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Background/aim: The sex-specific effect of the visceral-to-subcutaneous fat ratio (VSR) before gastrectomy on postoperative survival in patients with gastric cancer (GC) remains unclear. This study measured the preoperative VSR in patients with GC and analyzed its relationship with 5-year overall survival (OS) and relapse-free survival (RFS) by sex., Patients and Methods: This prospective study included 540 patients with GC undergoing gastrectomy. Preoperative visceral and subcutaneous fat volumes were measured using computed tomography, and the VSR was calculated. A cutoff value for the VSR was established using 5-year survival data, and its association with survival was analyzed using the Kaplan-Meier method, log-rank tests, and multivariate regression analysis., Results: Among the 459 patients analyzed (300 males and 159 females), OS and RFS were significantly lower in the low-VSR group than in the high-VSR group in males (OS: 76.2% vs. 88.1%, p=0.01; RFS: 74.6% vs. 86.0%, p=0.02). In females, no difference in OS was observed between the groups, whereas the high-VSR group had significantly lower RFS than that of the low-VSR group (RFS: 74.7% vs. 88.9%, p=0.01). Multivariate analysis showed that a low VSR was an independent poor predictor of OS in males and a high VSR was an independent poor predictor of RFS in females., Conclusion: In patients with GC, the sex-dependent preoperative VSR was a potentially useful predictor of postoperative survival., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A 63-year-old woman came to our hospital complaining of anemia and weight loss. The abdominal CT showed wall thickening from the upper to lower the body of stomach, and peritoneal dissemination. The EGD revealed a type 3 large tumor extending about 2/3 of the circumference. Adenocarcinoma was detected as a result of biopsy. The patient was diagnosed with unresected gastric cancer(cT4aN+M1, cStage Ⅳ). SOX plus nivolumab was selected as a first-line chemotherapy because of HER2 expression negative. Symptoms such as diarrhea developed, and the treatment was completed until 5 courses. Laparoscopic distal gastrectomy was performed after the disappearance of abdominal dissemination by CT scan and PET. Pathological examination revealed cancer cells were completely disappeared in the tumor, regional lymph nodes and white nodules in the peritoneum, and final diagnosis was ypT0N0M0, ypStage 0(histological effect determination is Grade 3). Six months after the operation, the patient has been free of recurrence.

An 85-year-old female patient presented to the emergency department with the chief complaint of sudden upper abdominal pain. The patient suffered from anorexia and epigastric pain for a month, and a local physician suspected a diagnosis of gastric ulcer. An abdominal computed tomography(CT)scan showed intraperitoneal free air as well as irregular thickening and thinning of the gastric wall. Gastric ulcer perforation was suspected, and an emergency operation was performed. Surgical findings showed thickening of the gastric wall in the pylorus and gastric corpus but partial thinning of areas of the anterior wall of the gastric corpus with a perforation measuring 5 mm. A distal gastrectomy and reconstruction were performed using the Billroth Ⅱ method. The histopathological diagnosis was malignant gastric lymphoma(diffuse large B- cell lymphoma). Considering the patient's age and general condition, chemotherapy was not administered after surgery. The patient was alive without recurrence 8 months after the operation.

Background/aim: Ramucirumab plus paclitaxel has been widely used as a second-line chemotherapy for treating advanced gastric cancer. However, the real-world data of this regimen for older patients with gastric cancer (GC) remains unrevealed. The aim of this study was to clarify the feasibility and efficacy of this regimen for older patients with GC in a single-arm, phase II study., Patients and Methods: Patients aged ≥70 years having unresectable or recurrent GC who met the eligible criteria were enrolled. Paclitaxel was administered at a dose of 80 mg/m 2 on days 1, 8, and 15, and ramucirumab was administered at a dose of 8 mg/kg on day 1 and day 15 of a 4-week cycle. Primary endpoint was the incidence of adverse events and secondary endpoints were response rate, progression-free survival, and overall survival. A total of 25 patients were enrolled in the full-set analysis., Results: Grade 3 or more adverse events were observed in 21 patients (84.0%). Neutropenia was most frequently observed (68.0%), followed by peripheral sensory neuropathy (12.0%), and febrile neutropenia (12.0%). Median progression-free survival and overall survival were 6.9 months and 13.4 months, respectively. Disease control rate was 88.0%, and response rate of patients with measurable lesions was 52.9%. Notably, no treatment-related deaths occurred., Conclusion: Ramucirumab plus paclitaxel as a second-line chemotherapy demonstrated acceptable oncological outcomes, despite the occurrence of frequent adverse events. It is necessary to carefully select patients and adjust treatment regimens in older patients with GC to safely administer chemotherapy and subsequently achieve satisfactory long-term outcomes., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: HER2 signaling might be involved in the regulation of immune cell activation in the tumor microenvironment (TME) of gastric cancer (GC). However, the relationship between HER2 status and immune cell condition in the HER2-positive GC TME is not clearly understood., Methods: To investigate the effect of HER2 signaling on the activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which contributes to immune cell activation in the GC TME, we evaluated the associations among the expressions of HER2, cGAS-STING, and the number of CD8 + tumor-infiltrating lymphocytes (TIL) by considering HER2 heterogeneity in HER2-positive GC tissues. We also examined the effect of HER2 signaling on the activation of STING signaling in vitro using human HER2-positive GC cell lines., Results: The expression of HER2 is highly heterogeneous in HER2-positive GC tissues, and we found that the number of CD8 + TIL in HER2 high areas was significantly lower than that in HER2 low areas in HER2-positive GC tissues. Intriguingly, the tumor cell-intrinsic expression of STING, but not cGAS, was also significantly lower in the HER2 high areas than the HER2 low areas in HER2-positive GC tissues. Moreover, in vitro experiments, we demonstrated that the blockade of HER2 signaling increased the expression of STING and its target genes, including IFNB1, CXCL9/10/11, and CCL5, in HER2-positive GC cell lines., Conclusions: Our results suggest that HER2 signaling might suppress immune cell activation in the GC TME by inhibiting STING signaling in tumor cells in HER2-positive GC., (© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Objectives. The diversifying modalities of treatment for gastric cancer raise urgent demands for the rapid and precise diagnosis of metastases in regional lymph nodes, thereby significantly impact the workload of pathologists. Meanwhile, the recent advent of whole-slide scanners and deep-learning techniques have enabled the computer-assisted analysis of histopathological images, which could help to alleviate this impact. Thus, we developed a deep learning-based diagnostic algorithm to detect lymph node metastases of gastric adenocarcinoma and evaluated its performance. Methods. We randomly selected 20 patients with gastric adenocarcinoma who underwent surgery as definitive treatment and were found to be node metastasis-positive. HEMATOXYLIN-eosin (HE) stained glass slides, including a total of 51 metastasis-positive nodes, were retrieved from the specimens of these cases. Other slides with 776 metastasis-negative nodes were also retrieved from other twenty cases with the same disease that were diagnosed as metastasis-negative by the final pathological examinations. All glass slides were digitized using a whole-slide scanner. A deep-learning algorithm to detect metastases was developed using the data in which metastasis-positive parts of the images were annotated by a well-trained pathologist, and its performance in detecting metastases was evaluated. Results. Cross-validation analysis indicated an area of 0.9994 under the receiver operating characteristic curve. Free-response receiver operating characteristic curve (FROC) analysis indicated a sensitivity of 1.00 with three false positives. Further evaluation using an independent dataset also showed similar level of accuracies. Conclusion. This deep learning-based diagnosis-aid system is a promising tool that can assist pathologists involved in gastric cancer care and reduce their workload.

