Clinical value of oral contrast-enhanced ultrasonography in diagnosis of gastric tumors

BACKGROUND The incidence of gastric cancer remains high,and it is the sixth most common cancer and the fourth leading cause of cancer deaths worldwide.Oral contrastenhanced ultrasonography is a simple,non-invasive,and painless method for the diagnosis of gastric tumors.AIM To explore the diagnostic value of oral contrast-enhanced ultrasonography for the detection of gastric tumors.METHODS The screening results based on oral contrast-enhanced ultrasonography and electronic gastroscopy were compared with those of the postoperative pathological examination.RESULTS Among 42 patients with gastric tumors enrolled in the study,the diagnostic accordance rate was 95.2%for oral contrast-enhanced ultrasonography(n=40)and 90.5%for electronic gastroscopy(n=38)compared with postoperative pathological examination.The Kappa value of consistency test with pathological findings was 0.812 for oral contrast-enhanced ultrasonography and 0.718 for electronic gastroscopy,and there was no significant difference between them(P=0.397).For the TNM staging of gastric tumors,the accuracy rate of oral contrast enhanced ultrasonography was 81.9%for the overall T staging and 50%,77.8%,100%,and 100%for T1,T2,T3,and T4 staging,respectively.The sensitivity and specificity were both 100%for stages T3 and T4.The diagnostic accuracy rate of oral contrast-enhanced ultrasonography was 93.8%,80%,100%,and 100%for stages N0,N1-N3,M0,and M1,respectively.CONCLUSION The accordance rate of qualitative diagnosis by oral contrast-enhanced ultrasonography is comparable to that of gastroscopy,and it could be used as the preferred method for the early screening of gastric tumors.

Tumor recurrence and survival prognosis in patients with advanced gastric cancer after radical resection with radiotherapy and chemotherapy

BACKGROUND Advanced gastric cancer is a common malignancy that is often diagnosed at an advanced stage and is still at risk of recurrence after radical surgical treatment.Chemoradiotherapy,as one of the important treatment methods for gastric cancer,is of great significance for improving the survival rate of patients.However,the tumor recurrence and survival prognosis of gastric cancer patients after radio-therapy and chemotherapy are still uncertain.AIM To analyze the tumor recurrence after radical radiotherapy and chemotherapy for advanced gastric cancer and provide more in-depth guidance for clinicians.METHODS A retrospective analysis was performed on 171 patients with gastric cancer who received postoperative adjuvant radiotherapy and chemotherapy in our hospital from 2021 to 2023.The Kaplan-Meier method was used to calculate the recurrence rate and survival rate;the log-rank method was used to analyze the single-factor prognosis;and the Cox model was used to analyze the prognosis associated with multiple factors.RESULTS The median follow-up time of the whole group was 63 months,and the follow-up rate was 93.6%.Stage Ⅱ and Ⅲ patients accounted for 31.0%and 66.7%,respec-tively.The incidences of Grade 3 and above acute gastrointestinal reactions and hematological adverse reactions were 8.8%and 9.9%,respectively.A total of 166 patients completed the entire chemoradiotherapy regimen,during which no adverse reaction-related deaths occurred.In terms of the recurrence pattern,17 patients had local recurrence,29 patients had distant metastasis,and 12 patients had peritoneal implantation metastasis.The 1-year,3-year,and 5-year overall survival(OS)rates were 83.7%,66.3%,and 60.0%,respectively.The 1-year,3-year,and 5-year disease-free survival rates were 75.5%,62.7%,and 56.5%,respectively.Multivariate analysis revealed that T stage,peripheral nerve invasion,and the lymph node metastasis rate(LNR)were independent prognostic factors for OS.CONCLUSION Postoperative intensity-modulated radiotherapy combined with chemotherapy for gastric cancer treatment is well tolerated and has acceptable adverse effects,which is beneficial for local tumor control and can improve the long-term survival of patients.The LNR was an independent prognostic factor for OS.For patients with a high risk of local recurrence,postoperative adjuvant chemoradiation should be considered.

