Search

The detection of copy number variations (CNVs) and somatic mutations in cancer is important for the selection of specific drugs for patients with cancer. In cancers with sporadic tumor cells, low tumor content prevents the accurate detection of somatic alterations using targeted sequencing. To efficiently identify CNVs, we performed tumor cell enrichment using tissue suspensions of formalin-fixed paraffin-embedded (FFPE) tissue sections with low tumor cell content. Tumor-enriched and residual fractions were separated from FFPE tissue suspensions of intestinal and diffuse-type gastric cancers containing sporadic tumor cells, and targeted sequencing was performed on 225 cancer-related genes. Sequencing of a targeted panel of cancer-related genes using tumor-enriched fractions increased the number of detectable CNVs and the copy number of amplified genes. Furthermore, CNV analysis using the normal cell-enriched residual fraction as a reference for CNV scoring allowed targeted sequencing to detect CNV characteristics of diffuse-type gastric cancer with low tumor content. Our approach improves the CNV detection rate in targeted sequencing with tumor enrichment and the accuracy of CNV detection in archival samples without paired blood., (© 2024. The Author(s).)

Background: Laparoscopic gastrectomy (LG) indications have been extended to advanced gastric cancer requiring expansive lymph node dissection. Despite the huge benefits of this minimally invasive surgery, major complications such as postoperative pancreatic fistula (POPF) remain a concern. With technical advances in surgical procedures, the treatment outcomes of gastric cancer surgery have improved. However, effective methods for preventing POPF have not yet been established. Herein, we examined the usefulness of polyglycolic acid (PGA) sheets for preventing POPF after LG., Methods: We retrospectively assessed 142 patients who underwent curative LG at our institution between January 2017 and August 2022. The 142 patients were divided into 2 groups; PGA group (n = 61): the site of lymph node dissection at the superior margin of the pancreas and pancreatic head was covered with PGA sheets, and nPGA group (n = 81): the site was not covered. We retrospectively compared the short-term surgical outcomes including POPF incidence., Results: There was no significant difference in the background factors between the 2 groups and in the incidence of Grade II or higher postoperative complications according to the Clavien-Dindo (CD) classification. However, the incidence of CD Grade II or higher POPF was significantly lower in the PGA group than in the nPGA group (.0% vs 2.3%, respectively, P = .007)., Conclusions: There was no POPF in any of the 61 patients in the PGA group. This outcome suggests that POPF incidence may be reduced by covering the lymph node dissection site with PGA sheets after LG., Competing Interests: Declaration of Conflicting InterestsThe authors declare that they have no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Lipopolysaccharides are a type of polysaccharide mainly present in the bacterial outer membrane of Gram-negative bacteria. Recent studies have revealed that lipopolysaccharides contribute to the immune response of the host by functioning as a cancer antigen. We retrospectively recruited 198 patients with gastric cancer who underwent surgery. The presence of lipopolysaccharides was determined using immunohistochemical staining, with the intensity score indicating positivity. The relationship between lipopolysaccharides and CD8, PD-L1, TGFBI (a representative downstream gene of TGF-β signaling), wnt3a, and E-cadherin (epithelial-mesenchymal transition marker) was also investigated. Thereafter, we identified 20 patients with advanced gastric cancer receiving nivolumab and investigated the relationship between lipopolysaccharides and nivolumab sensitivity. After staining for lipopolysaccharides in the nucleus of cancer cells, 150 negative (75.8%) and 48 positive cases (24.2%) were found. The lipopolysaccharide-positive group showed increased cancer stromal TGFBI expression ( p < 0.0001) and PD-L1 expression in cancer cells ( p = 0.0029). Lipopolysaccharide positivity was significantly correlated with increased wnt3a signaling ( p = 0.0028) and decreased E-cadherin expression ( p = 0.0055); however, no significant correlation was found between lipopolysaccharide expression and overall survival rate ( p = 0.71). In contrast, high TGFBI expression in the presence of LPS was associated with a worse prognosis than that in the absence of LPS ( p = 0.049). Among cases receiving nivolumab, the lipopolysaccharide-negative and -positive groups had disease control rates of 66.7% and 11.8%, respectively ( p = 0.088). Lipopolysaccharide positivity was associated with wnt3a, TGF-β signaling, and epithelial-mesenchymal transition and was considered to tend to promote therapeutic resistance to nivolumab.

Background: Remnant gastric cancer (RGC) encompasses all cancers arising from the remnant stomach. Various studies have reported on RGC and its prognosis, but no consensus on its surgical treatment and postoperative management has been reached. Moreover, the correlation between the clinicopathological characteristics and long-term outcomes of RGC remains unclear. This study investigated the clinicopathological factors associated with the long-term survival of RGC patients., Methods: The medical records (March 1993-September 2020) of 104 RGC patients from Tokyo Medical University Hospital database were analyzed. Of these 104 patients, the medical records of 63 patients who underwent surgical curative resection were analyzed using R. Kaplan-Meier plots of cumulative incidence of RGC were made. Differences in survival rates were compared using the log-rank test. Prognostic factors were analyzed using multivariate Cox regression analysis ( P < .05)., Results: Of the 104 RGC patients, 63 underwent total remnant stomach excision. The median time from the first surgery to the total excision was 10 years. The 5-year survival rate of the 63 RGC patients was .55 ((95% CI); .417-.671). The clinicopathological factors that were significantly associated with the long-term outcome of the RGC patients were tumor diameter (≥3.5 cm), presence or absence of combined resection of multiple organs, tumor invasion (deeper than T2), TNM stage, and postoperative morbidity. The multivariate Cox regression analysis showed that tumor invasion depth was the only independent prognostic factor for RGC patients [HR (95% CI): 5.49 (2.629-11.5), P ≤ .005]., Conclusions: Among prognostic factors, tumor invasion depth was the only independent factor affecting RGC's long-term outcome.

