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ABSTRACT The gastric microbial community plays a fundamental role in gastric cancer (GC), and the two main anatomical subtypes of GC, non-cardia and cardia GC, are associated with different risk factors (Helicobacter pylori for non-cardia GC). To decipher the different microbial spatial communities of GC, we performed a multicenter retrospective analysis to characterize the gastric microbiota in 223 GC patients, including H. pylori-positive or -negative patients, with tumors and paired adjacent normal tissues, using third-generation sequencing. In the independent validation cohort, both dental plaque and GC tumoral tissue samples were collected and sequenced. The prevalence of H. pylori and oral-associated bacteria was verified using fluorescence in situ hybridization (FISH) assays in GC tumoral tissues and matched nontumoral tissues. We found that the vertical distribution of the gastric microbiota, at the upper, middle, and lower third sites of GC, was likely an important factor causing microbial diversity in GC tumor tissues. The oral-associated microbiota cluster, which included Veillonella parvula, Streptococcus oralis, and Prevotella intermedia, was more abundant in the upper third of the GC. However, H. pylori was more abundant in the lower third of the GC and exhibited a significantly high degree of microbial correlation. The oral-associated microbiota module was co-exclusive with H. pylori in the lower third site of the GC tumoral tissue. Importantly, H. pylori-negative GC patients with oral-associated gastric microbiota showed worse overall survival, while the increase in microbial abundance in H. pylori-positive GC patients showed no difference in overall survival. The prevalence of V. parvula in both the dental plaque and GC tissue samples was concordant in the independent validation phase. We showed that the oral-associated species V. parvula and S. oralis were correlated with overall survival. Our study highlights the roles of the oral-associated microbiota in the upper third of the GC. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for H. pylori-negative GCs.IMPORTANCEOur study highlights the roles of the oral-associated microbiota in the upper third of gastric cancer (GC).We showed that the oral-associated species Veillonella parvula and Streptococcus oralis were correlated with overall survival. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for Helicobacter pylori-negative GCs.

Abstract Background Following neoadjuvant chemotherapy, surgical resection is one of the most preferred treatment options for locally advanced gastric cancer patients. However, the optimal time interval between chemotherapy and surgery is unclear. This review aimed to identify the optimal time interval between neoadjuvant chemotherapy and surgery for advanced gastric cancer. Methods Beginning on November 12, 2022, we searched the PubMed, Cochrane Library, Web of Science databases, and Embase.com databases for relevant English-language research. Two authors independently screened the studies, assessed their quality, extracted the data, and analyzed the results. The primary goal was to investigate the relationship between the time interval to surgery (TTS) and long-term survival outcomes for patients. This study has been registered with PROSPERO (CRD42022365196). Results After an initial search of 4880 articles, the meta-analysis review ultimately included only five retrospective studies. Ultimately, this meta-analysis included 1171 patients, of which 411 patients had TTS of 6 weeks. In survival analysis, patients with TTS of > 6 weeks had poorer overall survival outcomes than patients with TTS of 4–6 weeks (HR = 1.34, 95% CI: 1.03–1.75, P = 0.03). No significant differences were found in terms of disease-free survival the groups. Conclusion Based on the current clinical evidence, patients with locally advanced gastric cancer may benefit better with a TTS of 4–6 weeks; however, this option still needs additional study.

Background: Due to the complex histological type and anatomical structures, there has been considerable debate on the classification of adenocarcinoma of the esophagogastric junction (AEG), especially Siewert II AEG. Furthermore, neither the American Joint Committee on Cancer (AJCC) 7th tumor–node–metastasis (TNM) [esophageal adenocarcinoma (E) or gastric cancer (G)] nor the AJCC 8th TNM (E or G) accurately predicted the prognosis of patients with Siewert II AEG. Objective: This study aimed to investigate the factors influencing the survival and prognosis of patients with Siewert II AEG and establish a new and better prognostic predictive model. Design: A retrospective study. Methods: Patients with Siewert II AEG, retrieved from the Surveillance, Epidemiology, and End Results (SEER) databases, were assigned to the training set. Patients retrieved from a single tertiary medical center were assigned to the external validation set. Significant variables were selected using univariate and multivariate Cox regression analyses to construct the nomogram. Nomogram models were assessed using the concordance index (C-index), a calibration plot, decision curve analysis (DCA), and external validation. Results: Age, tumor grade, and size, as well as the T, N, and M stages, were included in the nomograms. For the SEER training set, the C-index of the nomogram was 0.683 (0.665–0.701). The C-index of the nomogram for the external validation set was 0.690 (0.653–0.727). The calibration curve showed good agreement between the nomogram estimations and actual observations in both the training and external validation sets. The DCA showed that the nomogram was clinically useful. Conclusion: The new predictive model showed significant accuracy in predicting the prognosis of Siewert II AEG.

Abstract In the past period, due to the rapid development of next-generation sequencing technology, accumulating evidence has clarified the complex role of the human microbiota in the development of cancer and the therapeutic response. More importantly, available evidence seems to indicate that modulating the composition of the gut microbiota to improve the efficacy of anti-cancer drugs may be feasible. However, intricate complexities exist, and a deep and comprehensive understanding of how the human microbiota interacts with cancer is critical to realize its full potential in cancer treatment. The purpose of this review is to summarize the initial clues on molecular mechanisms regarding the mutual effects between the gut microbiota and cancer development, and to highlight the relationship between gut microbes and the efficacy of immunotherapy, chemotherapy, radiation therapy and cancer surgery, which may provide insights into the formulation of individualized therapeutic strategies for cancer management. In addition, the current and emerging microbial interventions for cancer therapy as well as their clinical applications are summarized. Although many challenges remain for now, the great importance and full potential of the gut microbiota cannot be overstated for the development of individualized anti-cancer strategies, and it is necessary to explore a holistic approach that incorporates microbial modulation therapy in cancer.

