GC which predicts the survival in patients undergoing radical gastrectomy., Methods: The present study included 499 Japanese patients with advanced GC undergoing radical (R0/R1) gastrectomy. Whole-exome sequencing, panel sequencing, and gene expression profiling were conducted (High-tech Omics-based Patient Evaluation [Project HOPE]). We classified patients according to TCGA and ACRG subtypes, and evaluated the clinicopathologic features and survival. Then, we attempted to classify patients according to their molecular profiles associated with biological features and survival (HOPE classification)., Results: TCGA and ACRG classifications failed to predict the survival. In HOPE classification, hypermutated (HMT) tumors were selected first as a distinctive feature, and T-cell-inflamed expression signature-high (TCI) tumors were then extracted. Finally, the remaining tumors were divided by the epithelial-mesenchymal transition (EMT) expression signature. HOPE classification significantly predicted the disease-specific and overall survival (p < 0.001 and 0.020, respectively). HMT + TCI showed the best survival, while EMT-high showed the worst survival. The HOPE classification was successfully validated in the TCGA cohort., Conclusions: We established a new molecular classification of gastric cancer that predicts the survival in patients undergoing radical surgery., (© 2021. The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Background: Phase III trials have shown the non-inferiority of minimally invasive distal gastrectomy (MIDG) comparison with open distal gastrectomy (ODG) in patients with gastric cancer; however, it remains unclear whether MIDG is also effective in the elderly. This study aimed to clarify the efficacy of MIDG in elderly gastric cancer patients., Patients and Methods: This study included 316 patients older than 75 years with clinical stage I/IIA gastric cancer who underwent distal gastrectomy from August 2008 to December 2016 at the Shizuoka Cancer Centre. The long-term outcomes between MIDG and ODG were compared after propensity score matching., Results: After propensity score matching, there were 97 patients each in the MIDG and ODG groups, with an improved balance of confounding factors between the two groups. MIDG was associated with significantly longer operative time and a lower level of blood loss than ODG. The incidence of complications was comparable between the two groups. Survival outcomes were better in the MIDG group than in the ODG group (overall survival; P = 0.034, relapse-free survival; P = 0.027). In the multivariable analysis, ODG [hazard ratio (HR) 1.971, P = 0.046], being 80 years or older (HR 2.285, P = 0.018), male sex (HR 2.428, 95% P = 0.024), and poor physical status (HR 2.324, P = 0.022) were identified as independent prognostic factors for overall survival., Conclusions: We found that MIDG showed better efficacy than ODG in elderly gastric cancer patients. MIDG is an acceptable option for elderly patients., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Background: Gallstones are known to occur quite frequently after gastrectomy. Most of the studies about postoperative cholelithiasis have focused on open gastrectomy, whereas laparoscopic gastrectomy has recently gained popularity as a type of minimally invasive surgery (MIS). Hence, the efficacy of MIS in preventing post-gastrectomy gallstone formation remains to be elucidated. This study aimed to evaluate the risk of gallstone formation after MIS for clinical stage I/IIA gastric cancer., Methods: A total of 1166 patients undergoing gastrectomy for clinical stage I/IIA gastric cancer between 2009 and 2016 were included in this study. Gallstones were detected on abdominal ultrasound and/or computed tomography. Multivariate logistic regression analysis was used to determine factors associated with postoperative gallstone formation., Results: Gallstone formation was observed in 174 patients (15%), of whom 22 (2%) experienced symptomatic cholelithiasis. In multivariate analysis, the following were identified as risk factors for post-gastrectomy gallstone formation: open approach with an odds ratio (OR) of 1.670 and a 95% confidence interval (CI) of 1.110-2.510 (P = 0.014), older age (OR 1.880; 95% CI 1.290-2.730; P < 0.001), high body mass index (OR 1.660; 95% CI 1.140-2.420; P = 0.008), Roux-en-Y (RY) reconstruction (OR 1.770; 95% CI 1.230-2.530; P = 0.002), hepatic branch vagotomy (OR 1.600; 95% CI 1.050-2.440; P = 0.029), and intra-abdominal infectious complications (OR 3.040; 95% CI 1.680-5.490; P < 0.001)., Conclusion: Our study suggested that MIS along with the preservation of the hepatic vagus nerve and non-RY reconstruction could help prevent post-gastrectomy gallstone development., (© 2021. Société Internationale de Chirurgie.)

