Metastatic stomach lymphoepithelioma-like carcinoma and immune checkpoint inhibitor therapy:A case report

BACKGROUND Pulmonary lymphoepithelioma-like carcinoma(PLELC)is a rare type of nonsmall-cell lung cancer.Stomach lymphoepithelioma-like carcinoma(LELC)metastasis secondary to PLELC has not been reported recently.CASE SUMMARY A 64-year-old female was admitted to our hospital for a regular gastroscopy examination with a 6-year history of surgical resection for left PLELC.Positron emission tomography/computed tomography suggested high accumulation of 18F-fludeoxyglucose in the gastric cardia region.Upper gastrointestinal endoscopy confirmed a large mass at the stomach fundus.Immunohistochemistry(IHC)of the biopsy suggested metastatic stomach LELC.Proximal gastrectomy showed that this 6.5 cm×5.0 cm mass was located in the stomach fundus near the cardia.Histopathological examination showed a poorly differentiated carcinoma with prominent lymphoplasmacytic infiltration.IHC demonstrated that the tumor was positive for CK(AE1/AE3),p63,p40,p53,Ki-67(70%),and EGFR(3+)and negative for CK7,CK20,Her2,and CD10.In situ hybridization analysis showed positive staining Epstein-Barr virus-encoded RNA.Tumor programmed cell death ligand 1(PD-L1)expression score was 98%,and the combined positive score was 100,with no evidence of microsatellite instability.Thus,the patient was unequivocally diagnosed with metastatic stomach LELC secondary to pulmonary LELC.After discharge,this patient underwent PD-1 inhibitor treatment(toripalimab,240 mg)every 3 wk for ten cycles,and she has had no tumor recurrence.CONCLUSION For gastric LELC metastasis,PD-1 inhibitor therapy could become a new therapeutic approach,though there is still no evidence from large data sets to support this.

Extraskeletal Ewing sarcoma of the stomach:A rare case report

BACKGROUND Extraskeletal Ewing sarcoma(EES)is a rare and highly malignant small round cell tumor associated with a poor clinical outcome.Ewing sarcoma(ES)involving the stomach is an uncommon presentation and can be easily confused with other small round cell tumors.We herein present a rare case of ES involving the gastric area.CASE SUMMARY We report a case of gastric ES in a 19-year-old female patient who initially presented with a complaint of a tender epigastric mass for 5 d.Contrast-enhanced abdominal computed tomography revealed a soft-tissue-density mass with a diameter of 8.5 cm between the liver and stomach;the mass was connected to the gastric antrum.Then,the mass was surgically excised completely.Upon histopathological,immunophenotype and molecular analysis,the mass was identified to be a primary gastric ES.CONCLUSION EES is an aggressive tumor with poor prognosis.Therefore,early diagnosis and timely intervention are essential for a good prognosis.It is imperative for us to raise awareness about this rare tumor.Surgical resection is still the best treatment option.

Construction and validation of a risk-prediction model for anastomotic leakage after radical gastrectomy: A cohort study in China

Objectives:Anastomotic leakage(AL)stands out as a prevalent and severe complication following gastric cancer surgery.It frequently precipitates additional serious complications,significantly influencing the overall survival time of patients.This study aims to enhance the risk-assessment strategy for AL following gastrectomy for gastric cancer.Methods:This study included a derivation cohort and validation cohort.The derivation cohort included patients who underwent radical gastrectomy at Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,from January 1,2015 to December 31,2020.An evidence-based predictor questionnaire was crafted through extensive literature review and panel discussions.Based on the questionnaire,inpatient data were collected to form a model-derivation cohort.This cohort underwent both univariate and multivariate analyses to identify factors associated with AL events,and a logistic regression model with stepwise regression was developed.A 5-fold cross-validation ensured model reliability.The validation cohort included patients from August 1,2021 to December 31,2021 at the same hospital.Using the same imputation method,we organized the validation-queue data.We then employed the risk-prediction model constructed in the earlier phase of the study to predict the risk of AL in the subjects included in the validation queue.We compared the predictions with the actual occurrence,and evaluated the external validation performance of the model using model-evaluation indicators such as the area under the receiver operating characteristic curve(AUROC),Brier score,and calibration curve.Results:The derivation cohort included 1377 patients,and the validation cohort included 131 patients.The independent predictors of AL after radical gastrectomy included age65 y,preoperative albumin<35 g/L,resection extent,operative time240 min,and intraoperative blood loss90 mL.The predictive model exhibited a solid AUROC of 0.750(95%CI:0.694e0.806;p<0.001)with a Brier score of 0.049.The 5-fold cross-validation confirmed these findings with a calibrated C-index of 0.749 and an average Brier score of 0.052.External validation showed an AUROC of 0.723(95%CI:0.564e0.882;p?0.006)and a Brier score of 0.055,confirming reliability in different clinical settings.Conclusions:We successfully developed a risk-prediction model for AL following radical gastrectomy.This tool will aid healthcare professionals in anticipating AL,potentially reducing unnecessary interventions.