ObjectivesThe efficacy of updated health policy in improving the generalization of Helicobacter pylori screening and eradication in southwest China was assessed in a longitudinal analysis of multiple cross-sectional studies from an institution.MethodsIn the periods 2009–2010, 2013–2014, and 2019–2021, 8,365, 16,914, and 18,281 urban observations from health check-ups at West China Hospital were analyzed, respectively. The 14C-urea or 13C-urea breath test was consistently used for H. pylori detection. The protocol has been reported elsewhere (PROSPERO Registration number: CRD42019120764).ResultsThe overall prevalence of H. pylori dramatically decreased from 53.1% to 30.7% over the past decade (OR = 0.39, 95% CI 0.37–0.41), with a similar decline in all sex-specific and age-specific subgroups. The age-specific prevalence consistently increased before 40 years of age and always peaked at 50–59 years. Longitudinal clearance increased along with aging, and prevalence dropped to 22.6%, 25.1%, and 23.6% in the 40–49, 50–59, and 60–69 years initial age groups, respectively.ConclusionThe generalization of H. pylori screening and eradication could greatly contribute to the control of H. pylori infection among urban health check-up populations and lower gastric cancer incidence.

Background: Research on the correlation between circulating tumor cells (CTCs) and gastric cancer (GC) has increased rapidly in recent years. However, whether CTCs are associated with GC patient prognosis is highly controversial. Objective: This study aims to evaluate the value of CTCs to predict the prognosis of GC patients. Design: A meta-analysis. Data Sources and Methods: We searched the PubMed, Embase, and Cochrane Library databases for studies that reported the prognostic value of CTCs in GC patients before October 2022. The association between CTCs and overall survival (OS) and disease-free survival (DFS)/recurrence-free survival (RFS) and progression-free survival (PFS) of GC patients was assessed. Subgroup analyses were stratified by sampling times (pre-treatment and post-treatment), detection targets, detection method, treatment method, tumor stage, region, and HR (Hazard Ratio) extraction methods. Sensitivity analysis was performed by removing individual studies to assess the stability of the results. Publication bias was evaluated using funnel plots, Egger’s test, and Begg’s test. Results: We initially screened 2000 studies, of which 28 were available for further analysis, involving 2383 GC patients. The pooled analysis concluded that the detection of CTCs was associated with poor OS (HR = 1.933, 95% CI 1.657–2.256, p

Background Anastomotic devices, including linear staplers (LSs) and circular staplers (CSs), have been widely used after laparoscopic gastric surgery. However, it is controversial whether linear stapling is superior to circular stapling for anastomosis. Thus, we conducted a meta-analysis to compare the aspects of postoperative complications, particularly anastomotic stricture and anastomotic leakage, on the use of the two techniques to assist clinical decision-making. Methods We conducted a systematic search using Embase, PubMed, and Cochrane Library to evaluate studies that compared LSs and CSs after laparoscopic gastric surgery. Results Pooled analysis suggested that patients who received LSs had fewer postoperative complications (P = 0.019), and anastomotic complications (P

Claudins are a tetraspan membrane protein multigene family that plays a structural and functional role in constructing tight junctions. Claudins perform crucial roles in maintaining cell polarity in epithelial and endothelial cell sheets and controlling paracellular permeability. In the last two decades, increasing evidence indicates that claudin proteins play a major role in controlling paracellular permeability and signaling inside cells. Several types of claudins are dysregulated in various cancers. Depending on where the tumor originated, claudin overexpression or underexpression has been shown to regulate cell proliferation, cell growth, metabolism, metastasis and cell stemness. Epithelial-to-mesenchymal transition is one of the most important functions of claudin proteins in disease progression. However, the exact molecular mechanisms and signaling pathways that explain why claudin proteins are so important to tumorigenesis and progression have not been determined. In addition, claudins are currently being investigated as possible diagnostic and treatment targets. Here, we discuss how claudin-related signaling pathways affect tumorigenesis, tumor progression, and treatment sensitivity.

Abstract Background The relationship between the type of anesthesia and the survival outcomes of gastric cancer patients is uncertain. This study compared the overall outcome of gastric cancer patients after surgery with total intravenous anesthesia (TIVA) or inhalation anesthesia (IHA). Methods Clinicopathological variables of gastric cancer patients were retrieved from the database of the Surgical Gastric Cancer Patient Registry in West China Hospital, Sichuan University. Patients were grouped according to whether they received TIVA or IHA during the operation. Propensity score (PS) matching was used to balance the baseline variables, and survival outcomes were compared between these two groups. In addition, studies comparing survival outcomes between TIVA and IHA used for gastric cancer surgery and published before April 20th, 2020, were identified, and their data were pooled. Results A total of 2827 patients who underwent surgical treatment from Jan 2009 to Dec 2016 were included. There were 323 patients in the TIVA group and 645 patients in the IHA group, with 1:2 PS matching. There was no significant difference in overall survival outcomes between the TIVA and IHA groups before matching the cohort (p = 0.566) or after matching the cohort (p = 0.679) by log-rank tests. In the Cox hazard regression model, there was no significant difference between the TIVA and IHA groups before (HR: 1.054, 95% CI: 0.881–1.262, p = 0.566) or after (HR: 0.957, 95% CI: 0.779–1.177, p = 0.679) PS matching. The meta-analysis of survival outcomes between the TIVA and IHA groups found critical statistical value in the before PS matching cohort (HR 0.74, 95% CI: 0.57–0.96 p