Background and Aim: Linked color imaging (LCI) is useful for screening in the gastrointestinal tract; however, its true clinical benefit has not been determined. The aim of this study was to determine the objective advantage of LCI for detection of upper gastrointestinal neoplasms., Methods: Nine endoscopists, including three novices, three trainees, and three experts, prospectively performed eye tracking. From 30 cases of esophageal or gastric neoplasm and 30 normal cases without neoplasms, a total of 120 images, including 60 pair images of white light imaging (WLI) and LCI taken at the same positions and angles, were randomly shown for 10 s. The sensitivity of tumor detection as a primary endpoint was evaluated and sensitivities by organ, size, and visual gaze pattern were also assessed. Color differences (ΔE using CIE1976 [L*a*b*]) between lesions and surrounding mucosa were measured and compared with detectability., Results: A total of 1080 experiments were completed. The sensitivities of tumor detection in WLI and LCI were 53.7% (50.1-56.8%) and 68.1% (64.8-70.8%), respectively (P = 0.002). LCI provided higher sensitivity than WLI for the novice and trainee groups (novice: 42.2% [WLI] vs 65.6% [LCI], P = 0.003; trainee: 54.4% vs 70.0%, P = 0.045). No significant correlations were found between sensitivity and visual gaze patterns. LCI significantly increased ΔE, and the diagnostic accuracy with WLI depended on ΔE., Conclusions: In conclusion, LCI significantly improved sensitivity in the detection of epithelial neoplasia and enabled epithelial neoplasia detection that is not possible with the small color difference in WLI. (UMIN000047944)., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: We investigated whether the infiltration of tumor-infiltrating lymphocytes (TILs) in gastric cancer (GC), as evaluated by hematoxylin and eosin (H&E) staining, could be a prognostic marker. We also explored on the relationship between TILs and mechanistic target of rapamycin (mTOR) and how it regulates immune effector responses in GC., Methods: A total of 183 patients with available data on TIL were included. TIL infiltration was evaluated using H&E staining. We also conducted immunohistochemistry to determine mTOR expression., Results: Positive TIL infiltration was defined as TILs ≥20%. There were 72 (39.3%) and 111 (60.7%) positive and negative cases, respectively. TILs positivity significantly correlated with both absence of lymph node metastasis (p = 0.037) and negative p-mTOR expression (p = 0.040). TIL infiltration correlated with a significantly better overall (p = 0.046) and disease-free (p = 0.020) survival., Conclusion: mTOR possibly suppresses TIL infiltration in GC. H&E staining is an effective tool for evaluating the immune status of GC patients. H&E staining may be used in clinical practice to monitor treatment response in GC., (© 2023 S. Karger AG, Basel.)

Background: Splenic hilar lymphadenectomy is not recommended for advanced proximal gastric cancer that does not invade the greater curvature according to the results of the previous studies. The efficacy of splenic hilar lymphadenectomy for type II and type III adenocarcinomas of the esophagogastric junction and easy spread to the greater curvature of the stomach remains unclear. This study aimed to investigate the efficacy of splenic hilar lymphadenectomy and identify the risk factors for metastasis to splenic hilar nodes., Methods: We examined patients who underwent R0/1 gastrectomy for Siewert types II and III at a single high-volume center in Japan. We analyzed the metastatic incidence, therapeutic value index, and risk factors for splenic hilar lymph node metastasis., Results: We examined 126 patients (74, type II; 52, type III). Splenectomy was performed in 76 patients. Metastatic incidence and the therapeutic value index of splenic hilar lymph nodes in patients with type II and type III tumors were 4.5% and 0, and 21.9% and 9.4, respectively. In the patients who underwent splenectomy, we identified Siewert type III tumors (odds ratio: 6.93, 95% confidence interval: 1.24-38.8, p = 0.027) and tumor location other than the lesser curvature (odds ratio: 7.36, 95% confidence interval: 1.32-41.1, p = 0.023) to be independent risk factors. The metastatic incidence (46.2%) and therapeutic value index (15.4) were high in patients with both risk factors., Conclusions: Splenic hilar lymphadenectomy may contribute to the survival of patients with Siewert type III tumors, especially when the predominant location is not the lesser curvature., Competing Interests: Declaration of competing interest Yasushi Rino has received speaker honorariums and research grants from Daiichi Sankyo, Johnson & Johnson, Otsuka, Lilly, Taiho Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, Abbott Nutrition, Asahi Kasei, Tsumura & Co., Covidien, Zeria Pharmaceutical and EA Pharma. The other authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: Despite improvements in surgical techniques and devices and perioperative care of gastric cancer (GC), the rate of postoperative complications still has not decreased. If patients at high risk for postoperative complications could be identified early using biomarkers, these complications might be reduced. In this study, we investigated usefulness of the preoperative Glasgow Prognostic Score (GPS) as a predictive factor for complications after surgery in patients with stage II/III GC., Methods: This study retrospectively analyzed the outcomes of 424 patients who underwent curative surgery for pathological stage II/III GC from February 2007 to July 2019 at a single center. The GPS was assessed within 4 days before surgery. To identify independent risk factors for postoperative complications, univariate and multivariate analyses were performed using a Cox proportional hazards model., Results: The numbers of patients with a GPS of 0, 1, and 2 were 357, 55, and 12, respectively. The rate of complications after surgery was significantly higher among patients with a GPS of 1 or 2 than among patients with a GPS of 0 (p = 0.008). Multivariate analysis identified a GPS of 1 or 2 as an independent predictive factor for postoperative complications (p = 0.037)., Conclusion: The preoperative GPS may be a useful predictive factor for postoperative complications in patients with stage II/III GC. Being aware of the risk of complications after surgery as indicated by the GPS before surgery may promote safe and minimally invasive surgery that we expect will improve outcomes in patients with a GPS of 1 or 2., (© 2021. The Author(s).)