Introduction: The outcomes of robotic gastrectomy (RG) for gastric cancer remain unclear due to a lack of prospective studies. We had previously designed and conducted a prospective phase II study of RG that showed favorable short-term outcomes. Herein, we aimed to determine the long-term outcomes of RG for clinical stage I gastric cancer., Patients and Methods: This single-center, prospective phase II study enrolled patients with clinical stage I gastric cancer undergoing RG. The survival outcomes, which were the secondary endpoints of the study, were evaluated., Results: Between December 2012 and April 2015, 120 patients were enrolled in this study. The 5-year overall survival (OS) was 96.7% (95% confidence interval [CI] 91.5-98.7%). The 5-year recurrence-free (RFS) and disease-specific survival (DSS) rates were 96.7% (95% CI 91.5-98.7%) and 99.2% (95% CI 94.3-99.9%), respectively. When confining the analysis to distal and pylorus-preserving gastrectomy, the 5-year OS, RFS, and DSS were 98.1% (95% CI 92.7-99.5%), 98.1% (95% CI 92.7-99.5%), and 100%, respectively. Only one patient died due to relapse of gastric cancer, while three died from other causes., Conclusions: Long-term outcomes of RG was comparable to those of open and laparoscopic gastrectomy when the surgeries were performed by experienced surgeons in a high-volume center.

Introduction: The current study aimed to evaluate the ability of a modified version of the age-adjusted Charlson Comorbidity Index (mACCI) in predicting cause-specific survival (CSS) among patients with gastric cancer who underwent curative gastrectomy and compared it with the conventional ACCI., Materials and Methods: Patients who underwent gastrectomy for gastric cancer from 2007 to 2016 (n = 2885) were included. A mACCI was established by excluding scores for other malignancies, such as other cancers, leukemia, and lymphoma. After determining the optimal cutoff ACCI and mACCI values for CSS, clinicopathological factors and survival outcomes were assessed according to the ACCI and mACCI., Results: Both ACCI and mACCI were identified as independent prognostic factors for overall survival (p < 0.001 and p < 0.001, respectively). However, only mACCI was identified as an independent prognostic factor for CSS (p < 0.001). The present study suggested that mACCI was a better indicator of CSS in patients with gastric cancer who underwent curative gastrectomy than ACCI., Conclusion: Our findings showed that the mACCI was a strong predictor of CSS in patients with gastric cancer who underwent curative gastrectomy. We believe that the mACCI will become a novel marker that would guide treatment decisions for patients with gastric cancer suffering from comorbidities., Competing Interests: Declaration of competing interest MT received research grants from Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan, Ono Pharmaceutical Co., Ltd., Bristol Myers Squib Japan, and Yakult Honsha Co., Ltd. EB has received research grants from EIZO Corporation, Kanehara-Shuppan, Terumo Corporation, and EIZAI., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Aim: Pancreas compression during minimally invasive gastrectomy causes blunt injury to the pancreas and leads to postoperative complications. However, the extent of practical compression associated with the incidence of postoperative complications remains unknown. This study aimed to evaluate the impact of pancreas compression, particularly the duration of compression, on short-term outcomes in minimally invasive gastrectomy for gastric cancer., Methods: This study included 178 patients who underwent laparoscopic or robotic gastrectomy at the Shizuoka Cancer Center in 2018. The total time of pancreas compression during gastrectomy was measured using video-reviews, and the correlation between the time and surgical outcomes was evaluated., Results: A duration of 3 min was selected as the cutoff value of pancreas compression time to predict high drain amylase concentration on postoperative day 1 (≥1000 U/L). The incidence of clinically relevant pancreatic fistula (1.5% vs 12.4%, P  = .011) and all postoperative complications (12.3% vs 30.1%, P  = .010) were significantly higher in the longer-compression group than in the shorter-compression group. The multivariable analysis identified longer compression as the only independent risk factor for postoperative complications., Conclusion: More than a few minutes of pancreas compression during minimally invasive gastrectomy was associated with a higher incidence of postoperative complications., Competing Interests: Funding: The authors declare that no external funding was received for this study. Conflict of Interest: The authors declare no Conflicts of Interest for this article. Author contributions: The authors meet all the criteria of the International Committee of Medical Journal Editors (ICMJE). Ethical statement: The protocol for this research project was approved by a suitably constituted Ethics Committee of the institution and it conforms to the provisions of the Declaration of Helsinki. Institutional Review Board of the Shizuoka Cancer Center, Approval No. J2019‐173. Informed consent was substituted by the informed opt‐out procedure because of the retrospective nature of the study, and anonymous clinical data were used for the analysis., (© 2021 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterology.)