Abstract Objectives This case–control study was aimed to investigate associations between HBV infection and extrahepatic digestive system cancers. Methods The patients of gastric, small intestinal, colonic, rectal, anal, biliary tract, and pancreatic cancers were retrospectively collected between 2016.5 and 2017.12. Simultaneously, the healthy controls were collected from the health check‐up registry, and cancer‐free status was confirmed based on medical records. Propensity score matching was performed to reduce bias. Multinomial logit model and conditional logistic regression model were used to assess the risk of individual cancer according to HBV serological markers and classifications. Results Totally, 4748 patients involving seven cancers, and 57,499 controls were included. After matching, HBsAg was associated with increased risk of gastric cancer (aOR = 1.39, 95% CI: 1.05–1.85), and anti‐HBs served as a protective factor for gastric (aOR = 0.72, 95% CI: 0.61–0.85), colonic (aOR = 0.73, 95% CI: 0.60–0.89), rectal (aOR = 0.73, 95% CI: 0.63–0.85), and pancreatic (aOR = 0.58, 95% CI: 0.42–0.82) cancers. Compared to subgroups with non‐infection and vaccination status, inactive HBsAg carriers and active HBV infection subgroup were correlated with gastric carcinogenesis (aOR = 1.41, 95% CI: 1.03–1.93). However, no clear association was found between HBV infection and other cancers. Conclusions HBV infection was potentially associated with an increased risk of gastric cancer. The development mechanism of HBV‐associated gastric cancer needs to investigate further.

Abstract Background A complete dissection of infrapyloric lymph nodes is the key to a curative gastrectomy, which can be sometimes technically challenging in laparoscopic surgery. Methods One hundred and eighteen patients with gastric cancer undergoing laparoscopic gastrectomy with D2 lymphadenectomy in which the infrapyloric lymph nodes were dissected through the right bursa omentalis approach were included. The clinicopathologic characteristics and surgical outcomes were analyzed retrospectively. Results The laparoscopic gastrectomy with D2 lymphadenectomy was successful in all 118 patients with no open conversion. The mean operation time was 246.6 ± 45.7 min. The mean estimated blood loss was 87.0 ± 35.9 mL. Postoperative complications occurred in 17.8% of the patients, which were treated successfully with conservative therapy or aspiration in all. There were no No.6 lymphadenectomy-associated complications, such as injury of transverse colon, vessels of mesocolon, pancreas or duodenum, no pancreatitis, pancreatic leakage or postoperative hemorrhage. The mean postoperative hospital stay was 9.6 ± 3.7 days. On average, the total lymph nodes harvested were 36.8 ± 12.9, in which the ones from the infrapyloric area were 5.1 ± 3.1. Conclusion Laparoscopic dissection of infrapyloric lymph nodes through the right bursa omentalis approach seems to be feasible and safe, facilitating a more complete No.6 lymphadenectomy for gastric cancer.

LN dissection is essential for accurately staging and improving GC patient prognosis. However, the compliance rate for No. 12a LND in practice is low, and its necessity is controversial. Data from GC patients who underwent total gastrectomy (TG)/distal gastrectomy (DG) plus D2 lymphadenectomy between January 2000 and December 2017 at West China Hospital, Sichuan University were reviewed. No. 12a LND noncompliance’s effect on the long-term prognosis of patients with GC after D2 gastrectomy was explored. Of the 2788 patients included, No. 12a LND noncompliance occurred in 1753 patients (62.9%). Among 1035 patients with assessable LNs from station 12a, 98 (9.5%) had positive LNs detected at station 12a. No. 12a LN metastasis patients (stage IV not included) had significantly better overall survival (OS) than TNM stage IV patients (p = 0.006). Patients with No. 12a LND compliance had a significantly higher OS than those without, both before (p < 0.001) and after (p < 0.001) PSM. Cox multivariate analysis confirmed that No. 12a LND noncompliance was an independent prognostic factor before (HR 1.323, 95% CI 1.171–1.496, p < 0.001) and after (HR 1.353, 95% CI 1.173–1.560, p < 0.001) PSM. In conclusion, noncompliance with No. 12a LND compromised the long-term survival of patients who underwent D2 gastrectomy for GC.

BackgroundWe aimed to generate and validate a nomogram to predict patients most likely to require intensive care unit (ICU) admission following gastric cancer surgery to improve postoperative outcomes and optimize the allocation of medical resources.MethodsWe retrospectively analyzed 3,468 patients who underwent gastrectomy for gastric cancer from January 2009 to June 2018. Here, 70.0% of the patients were randomly assigned to the training cohort, and 30.0% were assigned to the validation cohort. Least absolute shrinkage and selection operator (LASSO) method was performed to screen out risk factors for ICU-specific care using the training cohort. Then, based on the results of LASSO regression analysis, multivariable logistic regression analysis was performed to establish the prediction nomogram. The calibration and discrimination of the nomogram were evaluated in the training cohort and validated in the validation cohort. Finally, the clinical usefulness was determined by decision curve analysis (DCA).ResultsAge, the American Society of Anesthesiologists (ASA) score, chronic pulmonary disease, heart disease, hypertension, combined organ resection, and preoperative and/or intraoperative blood transfusions were selected for the model. The concordance index (C-index) of the model was 0.843 in the training cohort and 0.831 in the validation cohort. The calibration curves of the ICU-specific care risk nomogram suggested great agreement in both training and validation cohorts. The DCA showed that the nomogram was clinically useful.ConclusionsAge, ASA score, chronic pulmonary disease, heart disease, hypertension, combined organ resection, and preoperative and/or intraoperative blood transfusions were identified as risk factors for ICU-specific care after gastric surgery. A clinically friendly model was generated to identify those most likely to require intensive care.

Background: The greater omentum can limit abdominal inflammation and act as a protective cushion, but it is always involved in dissemination of gastric cancer. The purpose of this meta-analysis was to compare the survival and safety between total omentectomy and partial omentectomy for gastric cancer.Methods: Two investigators independently conducted a systematic search of PubMed, Embase, CNKI, and Cochrane Library ranging from January 2000 to November 2020. The pooled odds ratio (ORs) and weighted mean difference (WMD) with the 95% confidence interval (95% CI) were used to assess perioperative and survival parameters.Results: A total of 2,031 patients in 11 studies (574 patients in the partial omentectomy group and 1,457 patients in the total omentectomy group) were included. The results found shorter operation time (WMD = −25.584; P = 0.000) and less intraoperative blood loss (WMD = −47.301; P = 0.050) in the partial omentectomy group, compared to total omentectomy. There were no significant differences in terms of incidence of complications (OR = 0.770; P = 0.164), blood transfusions rates (OR = 0.269; P = 0.161), time to first flatus (WMD = 0.160; P = 0.345), hospital stay (WMD = −1.258; P = 0.087), and number of harvested lymph nodes (WMD = 1.265; P = 0.662). For the disease-free survival (OR = 0.80; P = 0.381) and overall survival, there were no statistical differences between the two procedures.Conclusions: The partial omentectomy could reduce operation time and trended to decrease intraoperative blood loss. And the survival in patients with partial omentectomy seemed to be comparable to that of patients with total omentectomy.