Advances in the study of gastric organoids as disease models

Gastric organoids are models created in the laboratory using stem cells and sophisticated three-dimensional cell culture techniques.These models have shown great promise in providing valuable insights into gastric physiology and advanced disease research.This review comprehensively summarizes and analyzes the research advances in culture methods and techniques for adult stem cells and induced pluripotent stem cell-derived organoids,and patient-derived organoids.The potential value of gastric organoids in studying the pathogenesis of stomach-related diseases and facilitating drug screening is initially discussed.The construction of gastric organoids involves several key steps,including cell extraction and culture,three-dimensional structure formation,and functional expression.Simulating the structure and function of the human stomach by disease modeling with gastric organoids provides a platform to study the mechanism of gastric cancer induction by Helicobacter pylori.In addition,in drug screening and development,gastric organoids can be used as a key tool to evaluate drug efficacy and toxicity in preclinical trials.They can also be used for precision medicine according to the specific conditions of patients with gastric cancer,to assess drug resistance,and to predict the possibility of adverse reactions.However,despite the impressive progress in the field of gastric organoids,there are still many unknowns that need to be addressed,especially in the field of regenerative medicine.Meanwhile,the reproducibility and consistency of organoid cultures are major challenges that must be overcome.These challenges have had a significant impact on the development of gastric organoids.Nonetheless,as technology continues to advance,we can foresee more comprehensive research in the construction of gastric organoids.Such research will provide better solutions for the treatment of stomach-related diseases and personalized medicine.

Assessment of programmed death-ligand 1 expression in primary tumors and paired lymph node metastases of gastric adenocarcinoma

BACKGROUND Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1)immuno-therapy has demonstrated promising results on gastric cancer(GC).However,PD-L1 can express differently between metastatic sites and primary tumors(PT).AIM To compare PD-L1 status in PT and matched lymph node metastases(LNM)of GC patients and to determine the correlation between the PD-L1 status and clinicopathological characteristics.METHODS We retrospectively reviewed 284 GC patients who underwent D2-gastrectomy.PD-L1 was evaluated by immunohistochemistry(clone SP142)using the com-bined positive score.All PD-L1+PT staged as pN+were also tested for PD-L1 expression in their LNM.PD-L1(-)GC with pN+served as the comparison group.RESULTS Among 284 GC patients included,45 had PD-L1+PT and 24 of them had pN+.For comparison,44 PD-L1(-)cases with pN+were included(sample loss of 4 cases).Of the PD-L1+PT,54.2%(13/24 cases)were also PD-L1+in the LNM.Regarding PD-L1(-)PT,9.1%(4/44)had PD-L1+in the LNM.The agreement between PT and LNM had a kappa value of 0.483.Larger tumor size and moderate/severe peritumoral inflammatory response were associated with PD-L1 positivity in both sites.There was no statistical difference in overall survival for PT and LNM according to the PD-L1 status(P=0.166 and P=0.837,respectively).CONCLUSION Intra-patient heterogeneity in PD-L1 expression was observed between the PT and matched LNM.This disagreement in PD-L1 status may emphasize the importance of considering different tumor sites for analyses to select patients for immunotherapy.