Background: Advances in whole-slide image capture and computer image analyses using deep learning technologies have enabled the development of computer-assisted diagnostics in pathology. Herein, we built a deep learning algorithm to detect lymph node (LN) metastasis on whole-slide images of LNs retrieved from patients with gastric adenocarcinoma and evaluated its performance in clinical settings., Methods: We randomly selected 18 patients with gastric adenocarcinoma who underwent surgery with curative intent and were positive for LN metastasis at Chiba University Hospital. A ResNet-152-based assistance system was established to detect LN metastases and to outline regions that are highly probable for metastasis in LN images. Reference standards comprising 70 LN images from two different institutions were reviewed by six pathologists with or without algorithm assistance, and their diagnostic performances were compared between the two settings., Results: No statistically significant differences were observed between these two settings regarding sensitivity, review time, or confidence levels in classifying macrometastases, isolated tumor cells, and metastasis-negative. Meanwhile, the sensitivity for detecting micrometastases significantly improved with algorithm assistance, although the review time was significantly longer than that without assistance. Analysis of the algorithm's sensitivity in detecting metastasis in the reference standard indicated an area under the curve of 0.869, whereas that for the detection of micrometastases was 0.785., Conclusions: A wide variety of histological types in gastric adenocarcinoma could account for these relatively low performances; however, this level of algorithm performance could suffice to help pathologists improve diagnostic accuracy., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background/aim: Gastrectomy with lymphadenectomy is a standard treatment for gastric cancer. Anastomotic leakage remains a potentially fatal complication of gastrectomy. Forceful stapler extraction may cause anastomotic complications. We focused on the duodenal peristalsis, as we hypothesized that it might cause forceful stapler extraction. We then retrospectively investigated duodenal peristalsis and reviewed videos of Da Vinci system cases to clarify the relationship between peristalsis and anastomotic complications., Patients and Methods: Forty-nine cases with stored videos of laparoscopic surgery using the Da Vinci system from 2015 to March 2021 were included. Peristalsis was defined by repeated contraction and expansion that was clearly visible three or more times in a row. The duodenum was investigated because it is frequently observed during gastrectomy. Suture failure was evaluated in cases with and without peristalsis., Results: The study population included 49 patients [male, n=32; female, n=17; median age, 71 (42-82) years]. Duodenal peristalsis was observed in 14 (28.6%) cases. Three patients experienced complications. A comparative study of cases with and without complications showed significant peristalsis in cases with complications (p=0.0198)., Conclusion: A new definition to evaluate duodenal peristalsis was established. Anastomotic complications were significantly more frequent in cases with peristalsis (p=0.0198). Our results suggest the utility of manual over-sewing or the use of reinforcement material., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Peritoneal lavage cytology positivity (CY1) has been identified as a prognostic factor for distant metastases that is equivalent to peritoneal dissemination in Japan. Peritoneal lavage cytology is usually diagnosed by microscopic findings; a diagnostic procedure using a liquid biopsy (LB) technique has not yet been established., Patients and Methods: We evaluated the feasibility of a LB approach using peritoneal lavage samples from 15 patients with gastric cancer. Samples were collected from both the Douglas pouch and the left subdiaphragmatic area, and cell-free DNA was extracted for analysis of TP53 mutations using droplet digital polymerase chain reaction., Results: All 10 patients with CY1 had positive cytology for the left subdiaphragmatic specimen. However, only six out of the 10 patients had positive cytology for their Douglas pouch specimens, and these six patients had peritoneal tumor DNA (ptDNA) in these specimens. In all five patients with CY0, ptDNA was not detected. The overall survival was significantly shorter in the ptDNA-positive group than in the ptDNA-negative group. The survival of the group with a high amount of DNA from free intraperitoneal cells (ficDNA) was significantly worse than that of those with a low amount. In contrast, the group with a high amount of DNA from peritoneal cell-free DNA (pcfDNA) had significantly better survival than the group with a low amount., Conclusion: LB cytology showed equivalent utility to that of conventional microscopic examinations regarding its diagnostic ability. Therefore ptDNA, pcfDNA and ifcDNA are expected to be useful as prognostic factors., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The clinical value of soluble forms of programmed cell death-1 (sPD-1), PD ligand 1 (sPD-L1) and cytotoxic T lymphocyte-associated protein-4 (sCTLA-4) for gastric cancer (GC) patients treated with nivolumab monotherapy has remained unknown., Methods: Blood samples collected before nivolumab treatment from 439 GC patients enrolled in the DELIVER (Japan Clinical Cancer Research Organisation GC-08) trial were analysed for sPD-1, sPD-L1 and sCTLA-4. Corresponding baseline clinical data were also retrieved., Results: Higher plasma levels of sPD-1 (hazard ratio [HR] = 1.27, p = 0.020), sPD-L1 (HR = 1.86, p < 0.001) and sCTLA-4 (HR = 1.33, p = 0.008) were significantly associated with shorter overall survival (OS), whereas only higher sPD-L1 levels was significantly associated with shorter progression-free survival (HR = 1.30, p = 0.008). The sPD-L1 concentration was significantly associated with the Glasgow prognostic score (GPS) (p < 0.001), but both sPD-L1 (HR = 1.67, p < 0.001) and GPS (HR = 1.39, p = 0.009 for GPS 0 versus 1; HR = 1.95, p < 0.001 for GPS 0 versus 2) were independently associated with OS. Patients with a GPS of 0 and low sPD-L1 thus showed the longest OS (median, 12.0 months) and those with a GPS of 2 and high sPD-L1 showed the shortest OS (median, 3.1 months), yielding a HR of 3.69 (p < 0.001)., Conclusion: Baseline sPD-L1 levels have the potential to predict survival for advanced GC patients treated with nivolumab, with the prognostic accuracy of sPD-L1 being improved by its combination with GPS., Competing Interests: Conflict of interest statement H. Kawakami has received consulting fees from Bristol-Myers Squibb Co. Ltd., Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co. Ltd., Daiichi-Sankyo Co. Ltd., and Taiho Pharmaceutical Co. Ltd.; honoraria from Bristol-Myers Squibb Co. Ltd., AstraZeneca K.K., Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Takeda Pharmaceutical Co. Ltd., and Taiho Pharmaceutical Co. Ltd.; lecture fees from Bristol-Myers Squibb Co. Ltd., Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Chugai Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., and Taiho Pharmaceutical Co. Ltd.; and research funding from Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd., and Eisai Co. Ltd. Y. Sunakawa has received consulting fees from Ono Pharmaceutical Co. Ltd., Merck Biopharma Co., Ltd, and Guardant Health Japan Co.; honoraria from Bristol-Myers Squibb Co. Ltd., Bayer Yakuhin Ltd., Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Takeda Pharmaceutical Co. Ltd., Merck Biopharma Co., Ltd, Guardant Health Japan Co., Sysmex Co., and Taiho Pharmaceutical Co. Ltd.; and research funding from Chugai Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., Sanofi, Taiho Pharmaceutical Co. Ltd., and Ohtsuka Pharmaceutical Co. E. Inoue has received consulting fees from Nippontect Systems Co. Ltd. as well as lecture fees from Bristol-Myers Squibb Co. Ltd. and Pfizer Japan Inc. K. R. Matoba is a director of the DNA Chip Research Inc. and holds shares in the company. Noda, T. Sato, C. Suminaka, and M. Yamaki are employees of Sysmex Corporation. Y. Sakamoto has received lecture fees from Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co. Ltd., Daiichi-Sankyo Co. Ltd., Taiho Pharmaceutical Co. Ltd.; Chugai Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Yakult Honsha Co. Ltd. Y. Kito has received honoraria from Ono Pharmaceutical Co. Ltd., Daiichi-Sankyo Co. Ltd., and Taiho Pharmaceutical Co. Ltd. A. Makiyama has received honoraria from Eli Lilly Japan K.K., Ono Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Taiho Pharmaceutical Co. Ltd., and Bristol-Myers Squibb Co. Ltd. H Hayashi has received honoraria from AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., Kyorin Pharmaceutical Co. Ltd., Merck Biopharma Co. Ltd., MSD K.K., Novartis Pharmaceuticals K.K., Ono Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd., and Takeda Pharmaceutical Co. Ltd.; consulting fees from AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., Pfizer Japan Inc., Shanghai Haihe Biopharma, Takeda Pharmaceutical Co. Ltd., and Merck Biopharma Co. Ltd.; and research funding from AstraZeneca K.K., Astellas Pharma, MSD K.K., Ono Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., grants, Pfizer Japan Inc., Bristol Myers Squibb Company, Eli Lilly Japan K.K., Chugai Pharmaceutical Co.,Ltd., Daiichi Sankyo Co., Ltd., Merck Serono Co., Ltd./Merck Biopharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Limited, AbbVie Inc, inVentiv Health Japan, ICON Japan K.K., GRITSONE ONCOLOGY.INC, PAREXEL International Corp., Kissei Pharmaceutical Co., Ltd., EPS Corporation, Syneos Health, Pfizer R&D Japan G.K., A2 Healthcare Corp., Quintiles Inc./IQVIA Services JAPAN K.K., EP-CRSU CO., LTD., Linical Co., Ltd., Eisai Co., Ltd., CMIC Shift Zero K.K., Kyowa Hakko Kirin Co., Ltd, Bayer Yakuhin, Ltd, EPS International Co., Ltd., Otsuka Pharmaceutical Co., Ltd. T. Honjo received a research grant from Sysmex Corporation and Ono Pharmaceutical Co. Ltd. related to this study. K. Nakagawa has received consulting fees from Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd., KYORIN Pharmaceutical Co., Ltd., Pfizer Japan Inc., Patents from Daiichi Sankyo Co., Ltd. Honoraria from Ono Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Amgen Inc., Kyowa Kirin Co., Ltd., Nippon Kayaku Co., Ltd., Takeda Pharmaceutical Co., Ltd., AstraZeneca K.K., 3H Clinical Trial Inc., Chugai Pharmaceutical Co., Ltd., Care Net, Inc., Eli Lilly Japan K.K., Medical Review Co., Ltd., MSD K.K., Medical Mobile Communications co., Ltd, Pfizer Japan Inc., YODOSHA CO., LTD., Nippon Boehringer Ingelheim Co., Ltd., Nikkei Business Publications, Inc., Taiho Pharmaceutical Co., Ltd., Japan Clinical Research Operations Bayer Yakuhin, Ltd., CMIC Co., Ltd., CMIC ShiftZero K.K., Novartis Pharma K.K., Life Technologies Japan Ltd., TAIYO Pharma Co., Ltd., Neo Communication KYORIN Pharmaceutical Co., Ltd., Roche Diagnostics K.K., Bristol-Myers Squibb K.K., AbbVie Inc. Research Funding from PAREXEL International Corp., Eisai Co., Ltd., PRA HEALTHSCIENCES, AstraZeneca K.K., EPS Corporation, Mochida Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., Covance Japan Inc., EPS International Co., Ltd., Japan Clinical Research Operations,Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., GlaxoSmithKline K.K., MSD K.K., Sanofi K.K., Ono Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., PPD-SNBL K.K., Nippon Boehringer Ingelheim Co., Ltd., SymBio Pharmaceuticals Limited,Sysmex Corporation, IQVIA Services JAPAN K.K., Medical Research Support,SYNEOS HEALTH CLINICAL K.K., Eli Lilly Japan K.K., Nippon Kayaku Co., Ltd.,Amgen Inc., EP-CRSU Co., Ltd., Novartis Pharma K.K., Mebix, Inc., Otsuka Pharmaceutical Co., Ltd., Bristol-Myers Squibb K.K., SRL, Inc.,Janssen Pharmaceutical K.K.,Pfizer R&D Japan G.K., AbbVie Inc., A2 Healthcare Corp., Bayer Yakuhin, Ltd., Pfizer Japan Inc. W. Ichikawa has received honoraria from Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Eli Lilly Japan K.K., Takeda Pharmaceutical Co.,Ltd., Shionogi & Co., Ltd., AstraZeneca K.K., Merck Biopharma Co., Ltd., Bristol-Myers Squibb Co. Ltd., Bayer Yakuhin Ltd., Nippon Kayaku Co., Ltd. All remaining authors declare no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The PI3K/AKT signaling pathway is frequently activated in gastric cancer (GC); however, AKT inhibitors are not effective in unselected GC patients in clinical trials. Mutations in AT-rich interactive domain 1A (ARID1A), which are found in approximately 30% of GC patients, activate PI3K/AKT signaling, suggesting that targeting the ARID1A deficiency-activated PI3K/AKT pathway is a therapeutic candidate for ARID1A-deficient GC., Methods: The effect of AKT inhibitors was evaluated using cell viability and colony formation assays in ARID1A-deficient and ARID1A knockdown ARID1A-WT GC cells as well as in HER2-positive and HER2-negative GC. The Cancer Genome Atlas cBioPortal and Gene Expression Omnibus microarray databases were accessed to determine the extent of dependence of GC cell growth on the PI3K/AKT signaling pathway., Results: AKT inhibitors decreased the viability of ARID1A-deficient cells and the inhibitory effect was greater in ARID1A-deficient/HER2-negative GC cells. Bioinformatics data suggested that PI3K/AKT signaling plays a greater role in proliferation and survival in ARID1A-deficient/HER2-negative GC cells than in ARID1A-deficient/HER2-positive cells, supporting the higher therapeutic efficacy of AKT inhibitors., Conclusions: The effect of AKT inhibitors on cell proliferation and survival is affected by HER2 status, providing a rationale for exploring targeted therapy using AKT inhibitors in ARID1A-deficient/HER2-negative GC., (© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Background: No studies have reported the effect of solitary living on adjuvant chemotherapy continuation in patients with gastric cancer. This study aimed to investigate the influence of solitary living on the efficacy of adjuvant chemotherapy after curative gastrectomy., Methods: We enrolled 155 patients with pathological stage II/III gastric cancer who underwent gastrectomy and adjuvant chemotherapy between January 2013 and March 2020. The patients were divided into two groups according to their living conditions, the solitary group (n = 34) versus the non-solitary group (n = 121). Clinicopathological features, predictive factors for the continuation of adjuvant chemotherapy, and long-term survival were compared between the two groups., Results: The median body weight loss (BWL) at one month after surgery (8.9% vs. 7.0%, p = 0.01), and the rates of failure to continue six courses of chemotherapy were higher in the solitary group (41.2% vs. 14.9%, p = 0.002) than in the non-solitary group. Multivariate analysis revealed that solitary living was an independent predictive factor for discontinuing adjuvant chemotherapy (odds ratio 3.36, 95% confidence interval [CI; 1.32-8.58], p = 0.01) as well as 10% BWL at one month after surgery (odds ratio 3.99, 95% CI [1.57-10.2], p = 0.004). The relapse-free survival was significantly worse in the solitary group (p = 0.03)., Conclusions: Solitary living may be an independent risk factor for discontinuation of adjuvant chemotherapy in patients with gastric cancer. It is necessary to examine whether social and medical support organized by medical institutes and the government improves the continuation of adjuvant chemotherapy in patients living alone., Competing Interests: Declaration of competing interest The authors declare that they have no conflict interest., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: Endoscopic full-thickness resection (EFTR) without laparoscopic assistance (pure EFTR) is an emerging, less invasive treatment for gastrointestinal stromal tumors (GISTs). However, the technique has seldom been performed outside China because of concerns regarding pneumoperitoneum, maintenance of endoscopic view, and endoscopic suturing. This study aimed to evaluate the efficacy and safety of endoscopic resection with one-port placement (EROPP) for gastric GISTs., Methods: This retrospective study included 17 patients with gastric GISTs originating from the muscularis propria who underwent EROPP between 2019 and 2022. One camera port was inserted in the umbilicus before initiating the endoscopic procedure to maintain intra-abdominal pressure, which was monitored and adjusted via this port. While allowing for conversion to laparoscopic surgery if needed, EFTR was performed as follows: (1) circumferential incision of the mucosal and submucosal layers around the lesion was performed by typical endoscopic submucosal dissection; (2) an intentional perforation and subsequent seromuscular resection was made using dental floss and an endo-clip for traction; and (3) closure of the gastric full-thickness defect was performed with an over-the-scope clip (OTSC) after peroral retrieval of the specimen. We retrospectively assessed the short-term outcomes and safety., Results: All procedures were completed successfully without conversion to laparoscopic surgery. The median size of the resected tumors was 23 mm (range, 8-35 mm), the median resection time was 36 min (range, 22-95 min), and closure time was 18 min (range, 10-45 min). The rates of en bloc and complete resection were 100% and 88%, respectively. In 2 cases, another port was added to aspirate the leaking fluid or check the condition of the endoscopic closure. All gastric defects were endoscopically closed, mainly using OTSCs. The recovery course for all patients was uneventful, and no adverse events were reported., Conclusions: EROPP is a safe and minimally invasive treatment for gastric GISTs and appears to be suitable for introducing EFTR procedures., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background/aim: Preoperative sarcopenia is associated with various cancers and affects the long-term prognosis of patients. After gastrectomy for gastric cancer, dynamic changes in body composition occur, and sarcopenia becomes more apparent after surgery than before surgery. However, the relationship between sarcopenia in the early postoperative period and long-term survival is not fully understood. The aim of this study was to determine the effects of surgical sarcopenia on long-term outcomes of patents with gastric cancer., Patients and Methods: We included 408 patients who underwent curative gastrectomy (distal or total gastrectomy) for gastric cancer at the Kanagawa Cancer Center from December 2013 to November 2017. Sarcopenia was defined using the skeletal muscle index (SMI), using computed tomography (CT) one month after gastrectomy. We compared the long-term outcomes between patients with and without sarcopenia., Results: The 5-year overall survival (OS) rates were 83.2% and 91.4% in the surgical and non-surgical sarcopenia groups, respectively. The hazard ratio (HR) of surgical sarcopenia for OS was 2.410 (95% confidence interval (CI)=1.321-4.396). In addition, surgical sarcopenia was associated with non-cancer-related deaths and deaths from other cancers., Conclusion: Patients with surgical sarcopenia after gastrectomy should be carefully monitored not only for gastric cancer recurrence but also for the occurrence of other diseases, including other cancers., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Pancreas-related complications after laparoscopic gastrectomy (LG) for gastric cancer can be fatal. We developed a gastrectomy procedure with no pancreas contact to prevent such complications and herein report the surgical outcomes., Methods: We retrospectively reviewed 182 consecutive patients with gastric cancer who underwent LG at Kitasato University Hospital from January 2017 to January 2020. These patients were divided into a pancreas-contact group (C group) and pancreas-contactless group (CL group) for comparison of postoperative complications, and inflammatory parameters such as body temperature (BT) and C-reactive protein (CRP)., Results: Postoperative complications of CDc grade ≧ IIIa were significantly fewer in the CL group than in the C group [0/76 (0%) vs. 6/106 (5.7%), P = 0.035]. The median drain amylase (drain-AMY) on postoperative day 1 (POD1) was significantly lower in the CL group than in the C group (641 vs. 1162 IU/L, P = 0.02), as was BT at POD1 (37.4 °C vs. 37.7 °C, P = 0.04), the patient group with a BT above 37.5 °C at POD3 [5/76 (6.5%) vs. 18/106 (17%), P = 0.037], and those showing a CRP above 20.0 mg/dL at POD3 [5/76 (6.5%) vs. 20/106 (19%), P = 0.018]., Conclusions: Our technique to prevent pancreas contact during supra-pancreatic lymph node dissection during LG could minimize the inflammatory response and prevent further postoperative complications. Further large-scale, prospective studies are now required., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The steroidal alkaloid tomatidine is an aglycone of α-tomatine, which is abundant in tomato leaves and has several biological activities. Tomatidine has been reported to inhibit the growth of cultured cancer cells in vitro, but its anti-cancer activity in vivo and inhibitory effect against gastric cancer cells remain unknown. We investigated the efficacy of tomatidine using human gastric cancer-derived 85As2 cells and its tumor-bearing mouse model and evaluated the effect of tomatidine-rich tomato leaf extract (TRTLE) obtained from tomato leaves. In the tumor-bearing mouse model, tumor growth was significantly inhibited by feeding a diet containing tomatidine and TRTLE for 3 weeks. Tomatidine and TRTLE also inhibited the proliferation of cultured 85As2 cells. Microarray data of gene expression analysis in mouse tumors revealed that the expression levels of mRNAs belonging to the type I interferon signaling pathway were altered in the mice fed the diet containing tomatidine and TRTLE. Moreover, the knockdown of one of the type I interferon-stimulated genes (ISGs), interferon α-inducible protein 27 ( IFI27 ), inhibited the proliferation of cultured 85As2 cells. This study demonstrates that tomatidine and TRTLE inhibit the tumor growth in vivo and the proliferation of human gastric cancer-derived 85As2 cells in vitro, which could be due to the downregulation of ISG expression.