N6-methyladenosine methylation regulates the tumor microenvironment of Epstein-Barr virus-associated gastric cancer

BACKGROUND N6-methyladenosine(m6A)methylation modification exists in Epstein-Barr virus(EBV)primary infection,latency,and lytic reactivation.It also modifies EBV latent genes and lytic genes.EBV-associated gastric cancer(EBVaGC)is a distinctive molecular subtype of GC.We hypothesized EBV and m6A methylation regulators interact with each other in EBVaGC to differentiate it from other types of GC.AIM To investigate the mechanisms of m6A methylation regulators in EBVaGC to determine the differentiating factors from other types of GC.METHODS First,The Cancer Gene Atlas and Gene Expression Omnibus databases were used to analyze the expression pattern of m6A methylation regulators between EBVaGC and EBV-negative GC(EBVnGC).Second,we identified Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional enrichment of m6A-related differentially expressed genes.We quantified the relative abundance of immune cells and inflammatory factors in the tumor microenvironment(TME).Finally,cell counting kit-8 cell proliferation test,transwell test,and flow cytometry were used to verify the effect of insulin-like growth factor binding protein 1(IGFBP1)in EBVaGC cell lines.RESULTS m6A methylation regulators were involved in the occurrence and development of EBVaGC.Compared with EBVnGC,the expression levels of m6A methylation regulators Wilms tumor 1-associated protein,RNA binding motif protein 15B,CBL proto-oncogene like 1,leucine rich pentatricopeptide repeat containing,heterogeneous nuclear ribonucleoprotein A2B1,IGFBP1,and insulin-like growth factor 2 binding protein 1 were significantly downregulated in EBVaGC(P<0.05).The overall survival rate of EBVaGC patients with a lower expression level of IGFBP1 was significantly higher(P=0.046).GO and KEGG functional enrichment analyses showed that the immunity pathways were significantly activated and rich in immune cell infiltration in EBVaGC.Compared with EBVnGC,the infiltration of activated CD4+T cells,activated CD8+T cells,monocytes,activated dendritic cells,and plasmacytoid dendritic cells were significantly upregulated in EBVaGC(P<0.001).In EBVaGC,the expression level of proinflammatory factors interleukin(IL)-17,IL-21,and interferon-γ and immunosuppressive factor IL-10 were significantly increased(P<0.05).In vitro experiments demonstrated that the expression level of IGFBP1 was significantly lower in an EBVaGC cell line(SNU719)than in an EBVnGC cell line(AGS)(P<0.05).IGFBP1 overexpression significantly attenuated proliferation and migration and promoted the apoptosis levels in SNU719.Interfering IGFBP1 significantly promoted proliferation and migration and attenuated the apoptosis levels in AGS.CONCLUSION m6A regulators could remodel the TME of EBVaGC,which is classified as an immune-inflamed phenotype and referred to as a“hot”tumor.Among these regulators,we demonstrated that IGFBP1 affected proliferation,migration,and apoptosis.

Postoperative encapsulated hemoperitoneum in a patient with gastric stromal tumor treated by exposed endoscopic full-thickness resection: A case report