Annual cost of illness of stomach and esophageal cancer patientsin urban and rural areas in China： A multi-center study

Objective： Stomach and esophageal cancer are imposing huge threats to the health of Chinese people whereasthere were few studies on the financial burden of the two cancers.Methods： Costs per hospitalization of all patients with stomach or esophageal cancer discharged betweenSeptember 2015 and August 2016 in seven cities/counties in China were collected, together with their demographicinformation and clinical details. Former patients in the same hospitals were sampled to collect information onannual direct non-medical cost, indirect costs and annual number of hospitalization. Annual direct medical cost wasobtained by multiplying cost per hospitalization by annual number of hospitalization. Annual cost of illness （ACI）was obtained by adding the average value of annual direct medical cost, direct non-medical cost and indirect cost,stratified by sex, age, clinical stage, therapy and pathologic type in urban and rural areas. Costs per hospitalizationwere itemized into eight parts to calculate the proportion of each part. All costs were converted to 2016 US dollars（1 USD：6.6423 RMB）.Results： Totally 19,986 cases were included, predominately male. Mean ages of stomach cancer and urbanpatients were lower than that of esophageal cancer and rural patients. ACI of stomach and esophageal cancerpatients were $10,449 and $13,029 in urban areas, and $2,927 and $3,504 in rural areas, respectively. Greater ACIwas associated with male, non-elderly patients as well as those who were in stage I and underwent surgeries.Western medicine fee took the largest proportion of cost per hospitalization.Conclusions： The ACI of stomach and esophageal cancer was tremendous and varied substantially among thepopulation in China. Preferential policies of medical insurance should be designed to tackle with this burden andfurther reduce the health care inequalities.

Diagnostic value of conventional endoscopic ultrasound for lymph node metastasis in upper gastrointestinal neoplasia:A metaanalysis

BACKGROUND Upper gastrointestinal neoplasia mainly includes esophageal cancer and gastric cancer,both of which have high morbidity and mortality.Lymph node metastasis(LNM),as the most common metastasis mode of both diseases,is an important factor affecting tumor stage,treatment strategy and clinical prognosis.As a new fusion technology,endoscopic ultrasound(EUS)is becoming increasingly used in the diagnosis and treatment of digestive system diseases,but its use in detecting LNM in clinical practice remains limited.AIM To evaluate the diagnostic value of conventional EUS for LNM in upper gastrointestinal neoplasia.METHODS Using the search mode of“MeSH+Entry Terms”and according to the predetermined inclusion and exclusion criteria,we conducted a comprehensive search and screening of the PubMed,EMBASE and Cochrane Library databases from January 1,2000 to October 1,2022.Study data were extracted according to the predetermined data extraction form.The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool,and the results of the quality assessment were presented using Review Manager 5.3.5 software.Finally,Stata14.0 software was used for a series of statistical analyses.RESULTS A total of 22 studies were included in our study,including 2986 patients.The pooled sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,diagnostic score and diagnostic odds ratio of conventional EUS in the diagnosis of upper gastrointestinal neoplasia LNM were 0.62[95%confidence interval(CI):0.50-0.73],0.80(95%CI:0.73-0.86),3.15(95%CI:2.46-4.03),0.47(95%CI:0.36-0.61),1.90(95%CI:1.51-2.29)and 6.67(95%CI:4.52-9.84),respectively.The area under the summary receiver operating characteristic curve was 0.80(95%CI:0.76-0.83).Sensitivity analysis indicated that the results of the meta-analysis were stable.There was considerable heterogeneity among the included studies,and the threshold effect was an important source of heterogeneity.Univariable meta-regression and subgroup analysis showed that tumor type,sample size and EUS diagnostic criteria were significant sources of heterogeneity in specificity(P<0.05).No significant publication bias was found.CONCLUSION Conventional EUS has certain clinical value and can assist in the detection of LNM in upper gastrointestinal neoplasia,but it cannot be used as a confirmatory or exclusionary test.

Prolonged hyperthermic intraperitoneal chemotherapy duration with 90 minutes cisplatin might increase overall survival in gastric cancer patients with peritoneal metastases