Background: Laparoscopic and endoscopic cooperative surgery (LECS) is a well-recognized surgical procedure for gastric gastrointestinal stromal tumor (GIST). In this report, we describe the clinical outcomes of LECS procedures for gastric GIST in our institution., Methods: We performed LECS procedures, including classical LECS, inverted LECS, closed LECS, and combination of laparoscopic and endoscopic approaches to neoplasia with non-exposure technique (CLEAN-NET), in 40 gastric intraluminal and intramural type GIST patients, whose tumors were ≤ 50 mm in diameter, between September 2012 and December 2020. The patient background, surgical outcomes, postoperative morbidity and mortality, as well as the tumors' clinicopathological characteristics were analyzed retrospectively., Results: Pathological findings showed that most patients had a low or very low risk of tumor recurrence, while one patient had a high risk according to the modified-Fletcher's classification. The median length of postoperative hospital stay was 7 days. Only one patient had severe postoperative grade III complications according to the Clavien-Dindo (C-D) classification, after closed LECS, but was treated successfully with endoscopic hemostasis for postoperative hemorrhage. The remaining patients treated with LECS did not have severe complications. During the follow-up period (median, 31 months), all patients were disease-free, with no tumor recurrence or metastases., Conclusion: LECS is a safe surgical procedure for gastric intraluminal and intramural type GIST ≤ 50 mm in diameter, with good clinical outcomes.