BACKGROUND Gastric stromal tumors,originating from mesenchymal tissues,are one of the most common tumors of the digestive tract.For stromal tumors originating from the muscularis propria,compared with conventional endoscopic submucosal dissection(ESD),endoscopic full-thickness resection(EFTR)can remove deep lesions and digestive tract wall tumors completely.However,this technique has major limitations such as perforation,postoperative bleeding,and post-polypectomy syndrome.Herein,we report a case of postoperative serous surface bleeding which formed an encapsulated hemoperitoneum in a patient with gastric stromal tumor that was treated with exposed EFTR.Feasible treatment options to address this complication are described.CASE SUMMARY A 47-year-old male patient had a hemispherical protrusion found during gastric endoscopic ultrasonography,located at the upper gastric curvature adjacent to the stomach fundus,with a smooth surface mucosa and poor mobility.The lesion was 19.3 mm×16.1 mm in size and originated from the fourth ultrasound layer.Computed tomography(CT)revealed no significant evidence of lymph node enlargement or distant metastasis.Using conventional ESD technology for mucosal pre-resection,exposed EFTR was performed to resect the intact tumor in order to achieve a definitive histopathological diagnosis.Based on its morphology and immunohistochemical expression of CD117 and DOG-1,the lesion was proven to be consistent with a gastric stromal tumor.Six days after exposed EFTR,CT showed a large amount of encapsulated fluid and gas accumulation around the stomach.In addition,gastroscopy suggested intracavitary bleeding and abdominal puncture drainage indicated serosal bleeding.Based on these findings,the patient was diagnosed with serosal bleeding resulting in encapsulated abdominal hemorrhage after exposed EFTR for a gastric stromal tumor.The patient received combined treatments,such as hemostasis under gastroscopy,gastrointestinal decompression,and abdominal drainage.All examinations were normal within six months of follow-up.CONCLUSION This patient developed serous surface bleeding in the gastric cavity following exposed EFTR.Serosal bleeding resulting in an encapsulated hemoperitoneum is rare in clinical practice.The combined treatment may replace certain surgical techniques.

Clinical application of reserved gastric tube in neuroendoscopic endonasal surgery for pituitary tumor

BACKGROUND The neuroendoscopic approach has the advantages of a clear operative field,convenient tumor removal,and less damage,and is the development direction of modern neurosurgery.At present,transnasal surgery for sphenoidal pituitary tumor is widely used.But it has been found in clinical practice that some patients with this type of surgery may experience post-operative nausea and vomiting and other discomforts.AIM To explore the effect of reserved gastric tube application in the neuroendoscopic endonasal resection of pituitary tumors.METHODS A total of 60 patients who underwent pituitary adenoma resection via the endoscopic endonasal approach were selected and randomly divided into the experimental and control groups,with 30 in each group.Experimental group:After anesthesia,a gastric tube was placed through the mouth under direct vision using a visual laryngoscope,and the fluid accumulated in the oropharynx was suctioned intermittently with low negative pressure throughout the whole process after nasal disinfection,during the operation,and when the patient recovered from anesthesia.Control group:Given the routine intraoperative care,no gastric tube was left.The number of cases of nausea/vomiting/aspiration within 24 h post-operation was counted and compared between the two groups;the scores of pharyngalgia after waking up,6 h post-operation,and 24 h postoperation.The frequency of postoperative cerebrospinal fluid leakage and intracranial infection were compared.The hospitalization days of the two groups were statistically compared.RESULTS The times of postoperative nausea and vomiting in the experimental group were lower than that in the control group,and the difference in the incidence of nausea was statistically significant(P<0.05).After the patient woke up,the scores of sore throat 6 h after the operation and 24 h after operation were lower than those in the control group,and the difference was statistically significant(P<0.05).The number of cases of postoperative cerebrospinal fluid leakage and intracranial infection was higher than that of the control group,but there was no statistically significant difference from the control group(P>0.05).The hospitalization days of the experimental group was lower than that of the control group,and the difference was statistically significant(P<0.05).CONCLUSION Reserving a gastric tube in the endoscopic endonasal resection of pituitary tumors,combined with intraoperative and postoperative gastrointestinal decompression,can effectively reduce the incidence of nausea,reduce the number of vomiting and aspiration in patients,and reduce the complications of sore throat The incidence rate shortened the hospitalization days of the patients.

Tumor infiltrating lymphocytes in gastric cancer:Unraveling complex interactions for precision medicine

This editorial will focus on tumor immunity and the factors that alter the tumor immune micro-environment.The role of tumor infiltrating lymphocytes(TILs)will also be discussed in detail,including the types,mechanism of action,and role.Gastric cancer(GC)often presents in the advanced stage and has various factors predicting the outcomes.The interplay of these factors and their correlation with the TILs is discussed.A literature review revealed high intratumoral TILs associated with higher grade,HER2-,and Helicobacter pylori negativity.Moreover,stromal(ST)TILs correlated with lower grade and lesser recurrence risk in GC.High TILs in ST and invasive border also correlated with mismatch repair deficiency status.Further characterization of the CD3+,CD8+,and other cells is also warranted.In the future,this complex correlation of cancer cells with the immune system can be explored for therapeutic avenues.