BACKGROUND Advanced gastric cancer with synchronous peritoneal metastases(GC-PM)is associated with a poor prognosis.Although cytoreductive surgery with hyperthermic intraperitoneal chemotherapy(CRS-HIPEC)is a promising approach,only a limited number of Western studies exist.AIM To investigate the clinicopathological outcomes of patients who underwent CRSHIPEC for GC-PM.METHODS A retrospective analysis of patients with GC-PM was conducted.All patients were seen at the Department of General and Visceral Surgery,Hospital Barmherzige Brüder,Regensburg,Germany between January 2011 and July 2021 and underwent CRS-HIPEC.Preoperative laboratory results,the use of neoadjuvant trastuzumab,and the details of CRS-HIPEC,including peritoneal carcinomatosis index,completeness of cytoreduction,and surgical procedures were recorded.Disease-specific(DSS),and overall survival(OS)of patients were calculated.RESULTS A total of 73 patients were included in the study.Patients treated with neoadjuvant trastuzumab(n=5)showed longer DSS(P=0.0482).Higher white blood cell counts(DSS:P=0.0433)and carcinoembryonic antigen levels(OS and DSS:P<0.01),and lower hemoglobin(OS and DSS:P<0.05)and serum total protein(OS:P=0.0368)levels were associated with shorter survival.Longer HIPEC duration was associated with more advantageous median survival times[60-min(n=59):12.86 mo;90-min(n=14):27.30 mo],but without statistical difference.To obtain additional data from this observation,further separation of the study population was performed.First,propensity score-matched patient pairs(n=14 in each group)were created.Statistically different DSS was found between patient pairs(hazard ratio=0.2843;95%confidence interval:0.1119-0.7222;P=0.0082).Second,those patients who were treated with trastuzumab and/or had human epidermal growth factor receptor 2 positivity(median survival:12.68 mo vs 24.02 mo),or had to undergo the procedure before 2016(median survival:12.68 mo vs 27.30 mo;P=0.0493)were removed from the original study population.CONCLUSION Based on our experience,CRS-HIPEC is a safe and secure method to improve the survival of advanced GC-PM patients.Prolonged HIPEC duration may serve as a good therapy for these patients.

Nomogram for predicting early complications after distal gastrectomy

BACKGROUND Reducing or preventing postoperative morbidity in patients with gastric cancer(GC)is particularly important in perioperative treatment plans.AIM To identify risk factors for early postoperative complications of GC post-distal gastrectomy and to establish a nomogram prediction model.METHODS This retrospective study included 131 patients with GC who underwent distal gastrectomy at the Second Hospital of Shandong University between January 2019 and February 2023.The factors influencing the development of complications after distal gastrectomy in these patients were evaluated using univariate and multivariate logistic regression analysis.Based on the results obtained,a predictive nomogram was established.The nomogram was validated using internal and external(n=45)datasets.Its sensitivity and specificity were established by receiver operating characteristic curve analysis.Decision curve(DCA)analysis was used to determine its clinical benefit and ten-fold overfitting was used to establish its accuracy and stability.RESULTS Multivariate logistic regression analysis showed that hypertension,diabetes,history of abdominal surgery,and perioperative blood transfusion were independent predictors of postoperative complications of distal gastrectomy.The modeling and validation sets showed that the area under the curve was 0.843[95%confidence interval(CI):0.746-0.940]and 0.877(95%CI:0.719-1.000),the sensitivity was 0.762 and 0.778,respectively,and the specificity was 0.809 and 0.944,respectively,indicating that the model had good sensitivity and specificity.The C-indexes of the modeling and validation datasets were 0.843(95%CI:0.746-0.940)and 0.877(95%CI:0.719-1.000),respectively.The calibration curve(Hosmer Lemeshow test:χ^(2)=7.33)showed that the model had good consistency.The results of the DCA analysis indicated that this model offered good clinical benefits.The accuracy of 10-fold cross-validation was 0.878,indicating that the model had good accuracy and stability.CONCLUSION The nomogram prediction model based on independent risk factors related to postoperative complications of distal gastrectomy can facilitate perioperative intervention for high-risk populations and reduce the incidence of postoperative complications.

Risk factors for blood transfusion and its prognostic implications in curative gastrectomy for gastric cancer