We retrospectively analyzed clinicopathological and survival data of 8 patients with unresectable gastric cancer who underwent conversion surgery(CS)following second-line chemotherapy from April 2013 to December 2020. There were 7 males and 1 female patients with a median age of 69(64-76)years old. Five patients had 1 unresectable factor, 2 had 2 unresectable factors, and 1 had 3 unresectable factors. All patients achieved R0 resection. The median survival time(MST) of patients with CS following second-line chemotherapy was significantly longer than that without CS(73.4 vs 12.3 months, respectively). The MST of patients with CS following first-line chemotherapy was significantly longer than that without CS (22.9 vs 12.3 months, respectively). This study suggested that CS following first- or second-line chemotherapy may improve survival duration for unresectable gastric cancer.

Patients and Methods: Patients with gastric cancer who underwent laparoscopic-assisted pylorus-preserving gastrectomy (LAPPG group)or laparoscopic-assisted distal gastrectomy(LADG group)between January 2010 and December 2019 were reviewed and their postoperative nutritional status and long-term outcomes retrospectively evaluated., Results: In total, 83 patients(LAPPG group, n=23; LADG group, n=60)were included. Weight loss rates 1, 6, 12, and 24 months postoperatively in the LAPPG and LADG groups were 5.7% and 7.1%, 6.6% and 9.6%, 5.8% and 10.1%, and 5.2% and 8.7%, respectively. The LADG group exhibited a significantly higher weight loss than the LAPPG group at 6, 12, and 24 months (p=0.007, 0.002, and 0.022, respectively). No recurrence was observed in either group within 5 years of surgery. The 5- year overall survival rate of patients with pathological Stage Ⅰ cancer( LAPPG group, n=23, LADG group, n=51) was higher in the LAPPG group than in the LADG group(100% vs 82.9%, p=0.027). There were 6 cases of death from other diseases in the LADG group(pneumonia, n=2, other cancer, n=2, postoperative bleeding, n=1, and heart failure, n=1)but none in the LAPPG group., Conclusion: The weight loss after LAPPG was significantly lower than that after LADG. Furthermore, the former showed a good prognosis without death from other diseases, such as pneumonia.

Background/aim: The number of patients who have cardiovascular-morbidities and use antiplatelet and/or anticoagulation therapy is rapidly growing worldwide. The present study evaluated the safety and feasibility of gastrectomy for gastric cancer in patients who received antiplatelet and/or anticoagulation therapy in the perioperative period., Patients and Methods: Cases were selected from the medical records of consecutive patients who were diagnosed with gastric cancer and underwent complete resection at the Kanagawa Cancer Center from 2013 to 2017. The patients were divided into the antiplatelet and/or anticoagulation treatment group and the non-antiplatelet and/or anticoagulation treatment group., Results: Five hundred and six patients underwent gastrectomy for gastric cancer and were analyzed in the present study. Among them, 62 patients (12.3%) received anticoagulation therapy (anticoagulation group). When the anticoagulation and non-anticoagulation groups were compared, although there were some differences in patient background factors, the surgical findings, perioperative clinical course, and details of postoperative complications were similar. The incidence of postoperative bleeding was 0.8% (4/506) in all patients. The incidence of postoperative bleeding was 1.6% (1/62) in the anticoagulation group and 0.7% (3/446) in the non-anticoagulation group. Preoperative anticoagulation therapy was not identified as a significant independent risk factor for postoperative bleeding., Conclusion: These results suggest that curative gastrectomy for gastric cancer is safe and feasible, regardless of the perioperative use of antiplatelet and/or anticoagulation treatment. In addition, the perioperative use of antiplatelet and/or anticoagulation treatment was not a significant risk factor for postoperative bleeding after gastrectomy for gastric cancer., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The procedure of mediastinoscopic-assisted transhiatal esophagectomy (MATE) is only performed in a few institutions, despite this being the ultimate form of minimally invasive surgery for performing esophagectomy for esophageal and esophagogastric cancer in that it entails no chest wall trauma. We have developed a novel, universally applicable, surgical procedure for performing bilateral transcervical mediastinoscopic-assisted transhiatal laparoscopic esophagectomy (BTC-MATLE) that is an improvement on standard MATE surgery for esophageal and esophagogastric cancer., Methods: The patient is placed in a supine position under general anesthesia with bilateral lung ventilation. BTC-MATLE combined with mediastinoscopic and transhiatal laparoscopic esophagectomy with total mediastinal lymph node dissection are performed synchronously. After lymph node dissection along both recurrent laryngeal nerves through bilateral cervical skin incisions, bilateral transcervical mediastinoscopic esophagectomy is performed to avoid collision outside the cervical region and ensure operability even in patients with narrow mediastimun. Laparoscopic gastric mobilization and subsequent lower esophageal mobilization meet the bilateral transcervical mediastinoscopic esophagectomy at the border of the middle and lower third of the esophagus. The gastric tube is pulled up into the cervical region via a posterior mediastinal route and anastomosed in the neck., Results: BTC-MATLE was performed on 16 high-risk patients (Charlson Comorbidity Index ≥ 3 in 14 patients and two octogenarians with complex comorbidities). Median operation time and postoperative hospital stay were 231 min and 15 days, respectively. R0 resection was achieved in 15 patients (94%), and there were no in-hospital deaths., Conclusions: BTC-MATLE, a procedure for performing minimally invasive esophagectomy, is likely to become the applicable form of MATE surgery for esophageal and esophagogastric cancer, even in high-risk patients because it is truly minimally invasive and has excellent short-term outcomes., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The significance of the dimensional factors (tumor diameter, area and volume) as the prognostic factor has not been precisely evaluated in pT1 gastric cancer., Objectives: This study aimed to identify the clinical impact and to confirm the clinical feasibility of the dimensional factors as prognostic factors in pT1 gastric cancer., Methods: We analyzed prognostic factors for disease-specific survival (DSS), overall survival (OS) using clinicopathological factors by univariate and multivariate analyses and the pattern of recurrence in 2011 pT1 gastric cancer (mucosal and submucosal cancers) undergoing R0 gastrectomy. The cut-off values of each dimensional factor was decided by the ROC curve., Results: Cox proportional hazard regression model showed that older age (≥75) and more advanced pN stage were adverse independent prognostic factors for DSS, and revealed that older age (≥75), greater preoperative co-morbid diseases, proximal and total gastrectomy, operative method and Clavien-Dindo classification (≥grade III) were independent adverse factors for OS. Any dimensional factors were not independent prognostic factors for any survival., Conclusions: The dimensional factors do not influence both OS and DSS in pT1 gastric cancer patients and so it is difficult to apply these dimensional factors for conducting therapeutic strategies., (Copyright © 2021. Published by Elsevier Ltd.)