Background: Robotic gastrectomy (RG) has been developed to address the drawbacks of laparoscopic gastrectomy (LG); however, whether or not RG is superior to conventional LG remains to be seen. The present study aimed to clarify the impact of RG on clinical stage I/II gastric cancer patients., Methods: The present study included 1208 patients with clinical stage I/II gastric cancer who had minimally invasive gastrectomy from January 2012 to March 2020 at the Shizuoka Cancer Center. The short- and long-term outcomes of RG and LG were compared after propensity score matching., Results: This study involved 835 LG and 345 RG patients. After propensity score matching, there were 342 patients each in the RG and LG groups, with an improved balance of confounding factors between the two groups. RG was associated with a significantly longer operative time and lower amylase concentration in the drainage fluid on the first postoperative day than LG. Furthermore, the incidence of intra-abdominal infectious complications in the RG was lower than that in the LG (4.4% vs. 9.4%; P = 0.015). The survival of the RG and LG groups was equivalent., Conclusions: RG reduced the risk of intra-abdominal infectious complications in comparison with LG in the propensity score-matched analysis. Patients treated by the two approaches showed equivalent survival.

Introduction: Extra-nodal metastasis (ENM) is defined as a tumor nodule without histological evidence of a lymph node structure. Although ENM has pathological features distinct from those of metastatic lymph nodes, both ENM and metastatic lymph nodes are considered within the same category in the pathological nodal (pN) classification. This study aimed to clarify the clinicopathological characteristics and prognostic relevance of ENM in gastric cancer patients who underwent curative gastrectomy., Materials and Methods: We retrospectively evaluated 1207 Japanese patients who underwent curative gastrectomy at a single center between January 2009 and December 2013. All resected specimens were fixed in 10% formalin, processed, and stained using hematoxylin and eosin, and subsequently reviewed by two pathologists. Survival times were analyzed using the Kaplan-Meier method, and independent prognostic factors were identified using a Cox proportional hazards regression model., Results: Patients who were ENM-positive had significantly poorer overall survival; multivariable analysis revealed that independent prognostic factors were older age (hazard ratio [HR]: 3.68, 95% confidence interval [CI]: 2.60-5.20), higher pathological tumor classification (HR: 2.28, 95% CI: 1.43-3.62), presence of metastatic lymph nodes (HR: 1.57, 95% CI: 1.0-2.36), and ENM-positive status (HR: 2.33, 95% CI: 1.48-3.66). ENM-positive patients had similar survival outcomes to those of ENM-negative patients with ≥16 metastatic lymph nodes., Conclusions: Among Japanese patients with gastric cancer who underwent curative gastrectomy, ENM was an independent prognostic factor with a prognostic significance different from that of lymph node metastasis. These results suggest that ENM and lymph node metastasis should be classified separately., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Resection for hepatic recurrence after gastrectomy in patients with gastric cancer may be curative; however, the prediction of hepatic recurrence remains intractable. Therefore, we aimed to explore predictive markers for hepatic recurrence in gastric and gastroesophageal junction cancer based on genetic information., Methods: This study recruited 154 patients who underwent curative gastrectomy for pathological stage II or III primary gastric and gastroesophageal junction adenocarcinoma. Genes associated with hepatic recurrence were comprehensively analyzed using whole-exome sequencing and gene expression profiling (GEP), followed by immunohistochemistry analysis for MAGEA10. The cumulative incidences of hepatic recurrence, relapse-free survival, and overall survival were evaluated., Results: A total of 12 patients with early hepatic recurrences were found within 2 years of surgery. Although there were no distinct gene mutations in recurrent patients, upregulation of MAGEA10 was identified in patients with early hepatic recurrence using GEP analysis. Immunostaining for MAGEA10 stained the cell nuclei in 29 (18.8%) of 154 samples. Furthermore, protein expression of MAGEA10 on immunohistochemistry was significantly related to a high MAGEA10 mRNA expression, high cumulative incidences of hepatic recurrence, and poor relapse-free survival. Overall survival did not differ significantly between positive and negative immunohistochemical staining for MAGEA10. The sensitivity and specificity of MAGEA10 staining for early hepatic recurrence were 58.3% and 84.5%, respectively., Conclusions: MAGEA10 represents a promising predictive marker for early hepatic recurrence after curative gastrectomy for gastric and gastroesophageal junction cancer.

