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Abstract In cancer genome analysis, identifying pathogenic alterations and assessing their effects on oncogenic processes is important. Although whole exome sequencing (WES) can effectively detect such changes, driver alterations could not be identified in 27.8% of the cases, according to a previous study. The objectives of the present study were to evaluate the utility of whole genome sequencing (WGS) and clarify its differences with WES in terms of driver alteration detection. For this purpose, WGS analysis was conducted on 177 driverless WES samples, selected from 5,480 fresh frozen samples derived from 5,140 Japanese patients with cancer. These samples were selected as primary tumor, both WES and transcriptome profiling were performed, estimated tumor content of ≥ 30%, and no driver alterations were identified by WES. WGS identified driver and likely driver alterations in 68.4 and 22.6% of the samples, respectively. The most frequent alteration type was oncogene amplification, followed by tumor suppressor gene deletion and small variants located outside the coding region. In the remaining 9.0% of samples, no such signals were identified; therefore, further investigations are required. The current study clearly demonstrated the role and utility of WGS in identifying genomic alterations that contribute to tumorigenesis.

Abstract Aim We conducted a multicenter study on classical laparoscopic and endoscopic cooperative surgery (LECS) and LECS‐related procedures to retrospectively clarify the safety, problems, and mid‐term outcomes of these methods after their coverage by the national health insurance. Methods A total of 201 patients who underwent classical LECS/LECS‐related procedures for gastric submucosal tumors (G‐SMTs) in 21 institutions affiliated with the Laparoscopy Endoscopy Cooperative Surgery Study Group from April 2014 to March 2016 were included. Data was retrospectively obtained from the patients' charts. Results The most common surgical procedure was classical LECS (155 patients, 77.1%), non‐exposed endoscopic wall inversion surgery (22 patients, 11.4%), a combination of laparoscopic and endoscopic approaches to neoplasia with non‐exposure technique (16 patients, 8%), and closed LECS (two patients, 1%). Only six (3%) patients underwent LECS with gastrostomy. The mean operative time and blood loss were 188.4 (70–462) minutes and 23.3 (0–793) g, respectively. Ten (5%) patients developed postoperative complications (Clavien–Dindo classification grade II or higher). Two patients needed reoperation due to postoperative bleeding or anastomotic leakage. All tumors were resected with negative margins. A total of 127 (63.2%) patients underwent follow‐up observations for over 36 months, one of whom had a recurrence of peritoneal dissemination and one had poor oral intake. Conclusion Classical LECS and LECS‐related procedures for G‐SMTs have favorable short/mid‐term outcomes.

Abstract 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.

Abstract Aim Postoperative small bowel obstruction (SBO) is one of the major complications that is mainly caused by postoperative adhesion. Recently, the antiadhesion membrane has become popular for postoperative SBO prevention. However, its efficacy is yet to be confirmed in the gastric cancer surgery field. Here, we conducted the supplemental analysis of the randomized controlled trial JCOG1001 to investigate the efficacy of the antiadhesion membrane on SBO prevention in patients with open gastrectomy for gastric cancer. Methods Of the 1204 patients enrolled in JCOG1001, 1200 patients were included. The development of SBO of Grade ≥ IIIa according to the Clavien–Dindo classification was recorded. Univariable and multivariable analyses were performed using the Fine and Gray model to determine the risk factors for SBO. Results Fifty‐one patients developed SBO (median follow‐up duration: 5.6 years). Total gastrectomy, combined resection, and blood loss significantly increased the risk for SBO development in the univariable analysis. Large amount of blood loss was independently associated with SBO development in the multivariable analysis (hazard ratio [HR], 3.089; 95% confidence interval [CI], 1.562–6.109, p = 0.0012). Antiadhesion membrane did not reduce the risk for SBO (HR, 1.299; 95% CI 0.683–2.470; p = 0.4246). In the patients belonging to subgroup analyses who received distal and total gastrectomy, the antiadhesion membrane was not associated with the incidence of SBO. Conclusions Antiadhesion membrane did not decrease SBO occurrence rate after open gastrectomy. Therefore, the use of antiadhesion membrane would not be effective for preventing SBO in gastric cancer surgery.