Background: A persistently high methylation level in gastric mucosa after Helicobacter pylori (H. pylori) eradication is presumed to be a risk for metachronous gastric cancer (MGC); however, long-term changes in aberrant DNA methylation and histological gastritis have been unclear. Our aim was to examine changes in DNA methylation and histological gastritis according to the occurrence of MGC., Methods: Subjects were classified into three groups: 25 patients in whom MGCs occurred after the initial endoscopic resection (ER) for early gastric cancer and H. pylori eradication (MGC group), 17 patients in whom MGC did not occur for more than 5 years after the initial ER and H. pylori eradication (non-MGC group) and 29 patients without a history of gastric cancer who succeeded in eradication more than 5 years ago (HP group). Aberrance of DNA methylation in three genes (miR-124a-3, EMX1, NKX6-1) and histological score of atrophy and intestinal metaplasia (IM) were evaluated using biopsy samples before and more than a mean of 5 years after H. pylori eradication. Also, the mean Z-score was calculated using Z-score values of the three genes., Results: The methylation level of miR-124a-3 in the HP group and non-MGC group and that of EMX1 in the HP group significantly decreased in the long term after eradication. In the MGC group, H. pylori eradication did not improve aberrant methylation, and the mean Z-score significantly increased. There were significant positive correlations between methylation levels in miR-124a-3 and EMX1 and histological findings after eradication., Conclusions: A persistently high methylation level after H. pylori eradication reflected precancerous mucosal conditions and led to long-term MGC., (© 2022 John Wiley & Sons Ltd.)

Introduction: Patients requiring total gastrectomy for gastric cancer experience a decrease in food intake leading to severe body weight loss after surgery. This loss may be prevented using a high-density liquid diet of high caloric content and minimal volume. This phase II study evaluated the feasibility and safety of a high-density liquid diet (UpLead ® ; Terumo Corporation, Tokyo, Japan) after total gastrectomy., Methods: UpLead ® (1 pack, 100 mL, 400 kcal/day) was administered after surgery for 28 days. The primary endpoint was the % relative dose intensity of 28 days of UpLead intake ® . The secondary endpoint was % body weight loss at 1 and 3 months after surgery. The sample size was 35 considering expected and threshold values of 80 and 60%, respectively, with a one-sided alpha error of 10% and statistical power of 80%., Results: Among 35 patients enrolled before surgery between April 2018 and December 2019, 29 patients who could initiate UpLead ® after surgery were analyzed. Seven patients had interrupted UpLead ® intake due to taste intolerance (n = 6) and due to a duodenal stump fistula (n = 1). The remaining 22 patients completed 28 days of UpLead ® intake, including temporary interruption, with no associated adverse events. The median relative dose intensity was 25.8% (95% confidence interval: 20.6-42.0%). The median body weight loss at 1 and 3 months after surgery was 7.2% (range: 3.2-13.9%) and 13.1% (range: 2.5-20.4%), respectively., Conclusions: Oral nutritional supplementation with a high-density liquid diet (UpLead ® ) was safely administered but was not feasible after total gastrectomy for gastric cancer. Clinical trial registration number UMIN000032291., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

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.)

Purpose: To assess the utility of the Glasgow Prognostic Score (GPS) obtained before curative resection for predicting outcomes in patients with advanced gastric cancer (GC)., Methods: This study retrospectively analyzed the outcomes of 337 consecutive patients with GC who underwent curative surgery for locally advanced gastric cancer between January 2003 and June 2014. GPS was assessed within 4 days prior to surgery., Results: The number of patients with GPS scores of 0, 1, and 2 was 302, 26, and 9, respectively. There was significantly more blood loss during surgery and more postoperative complications in the GPS 1/2 group than in the GPS 0 group. Patients in the GPS 1/2 group had significantly poorer overall survival than those in the GPS 0 group (p = 0.001). On multivariate analysis, GPS 1/2 was identified as an independent factor for poor survival (p = 0.019)., Conclusion: GPS before curative resection might be a useful predictive factor for perioperative complications and survival in locally advanced GC., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Neuroendocrine carcinoma (NEC) and mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) are extremely rare subtypes of gastric cancer. MiNEN is a mix of carcinomatous components and neuroendocrine neoplasm in the same lesion. NEC and MiNEN have a poor prognosis, are difficult to diagnose, and have no established treatment. Herein, we assessed the clinicopathological characteristics and long-term surgical outcomes of gastric NEC and MiNEN patients in our hospital., Methods: We retrospectively assessed 1538 patients pathologically diagnosed with gastric cancer and who underwent curative surgical resection at our institution between January 1999 and October 2021. Of these patients, 25 (1.6%) were pathologically diagnosed with neuroendocrine neoplasms. From these 25 patients, we retrospectively analyzed the clinicopathological characteristics and surgical outcomes of 13 (0.8%) patients pathologically diagnosed with NEC or MiNEN., Results: The NEC and MiNEN patients consisted of 11 men and 2 women [mean age, 74 (62-84) years]. The preoperative histological diagnoses were NEC (n = 4) and adenocarcinoma (n = 9). The final pathological diagnoses were large cell neuroendocrine carcinoma (LCNEC; n = 7) and MiNEN (n = 6). Total gastrectomy was the most common surgical procedure (9/13, 69.2%), followed by distal gastrectomy (3/13, 23.1%) and proximal gastrectomy (1/13, 7.7%). Immunohistochemical staining showed 8 CD56-positive patients. All 13 patients were positive for chromogranin A and synaptophysin. The mean Ki-67 value was 64.8 (0-95)%, and the mean mitotic score was 107.9 (0-400). Nine patients survived without recurrence postresection. The median postresection overall survival time was 68.7 (8.0-129) months. The 5-year survival rate was 0.75 ([95% CI] 0.408-0.912)., Conclusion: The surgical treatment outcomes of NEC and MiNEN patients were relatively favorable. Although evidence concerning the effectiveness of surgery alone is meager, radical resection as part of multidisciplinary treatment including chemotherapy can potentially improve prognosis., (© 2022. The Author(s).)