Abstract Background Due to the controversy over the prognostic significance of Borrmann type in patients with gastric cancer (GC), the present study was to investigate the clinical value of Borrmann type in advanced GC. Methods We retrospectively evaluated 2092 patients with advanced GC and subsequently examined the clinicopathological characteristics and prognosis of patients stratified by Borrmann type. Results Patients were divided into three groups according to Borrmann type (Borrmann types I+II, III, and IV). Patients with Borrmann types III and IV had larger size, more poorly differentiated tumor type, more advanced tumor stage, and higher chance of involving the entire stomach. The overall survival (OS) rates were significantly different among the three groups (p < 0.001). Stratification analysis revealed significant OS rates among the three groups in tumor-node-metastasis (TNM) stage III (p < 0.001) and TNM stage IV (p = 0.008). Multivariate analysis revealed that Borrmann types, adjuvant chemotherapy, curative resection, and TNM stage were all independent predictors of OS among GC patients. The subgroup analysis indicated that Borrmann type was an independent predictor of OS among GC patients who undergone curative resection and with TNM stage III cancer. However, curative resection and postoperative chemotherapy failed to prolong the survival of patients with Borrmann type IV. Conclusions The clinicopathological characteristics and prognosis of patients with three Borrmann types of GC were different. Borrmann type can be simply used as a valuable factor to predict survival in advanced GC patients, especially in those TNM stage III undergoing curative resection. Additionally, more attention should be paid to the treatment for Borrmann type IV GC.

ObjectiveWe previously established a gross tissue response (GTR) system to evaluate the intraoperative response of perigastric tissue in patients with gastric cancers to neoadjuvant chemotherapy. This prospective cohort study aims to confirm the relationship between gross tissue response and clinicopathological characteristics and explore the possibility of using the GTR system to predict the difficulty of surgery and the occurrence of postoperative complications within 30 days.MethodsA total of 102 patients with gastric cancer from January 2019 to April 2020 were enrolled in this study. The degrees of fibrosis, edema, and effusion in the perigastric tissues were assessed intraoperatively according to the GTR system. We systematically analyzed the relations between GTR and clinicopathological characteristics, and then a prediction model that includes GTR was established to predict the difficulty of surgery and the occurrence of postoperative complications within 30 days.ResultsFinally, the study included 71 male patients and 31 female patients. The patients had an average age of 58.79 ± 1.03 years, BMI of 22.89 ± 0.29, and tumor diameter of 4.50 ± 0.27 cm. Among these patients, 17 underwent laparoscopic gastrectomy, 85 underwent open gastrectomy, the average operation time was 294.63 ± 4.84 minutes, and the mean volume of intraoperative blood loss was 94.65 ± 5.30 ml. The overall 30-day postoperative complication rate was 19.6% (20/102). The total GTR was significantly related to the primary tumor stage, operation time and 30-day postoperative complication rate (p

BackgroundThis study aimed to evaluate the impact of postoperative complication and its etiology on long-term survival for gastric cancer (GC) patients with curative resection.MethodsFrom January 2009 to December 2014, a total of 1,667 GC patients who had undergone curative gastrectomy were analyzed. Patients with severe complications (SCs) (Clavien–Dindo grade III or higher complications or those causing a hospital stay of 15 days or longer) were separated into a “complication group.” Univariate and multivariate analyses were performed to reveal the relationship between postoperative complications and long-term survival. A 2:1 propensity score matching (PSM) was used to balance baseline parameters between the two groups.ResultsSCs were diagnosed in 168 (10.08%) patients, including different etiology: infectious complications (ICs) in 111 (6.66%) and non-infectious complications (NICs) in 71 (4.26%) patients. Multivariate analysis showed that presence of SCs (P=0.001) was an independent prognostic factor for overall survival, and further analysis by complication type demonstrated that the deteriorated overall survival was mainly caused by ICs (P=0.004) rather than NICs (P=0.068). After PSM, patients with SCs (p=0.002) still had a significantly decreased overall survival, and the presence of ICs (P=0.002) rather than NICs (P=0.067) showed a negative impact on long-term survival.ConclusionSerious complications, particularly of an infectious type, may have a negative impact on overall survival of GC patients. However, additional multicenter prospective studies with larger sample size are required to verify this issue.

BackgroundGiven the expanding clinical applications of laparoscopic surgery and neoadjuvant chemotherapy in advanced gastric cancer treatment, there is an emerging need to summarize the few evidences that evaluated the safety and efficacy of laparoscopic versus open gastrectomy in patients with advanced gastric cancer (AGC) following neoadjuvant chemotherapy (NAC).MethodsFrom January 1 to 2, 2021, we searched Ovid Embase, PubMed, Cochrane central register Trials (Ovid), and web of science to find relevant studies published in English, and two authors independently performed literature screening, quality assessment of the included studies, data extraction, and data analysis. This study was registered with PROSPERO (CRD42021228845).ResultsThe initial search retrieved 1567 articles, and 6 studies were finally included in the meta-analysis review, which comprised 2 randomized control trials and 4 observational studies involving 288 laparoscopic gastrectomy (LG) and 416 open gastrectomy (OG) AGC patients treated with NAC. For intraoperative conditions, R0 resection rate, blood transfusion, intraoperative blood loss, number of lymph nodes dissected, proximal margin, and distal margin were comparable between LG group and open OG group. For postoperative short-term clinical outcomes, LG has significantly less postoperative complications (OR = 0.65, 95%CI: 0.42–1.00, p = 0.05) and shorter postoperative time to first aerofluxus (WMD = -0.57d, 95%CI: -0.89–0.25, p = 0.0004) than OG, and anastomotic leakage, pulmonary infection, pleural effusion, surgical site infection, thrombosis, intestinal obstruction, peritoneal effusion or abscess formation, postoperative time to first defecation, postoperative time to first liquid diet, and postoperative length of stay were comparable between the two groups. For postoperative survival outcomes, there were no significant differences in disease-free survival (DFS) and overall survival (OS) between the two groups.ConclusionThe available evidences indicated that LG is an effective and feasible technology for the treatment of AGC patients treated with NAC, and LG patients have much less postoperative complications and faster bowel function recovery than OG patients.Systematic Review RegistrationPROSPERO database (identifier, CRD42021228845).