BACKGROUND Gastric cancer(GC)is still a prevalent neoplasm around the world and its main treatment modality is surgical resection.The need for perioperative blood transfusions is frequent,and there is a long-lasting debate regarding its impact on survival.AIM To evaluate the factors related to the risk of receiving red blood cell(RBC)transfusion and its influence on surgical and survival outcomes of patients with GC.METHODS Patients who underwent curative resection for primary gastric adenocarcinoma at our Institute between 2009 and 2021 were retrospectively evaluated.Clinicopathological and surgical characteristics data were collected.The patients were divided into transfusion and non-transfusion groups for analysis.RESULTS A total of 718 patients were included,and 189(26.3%)patients received perioperative RBC transfusion(23 intraoperatively,133 postoperatively,and 33 in both periods).Patients in the RBC transfusions group were older(P<0.001),and had morecomorbidities(P=0.014),American Society of Anesthesiologists classification III/IV(P<0.001),and lower preoperative hemoglobin(P<0.001)and albumin levels(P<0.001).Larger tumors(P<0.001)and advanced tumor node metastasis stage(P<0.001)were also associated with the RBCtransfusion group.The rates of postoperative complications(POC)and 30-d and 90-d mortalitywere significantly higher in the RBC transfusion group than in the non-transfusion group.Lowerhemoglobin and albumin levels,total gastrectomy,open surgery,and the occurrence of POC werefactors associated with the RBC transfusion.Survival analysis demonstrated that the RBCtransfusions group had worse disease-free survival(DFS)and overall survival(OS)compared withpatients who did not receive transfusion(P<0.001 for both).In multivariate analysis,RBCtransfusion,major POC,pT3/T4 category,pN+,D1 lymphadenectomy,and total gastrectomywere independent risk factors related to worse DFS and OS.CONCLUSIONPerioperative RBC transfusion is associated with worse clinical conditions and more advancedtumors.Further,it is an independent factor related to worse survival in the curative intentgastrectomy setting.

Preoperative albumin-bilirubin score is a prognostic factor for gastric cancer patients after curative gastrectomy

BACKGROUND Albumin-bilirubin(ALBI)score is an indicator of liver dysfunction and is useful for predicting prognosis of hepatocellular carcinomas.Currently,this liver function index has been used to predict prognosis in other neoplasms.However,the significance of ALBI score in gastric cancer(GC)after radical resection has not been elucidated.AIM To evaluate the prognostic value of the preoperative ALBI status in patients with GC who received curative treatment.METHODS Patients with GC who underwent curative intended gastrectomy were retrospectively evaluated from our prospective database.ALBI score was calculated as follows:(log10 bilirubin×0.660)+(albumin×-0.085).The receiver operating characteristic curve with area under the curve(AUC)was plotted to evaluate the ability of ALBI score in predicting recurrence or death.The optimal cutoff value was determined by maximizing Youden’s index,and patients were divided into low and high-ALBI groups.The Kaplan-Meier curve was used to analyze the survival,and the log-rank test was used for comparison between groups.RESULTS A total of 361 patients(235 males)were enrolled.The median ALBI value for the entire cohort was-2.89(IQR-3.13;-2.59).The AUC for ALBI score was 0.617(95%CI:0.556-0.673,P<0.001),and the cutoff value was-2.82.Accordingly,211(58.4%)patients were classified as low-ALBI group and 150(41.6%)as high-ALBI group.Older age(P=0.005),lower hemoglobin level(P<0.001),American Society of Anesthesiologists classification III/IV(P=0.001),and D1 lymphadenectomy P=0.003)were more frequent in the high-ALBI group.There was no difference between both groups in terms of Lauren histological type,depth of tumor invasion(pT),presence of lymph node metastasis(pN),and pathologic(pTNM)stage.Major postoperative complication,and mortality at 30 and 90 days were higher in the high-ALBI patients.In the survival analysis,the high-ALBI group had worse disease-free survival(DFS)and overall survival(OS)compared to those with low-ALBI(P<0.001).When stratified by pTNM,the difference between ALBI groups was maintained in stage I/II and stage III CG for DFS(P<0.001 and P=0.021,respectively);and for OS(P<0.001 and P=0.063,respectively).In multivariate analysis,total gastrectomy,advanced pT stage,presence of lymph node metastasis and high-ALBI were independent factors associated with worse survival.CONCLUSION The preoperative ALBI score is able to predict the outcomes of patients with GC,where high-ALBI patients have worse prognosis.Also,ALBI score allows risk stratification of patients within the same pTNM stages,and represents an independent risk factor associated with survival.