Targeted sequencing offers an opportunity to select specific drugs for cancer patients based on alterations in their genome. However, accurate sequencing cannot be performed in cancers harboring diffuse tumor cells because of low tumor content. We performed tumor cell enrichment using tissue suspension of formalin-fixed, paraffin-embedded (FFPE) tissue sections with low tumor cell content. The enriched fractions were used to efficiently identify mutations by sequencing a target panel of cancer-related genes. Tumor-enriched and residual fractions were isolated from FFPE tissue sections of intestinal and diffuse gastric cancers harboring diffuse tumor cells and DNA of suitable quality was isolated for next-generation sequencing. Sequencing of a target panel of cancer-related genes using the tumor-enriched fraction increased the number of detectable mutations and variant allele frequency. Furthermore, mutation analysis of DNA isolated from tumor-enriched and residual fractions allowed us to estimate germline mutations without a blood reference. This approach of tumor cell enrichment will not only enhance the success rate of target panel sequencing, but can also improve the accuracy of detection of somatic mutations in archived specimens., (© 2022. The Author(s).)

Introduction: We investigated whether the expression of prospero homeobox protein-1 (PROX1) in gastric cancer (GC) could be a prognostic marker. We also focused on the relationship between PROX1 and LGR5 and Wnt/β-catenin activity in GC., Methods: A total of 196 patients who underwent potentially curative surgery were collected and reviewed retrospectively. Immunohistochemistry was conducted and evaluated the expression PROX1, LGR5, Wnt3a, and β-catenin expression. And we evaluated the relationship between PROX1 expression and clinicopathological features., Results: The PROX1 low-expression group consisted of 105 patients (53.6%) and the high-expression group consisted of 91 patients (46.4%). For LGR5 expression, 76 patients (38.8%) were classified as low-expression, and 120 patients (61.2%) were classified as high-expression. The PROX1 low-expression group was significantly younger (p = 0.0095), had more intestinal type (p = 0.014), and had smaller tumor size (p = 0.013). The PROX1 high-expression group was significantly correlated with high LGR5 expression (p < 0.0001) and high Wnt3a expression (p = 0.012). In addition, there were significantly more cases of postoperative recurrence in the PROX1 high-expression group (p = 0.013)., Conclusion: Our findings demonstrate that PROX1 correlated with the cancer stemness markers LGR5 and Wnt3a signaling in GC and had a poor prognosis including postoperative recurrence., (© 2022 S. Karger AG, Basel.)