Abstract Treatment strategy for locally advanced gastric cancer differs worldwide. Neoadjuvant chemotherapy (NAC) is considered one of the promising treatment options for locally advanced gastric cancer, even in Japan, and clinical trials have been conducted or are ongoing. A consensus meeting was organized at the 77th general meeting of the Japanese Society of Gastroenterological Surgery in 2022, in which the current status and future prospects of NAC for locally advanced gastric cancer were discussed. Participants at the meeting looked forward to the results of the JCOG1509 trial, providing solid evidence regarding NAC. The optimal indications and regimens for NAC were also debated. Patients with cStage III gastric cancer are the main targets of NAC in Japan, and a doublet regimen of S‐1 and oxaliplatin was preferred by the participants. However, the feasibility of a triplet regimen with S‐1, oxaliplatin, and docetaxel, and that with 5‐FU, leucovorin, oxaliplatin, and docetaxel has been demonstrated, and these could become treatment options in Japan. Other points of discussion include perioperative chemotherapy to avoid peritoneal recurrence and for patients with dMMR/MSI‐high tumors. The panel regarded NAC as a promising treatment option, and NAC will become the standard treatment for cStage III gastric cancer in Japan if an ongoing clinical trial successfully demonstrates its efficacy.

Abstract Background Laparoscopic gastrectomy (LG) is considered a standard treatment for clinical stage I gastric cancer. Nevertheless, LG has some drawbacks, such as motion restriction and difficulties in spatial perception. Robot-assisted gastrectomy (RG) overcomes these drawbacks by using articulated forceps, tremor-filtering capability, and high-resolution three-dimensional imaging, and it is expected to enable more precise and safer procedures than LG for gastric cancer. However, robust evidence based on a large-scale randomized study is lacking. Methods We are performing a randomized controlled phase III study to investigate the superiority of RG over LG for clinical T1-2N0-2 gastric cancer in terms of safety. In total, 1,040 patients are planned to be enrolled from 46 Japanese institutions over 5 years. The primary endpoint is the incidence of postoperative intra-abdominal infectious complications, including anastomotic leakage, pancreatic fistula, and intra-abdominal abscess of Clavien–Dindo (CD) grade ≥ II. The secondary endpoints are the incidence of all CD grade ≥ II and ≥ IIIA postoperative complications, the incidence of CD grade ≥ IIIA postoperative intra-abdominal infectious complications, relapse-free survival, overall survival, the proportion of RG completion, the proportion of LG completion, the proportion of conversion to open surgery, the proportion of operation-related death, and short-term surgical outcomes. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in January 2020. Approval from the institutional review board was obtained before starting patient enrollment in each institution. Patient enrollment began in March 2020. We revised the protocol to expand the eligibility criteria to T1-4aN0-3 in July 2022 based on the results of randomized trials of LG demonstrating non-inferiority of LG to open surgery for survival outcomes in advanced gastric cancer. Discussion This is the first multicenter randomized controlled trial to confirm the superiority of RG over LG in terms of safety. This study will demonstrate whether RG is superior for gastric cancer. Trial registration The protocol of JCOG1907 was registered in the UMIN Clinical Trials Registry as UMIN000039825 ( http://www.umin.ac.jp/ctr/index.htm ). Date of Registration: March 16, 2020. Date of First Participant Enrollment: April 1, 2020.

Abstract Background REGATTA trial failed to demonstrate the survival benefit of reduction gastrectomy in patients with advanced gastric cancer with a single non‐curable factor. However, a significant interaction was found between the treatment effect and tumor location in the subset analysis. Additionally, the treatment effect appeared to be different between Japan and Korea. This supplementary analysis aimed to elucidate the effect of reduction surgery based on tumor location and country. Methods Multivariable Cox regression analyses in each subgroup were performed to estimate the hazard ratio (HRadj), including the following variables as explanatory variables: country, age, sex, incurable factor, cT, cN, primary tumor, performance status, histological type, and macroscopic type. Results Patients (95 in Japan and 80 in Korea) were randomized to chemotherapy alone (86 patients) or gastrectomy plus chemotherapy (89 patients). The subgroup analysis according to the country revealed a worse overall survival in gastrectomy plus chemotherapy arm in Japan (hazard ratio: 1.32, 95% confidence interval: 0.85–2.05), but not in Korea (hazard ratio: 0.85.95% confidence interval: 0.52–1.40). Overall survival was better in distal gastrectomy plus chemotherapy compared with chemotherapy alone (hazard ratio = 0.69, 95% confidence interval: 0.42–1.13), and worse in total gastrectomy plus chemotherapy compared with chemotherapy alone (hazard ratio = 1.34, 95% CI: 0.93–1.94), which was more remarkable in Korea than in Japan. Conclusions Primary chemotherapy is a standard of care for advanced gastric cancer; however, the survival benefits from reduction by distal gastrectomy remained controversial.