Background: Postoperative intra-abdominal infectious complication (PIIC) after gastrectomy for gastric cancer worsens in-hospital death or long-term survival. However, the methodology for PIIC preoperative risk assessment remains unestablished. We aimed to develop a preoperative risk model for postgastrectomy PIIC., Methods: We collected 183,936 patients' data on distal or total gastrectomy performed in 2013-2016 for gastric cancer from the Japanese National Clinical Database and divided into development (2013-2015; n = 140,558) and validation (2016; n = 43,378) cohort. The primary outcome was the incidence of PIIC. The risk model for PIIC was developed using 18 preoperative factors: age, sex, body mass index, activities of daily living, 12 comorbidity types, gastric cancer stage, and surgical procedure in the development cohort. Secondarily, we developed another model based on the new scoring system for clinical use using selected factors., Results: The overall incidence of PIIC was 4.7%, including 2.6%, 1.7%, and 1.3% in anastomotic leakage, pancreatic fistula, and intra-abdominal abscess, respectively. Among the 18 preoperative factors, male [odds ratio, (OR) 1.92], obesity (OR, 1.52-1.96), peripheral vascular disease (OR, 1.55), steroid use (OR, 1.83), and total gastrectomy (OR, 1.89) strongly correlated with PIIC incidence. The entire model using the 18 factors had good discrimination and calibration in the validation cohort. We selected eight relevant factors to create a simple scoring system, using which we categorized the patients into three risk groups, which showed good calibration., Conclusion: Using nationwide clinical practice data, we created a preoperative risk model for postgastrectomy PIIC for gastric cancer.

Background: Pylorus-preserving gastrectomy (PPG) has the postoperative advantages of a better quality of life and less weight loss than distal gastrectomy. However, postoperative delayed gastric emptying (DGE) due to antral hypomotility can be a problem. Although preserving the infra-pyloric vein (IPV) is reported to improve congestion of the antrum and prevent DGE, the benefits of this procedure have not been confirmed. The present study aimed to clarify the preventive effect on DGE of preserving the IPV., Methods: A total of 148 patients [IPV-preserved (IPVP): 78 patients and IPV-non-preserved (IPVN): 70 patients] who underwent laparoscopic and robotic PPG (LRPPG) for early gastric cancer were enrolled in this study. The clinicopathologic characteristics and incidence of DGE were compared between the groups. The nutritional risk index (NRI) at 1, 2, and 3 years after the operation and the relapse-free survival (RFS) were also compared., Results: There were no significant differences in the clinicopathological characteristics between the two groups. DGE was observed in 15 of 148 patients (10.1%). The incidence of DGE did not differ markedly between the 2 groups (IPVP vs. IPVN; 11.5% vs. 8.6% p = 0.596). There were no significant differences in other complications between the groups either (IPVP vs. IPVN; 19.2% vs. 21.4%; p = 0.838). The NRI and 3-year RFS were not significantly different between the two groups., Conclusion: Regarding LRPPG, preserving the IPV did not help prevent DGE and resulted in no significant difference in the outcomes.

Background: Studies to identify predictive biomarkers of adjuvant chemotherapy with S-1 after gastrectomy in Stage II/III gastric cancer patients have been done; however, more clarity and understanding are needed. Our aim in the present study was to identify biomarkers predicting benefit due to S-1 adjuvant chemotherapy using comprehensive gene expression analysis., Methods: We retrospectively analyzed 102 patients receiving adjuvant chemotherapy with S-1 and 46 patients not receiving S-1 adjuvant chemotherapy after gastrectomy for gastric cancer treatment between January 2014 and December 2016. Hierarchical clustering analysis was performed based on the gene expression data obtained using cDNA microarray. Differentially expressed genes (DEGs) were identified using thresholds of absolute fold changes of > 4.0 and a false discovery rate P value of < 0.01. Gene Ontology (GO) analysis and GO network visualization were performed using the ClueGO app in Cytoscape., Results: Hierarchical clustering analysis in patients treated with S-1 adjuvant chemotherapy revealed two clusters with favorable and unfavorable survival outcomes. We identified 147 upregulated DEGs and 192 downregulated DEGs in the favorable outcome group. GO analysis to identify significantly upregulated genes showed enrichment in immune-related genes and GO terms. Upregulation of these immune-related genes was not associated with survival in patients not receiving S-1 adjuvant chemotherapy., Conclusions: The upregulation and enrichment of immune-related genes and GO terms may be predictive biomarkers in patients who would benefit from adjuvant S-1 chemotherapy to treat Stage II/III gastric cancer.