Background/aim: The changes of dietary intake (DI) after gastrectomy have not been objectively reported. It has not been clear how much DI loss is experienced after total gastrectomy (TG) in comparison to after distal gastrectomy (DG). This study quantified the changes of DI after gastrectomy, and clarified how much DI loss is experienced after TG., Patients and Methods: This was a prospective observational study. Patients who underwent gastrectomy for gastric cancer were enrolled. The DI loss was evaluated at 1 and 3 months postoperatively., Results: Thirty-three patients underwent TG, and 117 patients underwent DG. The median %DI loss of the overall study population at 1 and 3 months after surgery was -9.3% and -3.6%. The median %DI loss at 1 and 3 months postoperatively was -15.6% and -5.3% in TG group, -8.9% and -3.3% in DG group (p=0.10 and 0.49, respectively)., Conclusion: The patients experienced DI loss of approximately 10% at 1 month after gastrectomy. Patients who received TG tended to show a greater %DI loss at 1 month postoperatively., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Laparoscopic gastrectomy has become a standard procedure for treatment of gastric cancer, and hence, the opportunity for trainees to perform open gastrectomies may decrease. We investigated whether laparoscopic distal gastrectomy, performed by surgical trainees without sufficient experience performing open gastrectomies, was feasible and safe., Patients and Methods: We compared short-term outcomes in patients when laparoscopic distal gastrectomies were performed by experienced trainees (ET group; n = 124) and inexperienced trainees (IT group; n = 98) from 2013 to 2019., Results: The operation time was significantly shorter in the ET group (median time: 253 minutes vs 286 minutes, P < 0.001). The incidence of grade ≥ 2 postoperative complications did not differ significantly between the groups. In the multivariate analysis, experience performing open gastrectomies was not an independent predictor of postoperative complications., Conclusion: Laparoscopic distal gastrectomies performed by trainees, with insufficient experience performing open gastrectomies, are as feasible and safe as that performed by ET., (© 2020 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Background/aim: To identify prognostic factors for patients with stage IV gastric cancer (GC) and a single stage IV factor before chemotherapy who underwent conversion surgery (R0 resection)., Patients and Methods: This study retrospectively analysed 32 GC patients with a single stage IV factor before chemotherapy and who underwent conversion surgery (R0 resection) between January 2001 and September 2015. The univariate and multivariate analyses were performed to identify independent prognostic factors., Results: The five-year survival rate was 39.6%, and the median survival time was 47.0 months. In the univariate analysis, diffuse-type according to Lauren classification was significantly associated with worse overall survival (p<0.001). In the multivariate analysis, diffuse-type was selected as an independent prognostic factor (hazard ratio=15.970, 95% confidence interval=3.804-67.043, p<0.001)., Conclusion: Diffuse-type may be a useful prognostic factor in GC patients with a single stage IV factor who undergo conversion surgery (R0 resection)., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Programmed death-ligand 1 (PD-L1) expression is a prognostic marker for gastric cancer that correlates with tumor diameter and depth of penetration. But the role of PD-L1 and mechanism(s) employed in the initial phase of invasion in early gastric cancer is yet to be understood., Objective: This study aims to elucidate the role of PD-L1 during the progression of gastric cancer, specifically invading the submucosa beyond the lamina muscularis mucosa., Methods: Using 107 patients with pathological submucosal gastric cancer, we determined the expression of PD-L1 based on the staining of the cell membrane or cytoplasm of tumor cells in the central and invasive front of the tumor. Samples were categorized into 3 groups based on the intensity of PD-L1 expression. CD8+ lymphocytes expressing PD-1 and CD163+ macrophages were used to determine the number of cell nuclei at the invasive front, similar to PD-L1. CMTM6 levels were determined and used to stratify samples into 3 groups., Results: PD-L1 expression was higher in the invasive front (26.2%) than in the central portion of the tumors (7.4%; p < 0.001). Moreover, lymphatic and vascular invasion were more frequently observed in samples with high levels of PD-L1 (lymphatic invasion: 60.7 vs. 35.4%, p = 0.0026, and vascular invasion: 39.3 vs. 16.5%, p = 0.0018). There was no correlation between PD-L1 expression and the levels of PD-1, CD8, CD163, and CMTM6., Conclusions: PD-L1-expressing cancer cells at the invasive front of gastric cancer influence the initial stages of tumor invasion and lymphovascular permeation in early-stage gastric cancers. Immune checkpoint signaling may be the driving force in the invasive front during the invasion of the submucosa beyond the lamina muscularis mucosa., (© 2020 S. Karger AG, Basel.)

Introduction: We investigated whether the expression of L-type amino acid transporter 1 (LAT-1) in clinical gastric cancer (GC) patients could predict patient therapeutic response to postoperative adjuvant chemotherapy., Methods: Immunohistochemistry was used to investigate LAT-1, CD98, and phosphorylated-mammalian target of rapamycin (p-mTOR) expression in 111 GC patients. To clarify whether LAT-1 influences the therapeutic effects of chemotherapy, the correlation between disease-free survival rates and LAT-1 was determined in 2 groups: 59 patients who did not undergo postoperative adjuvant chemotherapy and 52 patients who did undergo postoperative adjuvant chemotherapy., Results: LAT-1 was significantly correlated with CD98 and p-mTOR expressions. We did not find any statistically significant correlation between LAT-1 and recurrence in the nontreated group. In contrast, a significant association was found between LAT-1 expression and disease-free survival in the chemotherapy group. Moreover, multivariate regression analysis demonstrated that LAT-1 was an independent predictor of disease-free survival in the postoperative adjuvant chemotherapy group (p = 0.012)., Conclusion: Our findings demonstrate that LAT-1 is a useful predictive marker for a successful postoperative adjuvant chemotherapy treatment., (© 2021 S. Karger AG, Basel.)

Background: Lymph node ratio (LNR), defined as the ratio of metastatic nodes to the total number of examined lymph nodes, has been proposed as a sensitive prognostic factor in patients with gastric cancer (GC). We investigate its association with survival in pathological stage (pStage) II/III GC and explore whether this is a prognostic factor in each Union for International Cancer Control pStage (7th edition)., Patients and Methods: We retrospectively examined 838 patients with pStage II/III GC who underwent curative gastrectomy between June 2000 and December 2018. Patients were classified into low-LNR (L-LNR), middle-LNR (M-LNR), and high-LNR (H-LNR) groups according to adjusted X-tile cutoff values of 0.1 and 0.25 for LNR, and their clinicopathological characteristics and survival rates were compared., Results: The 5-year recurrence-free survival (RFS) and overall survival (OS) rates postsurgery showed significant differences among the groups (P < 0.001). Multivariate analysis demonstrated that LNR was a significant predictor of poor RFS [M-LNR: hazard ratio (HR) 3.128, 95% confidence interval (CI) 2.254-4.342, P < 0.001; H-LNR: HR 5.148, 95% CI 3.546-7.474, P < 0.001] and OS (M-LNR: HR 2.749, 95% CI 2.038-3.708, P < 0.001; H-LNR: HR 4.654, 95% CI 3.288-6.588, P < 0.001). On subset analysis stratified by pStage, significant differences were observed between the groups in terms of the RFS curves of pStage II and III GC (P < 0.001 and < 0.001, respectively) and OS curves of pStage II and III GC (P = 0.001 and < 0.001, respectively)., Conclusions: High LNR is a predictor of worse prognosis in pStage II/III GC, including each substage.