Abstract 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.

Abstract 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.

Abstract Aim Much attention has been paid to conversion therapy for stage IV gastric cancer, however, its operative comorbidities and survival benefit have not yet been clarified. CONVO‐GC‐1, an international retrospective cohort study, was designed to investigate the role of conversion surgery in Japan, Korea, and China. Methods The rate of operative complications was the primary endpoint and the overall survival (OS), according to the four‐category criteria previously published (Gastric Cancer:19; 2016), was analyzed as the secondary endpoint. Results A total of 1206 patients underwent surgery after chemotherapy with curative intent. Operative complications were observed in 290 (24.0%) patients in all grades, including pancreatic fistula and surgical site infection. The median survival time (MST) of all resected patients was 36.7 mo (M) and those of R0, R1, and R2 resection were 56.6 M, 25.8 M, and 21.7 M, respectively. Moreover, the MST of R0 patients were 47.8 M, 116.7 M, 44.8 M in categories 1, 2, and 3, respectively, and not reached in category 4. Interestingly, the MST of P1 patients was as favorable as that of P0CY1 patients if R0 resection was achieved. The MST of patients with liver metastasis was also favorable regardless of the number of lesions, and the MST of patients with para‐aortic lymph node (LN) No 16a1/b2 metastasis was not inferior to that of patients with para‐aortic LN No 16a2/b1 metastasis. Conclusion Conversion therapy for stage IV gastric cancer is safe and could be a new therapeutic strategy to improve the survival of patients, especially those with R0 resection.

Abstract 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.

Abstract Background In the JCOG1108/WJOG7312G trial, a combination (FLTAX) of 5‐fluorouracil (FU) /leucovorin (FL) and paclitaxel (PTX) did not show superiority in overall survival (OS) to FL in untreated patients with severe peritoneal metastasis of gastric cancer (GC‐SPM), some of whom received second‐line chemotherapy with PTX after FL. This post hoc study aimed to investigate the clinical implications of using both FU and PTX either sequentially or in combination for patients with GC‐SPM. Methods A total of 94 patients were enrolled and categorized into the following three subgroups: patients treated with (1) FL followed by PTX (FL/PTX, N = 25), (2) FL followed by best supportive care (BSC) (FL/BSC, N = 21), and (3) FLTAX (N = 48). OS was compared between the subgroups. By comparing baseline factors between the FL/PTX and FL/BSC subgroups, factors preventing the sequential use of PTX (SUP) were explored using logistic regression model. The efficacy of FL and FLTAX was compared according to the presence of risk factors preventing SUP. Results The FL/PTX subgroup showed better and equivalent OS compared to the FL/BSC (median 7.8 vs. 2.0 months, p

Abstract Background In several reports, gastric cancer nomograms for predicting overall or disease‐specific survival have been described. The American Joint Committee on Cancer (AJCC) introduced the attractiveness of disease‐specific mortality (DSM) as an endpoint of risk model. This study aimed to develop the first pretreatment gastric cancer nomogram for predicting DSM that considers competing risks (CRs). Methods The prediction model was developed using data for 5231 gastric cancer patients. Fifteen prognosticators, which were registered at diagnosis, were evaluated. The nomogram for DSM was created as visualizations of the multivariable Fine and Gray regression model. An independent cohort for external validation consisted of 389 gastric cancer patients from a different institution. The performance of the model was assessed by discrimination (Harrell's concordance (C)‐index), calibration, and decision curve analysis. DSM and CRs were evaluated, paying special attention to host‐related factors such as age and Eastern Cooperative Oncology Group performance status (ECOG PS), by using Gray's univariable method. Results Fourteen prognostic factors were selected to develop the nomogram. The new nomogram for DSM exhibited good discrimination. Its C‐index of 0.887 surpassed that of the American Joint Committee on Cancer (AJCC) clinical staging (0.794). The C‐index was 0.713 (AJCC, 0.582) for the external validation cohort. The nomogram showed good performance internally and externally, in the calibration and decision curve analysis. Host‐related factors including age and ECOG PS, were strongly correlated with competing risks. Conclusions The newly developed nomogram accurately predicts DSM, which can be used for patient counseling in clinical practice.