Delineation of fatty acid metabolism in gastric cancer:Therapeutic implications

BACKGROUND The prognosis of gastric cancer is extremely poor.Metabolic reprogramming involving lipids has been associated with cancer occurrence and progression.AIM To illustrate fatty acid metabolic mechanisms in gastric cancer,detect core genes,develop a prognostic model,and provide treatment options.METHODS Raw data from The Cancer Genome Atlas and Gene Expression Omnibus databases were collected and analyzed.Differentially expressed fatty acid metabolism genes were identified and incorporated into a risk model based on least absolute shrinkage and selection operator regression analysis.Then,patients from The Cancer Genome Atlas were assigned to high-and low-risk cohorts according to the mean value of the risk score as the threshold,which was verified in the Gene Expression Omnibus database.Relationships between chemotherapeutic sensitivity and tumor microenvironment features were assessed.RESULTS An integrated evaluation was performed in this study.Fatty acid metabolismrelated genes were used to construct the risk model.Patients classified into the high-risk cohort were considered to be resistant to chemotherapy based on results of the“pRRophetic”R package.Patients in the high-risk cohort were associated with type Ⅰ/Ⅱ interferon activation,increased inflammation level,immune cell infiltration,and tumor immune dysfunction based on the exclusion algorithm,indicating the potential benefit of immunotherapy in these patients.CONCLUSION We constructed a fatty acid-related risk score model to assess the comprehensive fatty acid features in gastric cancer and validated its vital role in prognosis,chemotherapy sensitivity,and immunotherapy.

Meta analysis of safety and effectiveness of anastomosis of esophagus and jejunum overlap in total laparoscopic total gastrectomy

Objective:To systematically evaluate and compare the safety and effectiveness of esophagojejunostomy and traditional esophagojejunostomy in total laparoscopic total gastrectomy in the treatment of gastric cancer,providing evidence-based medical evidence for clinical practice.Methods:PubMed,Embase,Cochrane Library,Web of Science,CNKI,Wanfang and VIP databases were searched by computer,and the retrieval time was up to December 2021.Relevant literatures were obtained,and eligible studies were gradually screened and included.Cochrane ROB bias risk assessment tool and NOS scale were used to evaluate the quality of the articles,and required data were extracted from high-quality literatures.Finally,meta-analysis was performed using Review Manager 5.3 software.Results:Eleven studies were finally included,including 1398 patients,including 566 patients receiving overlap anastomosis and 832 patients receiving traditional anastomosis.The results show that overlap anastomosis and traditional anastomosis had the advantages of operation time(MD=0.63,95%CI=7.22,8.48,P=0.88),postoperative first exhaust time(MD=-0.13,95%CI=0.43,0.18,P=0.42),postoperative first feeding time(MD=0.02,95%CI=0.33,0.37,P=0.91),anastomotic leakage(OR=1.38,95%CI=0.73,2.63,P=0.32),and postoperative hospital stay(MD=-0.16,95%CI=0.82,0.51,P=0.64)had no significant differences(all P>0.05).Compared with traditional anastomosis,overlap anastomosis had longer anastomosis time(MD=5.60,95%CI=0.59,10.62,P=0.03),higher incidence of anastomotic bleeding(OR=2.48,95%CI=1.08,5.69,P=0.03),less intraoperative bleeding(MD=-6.42,MD=-6.42,OR=2.48,95%CI=1.08,P=0.03).95%CI=10.28,-2.56,P=0.001)and anastomotic stenosis(OR=0.17,95%CI=0.06,0.46,P=0.0006).Conclusion:Overlap esophagojejunostomy is a safe,effective and prognostic surgical method,and is expected to become the standard esophagojejunostomy in total laparoscopic total gastrectomy.

Endoscopic techniques for gastric neuroendocrine tumors:An update

Gastric neuroendocrine neoplasms(gNENs)are a rare type of gastric neoplasm,even if their frequency is increasing according to the latest epidemiologic revisions of the main registries worldwide.They are divided into three main subtypes,with different pathogeneses,biological behaviors,and clinical characteristics.GNEN heterogeneity poses challenges,therefore these neoplasms require different management strategies.Update the knowledge on the endoscopic treatment options to manage g-NENs.This manuscript is a narrative review of the literature.In recent years,many advances have been made not only in the knowledge of both the pathogenesis and the molecular profiling of gNENs but also in the endoscopic expertise towards innovative treatment options,which proved to be less aggressive without losing the capa-bility of being radical.The endoscopic approach is increasingly applied in the field of gastrointestinal(GI)luminal neoplasms,and this is true not only for adenocarcinomas but also for gNENs.In particular,different techniques have been described for the endoscopic removal of suspected lesions,ranging from classical polypectomy(cold or hot snare)to endoscopic mucosal resection(both with“en bloc”or piecemeal technique),endoscopic submucosal dissection,and endoscopic full-thickness resection.GNENs comprise different subtypes of neoplasms with distinct management and prognosis.New endoscopic techniques offer a wide variety of approaches for GI localized neoplasms,which demonstrated to be appropriate and effective also in the case of gNENs.Correct evaluation of size,site,morphology,and clinical context allows the choice of tailored therapy in order to guarantee a definitive treatment.