Some gastric epithelial neoplasms show predominant chief cell differentiation (oxyntic gland neoplasms), in which the entity of "gastric adenocarcinoma of fundic gland type" was firstly designated, whereas a possible more aggressive subgroup "gastric adenocarcinoma of fundic gland mucosa type" (GA-FGM) was subsequently proposed. However, the histopathologic progression mode of these neoplasms has not been sufficiently reported. In this article, we describe a case of GA-FGM in which we could observe its progression during 5 years. The tumor was removed by endoscopic submucosal dissection 5 years after the first biopsy, which had already shown a feature of oxyntic gland neoplasm. During the follow-up period, the endoscopy revealed little change in the tumor appearance. However, the histology of endoscopic submucosal dissection showed submucosal extension with its histological progression. Besides, other oxyntic gland neoplasms of the stomach were observed metachronously or synchronously, giving an implication about a common pathogenetic basis of these lesions.

Background: Tumor-to-tumor metastasis is the rare phenomenon in which one tumor exhibits metastatic deposits from another. To the best of our knowledge, there has been no prior reported case of tumor-to-tumor metastasis of a diffuse large B cell lymphoma (DLBCL) to a primary gastric adenocarcinoma., Case Presentation: A 70-year-old man presented with chest discomfort. An echocardiogram showed the presence of a right ventricular tumor. A positron emission tomogram showed multiple foci of abnormal activity in right cervical lymph nodes, cardiac wall, and stomach. A right cervical lymph node biopsy specimen revealed histological features of DLBCL. An esophagogastroduodenoscopy showed a large circumferential ulceration on the gastric body. Subsequent biopsy revealed adenocarcinoma cells surrounded by infiltrating lymphoma cells. On immunohistochemical staining, lymphoma cells were positive for CXCR4 and adenocarcinoma cells were positive for CXCL12/SDF-1. The patient was treated with six cycles of R-CHOP chemotherapy regimen, resulting in a complete remission., Conclusions: This patient's case implies that the interaction between a chemokine and its receptor may be the underlying mechanism for the observed tumor-to-tumor metastasis. Specifically, our case would suggest an involvement of the CXCL12 (SDF-1)/CXCR4 axis in the observed metastasis of DLBCL to primary gastric adenocarcinoma.

Background: Omentectomy is considered an essential part of curative gastrectomy for locally advanced gastric cancer (GC), albeit without solid evidence. We conducted a randomized phase II trial (the TOP-G trial) comparing omentectomy and omentum preservation for gastric cancer. This report describes the short-term findings regarding the trial's secondary endpoints., Methods: The trial protocol was submitted to the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/ : UMIN000005421). The key eligibility criteria were histologically confirmed cT2-4a and N0-2 gastric adenocarcinoma. Short-term surgical outcomes, including morbidity and mortality, were compared between the omentectomy group (group A, control arm) and the omentum-preserving surgery group (group B, test arm). All procedures were performed via an open approach. Based on a non-inferiority margin of 7%, statistical power of 0.7, and type I error of 0.2, the sample size was set to 250 patients., Results: A total of 251 patients were eligible and randomized (group A: 125 patients, group B: 126 patients) between April 2011 and October 2018. After excluding patients who had peritoneal metastasis or laparotomy history, safety outcomes were analyzed for 247 patients. Group A had a significantly longer median operation time (225 min vs. 204 min, p = 0.022) and tended to have greater median blood loss (260 mL vs. 210 mL p = 0.073). The incidences of morbidity were similar and < 10% in both groups (8% vs. 9%, p = 1.000). There was no mortality in either group., Conclusions: Operative risk was generally similar between omentectomy and omentum-preserving surgery for locally advanced gastric cancer.

The left renal vein lymph node (LRVLN) may be the extended locoregional node in esophagogastric junction cancer; however, only open-surgical methods of dissection have been reported. We therefore developed a novel minimally invasive laparoscopic method for LRVLN dissection. Following esophagectomy, the stomach was mobilized and LRVLN dissection was started by taping the pancreatic body using two silicone drains. The transverse mesocolon was then retracted through the superior duodenal fossa to expose the horizontal duodenum and permit LRVLN dissection. We carried out the procedure successfully in 17 patients with advanced esophagogastric cancer. The median total and laparoscopic operative times were 415 and 161 min, respectively. Postoperative esophagectomy-related complications occurred in six patients. The median estimated blood loss was 120 ml and hospital stay was 15 days. This minimally invasive laparoscopic LRVLN dissection method was safe and effective, and may support faster recovery and earlier postoperative adjuvant therapy in patients with esophagogastric junction cancer.

Objective Neuroendocrine neoplasms (NENs) are rare and indolent diseases, but the efficacy of treatment without surgical resection is temporary and limited. Targeted immunotherapy is an important treatment strategy in several cancers. However, the tumor and host immune reactions in the NEN microenvironment are poorly understood. Therefore, we investigated the immune checkpoint system and host immune response in pathological NEN specimens. Methods The expression of the mismatch repair proteins MSH2, MSH6, PMS2, and MLH1 was immunohistochemically detected in archival tissue samples obtained from 20 patients with gastroenteropancreatic NENs. We additionally assessed the expression of programmed death (PD)-1, PD-L1, and the tumor-infiltrating lymphocyte (TIL) markers CD8 and family of transcription factor P3 (FOXP3). Results All 20 NENs expressed the mismatch repair proteins MSH2, MSH6, PMS2, and MLH1. The PD-L1 and/or PD-1 expression in the tumor cells and/or TILs was confirmed in 75% of the cases. PD-1-, CD8-, and FOXP3-positive TILs were more frequently associated with PD-L1-positive tumors than with PD-L1 negative tumors (PD-1: 19.5 vs. 7.3, CD8: 18.1 vs. 7.1, FOXP3: 13.2 vs. 3.2, p=0.438, p=0.419, P=0.603, respectively). The number of cells positive for PD-1 tended to gradually increase in increasing grade of NENs but did not reach significance (Grade 1: 5.8, Grade 2: 10.2, NEC: 18.1, p=0.903). Conclusion NENs consistently express mismatch repair proteins but have a high expression of PD-L1 and/or PD-1 in the tumor microenvironment. NEC and PD-L1-positive NENs may be immunologically "hot" tumors, so an immunological approach may be an appropriate treatment strategy for these tumors.

Cisplatin (CDDP) is one of the chemotherapeutic drugs being used to treat various cancers. Although effective in many cases, as high doses of CDDP cause cytotoxic effects that may worsen patients' condition, therefore, a marker of sensitivity to CDDP is necessary to enhance the safety and efficiency of CDDP administration. This study focused on adipose most abundant 2 (APM2) to examine its potential as a marker of CDDP sensitivity. The relationship of APM2 expression with the mechanisms of CDDP resistance was examined in vitro and in vivo using hepatocellular carcinoma (HCC) cells, tissues and serum of HCC patients (n = 71) treated initially with intrahepatic arterial infusion of CDDP followed by surgical resection. The predictability of serum APM2 for CDDP sensitivity was assessed in additional 54 HCC patients and 14 gastric cancer (GC) patients. APM2 expression in CDDP-resistant HCC was significantly higher both in serum and the tissue. Bioinformatic analyses and histological analyses demonstrated upregulation of ERCC6L (DNA excision repair protein ERCC6-like) by APM2, which accounts for the degree of APM2 expression. The serum APM2 level and chemosensitivity for CDDP were assessed and cut-off value of serum APM2 for predicting the sensitivity to CDDP was determined to be 18.7 µg/mL. The value was assessed in HCC (n = 54) and GC (n = 14) patients for its predictability of CDDP sensitivity, resulted in predictive value of 77.3% and 100%, respectively. Our study demonstrated that APM2 expression is related to CDDP sensitivity and serum APM2 can be an effective biomarker of HCC and GC for determining the sensitivity to CDDP.Trial registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000028487).

Background: A multi-institutional phase II study was conducted to evaluate the efficacy and safety of preoperative docetaxel, cisplatin and S-1 therapy in marginally resectable advanced gastric cancer., Methods: Patients with macroscopic type 4, large macroscopic type 3 and bulky lymph node metastasis received two cycles of preoperative docetaxel, cisplatin and S-1 therapy (docetaxel 40 mg/m2 and cisplatin 60 mg/m2 on day 1, and S-1 80 mg/m2 for 14 days, every 4 weeks). The primary endpoint was the pathological response rate, with an expected value of 65%., Results: Thirty-one patients were enrolled in this study. The pathological response rate was 54.8%, and it was higher than the threshold value but lower than the expected rate. The R0 resection rate was 93.5%. The frequencies of grade 3-4 toxicities during docetaxel, cisplatin and S-1 therapy were 41.9% for neutropenia, 6.5% for febrile neutropenia and 32.3% for nausea/vomiting. Grade 2 and 3 surgical morbidities occurred in 23.3 and 6.7% of the patients, respectively., Conclusions: Preoperative docetaxel, cisplatin and S-1 therapy was feasible in terms of chemotherapy-related toxicities and surgical morbidity, but the effect did not achieve the expected value. The association between the pathological response rate and survival will be evaluated in the final analysis of this clinical trial., (© The Author(s) 2020. Published by Oxford University Press.)