Abstract After the initial achievement by Billroth in 1881, surgery for gastric cancer has become increasingly extended. However, it turned out to be limited in Western countries after the publication that denied the role of extended surgery in the 1960s. While surgeons in Japan were still enthusiastic about extended surgery, the Japan Clinical Oncology Group (JCOG) conducted clinical trials to validate the role of extended surgery. Contrary to expectations, the efficacy of extended surgery was not demonstrated. In gastric cancer surgery, postoperative complications were reported to be associated with poor survival. A survival benefit could not be obtained by extended surgery, with high morbidity. Therefore, the paradigm had been changed from extended surgery to minimally invasive surgery (MIS). As an MIS for gastric cancer, laparoscopic surgery has been considered a practical method. Initial laparoscopic gastrectomy (LG) was first performed by Kitano in 1991. Thereafter, LG became increasingly common. Several clinical trials demonstrated the noninferiority of LG to open gastrectomy. LG is now regarded as the standard for cStage I gastric cancer, and the indication is expanding to advanced cancer. However, LG has some drawbacks owing to the restriction of movement caused by straight‐shaped forceps. Robotic gastrectomy (RG) is considered a major breakthrough to circumvent the drawbacks in LG using articulated devices. However, the solid evidence demonstrating the advantage of RG has not been proved yet. The JCOG is now conducting a randomized controlled trial to evaluate the superiority of RG to LG in terms of reducing morbidity.

Abstract Background Pretreatment clinical staging is essential to select therapy. However, there have been no published pretreatment gastric cancer nomograms constructed using pretreatment clinical prognostic factors, including in nonresection patients. We aimed to develop a new pretreatment gastric cancer nomogram for individualized prediction of overall survival (OS). Methods The nomogram was developed using data of 5231 Japanese gastric cancer patients, and it was created with a Cox regression model. Fifteen clinical variables, which were obtained at pretreatment, were collected and registered. Data of two independent cohorts of patients from Seoul St. Mary's Hospital (1001 patients), and the University of Verona (389 patients) formed the external validation cohorts. The model was validated internally and externally using measures of discrimination (Harrell's C‐index), calibration, and decision curve analysis. Results The developed nomogram showed good discrimination, with a C‐index of 0.855; that of the American Joint Committee on Cancer (AJCC) clinical stage was 0.819. In the external validation procedure, the C‐indexes were 0.856 (AJCC, 0.795) in the Seoul St. Mary's cohort and 0.714 (AJCC, 0.648) in the University of Verona cohort. The nomogram performed well in the calibration and decision curve analyses when applied to both the internal and external validation cohorts. A stage‐specific subset survival analysis of the three risk groups calculated using the nomogram also showed the superiority of nomogram‐prediction when compared to AJCC. Conclusion This new pretreatment model accurately predicts OS in gastric cancer and can be used for patient counseling in clinical practice and stratification in clinical trials.

Abstract Background Laparoscopic gastrectomy is regarded a standard treatment procedure for early gastric cancer and is widely used in clinical practice. However, the feasibility of laparoscopic gastrectomy for patients with a prior history of open surgery, especially in the case of a complicated operation, remains unclear. Here, we report a laparoscopic gastrectomy case with a prior history of right hepatectomy. Case presentation A 70-year-old man was diagnosed with early gastric cancers preceding a right hepatectomy for a solitary hepatocellular carcinoma at risk of rupture. An additional gastrectomy, after non-curative endoscopic submucosal dissection, was planned after the hepatectomy. Extensive adhesions were found around the liver. Rigid adherence of the duodenum to the adjacent hepatoduodenal ligament had formed. In addition, identification of the hepatic artery was difficult due to stiffening of the mesentery. Peeling off the adhesions from the ventral side of the duodenum revealed the supra-pyloric vessels and enabled us to transect the duodenum safely. Further, exposing the proper hepatic artery via the dorsal side of the mesentery and subsequent supra-pancreatic dissection on the outermost layer allowed effective identification of the right gastric artery. The postoperative course was uneventful. Conclusions We successfully performed total laparoscopic distal gastrectomy on a patient with a prior history of major hepatectomy.

Abstract 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.