Influence of interleukin polymorphisms on development of gastric cancer and peptic ulcer

Pro-inflammatory cytokines are produced in the gastric mucosa by inflammatory cells activated by chronic Helicobacter pylori (H. pylori) infection. Polymorphisms of these cytokine genes are associated with individual differences in gastric mucosal cytokine mRNA level, which result in differences in gastric mucosal inflammation, acid inhibition and gastroduodenal disease risk in response to H. pylori infection. Although polymorphisms of interleukin (IL)-1B, IL-1RN and TNF-A have been reported to relate well with gastric cancer and peptic ulcer risk, those of IL-2, IL-4, IL-6 and IL-8 genes are unclear. In combined analyses using data from previous studies, we found that the risk of gastric non-cardia cancer development was significantly associated with IL-4-168 C allele (OR: 0.81, 95% CI: 0.69-1.00) and IL-4-590 T allele carrier status (0.61, 0.53-0.73), and IL-6-174 G/G genotype (2<Abstract>Pro-inflammatory cytokines are produced in the gastric mucosa by inflammatory cells activated by chronic Helicobacter pylori (H. pylori) infection. Polymorphisms of these cytokine genes are associated with individual differences in gastric mucosal cytokine mRNA level, which result in differences in gastric mucosal inflammation, acid inhibition and gastroduodenal disease risk in response to H. pylori infection. Although polymorphisms of interleukin (IL)-1B, IL-1RN and TNF-A have been reported to relate well with gastric cancer and peptic ulcer risk, those of IL-2, IL-4, IL-6 and IL-8 genes are unclear. In combined analyses using data from previous stud- ies, we found that the risk of gastric non-cardia cancer development was significantly associated with IL-4-168 C allele (OR: 0.81, 95% CI: 0.69-1.00) and IL-4-590 T allele carrier status (0.61, 0.53-0.73), and IL-6-174 G/G genotype (2.02, 1.31-3.10). In peptic ulcer development, IL-2-330 G and IL-4-590 T allele carriers had a significantly decreased risk (0.37, 0.27-0.50 and 0.58, 0.34-0.99, respectively). Moreover, IL-2, IL-4, IL-6 and IL-8 gene genotypes prevalence differs among popula- tions. The inflammatory cytokine gene polymorphisms (e.g. IL-4 -590 and IL-6 -572 for gastric cancer, and IL-4-590, IL-6-572 and IL-8-251 for peptic ulcer) have a more potent influence on development of gastroduo- denal diseases in Western than East Asian populations. These cytokine gene polymorphisms, as well as those of IL-1B, IL-1RN and TNF-A, may be used to identify groups at higher risk of gastric cancer and peptic ulcer, and those suitable for their prevention by H. pylori eradication therapy in Western populations..02, 1.31-3.10). In peptic ulcer development, IL-2-330 G and IL-4-590 T allele carriers had a significantly decreased risk (0.37, 0.27-0.50 and 0.58, 0.34-0.99, respectively). Moreover, IL-2, IL-4, IL-6 and IL-8 gene genotypes prevalence differs among populations. The inflammatory cytokine gene polymorphisms (e.g. IL-4 -590 and IL-6 -572 for gastric cancer, and IL-4-590, IL-6-572 and IL-8-251 for peptic ulcer) have a more potent influence on development of gastroduo-denal diseases in Western than East Asian populations. These cytokine gene polymorphisms, as well as those of IL-1B, IL-1RN and TNF-A, may be used to identify groups at higher risk of gastric cancer and peptic ulcer, and those suitable for their prevention by H. pylori eradication therapy in Western populations.