Background and Aims: Diffuse-type gastric cancer (GC) is currently subdivided into signet-ring cell carcinoma (SRCC) and non-SRCC, referred to as poorly cohesive carcinoma not otherwise specified (PCC-NOS). Although these subtypes are considered to be independent, they often coexist in the same tumors, raising a question of whether they clonally differ or not. To tackle this question, we established an experimental platform for human diffuse GC that enables accurate modeling of histologic subtypes., Methods: Seven patient-derived diffuse GC organoid lines were established, characterized by histopathologic analysis, in situ hybridization, and gene expression analysis. For genetic modeling of diffuse GC, we knocked out CDH1 and/or TP53 in human normal gastric organoids. Green fluorescent protein-labeled GC organoids were xenotransplanted into immune-deficient mice for in vivo assessment., Results: PCC-NOS organoids transformed into SRCC-like structures on removal of Wnt and R-spondin from the culture medium. This morphologic change paralleled downregulation of Wnt-target and gastric stem cell genes, including LGR5, and elevation of differentiation markers, such as KRT20 and MUCs. The association between Wnt target gene expression and histologic subtypes was confirmed in 3 patient-derived GC tissues. In vivo, single clone-derived organoids formed tumors that comprised 2 distinct histologic compartments, each corresponding to SRCC and PCC-NOS. The transition from PCC-NOS to SRCC histology reflected the abundance of surrounding R-spondin-expressing fibroblasts., Conclusions: SRCC and PCC-NOS were clonally identical, and their morphology was regulated by extracellular Wnt and R-spondin expression. Our results decoded how genetic mutations and the tumor environment shape pathohistologic and biologic phenotypes in human diffuse GCs., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The predictive factors for discontinuation of S-1 administration and prognostic factors in elderly patients with pStage II/III gastric cancer receiving S-1 adjuvant chemotherapy remain unclear., Methods: Between January 2004 and December 2016, 80 elderly gastric cancer patients (≥70 years) undergoing curative D2 gastrectomy were enrolled in this study. Predictive factors for completion of S-1 administration over 1 year, adverse events due to S-1 administration, and prognostic factors for overall survival (OS) and relapse-free survival (RFS) were evaluated., Results: Twenty-eight patients (35%) completed 8 courses of S-1. The median relative dose intensity was 82.1% (IQR 31.1-100%). The incidence rates of hematological and nonhematological adverse events were acceptable. Distal gastrectomy was an independent predictive factor for completion of S-1 administration (odds ratio [OR] 0.364; 95% confidence interval [CI] 0.141-0.939; p = 0.037). Higher postoperative neutrophil count/lymphocyte count (N/L) ratio and more advanced stage adversely influenced OS. Multivariate analysis revealed that a higher postoperative N/L ratio and more advanced stage adversely affected RFS., Conclusion: To complete adjuvant S-1 administration to elderly patients with pStage II/III gastric cancer, total gastrectomy should be avoided if possible. A new regimen for elderly gastric cancer patients with higher postoperative N/L ratios and more advanced stage should be established., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Background/aim: Prophylactic splenectomy has shown no inferiority for tumors not invading the greater curvature side. Despite this, the clinical impact of prophylactic splenectomy for proximal advanced gastric cancer is not clear. This review aimed to clarify the impact of splenectomy for advanced gastric cancer in the upper third of the stomach., Materials and Methods: A systematic review and meta-analysis were conducted based on PubMed and EMBASE databases. The following search terms were used: "gastric cancer" OR "splenectomy" OR upper third of the stomach" OR preservation of the spleen., Results: Out of 765 articles, 18 studies (combined n=6,341) were included in the analysis. Four randomized controlled trials (RCT) and eight retrospective studies suggested the benefits of spleen-preserving gastrectomy. Six retrospective studies showed no significant benefit of spleen-preserving gastrectomy. Prophylactic splenectomy showed a close association with a higher incidence of postoperative morbidity (pancreatic fistula and anastomotic leakage) with no concomitant improvement in overall survival. Prophylactic splenectomy should not be routinely performed and RCTs are necessary to confirm the impact of splenectomy for cN(+) at the splenic hilum tumors and tumors invading the greater curvature., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The purpose of this study is to evaluate the long-term survival outcomes of KDOG1001 trial after a minimum follow-up of 3 years., Methods: Patients with bulky N2 lymph nodes, linitis plastica (type 4), or large ulcero-invasive-type tumors (type 3) received up to four 28-day cycles of DCS neoadjuvant chemotherapy (docetaxel at 40 mg/m 2 , cisplatin at 60 mg/m 2 on day 1, and S-1 at 40 mg/m 2 twice daily for 2 weeks) followed by gastrectomy with D2 lymphadenectomy plus adjuvant S-1 therapy for 1 year. The final preplanned analysis of long-term outcomes including overall survival and relapse-free survival was conducted after minimum follow-up of 3 years. This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN 000003642, and has been completed., Results: From May 2010 through January 2017, 40 patients were enrolled. All included patients underwent neoadjuvant chemotherapy with DCS followed by gastrectomy with D2 lymphadenectomy, and 32 (80%) completed adjuvant S-1 therapy for 1 year. After a median follow-up for surviving patients of 68 months at the last follow-up in January 2020, 3-year overall survival rate was 77.5% (95% confidence interval 62.1-87.9%), while 3-year relapse-free survival rate was 62.5% (95% confidence interval 46.8-76.0%)., Conclusion: Neoadjuvant chemotherapy with 4 cycles of DCS followed by D2 gastrectomy plus adjuvant S-1 was associated with relatively good long-term oncologic outcomes for patients with the high-risk gastric cancer.

Background: The aim of this study was to evaluate the impact of postoperative infectious complications on long-term outcomes after curative resection of gastric cancer., Patients and Methods: Patients who underwent curative gastrectomy with lymphadenectomy for gastric cancer at Yokohama City University and Kanagawa Cancer Center from January 2000 to August 2015 were retrospectively selected from medical records. Clinicopathological factors between patients with and without infectious complications were compared. Prognostic factors of long-term survival were analyzed by univariate and multivariate Cox proportional hazards analyses., Results: A total of 2,254 patients were eligible for inclusion in the present study. Fifty-eight patients had postoperative infectious complications (IC group); 2,196 had no postoperative infectious complications (NC group). In the IC group, the median age (p=0.031), body mass index (p=0.004), American Society of Anesthesiologists physical status (p=0.006) and percentage of male patients (p<0.001) were higher in comparison to the NC group. The operation time was longer (p<0.001) and the incidence of intestinal-type histology was higher (p=0.017) in the IC group. The 5-year overall survival rates of the IC and NC groups were 59.8% and 83.2%, respectively (p<0.001). Univariate and multivariate analyses demonstrated that postoperative infectious complications were a significant risk factor for poorer overall survival (hazard ratio=2.38; 95% confidence interval=1.47-3.85, p<0.001)., Conclusion: Perioperative management is necessary to reduce the incidence of postoperative infectious complications and improve the survival of patients after curative resection of gastric cancer., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Different approaches are used to treat resectable tumours in patients having adenocarcinoma at the oesophagogastrointestinal junction (EGJ) or in the stomach. However, there is limited information about treatment efficacy for patients at metastatic stage. A recent molecular analysis of upper gastrointestinal tract adenocarcinoma revealed that the anatomical location can influence the molecular backgrounds of tumours. This study sought to elucidate whether different therapeutic approaches should be used for EGJ tumours relative to those in the stomach., Methods: This retrospective cohort study was conducted at a single institute in Japan. Patients having metastatic or recurrent adenocarcinoma in the EGJ or stomach who underwent platinum doublet chemotherapy between January 2007 and August 2014 were enrolled. Patients in the EGJ tumour group had tumours having an epicentre within 2 cm proximal or 5 cm distal to the estimated anatomical EGJ and cardia., Results: Among 378 consecutively enrolled patients, 61 were grouped into the EGJ group and the remainder comprised the stomach group. The EGJ group had more men and lower incidence of diffuse type and Borrmann type IV tumours and peritoneum metastasis compared with the stomach group. The median overall survival of patients in the EGJ and stomach groups was similar (17.3 months (95% CI 13.5 to 23.2) vs 14.5 months (95% CI 13.3 to 16.4)). No statistically significant difference was observed in progression-free survival. Although the overall postprogression survival differed significantly between the EGJ and stomach groups (8.2 months (95% CI 5.7 to 12.7) vs 7.1 months (95% CI 6.1 to 7.8)), on grouping patients by histological type, the two groups exhibited similar postprogression survival. Multivariate analysis demonstrated that diffuse-type histology, higher serum CA19-9 levels and neutrophil to lymphocyte ratios were independent poor prognostic factors., Conclusions: Different clinicopathological features of EGJ adenocarcinoma were not associated with clinical outcomes of platinum doublet chemotherapy. Histological subtype rather than anatomical location has more significance for treatment decisions for advanced gastric cancers., Competing Interests: Competing interests: None declared., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Background: Gastric cancer with extensive lymph node metastasis(ELM)is commonly considered unresectable and has a poor prognosis. We conducted a phase Ⅱ study to evaluate the safety and efficacy of capecitabine and cisplatin(XP)as preoperative chemotherapy for gastric cancer with ELM., Methods: The patients received 2 21-day cycles of XP therapy(ca- pecitabine at 2,000mg/m2 twice daily for 2 weeks and cisplatin at 80 mg/m2 on day 1)followed by gastrectomy with D2 plus para-aortic nodal dissection. After R0 resection, S-1 chemotherapy was administered for 1 year. The primary end point was response rate(RR). The planned sample size was 30., Results: Between April 2015 and November 2016, 4 patients were enrolled, but the enrollment was terminated because of poor patient recruitment. The clinical RR was 50%, and R0 resection was achieved in 75% of the patients. The common Grade 3 adverse events during XP therapy were leukocytopenia(25%), anemia(25%), and hyperlipidemia(25%). The common Grade 3 surgical morbidity was abdominal abscess(33%)and pancreatic fistula(33%). The pathological RR was 25%., Conclusions: Preoperative XP therapy was feasible, but its efficacy was difficult to evaluate because of the small sample size.