Prognostic significance of tumor budding,desmoplastic reaction,and lymphocytic infiltration in patients with gastric adenocarcinoma

BACKGROUND Recent studies have shown that the tumor microenvironment significantly influences the behavior of solid tumors.In this context,Accumulated data suggests that pathological evaluation of tumor budding(TB),desmoplastic reaction(DR),and tumor-infiltrating lymphocytes(TILs)may be crucial in determining tumor behavior in the gastrointestinal tract.Regarding gastric adenocarcinoma(GAC),although some results suggest that TB and TILs may be effective in determining the course of the disease,the data do not agree.Moreover,very few studies have investigated the relationship between DR and survival.At present,the associations between tumor TB,DR and TILs in GAC patients have not been determined.AIM To establish the relationships between TB,DR,and TILs in patients with GAC and to assess their influence on prognosis.METHODS Our study group comprised 130 patients diagnosed with GAC.The definition of TB was established based on the International TB Consensus Conference.The DR was categorized into three groups according to the level of tumor stroma maturation.The assessment of TILs was conducted using a semiquantitative approach,employing a cutoff value of 5%.The statistical analysis of the whole group and 100 patients with an intestinal subtype of GAC was performed using SPSS version 27.RESULTS A significant correlation between peritumoral budding(PTB)and intratumoral budding(ITB)was noted(r=0.943).Tumors with high PTBs and ITBs had a greater incidence of immature DRs and low TILs(P<0.01).PTB and ITB were associated with histological subtype,lymph node metastasis(LNM),and stage(P<0.01).ITB,PTB,LNM,DR,and stage were significant risk factors associated with poor prognosis.The multivariate Cox regression analysis identified ITB,PTB,and LNM as independent prognostic variables(P<0.05).In intestinal-type adenocarcinomas,a positive correlation between PTB and ITB was noted(r=0.972).While univariate analysis revealed that LNM,stage,PTB,ITB,and DR were strong parameters for predicting survival(P<0.05),only PTB and ITB were found to be independent prognostic factors(P<0.001).CONCLUSION TB may be a potential prognostic marker in GAC.However,further studies are needed to delineate its role in pathology reporting protocols and the predictive effects of DR and TILs.

Incorporation of perigastric tumor deposits into the TNM staging system for primary gastric cancer

BACKGROUND The current prognostic significance of perigastric tumor deposits(TDs)in gastric cancer(GC)remains unclear.AIM To assess the prognostic value of perigastric TDs and put forward a new TNM staging framework involving TDs for primary GC.METHODS This study retrospectively analyzed the pathological data of 6672 patients with GC who underwent gastrectomy or surgery for GC with other diseases from January 1,2012 to December 31,2017 at the Chinese PLA General Hospital.According to the presence of perigastric TDs or not,the patients were divided into TD-positive and TD-negative groups by using the method of propensity score matching.The differences between TD-positive and TD-negative patients were analyzed using binary logistic regression modeling.The Kaplan-Meier method was used to plot survival curves.Multivariate Cox regression modeling and the log-rank test were used to analyze the data.RESULTS Perigastric TDs were found to be positive in 339(5.09%)of the 6672 patients with GC,among whom 237 were men(69.91%)and 102 were women(30.09%)(2.32:1).The median age was 59 years(range,27 to 78 years).Univariate and multivariate survival analyses indicated that TD-positive GC patients had a poorer prognosis than TD-negative patients(P<0.05).The 1-,3-,and 5-year overall survival rates of GC patients with TDs were 68.3%,19.6%,and 11.2%,respectively,and these were significantly poorer than those without TDs of the same stages.There was significant variation in survival according to TD locations among the GC patients(P<0.05).A new TNM staging framework for GC was formulated according to TD location.When TDs appear in the gastric body,the original stages T1,T2,and T3 are classified as T4a with the new framework,and the original stages T4a and T4b both are classified as T4b.When TDs appear in the lesser curvature,the previous stages N0,N1,N2,and N3 now both are classified as N3.When TDs appear in the greater curvature or the distant tissue,the patient should be categorized as having M1.With the new GC staging scheme including TDs,the survival curves of patients in the lower grade TNM stage with TDs were closer to those of patients in the higher grade TNM stage without TDs.CONCLUSION TDs are a poor prognostic factor for patients with primary GC.The location of TDs is associated with the prognosis of patients with primary GC.Accordingly,we developed a new TNM staging framework involving TDs that is more appropriate for patients with primary GC.