Background: There is controversy about the characteristics and prognostic implications of signet ring cell gastric cancers and non-signet ring cell gastric cancers.Objective: This study aims to evaluate clinicopathological characteristics and prognoses of signet ring cell carcinoma (SRCC) and non-signet ring cell carcinoma (NSRCC) of stomach.Methods: Studies compared between SRCC and NSRCC of the stomach after gastrectomy and published before September 1st, 2020, in the PubMed, Cochrane, and Embase databases, were identified systematically.Results: A total of 2,865 studies were screened, and 36 studies were included, with 19,174 patients in the SRCC group and 55,942 patients in the NSRCC group. SRCC patients were younger in age (P < 0.001), less likely to be male patients (P < 0.001), more afflicted with upper third lesions (P < 0.001), and presenting with more Borrmann type IV tumors (P = 0.005) than NSRCC patients. Lymph nodes metastasis was similar between SRCC and NSRCC patients with advanced tumor stage (OR: 0.86, 95% CI: 0.67–1.10, P = 0.23), but lower in the SRCC than NSRCC patients with early tumor stage (OR: 0.73; 95% CI: 0.56–0.98, P = 0.02). SRCC patients had comparable survival outcomes with NSRCC patients for early gastric cancers (HR: 1.05, 95% CI: 0.65–1.68, P < 0.001) but had significantly poor prognosis for patients with advanced tumor stage (HR: 1.50, 95% CI: 1.28–1.76, P < 0.001).Conclusions: Signet ring cell carcinomas of the stomach are an increasingly common histopathological subtype of gastric cancers. These kinds of patients tend to be younger in age and more often female. Although, signet ring cell gastric cancer is a negative prognostic factor for patients with advanced stage. The difference is that for early stage of signet ring cell gastric cancers, it has low lymph nodes metastasis rate and comparable prognosis with non-signet ring cell cancers.

BackgroundSplenectomy was traditionally performed to dissect the splenic hilar lymph nodes. Considering the important functions of spleen, whether splenectomy would bring beneficial to gastric cancer patients is debatable. This meta-analysis aimed to make an updated evaluation on the effectiveness and safety of splenectomy.MethodsLiterature searches were performed to identify eligible RCTs concerning effectiveness or safety of splenectomy with gastrectomy from PubMed, MEDLINE, CBMdisc, EMBASE, and Cochrane Central Register of Controlled Trials. Two reviewers completed the study selection, data extraction, and quality assessment independently. The meta-analyses were performed by RevMan 5.3.ResultsA total of 971 patients from four studies were included (485 in splenectomy group and 486 in spleen preservation group). Splenectomy did not increase 5-year overall survival rate (RR=1.05, 95% CI: 0.96, 1.16) or increase postoperative mortality (RR=1.21, 95% CI: 0.41, 3.54). However, the analysis demonstrated that gastrectomy with splenectomy had significantly higher incidence of postoperative complications (RR=1.80, 95% CI: 1.33, 2.45). No significant differences were found in terms of the number of resected lymph nodes and reoperation rate; however, splenectomy had a tendency to prolong the duration of surgery and hospital stays. Subgroup analyses indicated that splenectomy could not increase overall survival rate for either whole or proximal gastric cancer. Sensitivity analyses also found similar results compared to the primary analyses.ConclusionsSplenectomy cannot benefit the survival of patients with tumor located at lesser curvature, and it could instead increase postoperative morbidity.

Objective: The objective of this study was to summarize the clinicopathological characteristics of the CLDN18-ARHGAP fusion gene in gastric cancer patients.Background: The CLDN18-ARHGAP26 fusion gene is one of the most frequent somatic genomic rearrangements in gastric cancer, especially in the genomically stable (GS) subtype. However, the clinical and prognostic meaning of the CLDN18-ARHGAP fusion in gastric cancer patients is unclear.Methods: Studies that investigated CLDN18-ARHGAP fusion gastric cancer patients were identified systematically from the PubMed, Cochrane, and Embase databases through the 28th of February 2020. A systematic review and meta-analysis were performed to estimate the clinical significance of CLDN18-ARHGAP fusion in patients.Results: A total of five eligible studies covering 1908 patients were selected for inclusion in the meta-analysis based on specified inclusion and exclusion criteria. Several fusion patterns were observed linking CLDN18 and ARHGAP26 or ARHGAP6, with the most common type being CLDN18/exon5-ARHGAP26/exon12. The survival outcome meta-analysis of the CLDN18-ARHGAP fusion gene showed that it was associated with overall survival outcomes in gastric cancer (HR, 2.03, 95% CI 1.26–3.26, P < 0.01, random-effects). In addition, diffuse gastric cancer had a greater proportion of CLDN18-ARHGAP fusions than intestinal gastric cancer (13.3%, 151/1,138 vs. 1.8%, 8/442; p < 0.001). Moreover, gastric cancer patients with the CLDN18-ARHGAP fusion gene are more likely to be female or have a younger age, lymph node metastasis and advanced TNM stages.Conclusion: The CLDN18-ARHGAP fusion is one of the molecular characteristics of diffuse gastric cancer and is also an independent prognostic risk factor for gastric cancer. In addition, it is also related to multiple clinical characteristics, including age, sex, lymph node metastasis and tumor stage. However, the mechanism of the CLDN18-ARHGAP fusion gene and potential targeted therapeutic strategies need further exploration.