Background: In 2017, nivolumab monotherapy was shown to be effective as third- or later-line therapy in patients with advanced gastric or gastroesophageal junction cancer., Objective: In this study, we investigated the relationship between the neutrophil-to-lymphocyte ratio (NLR) and the outcomes of nivolumab monotherapy in patients with gastric or gastroesophageal junction cancer., Patients and Methods: The long-term outcomes and treatment responses to nivolumab monotherapy were assessed in patients with gastric or gastroesophageal junction cancer. We compared patients with a NLR > 2.5 and those with a NLR ≤ 2.5 at the time of starting nivolumab monotherapy., Results: The proportion of patients who have received three or more regimens was higher in the NLR > 2.5 group than in the NLR ≤ 2.5 group. The disease control rate was significantly worse in the NLR > 2.5 group than in the NLR ≤ 2.5 group (23% and 46%, respectively; p = 0.044). Overall survival was significantly better in the NLR ≤ 2.5 group than in the NLR > 2.5 group. Multivariate analysis showed that the macroscopic type, primary site resection, and the NLR were independent prognostic factors for overall survival (hazard ratio [95% confidence interval], 2.586 [1.286-5.203], 0.473 [0.260-0.861], and 1.736 [1.007-2.992], respectively)., Conclusions: This study demonstrates that the NLR is an independent prognostic factor in patients with gastric or gastroesophageal junction cancer treated with nivolumab monotherapy. Careful attention must be paid when nivolumab monotherapy is used to treat patients with gastric cancer with a NLR > 2.5.

Background: Cancer cells are often found postoperatively at surgical resection margins (RM) in patients with gastric cancer because of submucosal infiltration or hesitation to secure adequate RM. This study was designed to evaluate risk factors for microscopic positive RM and to clarify which patients should undergo intraoperative frozen section diagnosis (IFSD)., Methods: Patients who underwent R0/1 gastrectomy for gastric adenocarcinoma between 2000 and 2018 in a single cancer center in Japan were studied. We divided the patients into a positive RM group and negative RM group according to the results of definitive histopathological examinations. We performed multivariate analysis to analyze risk factors for positive RM by and used the identified risk factors to risk stratify the patients., Results: A total of 2757 patients were studied, including 49 (1.8%) in the positive RM group. The risk factors significantly associated with positive RM were remnant gastric cancer (odds ratio [OR] 4.7), esophageal invasion (OR 6.3), tumor size ≥80 mm (OR 3.9), and a histopathological diagnosis of undifferentiated type (OR 3.6), macroscopic type 4 (OR 3.7), or pT4 disease (OR 4.6). On risk stratification analysis, the incidence of positive RM was 0.1% without any risk factors, increasing to 0.4% with one risk factor, 3.1% with two risk factors, 5.3% with three risk factors, 21.3% with four risk factors, and 85.7% with five risk factors., Conclusions: The risk of macroscopically positive RM increased in patients who have risk factors. IFSD should be performed in patients who have four or more risk factors.

Background/aim: Lymphovascular invasion (LVI) is recognized as a prognostic predictor of recurrence in certain carcinomas. According to current Japanese guidelines, however, in gastric cancer, LVI is not clinically useful information, except for predicting the curability of endoscopic resection. We clarified the clinical significance of LVI in gastric cancer and its correlation with disease prognosis., Patients and Methods: A total of 2,090 cases of gastric cancer undergoing radical gastrectomy were enrolled. The correlation of LVI and other histopathological factors was evaluated with regards to patient prognosis., Results: LVI(+) was noted in 894 cases. A multivariate analysis showed that pT, pN, and LVI were independent risk factors for patient prognosis. In pT2-4 patients with nodal metastasis, a significant difference was revealed, and the 5-year overall survival rates in LVI(+) cases were lower than those in LVI(-) (60.9% vs. 76.7%, p=0.005)., Conclusion: LVI in gastric cancer is an independent prognostic factor, and tends to worsen prognosis, especially in advanced cancers with lymph node metastases., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: We propose a novel technique to close Petersen's defect using barbed sutures and evaluate the safety and usefulness of this technique by assessing postoperative complications and measuring the time required to close Petersen's defect., Materials and Surgical Technique: Petersen's defect was closed laparoscopically with running non-absorbable barbed sutures (V-loc®) after a nodal dissection and reconstruction procedure. First, the transverse colon was elevated cranially, making the dorsal side of the transverse mesocolon a flattened surface. The intersection of the transverse mesocolon and Roux limb mesentery was then identified, and closure was started from this point. We continued to sew the transverse mesocolon and Roux limb mesentery toward the transverse colon with a running suture. At the end of suturing, we placed one or two stitches in the fatty appendices of the transverse colon and cut the free tail of thread as short as possible., Discussion: We investigated postoperative complications and measured the time required to close Petersen's defect in 64 patients who underwent this technique. The results showed that this closure technique could be performed promptly and safely regardless of the patient, surgical procedure, and the experience of the operator., (© 2019 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.)