Introduction: Recent reports on gene expression profiling (GEP) show several genes associated with malignant progression of GIST. However, genes associated with malignant transformation have not been clarified. Here, we aimed to reveal distinct genes in aggressive malignant GIST, using comprehensive gene expression analysis., Materials and Methods: We investigated GEP obtained by microarrays for 43 gastric GISTs, which mostly harbored KIT and PDGFRA mutations and integrated clinicopathological risk information. RT-PCR and immunohistochemistry were performed for FZD7, a receptor of Wnt ligands., Results: GEP divided 43 gastric GISTs into two clusters. A cluster included seven of eight high-risk GISTs (88%) in modified NIH classification and was defined as high-risk cluster; the other cluster was defined as low-risk cluster. The number of probes with over 3-fold changes between the two clusters was 1,177, in which probes corresponding to 16 oncogenes were included. Genes involved in the Wnt signaling pathway were the most abundant among the 16 oncogenes. Focusing on 73 Wnt signaling pathway genes of the 21,578 probes, 12 upregulated and 5 downregulated genes were found in the high-risk cluster. Major cascade genes promoting the Wnt/β-catenin signaling pathway, including WNT11, FZD family, and DVL2, were upregulated in the high-risk cluster. SNAI1, SNAI2, and BIRC5, which are activated by this pathway and increase cell proliferation, were also upregulated. These gene expression alterations were consistent in the positive direction of this pathway. GISTs in high-risk cluster strongly expressed FZD7., Conclusion: Wnt/β-catenin signaling pathway may play an important role in malignant transformation of indolent GIST., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Mutually exclusive KIT and PDGFRA mutations are considered to be the earliest events in gastrointestinal stromal tumors (GIST), but insufficient for their malignant progression. Herein, we aimed to identify driver genes and signaling pathways relevant to GIST progression. We investigated genetic profiles of 707 driver genes, including mutations, gene fusions, copy number gain or loss, and gene expression for 65 clinical specimens of surgically dissected GIST, consisting of six metastatic tumors and 59 primary tumors from stomach, small intestine, rectum, and esophagus. Genetic alterations included oncogenic mutations and amplification-dependent expression enhancement for oncogenes (OG), and loss of heterozygosity (LOH) and expression reduction for tumor suppressor genes (TSG). We assigned activated OG and inactivated TSG to 27 signaling pathways, the activation of which was compared between malignant GIST (metastasis and high-risk GIST) and less malignant GIST (low- and very low-risk GIST). Integrative molecular profiling indicated that a greater incidence of genetic alterations of driver genes was detected in malignant GIST (96%, 22 of 23) than in less malignant GIST (73%, 24 of 33). Malignant GIST samples groups showed mutations, LOH, and aberrant expression dominantly in driver genes associated with signaling pathways of PI3K (PIK3CA, AKT1, and PTEN) and the cell cycle (RB1, CDK4, and CDKN1B). Additionally, we identified potential PI3K-related genes, the expression of which was upregulated (SNAI1 and TPX2) or downregulated (BANK1) in malignant GIST. Based on our observations, we propose that inhibition of PI3K pathway signals might potentially be an effective therapeutic strategy against malignant progression of GIST., (© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Patients with stage I gastric cancer tend to wait for surgery. Although the cancer may progress during such a delay, effects of wait time for surgery on survival remain inconsistent. Here, we evaluated the safety of surgical wait time on survival of patients with clinical stage I gastric cancer., Methods: The outcomes of 556 patients who underwent gastrectomy for clinical stage I gastric cancer between January 2007 and December 2011 were retrospectively evaluated. Patients were stratified into three groups based on wait time: short- (<61 days, n = 185), intermediate- (61-90 days, n = 218), and long-wait (91-180 days, n = 153) groups. Clinicopathological findings and survival were compared among the groups., Results: The median wait time was 72 days. Age and comorbidities differed among the groups, but clinical and pathological cancer stages did not. Overall survival was comparable; the 5-year overall survival was 90.2%, 93.6%, and 88.8% in the short-, intermediate-, and long-wait groups, respectively. Multivariate analysis revealed that wait time was not an independent prognostic factor for overall survival. Adjusted hazard ratios (HRs) were 0.69 (p = 0.262) and 1.03 (p = 0.926) in the intermediate- and long-wait groups, respectively, with short wait time as the reference. Relapse-free survival was comparable among the groups (intermediate-wait HR = 0.80, p = 0.476; long-wait HR = 1.10, p = 0.740)., Conclusion: A half-year wait time for surgery was not independently associated with survival of patients with clinical stage I gastric cancer and may therefore be acceptable., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Preoperative wait time is affected by various factors, and a certain time is needed before surgery. There is a concern that cancer treatment delay can lead to poor survival. The present study aimed to evaluate the impact of preoperative wait time on survival in patients with clinical stage (cStage) II/III gastric cancer., Methods: The study included patients with cStage II/III primary gastric cancer undergoing surgery between 2002 and 2012. Preoperative wait time was defined as the time from endoscopy for initial diagnosis to surgery. Patients were divided into the following three groups according to wait time: short wait group (≤ 30 days), intermediate wait group (> 30 and ≤ 60 days), and long wait group (> 60 and ≤ 90 days). Patient characteristics and survival were compared among the groups., Results: This study included 467 male (67%) and 229 female (33%) patients, and the median patient age was 67 years. The numbers of cStage II and III patients were 332 (48%) and 364 (52%), respectively. The median wait time was 45 days. The body mass index was lower in the short wait group than in the other groups. A shorter wait time tended to be associated with a more advanced cStage. Although survival was significantly worse in the short wait group than in the long wait group, wait time was not identified as an independent prognostic factor in multivariate analysis., Conclusion: Preoperative wait time up to 90 days does not affect survival in patients with cStage II/III gastric cancer.