BackgroundDeregulation of HER2 expression could affect the biological characteristics of gastric cancer cells and treatment option for gastric cancer patients. This research aims to investigate the impact of HER2 on biological characteristics of gastric cancer stem cells (GCSCs) and prognosis of gastric cancer patients.MethodsHER2 knockdown in GCSCs were constructed by lentivirus transfection. Alterations of proliferation, self-renewal, invasion, migration, colony formation, and tumorigenicity of GCSCs were examined. The changes of gene expressions after HER2 interference in GCSCs were detected by gene microarray. The impact of concentration of serum HER2 and expression of HER2 in tumor tissues on survival of 213 gastric cancer patients was also analyzed.ResultsDown-regulation of HER2 decreased the self-renewal, colony formation, migration, invasion, proliferation, and chemotherapy resistance of GCSCs. However, the tumorigenicity of GCSCs in vivo was increased after down-regulation of HER2. The results of gene microarray showed that HER2 gene might regulate the signal transduction of mTOR, Jak-STAT, and other signal pathways and affect the biological characteristics of GCSCs. Furthermore, survival analyses indicated that patients with high concentration of HER2 in serum had a favorable overall survival. However, there was no significant correlation between expression of HER2 in tumor tissue and overall survival.ConclusionInterference of HER2 in GCSCs decreased the capacity of self-renewal, proliferation, colony formation, chemotherapy resistance, invasion, and migration but might increase the tumorigenicity in vivo. Patients with high concentration of HER2 in serum seemed to have a favorable prognosis.

Objective: The prognostic significance of serum CA19-9 levels in gastric cancer patients remains a matter debate. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative serum CA19-9 levels in patients with gastric cancer.Methods: A total of 1,046 gastric cancer patients who underwent curative gastrectomy in West China Hospital of Sichuan University from January 2011 to December 2016 were analyzed retrospectively. Patients were categorized by minimum P-value using X-tile, while the baseline confounders for CA19-9 changes were balanced through propensity score matching (PSM). The relationships between CA19-9 changes and other clinicopathologic features were measured. Univariate and multivariate analysis were performed to explore the risk factors associated with survival outcomes.Results: We included 653 patients. Changes in CA19-9 levels significantly correlated with age, tumor size, macroscopic type, histological grade, T stage and TNM stage. Kaplan–Meier curves revealed that patients with CA19-9 changes

Objectives. This preliminary study is aimed at enriching and isolating peritoneal metastatic cancer stem cells (pMCSCs) of gastric cancer and assessing their epithelial-mesenchymal transition (EMT) phenotype and invasiveness. Methods. Cancer stem cells of human gastric cancer (CSC-hGC) were previously isolated and transfected with green fluorescent protein and luciferase genes to validate the mouse model of peritoneal metastasis established via transplantation. The first and second generations ([G1] and [G2], respectively) of pMCSCs were isolated from intraperitoneally transplanted CSC-hGC (pMCSC-tGC) by spherical culture. CSC and EMT-related markers and regulators in the two generations of intraperitoneally transplanted tumors were examined by immunohistochemistry, immunofluorescence staining, and quantitative PCR. Cell mobility was examined by a transwell assay. Results. The nude mouse model of intraperitoneally transplanted CSC-hGC was successful in establishing sequential formation of peritoneal tumors and enrichment of pMCSCs. CD44 and CD54 were consistently expressed in the two generations of transplanted tumors. In vitro cell (migration) assays and immunocytofluorescence assays showed that in pMCSC-tGC[G2], E-cad, Survivin, and Vimentin expression was stable; α-SMA expression was decreased; and OVOL2, GRHL2, and ZEB1 expression was increased. PCR analysis indicated that in pMCSC-tGC[G2], the mRNA expression of E-cad, α-SMA, MMP9, MMP2, and Vimentin was downregulated, while that of ZEB1, OVOL2, and GRHL2 was upregulated. In vivo tumor (homing) assays and immunohistochemical assays demonstrated that in pMCSC-tGC[G2], E-cad and Snail were upregulated, while α-SMA was downregulated. The numbers of migrated and invaded pMCSC-tGC[G1] and pMCSC-tGC[G2] were significantly higher than those of CSC-hGC in migration and invasion assays. Conclusions. pMCSCs might be a specific subpopulation that can be sequentially enriched by intraperitoneal transplantation. pMCSCs exhibited a tendency towards partial mesenchymal-epithelial transition, enhancing their invasiveness during homing and the formation of peritoneal tumors. However, these preliminary findings require validation in further experiments.

Abstract Background To study metastasis to the infra-pyloric (no. 6) lymph nodes and their subgroups and the related risk factors of gastric cancer patients. Methods Gastric cancer patients who underwent gastrectomy with complete postoperative pathological information on the no. 6 lymph node station and its subgroups from January 1, 2008, to December 31, 2011, were included. The clinicopathological characteristics and survival outcomes were analyzed. Results A total of 121 patients were included; they had 6.1 ± 7.7 positive lymph nodes, and 35.1 ± 14.2 lymph nodes were examined. The overall lymph node positivity rate was 67.8% (82/121) with a positivity rate of 28.1% (34/121) for the no. 6 lymph nodes. The metastasis rate was 6.6% for the no. 6a nodes, 6.6% for the no. 6b nodes, and 21.5% for the no. 6c nodes. Also, no. 8a (OR = 1.329, p = 0.017) and no. 9 (OR = 1.250, p = 0.022) nodal positivity and lower third tumor location (OR = 1.278, p = 0.001) were independent risk factors for no. 6 lymph nodal metastasis. There was a significant survival difference between patients with positive and negative no. 6 lymph nodes and patients with metastasis to other lymph node stations (p