Background: Surgery for gastric cancer should be performed as soon as possible after diagnosis. However, sometimes the waiting time for surgery tends to be longer. The relation between the waiting time for surgery and survival in patients with gastric cancer remains to be fully investigated., Methods: This retrospective, single-center cohort study evaluated patients with gastric cancer who underwent curative surgery from 2006 through 2012 at Kanagawa Cancer Center in Japan. Patients who received neoadjuvant chemotherapy were excluded. The waiting time for surgery was defined as the time between the first visit and surgery. We investigated whether the waiting time for surgery has a linear negative impact on outcomes by using a Cox regression model with clinical prognostic factors., Results: In total, 801 patients were eligible. The median waiting time was 45 days (range 10-269 days). The restricted cubic spline regression curve showed that the adjusted time-specific hazard ratios of waiting times did not indicate a linear negative trend on survival between 20 and 100 days (p = 0.759). In the Cox model with a quartile of waiting times, waiting times in the 32-44-day group, 43-62-day group, and ≥63 day groups were not associated with poorer overall survival as compared with the ≤31 day group (HR: 1.01, 95% CI 0.63-1.60, p = 0.984, HR: 1.17, 95% CI 0.70-1.94, p = 0.550, HR: 1.06, 95% CI 0.60-1.88, p = 0.831, respectively)., Conclusions: There was no negative relation between the waiting time for surgery (within 100 days) and survival in patients with gastric cancer.

Introduction: We retrospectively evaluated the blood coagulation activity using the D-dimer level in the early period after gastrectomy and investigated whether postoperative hypercoagulation affects tumor recurrence and long-term survival in gastric cancer patients., Methods: The study involved 650 patients who underwent curative resection for gastric cancer at Kanagawa Cancer Center between July 2009 and July 2013. They were divided into a low-D-dimer group (LD group) and high-D-dimer group (HD group) according to the median D-dimer level on postoperative day (POD) 7. The risk factors for overall survival (OS) and relapse-free survival (RFS) were identified., Results: Of the 448 enrolled patients, 218 were classified into the LD group and 230 into the HD group. The 5-year OS rates after surgery were 90.8% and 81.3% in the LD and HD groups, respectively (p < 0.001). The 5-year RFS rates after surgery were 89.9% and 76.1% in the LD and HD groups, respectively (p < 0.001). A high D-dimer level on POD 7 (≥ 4.9 μg/ml) was identified as an independent predictive factor for both the OS (hazard ratio [HR] 1.955, 95% confidence interval [CI] 1.158-3.303, p = 0.012) and RFS (HR 2.182, 95% CI 1.327-3.589, p = 0.002). Furthermore, hematological recurrence was significantly more frequent in the HD group than in the LD group (p = 0.014)., Conclusion: A high D-dimer level on POD 7 may predict tumor recurrence and the long-term survival in patients who undergo gastrectomy for locally advanced gastric cancer. Patients with an elevated postoperative D-dimer level need careful observation and diagnostic imaging to timely detect tumor recurrence.

Background/aim: To assess the prognostic effect of muscle loss after esophagectomy and before discharge., Patients and Methods: This study retrospectively analysed 159 consecutive patients with oesophageal and gastroesophageal junction cancer who underwent esophagectomy between August 2011 and October 2015. Body composition was evaluated one week before surgery and at discharge using a bioelectrical impedance analyser., Results: The median rate of muscle mass loss (RMML) was 4.38% (range=-3.3 to +18.8). Patients with increased RMML had significantly poorer outcomes of overall survival than those with decreased RMML (p=0.015). On multivariate analysis, RMML [≥4.38, hazard ratio (HR)=2.033, 95% confidence interval (CI)=1.018-5.924, p=0.044) and pathological tumour depth (≥2, HR=3.099, 95%CI=1.339-7.172, p=0.008) were selected as independent prognostic factors., Conclusion: RMML after esophagectomy is indicative of poor prognosis in patients with esophageal cancer., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: This study aimed to investigate the impact of postoperative complications (PCs) in patients with pathological stage (pStage) II or III gastric cancer (GC) who received adjuvant chemotherapy with S-1 after curative surgery., Patients and Methods: Altogether, data for 226 patients were examined retrospectively. The relationship between PCs and clinicopathological features and survival were examined., Results: Recurrence-free survival was significantly worse in the group with PCs than in the PC-negative group. On multivariate analysis, having PCs of grade 2 or more was an independent risk factor for recurrence (hazard ratio=1.721; 95% confidence intervaI=1.014-2.920; p=0.044). In addition, for each pStage analysis, having PCs of grade 2 or more was a risk factor for recurrence even in patients with pStage II GC., Conclusion: PC of grade 2 or more was an independent risk factor for recurrence in patients with pStage II GC who received adjuvant chemotherapy with S-1 after curative gastrectomy. Thus, for patients with PCs, even for those with pStage II GC, more effective adjuvant chemotherapy, such as S-1 plus docetaxel, may be needed., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: We examined whether the perioperative systemic inflammation score (SIS), which describes systemic inflammation and/or malnutrition, affected the tumor recurrence and survival in advanced gastric cancer patients., Patients and Methods: The study retrospectively analyzed 160 patients with stage II/III gastric cancer who underwent curative resection at the Kanagawa Cancer Center. The SIS was evaluated before surgery, one week after surgery and one month after surgery, as determined by the serum albumin level (cut-off value=4.0 g/dl) and lymphocyte-to-monocyte ratio (cut-off value=4.44)., Results: A high SIS at one month after surgery was identified as an independent predictor for overall survival [hazard ratio (HR)=2.143, p=0.020] and showed a marginal significance for the relapse-free survival (HR=1.814, p=0.053) in multivariate analyses., Conclusion: The SIS at one month after surgery is a useful biomarker for predicting the long-term outcome in patients with advanced gastric cancer., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

We experienced 2 cases in which strontium chloride was used for pain associated with gastric cancer bone metastasis. Case 1 was of a 69-year-old woman. In 2015, she underwent surgery for advanced gastric cancer followed by adjuvant chemotherapy with S-1 for 1 year. Multiple bone metastases were confirmed 2 years and 3 months after surgery. Obvious pain relief was obtained after 89Sr was administered, and SOX therapy was started. Case 2 was of a 62-year-old man. In 2016, he underwent curative surgery for stomach cancer. Chemotherapy with S-1 was performed for approximately 6 months, but 9 months after surgery multiple LN metastases, liver metastasis, and multiple bone metastases were observed . In case 2, 89Sr was administered, but good pain control was not obtained. The use of 89Sr for pain relief against multiple bone metastases should be based on the previous literature.