Robotic surgery using da Vinci®Surgical System which has the high resolution 3-dimensional images, the forceps with 7 degrees freedom, the function for prevention of tremors and motion scaling enables to perform meticulous operation circumventing the action of forceps movement which is the major problem in conventional laparoscopic surgery. In 2003, initial robotic gastrectomy for gastric cancer has been reported. Since then robotic gastrectomy has been developed mainly in Japan, Korea and Italy. From January 2012, we launched robotic gastrectomy at our institute as prospective clinical phase II trials to clarify the safety of robotic gastrectomy. The results of these trials have already been published and the safety of robotic gastrectomy was confirmed. In the several retrospective analyses, robotic gastrectomy has been reported to show longer operation time, less blood loss and lower morbidity compared with conventional laparoscopic surgery. However, the superiority of robotic gastrectomy to laparoscopic gastrectomy has not yet been demonstrated in terms of short- and long-term outcomes in a randomized controlled trial. Since robotic gastrectomy has been approved in Japanese health insurance system at April 2018, it is expected to rapidly expand throughout the country in the near future. Therefore, it is urgent matter to establish an evidence and educational program. In this article, the current status and future perspective about robotic surgery for gastric cancer are presented.

Purpose: The incidence of postoperative delirium is reported to range from 9 to 87%; however, no report has focused on cases of postoperative delirium in gastric cancer surgery alone. Therefore, we investigated the incidence of and risk factors for postoperative delirium after gastrectomy in patients with gastric cancer., Methods: A total of 1037 patients who underwent surgery were included in the study. Patients were divided into two groups-those with (delirium group) or without (non-delirium group) postoperative delirium-and their backgrounds were compared. The short-term outcomes and the overall survival were also investigated., Results: Postoperative delirium was observed in 47 of 1037 patients (4.5%). A multivariate analysis revealed that male gender, age ≥ 75 years, a history of cerebrovascular disease, and the habitual use of sleeping pills were independent predictive factors for postoperative delirium. The postoperative hospital stay was significantly longer in the postoperative delirium group than in the non-delirium group. Postoperative delirium was significantly associated with postoperative complications. The 3-year overall survival was 74.3% in the delirium group and 85.5% in the non-delirium group (log-rank p = 0.006). A multivariate analysis revealed that postoperative delirium was an independent prognostic factor, along with the age and cancer stage., Conclusion: The incidence of postoperative delirium was 4.5% in gastric cancer patients. Male gender, age ≥ 75 years, a history of cerebrovascular disease, and the habitual use of narcoleptic agents were risk factors for postoperative delirium after gastrectomy in gastric cancer patients. Postoperative delirium was strongly associated with other postoperative complications and a poor survival after surgery.