Incidence and prevalence of gastric neuroendocrine tumors in patients with chronic atrophic autoimmune gastritis

BACKGROUND The incidence of type I gastric neuroendocrine neoplasms(gNENs)has increased significantly over the past 50 years.Although autoimmune gastritis(AIG)increases the likelihood of developing gNENs,the exact incidence and prevalence of this association remain unclear.AIM To evaluate the incidence and prevalence of type I gNENs in a cohort of patients with a histological diagnosis of AIG.METHODS Patients with a histological diagnosis of AIG were enrolled between October 2020 and May 2022.Circulating levels of CgA and gastrin were assessed at enrollment.Included patients underwent regular endoscopic follow-up to detect gastric neoplastic lesions,enterochromaffin-like(ECL)cell hyperplasia,and the development of gNEN.RESULTS We included 176 patients[142 women(80.7%),median age 64 years,interquartile range(IQR)53–71 years]diagnosed with AIG between January 1990 and June 2022.At enrollment.One hundred and sixteen patients(65.9%)had ECL hyperplasia,of whom,29.5%had simple/linear,30.7%had micronodular,and 5.7%had macronodular type.The median follow-up time was 5(3–7.5)years.After 1032 person-years,33 patients developed a total of 50 type I gNENs,with an incidence rate of 0.057 person-years,corresponding to an annual cumulative incidence of 5.7%.Circulating CgA levels did not significantly differ between AIG patients who developed gNENs and those who did not.Conversely,gastrin levels were significantly higher in AIG patients who developed gNENs[median 992 pg/mL IQR=449–1500 vs 688 pg/mL IQR=423–1200,P=0.03].Calculated gastrin sensitivity and specificity were 90.9%and 1.4%,respectively,with an overall diagnostic accuracy of 30%and a calculated area under the gastrin receiver operating characteristic curve(AUROC or AUC)of 0.53.CONCLUSION Type I gNENs are a significant complication in AIG.Gastrin’s low diagnostic accuracy prevents it from serving as a marker for early diagnosis.Effective strategies for early detection and treatment are needed.

Tumor budding in gastric cancer

The tumor,nodes,metastasis(TNM)staging system has long been the gold standard for the classification and prognosis of solid tumors.However,the TNM staging system is not without limitations.Prognostic heterogeneity exists within patients at the same stage.Therefore,the pursuit of other biomarkers with the potential to classify patients with cancer has never stopped.One of them,tumor budding(TB),has gained much success in colorectal cancer.In recent years,TB in gastric cancer has attracted much attention from researchers,beginning to reveal the molecular and biological aspects of this phenomenon in gastric cancer,and has emerged as a promising prognostic biomarker in gastric cancer,predicting disease progression and unfavorable survival.Therefore,it is time and essential to provide a holistic overview of TB in gastric cancer,which has not been achieved and is the aim of this review.