We report a case of advanced gastric cancer with right gastroepiploic vein tumor thrombus treated using preoperative S-1 plus cisplatin(CDDP)in which pathological complete response was achieved. A 78-year-old man was diagnosed with type 2 gastric cancer located at the greater curvature of the antrum, accompanied by right gastroepiploic vein tumor thrombus. Four courses of S-1 plus CDDP were administered as neoadjuvant chemotherapy. After 2 courses, computed tomography(CT) revealed the disappearance of the tumor in the right gastroepiploic vein thrombus. Distal gastrectomy with D2 lymphadenec- tomy was performed, and the diagnosis was pathological complete response(CR). Eight courses of S-1(100mg/day on days 1-28, followed by 2 weeks of rest)were administered as adjuvant chemotherapy. During the 1-year postoperative follow up, the patient showed no recurrence. An S-1 plus CDDP regimen can be a useful preoperative chemotherapy option for advanced gastric cancer with tumor vein thrombus.

This case involved a 42-year-old woman who had no remarkable findings in terms of case history and family history. Upper gastrointestinal series performed during a medical examination revealed ulcerative lesions in the anterior wall of the stomach body. Upper gastrointestinal endoscopy was performed, and a submucosal tumor with a maximum diameter of 50mm accompanied by an ulcerative lesion was found in the anterior wall of the lower part of the stomach. She was diagnosed with a schwannoma based on endoscopic ultrasonography-guided fine needle aspiration, and we received consultation for surgical purpose. Surgery was performed with laparoscopic partial resection of the stomach and lymph nodes in the lesser curvature of the stomach. She was discharged on the 7th day after the surgery. The postoperative pathologic findings showed no nuclear fissure or atypia with a diagnosis of a schwannoma and no lymph node metastasis. Gastric schwannoma is a rare disease that arises from Schwann cells of the Auerbach's plexus of the gastric wall muscularis and comprises 0.1-0.2% of all stomach tumors. Preoperative diagnosis is often extremely difficult, and there are reports of malignancy. Treatments and surgical methods should be carefully considered. Herein, we encountered a case of a resected giant gastric schwannoma by laparoscopic surgery, which is reported with a literature review.

This is a case of a 76-year-old man who had no significant past medical or family history. In the current medical history, in November 2017, upper gastrointestinal endoscopy showed a semicircular protruding lesion in the posterior wall of the gastric antrum, and gastric cancer was diagnosed following biopsy. Endoscopic submucosal dissection(ESD)was performed in the same year for the treatment of gastric cancer(cT1aN0M0). Pathological findings after ESD treatment showed invasion into the submucosa requiring non-curative resection. For this reason, laparoscopic pylorus side gastrectomy(D1 dissection)and Billroth Ⅰ reconstruction were performed as additional procedures in March 2018. The patient was discharged on the 10th postoperative day and was followed-up on an outpatient basis. On the postoperative day 14, he was re-admitted with complaints of upper abdominal pain and exacerbation of inflammation. Medical treatment, such as antibiotic administration was followed, however, a high degree of inflammatory response, renal dysfunction, and occult blood in urine were observed. Because of suspicion of vasculitis-related nephritis, the case was diagnosed as anti-GBM antibody type rapid progressive nephritis. We came across a case of rapidly progressive glomerulonephritis after laparoscopic pylorus side gastrectomy performed for early gastric cancer, and hence, We will review the related literature.

Background and Aims: The recent advancement of next-generation sequencing (NGS) has enabled the identification of cancer-related somatic aberrations in advanced gastric cancer. However, these remain unclear in early gastric cancers, especially in intramucosal gastric cancers., Patients and Methods: Thirty-one well-differentiated (tub1) intramucosal gastric cancers obtained by endoscopic submucosal dissection (ESD) from 29 patients were analyzed. After precise collection of tumors and non-tumors from formalin-fixed paraffin-embedded tissues using laser-captured microdissection (LCM), target sequencing analysis of 50 cancer-related genes was performed using an Ion-Proton sequencer., Results: The most frequent hotspot mutation was found in TP53 (17 lesions, 54.8%) followed by the Wnt-signaling pathway genes, APC and CTNNB1 (6 lesions, 19.4%). The mutations in TP53 and the Wnt-signaling genes were mutually exclusive (p = 0.004). There was a tendency that H. pylori infection (p = 0.082) and macroscopic protrusion (p = 0.095) was associated with the presence of these mutations. Only 10 lesions (59%) among 17 lesions with proven TP53 mutations were positive for p53 immunostaining demonstrating the superiority of the mutational analysis. In addition, focal gene amplification of ERBB2 (16%) was found frequently in these early stage lesions., Conclusions: Using LCM and NGS, mutations in TP53 and the Wnt-signaling pathway were frequently found and were mutually exclusive in the earliest stage of gastric carcinogenesis.

AT-rich interactive domain 1A (ARID1A) functions as a tumor suppressor and several therapeutic targets in ARID1A-mutated cancers are under development. Here, we investigated the prognostic value of ARID1A for gastric cancer and its association with expression of PD-L1 and p53. ARID1A expression was examined by immunohistochemistry and negative expression of ARID1A was detected in 39 (19.5%) of 200 cases in a test cohort and in 40 (18.2%) of 220 cases in a validation cohort. Negative expression of ARID1A was associated with worse overall survival in undifferentiated cases, particularly early-stage cases. Negative expression of ARID1A was detected in 11 (50%) of 22 PD-L1-positive cases and in 68 (17.1%) of 398 PD-L1-negative cases in a combined cohort. Negative expression of ARID1A was detected in 45 (22%) of 205 p53-positive cases and in 34 (15.8%) of 215 p53-negative cases in a combined cohort. In addition, expression of EZH2, a potential synthetic lethal target in ARID1A-mutated tumors, was detected in 79 ARID1A-negative cases. An ARID1A-knockdown gastric cancer cell line was subjected to microarray analysis, but no actionable targets or pathways were identified. The present results indicate that ARID1A may serve as an early-stage prognostic biomarker for undifferentiated gastric cancer.

Background: Laparoscopy-assisted distal gastrectomy (LADG) has an advantage of earlier recovery after surgery due to having lower invasiveness and wound pain than open distal gastrectomy (ODG). However, whether the same enhanced recovery after surgery (ERAS) program for LADG is equally feasible and safe for ODG remains unclear., Methods: We retrospectively extracted the clinical data of the patients enrolled in JCOG0912 from the medical record system of our hospital and compared the treatment process and short-term surgical outcomes between LADG and ODG. Our ERAS program consisted of 13 elements (4 preoperative, 4 intraoperative, and 5 postoperative elements). The morbidity was defined as complications of grade 2 or more., Results: One hundred and sixty-three patients were entered from our hospital and randomized to undergo ODG (82 patients) or LADG (81 patients). The patient's backgrounds, surgical outcomes, and pathological outcomes were similar between the ODG and LADG groups. The rate of completing the clinical pathway was 95.1% in both groups, and the rates of completing each ERAS element were similar. However, the additional use of acetaminophen was significantly more frequent in the ODG group than in the LADG group (18.3% vs. 6.2%, p = 0.03). The median hospital stay after surgery was 9 days in both groups. Morbidity, defined as Clavien-Dindo classification > grade 2, was observed in 6.1% of the ODG group and 11.1% of the LADG group. No mortality occurred in either group., Conclusion: This study showed that the regimen of perioperative care performed by the ERAS program for LADG was equally feasible and safe for ODG with additional pain control. Less pain observed in LADG was not so apparent advantage for completion and safety of ERAS care.