Background: Randomized controlled trials, including the Japan Clinical Oncology Group (JCOG) 0912 trial, have shown the safety of laparoscopy-assisted distal gastrectomy (LADG) for select healthy patients. It is unclear whether LADG is feasible in patients who do not meet trial eligibility criteria., Methods: The present study retrospectively reviewed 547 patients with clinical stage I gastric cancer who underwent distal or pylorus-preserving gastrectomy. Of these, 185 were identified as not fulfilling the eligibility criteria of JCOG 0912; the short-term surgical outcomes between LADG and open distal gastrectomy (ODG) were compared in this group before and after propensity score matching., Results: Patients who were not eligible for inclusion in the trial comprised 33.8% of the total. After matching, there were 59 patients each in the LADG and ODG groups, with an improved balance of confounding factors between the two groups. LADG was associated with significantly longer operation time, less blood loss, and shorter postoperative hospital stay than ODG. The rate of overall postoperative complications of Clavien-Dindo Grade II or higher did not differ significantly between the LADG and ODG groups (23.7 vs. 18.6%, respectively; p = 0.653). The incidence of pneumonia (6.8 vs. 5.1%), intra-abdominal infectious complications (5.1 vs. 3.4%), and stasis syndrome (5.1 vs. 3.4%) was also comparable between the two groups., Conclusion: LADG was as safe as ODG in patients who did not meet the eligibility criteria of JCOG 0912. LADG could be a standard treatment option for patients with stage I gastric cancer, regardless of their general condition.

Background: Preoperative malnutrition can worsen morbidity and mortality; however, the role of postgastrectomy nutritional status remains unclear. Our purpose was to clarify whether malnutrition after gastrectomy could predict long-term survival., Methods: Patients with pathological stage I, II, and III gastric cancer who underwent gastrectomy between 2002 and 2013 were included. The nutrition risk index (NRI) was evaluated before and at 1, 3, 6 and 12 months after gastrectomy. The patients were divided into normal (NRI > 97.5) or malnutrition (NRI ≤ 97.5) groups, and we compared the correlations of clinicopathological characteristics, surgical treatment, and overall survival between the two groups., Results: Among the 760 participants, patients in the malnutrition group were significantly older and had higher incidences of comorbidity and advanced cancer than the patients in the normal group. Multivariate analysis showed that overall survival was poorer in the malnutrition group before gastrectomy [hazard ratio (HR) 1.68] and at 1 month (HR 1.77), 3 months (HR 2.18), 6 months (HR 1.81) and 12 months (HR 2.17) after gastrectomy (all p < 0.01). Malnutrition at 1 and 3 months after gastrectomy was significantly associated with poor cause-specific survival. Total gastrectomy, preoperative malnutrition, older age, and adjuvant chemotherapy were independent risk factors of postoperative malnutrition at 12 months postgastrectomy., Conclusions: Malnutrition before gastrectomy and at 1, 3, 6 and 12 months after gastrectomy significantly and adversely affects overall survival. Nutritional interventions to lessen the impact of postoperative malnutrition offer hope for prolonged survival.

Background: The standard treatment for clinical submucosal invasive (cT1b) early gastric cancer is gastrectomy. However, Japanese gastric cancer treatment guidelines list endoscopic submucosal dissection (ESD) as an option for treating limited early gastric cancer cases. ESD can be curative depending on the pathological characteristics of resected specimens. Thus, we aimed to clarify the benefits and disadvantages of preceding ESD for early gastric cancer., Methods: We retrospectively analyzed patients who underwent ESD or curative gastrectomy for cT1b gastric cancer with differentiated adenocarcinoma 30 mm or less in diameter. Patients who underwent ESD irrespective of undergoing gastrectomy were assigned to the ESD group (n = 107), and those who underwent gastrectomy without undergoing ESD were assigned to the non-ESD group (n = 181). Clinicopathological characteristics were assessed, and the short-term and long-term outcomes of patients were compared., Results: The criteria for curative resection were satisfied by 83 patients (28.8%), and preceding ESD did not affect the surgical outcomes of gastrectomy. Two patients (1.9%) who underwent ESD had an unscheduled total gastrectomy. The en bloc and complete resection rates of ESD were 99.0% and 84.1% respectively. Nine patients (8.4%) experienced intraprocedure perforation and postprocedure bleeding caused by ESD. Overall survival (hazard ratio 1.38; P = 0.302) and cause-specific survival (hazard ratio 0.96; P = 0.944) were comparable between groups., Conclusions: The stomach was preserved in 28.8% of patients, and preceding ESD did not show obvious disadvantages. Therefore, diagnostic ESD should be considered as an initial treatment for limited cT1b gastric cancer cases.