The efficacy of full-thickness endoscopic resection of subepithelial tumors in the gastric cardia

BACKGROUND Gastric subepithelial tumors(SETs)may harbor potential malignancy.Although it is well recognized that large SETs should be resected,the precise treatment strategy remains controversial.Compared to surgical resection,endoscopic resection(ER)has many advantages;however,ER of SETs in the cardia is challenging.AIM To evaluate the safety and efficacy of endoscopic full-thickness resection(EFTR)for the treatment of gastric cardia SETs.METHODS We retrospectively reviewed data from all patients with SETs originating from the muscularis propria layer in the gastric cardia that were treated by EFTR or submucosal tunneling ER(STER)at Zhongshan Hospital Fudan University between November 2014 and May 2022.Baseline characteristics and clinical outcomes,including procedure times and complications rates,were compared between groups of patients receiving EFTR and STER.RESULTS A total of 171 tumors were successfully removed[71(41.5%)tumors in the EFTR and 100(58.5%)tumors in the STER group].Gastrointestinal stromal tumors(GISTs)were the most common SET.The en bloc resection rate was 100%in the EFTR group vs 97.0%in STER group(P>0.05).Overall,the EFTR group had a higher complete resection rate than the STER group(98.6%vs 91.0%,P<0.05).The procedure time was also shorter in the EFTR group(44.63±28.66 min vs 53.36±27.34,P<0.05).The most common major complication in both groups was electrocoagulation syndrome.There was no significant difference in total complications between the two groups(21.1%vs 22.0%,P=0.89).CONCLUSION EFTR of gastric cardia SETs is a very promising method to facilitate complete resection with similar complications and reduced operative times compared to STER.In cases of suspected GISTs or an unclear diagnosis,EFTR should be recommended to ensure complete resection.

CD93 serves as a potential biomarker of gastric cancer and correlates with the tumor microenvironment

BACKGROUND The tumor microenvironment(TME)plays an important role in the growth and expansion of gastric cancer(GC).Studies have identified that CD93 is involved in abnormal tumor angiogenesis,which may be related to the regulation of the TME.AIM To determine the role of CD93 in GC.METHODS Transcriptomic data of GC was investigated in a cohort from The Cancer Genome Atlas.Additionally,RNA-seq data sets from Gene Expression Omnibus(GSE118916,GSE52138,GSE79973,GSE19826,and GSE84433)were applied to validate the results.We performed the immune infiltration analyses using ESTIMATE,CIBERSORT,and ssGSEA.Furthermore,weighted gene co-expression network analysis(WGCNA)was conducted to identify the immunerelated genes.RESULTS Compared to normal tissues,CD93 significantly enriched in tumor tissues(t=4.669,95%CI:0.342-0.863,P<0.001).Higher expression of CD93 was significantly associated with shorter overall survival(hazard ratio=1.62,95%CI:1.09-2.4,P=0.017),less proportion of CD8 T and activated natural killer cells in the TME(P<0.05),and lower tumor mutation burden(t=4.131,95%CI:0.721-0.256,P<0.001).Genes co-expressed with CD93 were mainly enriched in angiogenesis.Moreover,11 genes were identified with a strong relationship between CD93 and the immune microenvironment using WGCNA.CONCLUSION CD93 is a novel prognostic and diagnostic biomarker for GC,that is closely related to the immune infiltration in the TME.Although this retrospective study was a comprehensive analysis,the prospective cohort studies are preferred to further confirm these conclusions.

SR-BI expression regulates the gastric cancer tumor immune microenvironment and is associated with poor prognosis