We report a rare case of liver recurrence of gastric cancer 14 years and 3 months after curative gastrectomy. An 81-yearold man underwent total gastrectomy, D2 lymphadenectomy, Roux-en-Y reconstruction, and cholecystectomy for advanced gastric cancer in November 2002. H e was diagnosed pathologically with M, Type 5, 53×42 mm, tub2>tub1, pT4a, ly2, v2, pN1, pPM0, pDM0, M0, pStage ⅢA(JGCA 15th). Postoperative adjuvant therapy was not administered. He was followed up for 5 years after surgery without adjuvant therapy, and he did not exhibit recurrence. In February 2017, he experienced difficulties in swallowing and visited our hospital. Abdominal contrast-enhanced CT showed an 8×5 cm liver tumor in the lateral segment. Part of the tumor protruded to outside of the liver, and the tumor invaded and pushed the jejunum in the Roux limb. We performed liver biopsy and diagnosed him with liver metastasis of recurrent gastric cancer. Late relapse after gastrectomy, especially after 10 years or more, is very rare.

Objective Despite recent advances in endoscopic treatment and laparoscopic surgery for gastric cancers, an increase in the uptake of these therapeutic approaches has not yet been fully demonstrated. Therefore, the present study aimed to investigate the change in therapeutic approaches regarding the treatment of gastric cancers detected by cancer screening in Saga Prefecture, Japan between April 2002 and March 2011. Methods Gastric cancer screening by X-ray was performed on 311,074 subjects between April 2002 and March 2011. In total, 534 patients were thereafter diagnosed with gastric cancer. Eighteen subjects were excluded because precise details of their treatment were not available. To evaluate the changes in the therapeutic approach, the observation period was divided into three 3-year intervals: Period I: April 2002 to March 2005; Period II: April 2005 to March 2008; Period III: April 2008 to March 2011. Results The use of open laparotomy for the treatment of gastric cancer decreased, and laparoscopic surgery and endoscopic treatment increased markedly in a time-dependent manner. A 2.5-fold increase in endoscopic treatment, and a 18.4-fold increase in laparoscopic surgery were observed in Period III compared with Period I (after adjusting for age and tumor characteristics). Conclusion Endoscopic treatment and laparoscopic surgery for gastric cancer increased during the investigation period (2002-2011), although the tumor characteristics of the gastric cancers detected through cancer screening in Saga Prefecture, Japan did not show any changes.

A 59-year-old man with type 3 gastric cancer(signet-ring cell carcinoma)underwent simple laparotomy because of peritoneal dissemination.S -1/CDDP was started.Since the icterus of Grade 2 had appeared after 2 courses, S-1 and biweekly paclitaxel combination chemotherapy was started as second-line treatment.Throughout treatment, there was no adverse event, and this regimen was continued for 14 courses(25 months).He died 32 months after his first visit.S -1/PTX may play an important role as second-line chemotherapy for patients with unresectable advanced gastric carcinoma.

Background: EMR is currently a standard treatment for mucosal gastric tumors. Endoscopic submucosal dissection (ESD) has been developed for en bloc resection., Objective: We evaluated the clinical outcomes of ESD compared with conventional EMR., Design: Not applicable., Setting: A historical control study was performed between EMR and ESD., Patients: EMR of 245 gastric tumors was performed in 229 patients. Lesions were divided into two groups. Conventional EMR was performed in group A from February 1999 to June 2001, and ESD was performed in group B from July 2001 to March 2004. Group B was divided into subgroups: subgroup B-1 underwent ESD from July 2001 to March 2003 and subgroup B-2 from April 2003 to March 2004., Interventions: All lesions were resected with conventional EMR or with ESD., Main Outcome Measurements: En bloc resection rate, rate in completeness of resection, required time, remnant ratio, and complications were evaluated., Results: With regard to lesions >10 mm in size, the en bloc resection rate and the rate in completeness of resection of group B was significantly higher than that of group A (p < 0.01). Although the required time was longer in group B than A (p < 0.01), it was shorter in subgroup B-2 compared with B-1 (p < 0.05) with lesions < or =10 mm in size. The remnant ratio and perforation rate were not different between groups., Limitations: Not applicable., Conclusions: The en bloc resection rate was better with ESD than with conventional EMR. The required time was longer in ESD, but this disadvantage might be improved with experience.

67Ga scanning and upper gastrointestinal (UGI) series were performed in 13 patients with gastric lymphomas before any treatment was initiated. Seven of these patients also underwent both examinations after completing chemotherapy and/or radiation therapy. Prior to treatment, all 13 patients had abnormalities on the UGI examination, and 12 of them had abnormalities on the 67Ga scans. In 6 patients, more extensive gastric abnormalities were demonstrated by 67Ga scanning than by UGI examination. Although persistent 67Ga uptake after treatment was indicative of relatively poor therapeutic response, lack of uptake did not always indicate a good response to treatment.