Background: Amputation neuromas (ANs) are reactive hyperplasia of nerve tissues that occur after a trauma or surgery involving the peripheral nerves. Only two previous reports of ANs occurring around the stomach and post gastrectomy have been reported. We report the case of a patient with AN near the remnant stomach who underwent distal gastrectomy for gastric cancer., Case Presentation: A 76-year-old man underwent distal gastrectomy, D1+ lymphadenectomy, and Billroth-I reconstruction for early gastric cancer in another hospital at 63 years of age. A regular gastrointestinal endoscopic follow-up examination after gastrectomy revealed an ulcerative lesion on the lesser curvature of the remnant stomach, which was diagnosed as remnant gastric cancer based on the histopathological examination. Then, he was transferred to our hospital. An upper gastrointestinal series and endoscopy revealed an 18-mm Type 0-IIc lesion on the lesser curvature of the remnant stomach with an estimated depth within the mucosa (T1a). An abdominal contrast-enhanced computed tomography (CT) failed to detect the primary lesion; however, a slightly enhanced 13 × 10-mm nodule was detected near the lesser curvature of the remnant stomach. An endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) of the nodule showed no cancer cell; thus, endoscopic submucosal dissection (ESD) for the remnant gastric cancer was performed. Histopathological examination revealed noncurative resection due to T1b2 and UL (+). We planned an additional surgical resection. Before the resection, CT was performed, which had a 3-month interval with a previous CT, showing an enlargement of the nodule to 16 × 12 mm. We diagnosed the nodule as a lymph node metastasis and performed resection of the remnant stomach, D2 lymphadenectomy, splenectomy, and Roux-en-Y reconstruction. The nodule was later diagnosed as AN based on the histopathological examination. There was no residual cancer in the resected specimen., Conclusions: We report AN mimicking lymph node metastasis near the remnant stomach of a patient with remnant gastric cancer. When nodules appear in the previous operative field, the possibility of ANs should be considered, although the incidence may be quite low.

Background: There is no evidence that strict follow-up using cross-sectional imaging after curative gastrectomy benefits survival; however, nonperitoneal recurrence detected early might be treated with additional surgery. The present study examined whether early detection of recurrence by imaging modalities could increase survival, particularly in patients with nonperitoneal recurrence., Methods: We retrospectively analyzed 218 patients with recurrent gastric cancer after curative gastrectomy performed from 2002 to 2014. The patients were divided into an asymptomatic group (n = 117) and a symptomatic group (n = 101), according to the presence of symptoms at the time of recurrence, to compare clinicopathological characteristics and long-term survival., Results: Peritoneal recurrence was less frequent in the asymptomatic group (22.2%) than in the symptomatic group (62.4%), the median time to recurrence was shorter (12.7 months vs 18.9 months; P < 0.001), and the median survival time after recurrence was longer (18.7 months vs 7.5 months; P < 0.001). In the asymptomatic group, 10 of 117 patients (8.5%) received additional curative surgery after recurrence. Median overall survival after gastrectomy was not significantly different between the groups (30.1 months for the asymptomatic group vs 30.0 months for the symptomatic group; P = 0.132); however, it was significantly longer among asymptomatic patients with nonperitoneal recurrence compared with symptomatic patients (35.9 months vs 24.0 months; P = 0.039)., Conclusions: The presence of symptoms at recurrence did not affect survival in patients with recurrent gastric cancer. However, detection of nonperitoneal recurrence before the appearance of symptoms may provide survival benefit. Therefore, regular follow-up, including use of imaging modalities, is recommended.