Aim:Scavenger receptor class B,type I(SR-BI)is an integral plasma membrane protein that has been reported to be overexpressed in various malignancies,such as renal cancer,breast cancer,and prostate cancer,and is an independent prognostic factor.However,the clinical value and expression of SR-BI in GC are unknown.Our research aimed to explore the role of SR-BI in combination with immune markers as a diagnostic and prognostic marker for gastric cancer(GC).Methods:GC tissues,paracancerous tissues,and clinicopathological data of 149 patients were collected.The expression level of SR-BI,Tumor-infiltrating lymphocytes(TILs),and PD-L1 were evaluated by immunohistochemistry(IHC).The associations of the SR-BI staining intensity with clinicopathological features and immune markers were determined by the chi-square test.Univariate and multivariate COX regression analyses were used to evaluate independent prognostic factors.Kaplan–Meier analyses were performed to plot the survival curve.Results:Our results indicated that SR-BI was expressed at higher levels in tumor tissues than in adjacent paracancerous tissues(p<0.001),and patients with high levels of SR-BI expression had a worse prognosis.Univariate and multivariate analyses revealed that high SR-BI expression was an independent factor for poor prognosis.The chi-square test determined that the expression of SR-BI was negatively correlated with CD4+T cells and CD8+T cells(CD4+T cells,p=0.013;CD8+T cells,p=0.021),and positively correlated with PD-L1(p=0.022).Finally,survival analysis revealed that CD4+T cells were associated with the prognosis of GC patients(p=0.019),and the combined survival analysis of SR-BI and CD4+T cells was also statistically significant(p=0.030).Conclusion:SR-BI is highly expressed in GC tissue and associated with poor prognosis.Moreover,SR-BI can also regulate the GC tumor immune microenvironment.

Gastric neuroendocrine tumors in a BRCA2 germline mutation carrier:A case report

BACKGROUND The molecular changes present in gastric neuroendocrine tumors(NETs)include a loss of heterozygosity or mutation of MEN1,CDKN1B gene mutation,P27 heterozygous mutation,and ATP4A gene missense mutation.We identified and are the first to report a case of type 1 histamine-producing enterochromaffin-like cell NETs(ECL-cell NETs)with a BRCA2 gene germline mutation.CASE SUMMARY The patient had a history of iron-deficient anemia for 5 years,and gastroscopic examination indicated multiple gastric tumors.Then,the patient underwent distal gastrectomy.Microscopically,multifocal tumor cells were found in the mucosa and submucosa;tumor cells were organoid and arranged in nests and cords,and the stroma was rich in sinusoids.The surrounding gastric mucosa showed atrophy with mild intestinal metaplasia or pseudopyloric gland metaplasia.Neuroendocrine cells could be seen with diffuse linear,nodular,and adenomatous hyperplasia.Immunohistochemically,the tumor cells diffusely expressed cytokeratin,chromogranin,synaptophysin,and CD56.Whole-genome highthroughput molecular sequencing revealed a pathogenic germline mutation in the BRCA2 gene,a heterozygous germline frameshift mutation in exon 11,c.6443_6444del(p.S2148Yfs*2).The final diagnosis was gastric type 1 ECL-cell NETs with a BRCA2 gene germline mutation,accompanied by autoimmune gastritis.CONCLUSION This is the first report of a case of type 1 gastric ECL-cell NETs with a pathogenic germline mutation of the BRCA2 gene.The findings of this report will expand the germline mutation spectrum of gastric NETs and increase the understanding of the molecular changes present in these tumors for their improved diagnosis in the future.

Tousled-like kinase 1 promotes gastric cancer progression by regulating the tumor growth factor-beta signaling pathway

BACKGROUND The role of Tousled-like kinase 1(TLK1)in in gastric cancer(GC)remains unclear.AIM To investigate the expression,biological function,and underlying mechanisms of TLK1 in GC.METHODS We measured TLK1 protein expression levels and localized TLK1 in GC cells and tissues by western blot and immunofluorescence,respectively.We transfected various GC cells with lentiviruses to create TLK1 overexpression and knockdown lines and established the functional roles of TLK1 through in vitro colony formation,5-ethynyl-2`-deoxyuridine,and Transwell assays as well as flow cytometry.We applied bioinformatics to elucidate the signaling pathways associated with TLK1.We performed in vivo validation of TLK1 functions by inducing subcutaneous xenograft tumors in nude mice.RESULTS TLK1 was significantly upregulated in GC cells and tissues compared to their normal counterparts and was localized mainly to the nucleus.TLK1 knockdown significantly decreased colony formation,proliferation,invasion,and migration but increased apoptosis in GC cells.TLK1 overexpression had the opposite effects.Bioinformatics revealed,and subsequent experiments verified,that the tumor growth factor-beta signaling pathway was implicated in TLK1-mediated GC progression.The in vivo assays confirmed that TLK1 promotes tumorigenesis in GC.CONCLUSION The findings of the present study indicated that TLK1 plays a crucial role in GC progression and is,therefore,promising as a therapeutic target against this disease.