Immunogenic neoantigens derived from somatic mutations in cancer have been identified through clinical studies with the cloning of tumor-infiltrating T cells, and cancer driver gene mutation-derived epitopes have been reported; however, these are rare. At present, the validation of epitopes predicted in silico is difficult as human T-cell clonal diversity cannot be reproduced in vitro or in experimental animal models. To confirm the epitope peptides presented by human leukocyte antigen (HLA) class I molecules predicted in silico, biochemical methods such as major histocompatibility complex (MHC) stabilization assays and mass spectrometry-mediated identification have been developed based on HLA-A*02:01 monoallelic T2 cells and HLA-C*01:02 monoallelic LCL721.221 cells. Therefore, in the present study, to prevent confusion due to peptide cross-presentation among HLA molecules, HLA class I monoallelic B-cell clones were generated from the TISI cell line by knocking out HLA-ABC and TAP2, and knocking in HLA alleles. To explore cancer driver mutations as potential targets for immunotherapy, exome sequencing data from 5,143 patients with cancer enrolled in a comprehensive genome analysis project at the Shizuoka Cancer Center were used to identify somatic amino acid substituted mutations and the 50 most frequent mutations in five genes, TP53, EGFR, PIK3CA, KRAS and BRAF, were identified. Using NetMHC4.1, the present study predicted whether epitopes derived from these mutations are presented on major HLA-ABC alleles in Japanese individuals and synthesized 138 peptides for MHC stabilization assays. The authors also attempted to examine the candidate epitopes at physiological temperatures by using antibody clone G46-2.6, which can detect HLA-ABC, independent of ß2-microglobulin association. In the assays, although the peptide-induced HLA expression levels were associated with the predicted affinities, the respective HLA alleles exhibited varying degrees of responsiveness, and unexpectedly, p53-mutant epitopes with predicted weak affinities exhibited strong responses. These results suggested that MHC stabilization assays using completely monoallelic HLA-expressing B-cell lines are useful for evaluating the presentation of neoantigen epitopes. [ABSTRACT FROM AUTHOR]

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

Objective: The aim of the study was to determine the optimal extent of lymph node dissection for the 2 histological types of esophagogastric junction (EGJ) tumors based on the incidence of metastasis in a prospective nationwide multicenter study. Background: Because most previous studies were retrospective, the optimal surgical procedure for EGJ tumors has not been standardized. Methods: Patients with cT2-T4 adenocarcinoma or squamous cell carcinoma located within 2.0 cm of the EGJ were enrolled before surgery. Surgeons dissected all lymph nodes prespecified in the protocol, using either the abdominal transhiatal or right transthoracic approach. The primary endpoint was the metastasis rate of each lymph node. Lymph nodes were classified according to metastasis rate, as follows: category-1 (strongly recommended for dissection), rate more than 10%; category-2 (weakly recommended for dissection), rate from 5% to 10%; and category-3 (not recommended for dissection), rate less than 5%. Results: Between 2014 and 2017, 1065 patients with EGJ tumor were screened, and 371 were enrolled. Among 358 patients who underwent surgical resection, category-1 nodes included abdominal stations 1, 2, 3, 7, 9, and 11p, whereas category-2 nodes included abdominal stations 8a, 19, and lower mediastinal station 110. If esophageal involvement exceeded 2.0 cm, station 110 was assigned to category-1. Among 98 patients who had either adenocarcinoma with esophageal involvement over 3.0 cm or squamous cell carcinoma, there were no category-1 nodes in the upper/middle mediastinal field, whereas category-2 nodes included upper mediastinal station 106recR and middle mediastinal station 108. When esophageal involvement exceeded 4.0 cm, station 106recR was assigned to category-1. Conclusion: The study accurately identified the distribution of lymph node metastases from EGJ tumors and the optimal extent of subsequent lymph node dissection. [ABSTRACT FROM AUTHOR]