Background: For safe laparoscopic gastrectomy, it is essential to secure a good visual field by employing liver retraction. We have developed a safe and easy method for liver retraction using a silicone disc, and evaluated its feasibility., Methods: We analyzed retrospectively 36 patients with gastric cancer, who underwent laparoscopic distal gastrectomy employing liver retraction by a silicone disc and needle forceps (Silicone group) or by the Penrose drain method (Penrose group) between January 2013 and July 2016. The time needed for liver retraction, complications resulting from it, and postoperative liver dysfunction were compared between the two groups., Results: In all patients in both groups, the operation was performed successfully, obtaining an appropriate visual field. The mean time required for liver retraction was 633.8 ± 286.6 seconds in the Silicone group and 639.8 ± 328.6 seconds in the Penrose group (P = .954). Postoperative elevation of either aspartate transaminase (AST) or alanine aminotransferase (ALT) level was recognized in 13 (72.2%) of the Silicone group patients and 18 (100%) of the Penrose group patients (P = .0160). The mean AST and ALT levels in the Silicone group were significantly lower than those in the Penrose group on postoperative days 0, 1, and 3. Among intraoperative complications related to liver retraction, hemorrhage from the abdominal wall occurred in one Silicone group case and hemorrhage from liver occurred in one Penrose group case., Conclusion: Liver retraction using a silicone disc and needle forceps in laparoscopic gastrectomy is easy and safe, offering a good visual field and a reduced degree of liver dysfunction.

In a 65-year-old woman, anemia was observed during outpatient follow-up after right lung cancer surgery, and upper gastrointestinal endoscopy was performed for examination.Gastrointestinal endoscopy revealed a Type 2 tumor on the small curvature in the middle part of the stomach, and she was diagnosed with gastric cancer.Distal gastrectomy with D2 lymph node dissection and BillrothⅠ reconstruction was performed for the gastric cancer.There were no postoperative complications, and she was discharged on the ninth day after surgery.The pathological diagnosis was gastric cancer, ML, Less, Type 2, 67×55×15 mm, muc>sig>por, pT4a(SE)N2M0, fStage ⅢB.S -1 adjuvant chemotherapy was administered, but then discontinued in the second course due to the development of adverse events.Reflux symptoms appeared after the surgery, and her dietary intake was poor.Her body weight and serum albumin level at 3 and 5 months after surgery were 51 kg and 52.5 kg, respectively, and 3.2 g/dL and 2.7 g/dL, respectively.Because there was no improvement in the reflux symptom, oral administration of acotiamide hydrochloride was initiated 7 months after the surgery.After initiating oral intake of acotiamide hydrochloride, her dietary intake improved, and her body weight and serum albumin level at 11 and 15 months after surgery were 54 kg and 57 kg, respectively, and 3.0 g/dL and 2.7 g/dL, respectively.Peritoneal recurrence was observed 23 months after surgery, and her oral intake decreased, but the recurrence of reflux symptoms was not observed.Acotiamide hydrochloride could be an option for the treatment of reflux symptoms after gastrectomy.

We experienced a case of early gastric cancer. A 69-year-old woman with a thick gastric wall, thickened folds, and undifferentiated cancer cells in biopsy was diagnosed with scirrhous gastric cancer. The patient underwent total gastrectomy for scirrhous gastric cancer and was found to have only an early gastric cancer lesion located on the upper gastric wall. The thick wall diagnosed before surgery was diagnosed as angiodysplasia occupying the submucosal layer.

A 66-year-old woman diagnosed with advanced Stage Ⅳ gastric cancer(T4aN3M1[LYM])received RAM plus wPTX as third-line chemotherapy(ramucirumab 8mg/kg on the 1st and 15th day, paclitaxel 80mg/m2 on the 1st, 8th, and 15th day).After receiving 3 courses of this treatment, para-aortic lymphadenopathy had diminished but anemia had progressed because of tumor hemorrhage.Six weeks after the last administration of RAM, an open distal gastrectomy with D1 plus lymph node dissection and Billroth Ⅰ reconstruction was performed.The patient was discharged on the 9th day after surgery without complications such as postoperative bleeding and delayed wound healing.RAM plus wPTX therapy was restarted 6 weeks after the operation.Postoperative late complication there is no adverse event including adenocarcinoma and continues the same therapy at present.The perioperative treatment under the use of angiogenesis inhibitor has risk of postoperative bleeding and wound healing delay and includes surgery timing of treatment may be difficult.In our case, surgery was performed 6 weeks after the final administration of RAM.

Background: Body weight, especially lean body mass, significantly decreases after gastrectomy. Postoperative surgical complications are a major risk factor for changes in body weight and body composition after gastrectomy. However, the influence of postoperative surgical complications after gastrectomy on body weight and body composition changes remains unclear., Patients and Methods: This retrospective study examined patients who underwent curative surgery for gastric cancer between May 2010 and February 2017. Their body weight and composition were evaluated by a bioelectrical impedance analyzer within 1 week before surgery, and at 1 week, 1 month and 3 months after surgery. Patients were classified as those with surgical complications and those without., Results: Eight hundred and eighty-eight patients (156 in the group with complications and 732 in the group without) were entered in the present study. When comparing the two groups, the patients' background and surgical factors significantly differed, while the pathological findings were similar. The body weight losses at 1 week, 1 month, and 3 months after surgery were 3.8%, 7.0%, and 10.4%, respectively, in those with complications, and 3.3%, 5.6%, and 6.8%, respectively, in the group without, with p-values of 0.001, 0.002, and 0.001, respectively. The corresponding lean body mass losses were 3.7%, 6.5%, and 6.8%, and 3.2%, 4.2%, and 3.5%, respectively, with p-values of 0.001, 0.001, and 0.001, respectively., Conclusion: Decreases in body weight and lean body mass after gastrectomy were more serious in the patients with surgical complications than in those without. To maintain body weight and lean body mass in patients with surgical complications, additional care or treatments are needed., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Body weight, especially lean body mass, significantly decreases after gastrectomy for gastric cancer due to surgical invasion, reduced food intake, and reduced mobility, which can reduce the quality of life and induce associated toxicity or reduce compliance with adjuvant chemotherapy. Such risks can be particularly high in elderly patients with gastric cancer. However, whether or not changes in the weight and body composition differ between elderly and non-elderly patients remains unclear., Patients and Methods: This retrospective study examined patients who underwent curative surgery for gastric cancer between May 2010 and February 2017. Body weight and composition were evaluated by a bioelectrical impedance analyzer within 1 week before surgery, at 1 week after surgery, and at 1 and at 3 months after surgery. Patients were classified as elderly (≥80 years) or non-elderly (<80 years)., Results: Eight-hundred and eighty-eight patients (84 elderly and 804 non-elderly) were entered into the present study. Patient background, surgical and clinicopathological factors, and surgical complications did not significantly differ between the two groups. Body weight loss at 1 week, and at 1 and 3 months after surgery, defined as the decrease from the preoperative value, were -2.8%, -6.5%, and -9.0%, respectively, in the elderly and -3.5%, -6.0%, and -8.1%, respectively, in the non-elderly patients (p=0.111, 0.125, and 0.153, respectively). The corresponding losses of lean body mass were -2.6%, -6.0%, and -6.4%, respectively, in the elderly and -3.5%, -4.9%, and -4.7%, respectively, in the non-elderly patients, with p-values of 0.056, 0.036, and 0.029, respectively., Conclusion: Decreases in lean body mass after gastrectomy were greater in elderly than in non-elderly patients. In order to maintain lean body mass among elderly patients, additional care and treatments are needed., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The natural amino acid 5-aminolevulinic acid (ALA) is a protoporphyrin IX (PpIX) precursor and a new-generation photosensitive substance that accumulates specifically in cancer cells. When indocyanine green (ICG) is irradiated with near-infrared (NIR) light, it shifts to a higher energy state and emits infrared light with a longer wavelength than the irradiated NIR light. Photodynamic diagnosis (PDD) using ALA and ICG-based NIR fluorescence imaging has emerged as a new diagnostic technique. Specifically, in laparoscopic examinations for serosa-invading advanced gastric cancer, peritoneal metastases could be detected by ALA-PDD, but not by conventional visible-light imaging. The HyperEye Medical System (HEMS) can visualize ICG fluorescence as color images simultaneously projected with visible light in real time. This ICG fluorescence method is widely applicable, including for intraoperative identification of sentinel lymph nodes, visualization of blood vessels in organ resection, and blood flow evaluation during surgery. Fluorescence navigation by ALA-PDD and NIR using ICG imaging provides good visualization and detection of the target lesions that is not possible with the naked eye. We propose that this technique should be used in fundamental research on the relationship among cellular dynamics, metabolic enzymes, and tumor tissues, and to evaluate clinical efficacy and safety in multicenter cooperative clinical trials.