Background. The da Vinci robotic system was considered an effectively alternative treatment option for early gastric cancer patients in recent years. The aim of our study was to evaluate the safety and feasibility of robot-assisted gastrectomy in our center. Methods. This study included 33 patients who underwent robot-assisted gastrectomy (RAG) and 88 patients who underwent laparoscopic-assisted gastrectomy (LAG) between January 2016 and April 2018. Clinicopathological characteristics, surgical parameters, postoperative recovery, and the learning curves of RAG were evaluated. Results. Baseline characteristics between two groups were well balanced. The operation time of RAG was longer than that of LAG (333.1±61.4 min vs. 290.6±39.0 min, p=0.001), and the estimated blood loss was 62.4±41.2 ml in the RAG group and 77.7±32.3 ml in the LAG group (p=0.005), respectively. The mean number of examined lymph nodes in RAG was less than that in LAG (30.3±10.2 vs. 37.4±13.7, p=0.008). However, RAG had an advantage in the dissection of No. 9 lymph nodes (3.4±2.1 vs. 2.5±1.6, p=0.039). The incidence of postoperative complications was similar in both groups (p=0.735). There were no significant differences in terms of postoperative recovery between the two groups. The learning curve of RAG showed that the CUSUM value decreased from the 8th case, which suggested a rapid learning curve among experienced surgeons on LAG operations. Conclusions. RAG was safe and feasible for gastric cancer patients, with superiority in the dissection of No. 9 lymph nodes.

Background. The impact of perioperative blood transfusion on the prognosis of gastric adenocarcinoma patients is still controversial. The aim of this study was to elucidate the impact of perioperative blood transfusion on postoperative complications and prognosis of patients who underwent gastrectomy for gastric adenocarcinoma with different levels of preoperative hemoglobin value (POHb). Method. From 2003 to 2011, 1199 patients who underwent curative gastrectomy were retrospectively enrolled and followed up to December 2014. Clinicopathological features and survival outcomes were compared between transfused and nontransfused patients. Results. In this study, transfused patients had more postoperative complications than nontransfused ones (P=0.002). In survival analysis, the difference was not significant between transfused and nontransfused patients with POHb between 70 and 100 g/L (P=0.191). However, in patients with POHb >100 g/L, transfused patients had significantly worse prognosis (P100 g/L and transfused patients had more postoperative complications; thus it is better to refrain from unnecessary perioperative blood transfusion especially intraoperative transfusion.

Background. To evaluate prognostic value of metastatic No.8p LNs in patients with gastric cancer. Methods. From August 2002 to December 2011, a total of 284 gastric cancer patients who underwent gastrectomy with No.8p LNs dissection were analyzed retrospectively in this study. Patients were divided into two groups according to the status of No.8p LNs. Clinicopathological features were collected to conduct the correlation analysis. Follow-up was carried out up to December 31st, 2014. Overall survival was analyzed. Results. Out of 284 patients, metastatic No.8p LNs were found in 24 (8.5%) patients. Compared with other 260 cases, these patients suffered morphologically larger tumor (P=0.003), node stage (P=0.000), and metastatic stage (P=0.000). The 3-year overall survival rate was 26% in No.8p-positive group and 53% in No.8p-negative group. No significant difference of cumulative survival rates existed between the No.8p-positive group and No.8p-negative stage IV group (26% versus 28%, P=0.923). Patients with other distant metastasis or not in No.8p+ group had similar cumulative survival rates (24% versus 28%, P=0.914). Conclusions. Positive No.8p LNs were a poor but not an independent prognostic factor for patients with GC and should be recognized as distant metastasis.

Background. The studies on risk factors and metastatic rate of retropancreatic (number 13) lymph nodes in gastric adenocarcinoma were few and the results were still controversial. The aim of this study was to elucidate risk factors and prognostic significance of number 13 lymph nodes in gastric adenocarcinoma. Method. From January 2000 to December 2011, 114 patients who underwent gastrectomy with number 13 lymph nodes dissection were enrolled and followed up to January 2014. Patients were grouped according to whether number 13 lymph nodes were positive or negative. Results. The metastatic rate of number 13 lymph nodes was 22.8%. In multivariate analysis, pT stage (P=0.027), pN stage (P=0.005), and number 11p (P=0.015) lymph nodes were independent risk factors of positive number 13 lymph nodes. In all patients (P

To compare surgical efficacy and postoperative recovery of ultrasonic scalpel (USS) with conventional techniques for the resection of gastric carcinoma.A systematic search of major medical databases (PubMed, Embase, CCRT and CNKI) was conducted. Both randomized and non-randomized controlled trials (RCTs and nRCTs) were considered eligible. Operation time (OT), intraoperative blood loss (BL) and postoperative complications (POC) rates as well as postoperative hospitalization days, number of dissected lymph nodes, abdominal drainage volume and time for recovery of gastrointestinal functions were synthesized and compared.Nineteen studies were included (7 RCTs and 12 nRCTs), in which 1930 patients were enrolled totally (946 in the USS group and 984 in the conventional group). Monopolar electrocautery and ligation were used as the conventional methods. Comparative meta-analysis showed perioperative outcomes were significantly improved using USS compared with conventional surgical instrumentation. OT was reduced from a weighted mean of 185.3 min in the conventional group to 151.0 min in the USS group (MD = -33.30, 95% CI [-41.75, -24.86], p