Splenic hilar lymph node dissection has been the standard treatment for advanced proximal gastric cancer. Splenectomy is typically performed as part of this procedure. However, splenectomy has some disadvantages, such as increased risk of postoperative complications, especially pancreatic fistula. Moreover, patients who underwent splenectomy are vulnerable to potentially fatal infection caused by encapsulated bacteria. Furthermore, several studies have shown an association of splenectomy with cancer development and increased risk of thromboembolic events. Therefore, splenectomy should be avoided if it does not confer a distinct oncological advantage. Most studies that compared patients who underwent splenectomy and those who did not failed to demonstrate the efficacy of splenectomy. Based on the results of a randomized controlled trial conducted in Japan, prophylactic dissection with splenectomy is no longer recommended in patients with gastric cancer with no invasion of the greater curvature. However, patients with greater curvature invasion or those with remnant gastric cancer still need to undergo splenectomy to facilitate splenic hilar node dissection. Spleen-preserving splenic hilar node dissection is a new procedure that may help delink splenic hilar node dissection and splenectomy. In this review, we examine the evidence pertaining to the efficacy and disadvantages of splenectomy. We discuss the possibility of spleen-preserving surgery for prophylactic splenic hilar node dissection to overcome the disadvantages of splenectomy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Aging partly impairs swallowing function, which is considered a risk factor for postoperative pneumonia (PP). We evaluated the efficacy of a new team-based strategy to reduce the incidence of PP in elderly patients with gastric cancer. METHODS: This single-center, prospective phase II study included elderly patients (≥75 years old) with gastric cancer undergoing gastric surgery. The primary endpoint was the incidence of Clavien-Dindo grade II or higher PP. Patients were initially screened using three swallowing function screening tests: a symptom questionnaire, the modified water swallow test (MSWT), and the repetitive saliva swallowing test (RSST). All patients were provided standard preoperative oral checks and care and simple neck muscle training. For patients who screened positive, a videofluorographic swallowing study was performed; if an abnormality was found, the patient was given intensive swallowing rehabilitation both pre- and postoperatively. RESULTS: Of 86 eligible patients enrolled, PP developed in 3 (3.5%). The 60% confidence interval of 1.8-6.3% had an upper limit below the prespecified threshold of 7.8%. Positive screening results were found for 19 patients (22.1%) on the symptom questionnaire, 3 (3.5%) on the MSWT, and 1 (1.2%) on the RSST. PP was not observed in any patients who screened positive. CONCLUSION: In conclusion, although the screening tests we adopted here were not sufficient to identify patients at high risk of aspiration pneumonia, perioperative interventions using a team approach might be effective in reducing the incidence of PP in elderly patients with gastric cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND: Several studies have demonstrated the benefit of hepatectomy for treating gastric cancer (GC) with liver-limited metastases (LLM). The survival benefit of hepatectomy compared with that of systemic chemotherapy is unknown, particularly in patients with multiple LLM. This study investigated the survival benefit of hepatectomy compared with that of systemic chemotherapy administered to patients with GC with multiple LLM. METHODS: We retrospectively reviewed the data of consecutive patients with GC with two or three LLM who underwent hepatectomy or received systemic chemotherapy as initial treatment at the Shizuoka Cancer Center between December 2004 and December 2015. RESULTS: Nine of 24 patients who met the inclusion criteria underwent hepatectomy, and 15 received chemotherapy. In the hepatectomy group, all patients achieved R0 resection and none died during hospitalization. Three patients received adjuvant chemotherapy. Disease recurred in eight patients (88.9%). In the chemotherapy group, three patients underwent hepatectomy following initial chemotherapy and did not experience recurrence or death during follow-up. Median follow-up was 47.9 months and median overall survival (OS) was 38.1 and 24.8 months in the chemotherapy and hepatectomy groups, respectively. Multivariate analysis of OS, including initial treatment, revealed that unilobar liver metastasis was the only independent favorable prognostic factor. CONCLUSIONS: Although hepatectomy for patients with GC with multiple LLM is not recommended as the initial therapy, it prolonged the survival of patients with tumors controlled using systemic chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Complicated gastric lymphatic drainage potentially undermines the utility of sentinel node (SN) biopsy in patients with gastric cancer. Encouraged by several favorable single-institution reports, we conducted a multicenter, single-arm, phase II study of SN mapping that used a standardized dual tracer endoscopic injection technique., Patients and Methods: Patients with previously untreated cT1 or cT2 gastric adenocarcinomas < 4 cm in gross diameter were eligible for inclusion in this study. SN mapping was performed by using a standardized dual tracer endoscopic injection technique. Following biopsy of the identified SNs, mandatory comprehensive D2 or modified D2 gastrectomy was performed according to current Japanese Gastric Cancer Association guidelines., Results: Among 433 patients who gave preoperative consent, 397 were deemed eligible on the basis of surgical findings. SN biopsy was performed in all patients, and the SN detection rate was 97.5% (387 of 397). Of 57 patients with lymph node metastasis by conventional hematoxylin and eosin staining, 93% (53 of 57) had positive SNs, and the accuracy of nodal evaluation for metastasis was 99% (383 of 387). Only four false-negative SN biopsies were observed, and pathologic analysis revealed that three of those biopsies were pT2 or tumors > 4 cm. We observed no serious adverse effects related to endoscopic tracer injection or the SN mapping procedure., Conclusion: The endoscopic dual tracer method for SN biopsy was confirmed as safe and effective when applied to the superficial, relatively small gastric adenocarcinomas included in this study.