Huang's three-step maneuver for laparoscopic spleen-preserving No.10 lymph node dissection for advanced proximal gastric cancer

Due to the complexity of the splenic hilar vessels, their anatomical variation and the narrow and deep space, as well as the bleeding-prone splenic parenchyma and the difficulty to manage splenic or vascular bleeding at the splenic hilum,the procedure remains challenging and technically demanding procedure for the performance of laparoscopic pancreas- and spleen-preserving splenic hilar lymph nodes dissection. Based on our experiences, we gradually explored a set of procednral operation steps called ＂Huang＇s three-step maneuver＂. In this paper, we not only provide the concrete operation steps for the surgeon, but we also provide our recommended technique of pulling and exposure for assistants. This new maneuver simplifies the complicated procedure and improves the efficiency of laparoscopic spleen-preserving splenic hilar lymphadenectomy, making it easier to master and allowing for its widespread adoption.

Efficacy of rituximab in gastric diffuse large B cell lymphoma patients

AIM:To evaluate retrospectively the efficacy of rituximab plus chemotherapy in gastric diffuse large B cell lymphoma(DLBCL).METHODS:Sixty patients(median age:58 years)with histologically confirmed gastric DLBCL treated at four Italian institutions between 2000 and 2007,were included in this analysis.Patients were selected by stage (Ⅰ-Ⅳ,Lugano staging system),European Cooperative Oncology Group performance status(0-2)and treatment strategies.Treatment strategies were chemotherapy alone(group A,n=30)[scheduled as cyclophosphamide,doxorubicin,vincristine and prednisone (CHOP)and CHOP-like],and chemotherapy combined with rituximab(group B,n=30).The primary end point of the study was complete response(CR)rate;the secondary end points were disease-free survival (DFS)at 5 years and overall survival(OS).RESULTS:Median follow-up was 62 mo(range:31102 mo).We observed a significant difference between the two groups(A vs B)in terms of CR[76.6%(23/30) vs 100%,P=0.04)and DFS at 5 years[73.3%(22/30) vs 100%,P=0.03).To date,19 group A(63.3%) patients are alive and 11 have died,while all group B patients are alive.No significant differences in toxicity were observed between the two groups.CONCLUSION:Rituximab in combination with chemotherapy improves CR rate,DFS and OS.Further prospective trials are needed to confirm our results.

Significance of vascular endothelial growth factor messenger RNA expression in gastric cancer

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Totally laparoscopic total gastrectomy using the modified overlap method and conventional open total gastrectomy:A comparative study

BACKGROUND Although several methods of totally laparoscopic total gastrectomy(TLTG)have been reported.The best anastomosis technique for LTG has not been established.AIM To investigate the effectiveness and surgical outcomes of TLTG using the modified overlap method compared with open total gastrectomy(OTG)using the circular stapled method.METHODS We performed 151 and 131 surgeries using TLTG with the modified overlap method and OTG for gastric cancer between March 2012 and December 2018.Surgical and oncological outcomes were compared between groups using propensity score matching.In addition,we analyzed the risk factors associated with postoperative complications.RESULTS Patients who underwent TLTG were discharged earlier than those who underwent OTG[TLTG(9.62±5.32)vs OTG(13.51±10.67),P<0.05].Time to first flatus and soft diet were significantly shorter in TLTG group.The pain scores at all postoperative periods and administration of opioids were significantly lower in the TLTG group than in the OTG group.No significant difference in early,late and esophagojejunostomy(EJ)-related complications or 5-year recurrence free and overall survival between groups.Multivariate analysis demonstrated that body mass index[odds ratio(OR),1.824;95%confidence interval(CI):1.029-3.234,P=0.040]and American Society of Anaesthesiologists(ASA)score(OR,3.154;95%CI:1.084-9.174,P=0.035)were independent risk factors of early complications.Additionally,age was associated with≥3 Clavien-Dindo classification and EJrelated complications.CONCLUSION Although TLTG with the modified overlap method showed similar complication rate and oncological outcome with OTG,it yields lower pain score,earlier bowel recovery,and discharge.Surgeons should perform total gastrectomy cautiously and delicately in patients with obesity,high ASA scores,and older ages.

Expression of somatostatin mRNA in various differentiated types of gastric carcinoma

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