BACKGROUND: The metastatic rate and risk factors of splenic hilar (No.10) lymph nodes (LNs) in gastric adenocarcinoma were still variable and uncertain, and the prognostic significance of No.10 LNs was also controversial. The aim of this retrospective study was to analyze the metastatic rate, risk factors and prognostic significance of No.10 LNs in gastric adenocarcinoma. METHODS: From August 2007 to December 2011, 205 patients who were diagnosed with primary gastric adenocarcinoma and underwent total or proximal gastrectomy plus No.10 LNs dissection in West China Hospital were enrolled. Clinicopathological features and survival outcomes were retrospectively analyzed. RESULTS: Mean numbers of harvested LNs and metastatic LNs were 34.8±12.6 (15-73) and 8.7±10.8 (0-67), respectively. The proportion of cases with positive No.10 LNs was 8.8% (18/205). In all 204 dissected No.10 LNs, 47 LNs (23.0%) were metastatic. In 52.2% (107/205) patients, the dissected splenic hilar tissues were histologically determined as only fat tissues but without LNs structure. Histological evidence of LNs structure was found in 98 (47.8%) patients with 18.4% (18/98) metastatic No.10 LNs. In multivariate logistic regression analysis, metastasis of No.10 LNs was significantly correlated with No.4sa LNs (p = 0.010) and pN stage (p = 0.012). Regarding survival analysis, 199 (97.1%) patients were followed up (0.6-74.8 months). In all patients with R0 resection, metastatic No.10 LNs caused significantly worse prognosis both in Kaplan-Meier (p = 0.006) and Cox regression analysis (p = 0.031). CONCLUSIONS: Although the metastatic rate of No.10 LNs was 8.8%, dissection of No.10 LNs might be meaningful due to the poor prognosis of positive cases. And attentions should be also paid to its correlated factors including pN stage and No.4sa LNs.

To investigate the correlation between CD133-positive gastric cancer and clinicopathological features and its impact on survival.A search in the Medline and Chinese CNKI (up to 1 Dec 2011) was performed using the following keywords gastric cancer, CD133, AC133, prominin-1 etc. Electronic searches were supplemented by hand searching reference lists, abstracts and proceedings from meetings. Outcomes included overall survival and various clinicopathological features.A total of 773 gastric cancer patients from 7 studies were included. The median rate of CD133 expression by immunohistochemistry (IHC) was 44.8% (15.2%-57.4%) from 5 studies, and that by reverse transcription polymerase chain reaction (RT-PCR) was 91.3% (66.7%-100%) from 4 studies. The accumulative 5-year overall survival rates of CD133-positive and CD133-negative patients were 21.4% and 55.7%, respectively. Meta-analysis showed that CD133-positive patients had a significant worse 5-year overall survival compared to the negative ones (OR = 0.20, 95% CI 0.14-0.29, P

BACKGROUND: Gastric carcinoma (GC) is one of the highest cancer-mortality diseases with a high incidence rate in Asia. For surgically unfit but medically fit patients, palliative chemotherapy is the main treatment. The chemotherapy regimen of docetaxel, cisplatin and 5-fluorouracil (DCF) has been used to treat the advanced stage or metastatic GC. It is necessary to compare effectiveness and toxicities of DCF regimen with non-taxane-containing palliative chemotherapy for GC. METHODS: PubMed, EmBase, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure databases were searched to select relative randomized controlled trials (RCTs) comparing DCF to non-taxane-containing chemotherapy for patients with palliatively resected, unresectable, recurrent or metastatic GC. Primary outcome measures were 1-year and 2-year overall survival (OS) rates. Secondary outcome measures were median survival time (MST), median time to progression (TTP), response rate and toxicities. RESULTS: Twelve RCTs were eligible and 1089 patients were analyzed totally (549 in DCF and 540 in control). DCF regimen increased partial response rate (38.8% vs 27.9%, p = 0.0003) and reduced progressive disease rate (18.9% vs 33.3%, p = 0.0005) compared to control regimen. Significant improvement of 2-year OS rate was found in DCF regimen (RR = 2.03, p = 0.006), but not of 1-year OS rate (RR = 1.22, p = 0.08). MST was significantly prolonged by DCF regimen (p = 0.039), but not median TTP (p = 0.054). Both 1-year OS rate and median TTP had a trend of prolongation by DCF regimen. Chemotherapy-related mortality was comparable (RR = 1.23, p = 0.49) in both regimens. In grade I-IV toxicities, DCF regimen showed a major raise of febrile neutropenia (RR = 2.33, p

BACKGROUND: The aim of this meta-analysis is to evaluate the impact of transthoracic resection on long-term survival of patients with GEJ cancer and to compare the postoperative morbidity and mortality of patients undergoing transthoracic resection with those of patients who were not undergoing transthoracic resection. METHOD: Searches of electronic databases identifying studies from Medline, Cochrane Library trials register, and WHO Trial Registration etc were performed. Outcome measures were survival, postoperative morbidity and mortality, and operation related events. RESULTS: Twelve studies (including 5 RCTs and 7 non-RCTs) comprising 1105 patients were included in this meta-analysis, with 591 patients assigned treatment with transthoracic resection. Transthoracic resection did not increase the 5-y overall survival rate for RCTs and non-RCTs (HR = 1.01, 95% CI 0.80- 1.29 and HR = 0.89, 95% CI 0.70- 1.14, respectively). Stratified by the Siewert classification, our result showed no obvious differences were observed between the group with transthoracic resection and group without transthoracic resection (P>0.05). The postoperative morbidity (RR = 0.69, 95% CI 0.48- 1.00 and OR = 0.55, 95% CI 0.25- 1.22) and mortality (RD = -0.03, 95% CI -0.06- 0.00 and RD = 0.00, 95% CI -0.05- 0.05) of RCTs and non-RCTs did not suggest any significant differences between the two groups. Hospital stay was long with thransthoracic resection (WMD = -5.80, 95% CI -10.38- -1.23) but did not seem to differ in number of harvested lymph nodes, operation time, blood loss, numbers of patients needing transfusion, and reoperation rate. The results of sensitivity analyses were similar to the primary analyses. CONCLUSIONS: There were no significant differences of survival rate and postoperative morbidity and mortality between transthoracic resection group and non-transthoracic resection group. Both surgical approaches are acceptable, and that one offers no clear advantage over the other. However, the results should be interpreted cautiously since the qualities of included studies were suboptimal.