Synchronous occurrence of gastric cancer and gastrointestinal stromal tumor: A case report and review of the literature

BACKGROUND To evaluate the clinicopathological features and prognosis of gastric cancer(GC)occurring synchronously with gastrointestinal stromal tumor(GIST).CASE SUMMARY We report 19 patients with concurrent GC and GIST(17 male and 2 female,median age 62 years).GC was most often located in the lower third of the stomach.GIST was diagnosed preoperatively in four patients.GIST was most often located in the gastric body(n=8,42%).The most common growth pattern in GIST was extraluminal(n=12,63%).The positive expression rates of CD117 and CD34 in GIST were 100% and 95%,respectively.Most patients with GIST(n=17,89%)were very low or low risk.There was no recurrence of GIST during follow-up.The 3-year cumulative survival rate was 73.9%,and the 5-year cumulative survival rate was 59.2%.The combined analysis of this study and literature reports(47 reports,157 patients)found that GC and GIST were usually located in the lower third(42%)and middle third(51%)of the stomach.GC was usually early(stage I:42%),poorly differentiated(42%)intestinal-type adenocarcinoma(51%).GISTs were primarily small in diameter(median:1.2 cm)and very low or low risk(89%).CONCLUSION Synchronous GC and GIST may not be rare.They have specific clinicopathological characteristics,and may have mutual inhibition in pathogenesis and progression.

Goldilocks principle of minimally invasive surgery for gastric subepithelial tumors

BACKGROUND Minimally invasive surgery had been tailored to individual cases of gastric subepithelial tumors(SETs)after comparing the clinical outcomes of endoscopic resection(ER),laparoscopic resection(LR),and hybrid methods.AIM To study the use of Goldilocks principle to determine the best form of minimally invasive surgery for gastric SETs.METHODS In this retrospective study,194 patients of gastric SETs with high probability of surgical intervention were included.All patients underwent tumor resection in the operating theater between January 2013 and December 2021.The patients were divided into two groups,ER or LR,according to the tumor characteristics and the initial intent of intervention.Few patients in the ER group required further backup laparoscopic surgery after an incomplete ER.The patients who had converted open surgery were excluded.A logistic regression model was used to assess the associations between patient characteristics and the likelihood of a treatment strategy.The area under the curve was used to assess the discriminative ability of tumor size and Youden’s index to determine the optimal cut-off tumor size.RESULTS One-hundred ninety-four patients(100 in the ER group and 94 in the LR group)underwent tumor resection in the operating theater.In the ER group,27 patients required backup laparoscopic surgery after an incomplete ER.The patients in the ER group had small tumor sizes and shorter procedure durations while the patients in the LR group had large tumor sizes,exophytic growth,malignancy,and tumors that were more often located in the middle or lower third of the stomach.Both groups had similar durations of hospital stays and a similar rate of major postoperative complications.The patients in the ER group who underwent backup surgery required longer procedures(56.4 min)and prolonged stays(2 d)compared to the patients in the LR group without the increased rate of major postoperative complications.The optimal cut-off point for the tumor size for laparoscopic surgery was 2.15 cm.CONCLUSION Multidisciplinary teamwork leads to the adoption of different strategies to yield efficient clinical outcomes according to the tumor characteristics.

Gastric inflammatory myofibroblastic tumor, a rare mesenchymalneoplasm: A case report

BACKGROUND The inflammatory myofibroblastic tumor(IMT)is a rare mesenquimal tumor of doubtful biological behaviour.It’s characterised for affecting mainly children and young adults,although it can appear at any age,being the lungs the primary affected organ(in children it represents 20%of all primary pulmonary tumors).CASE SUMMARY We present the case of a 45 year old woman,with a computed tomography(CT)finding of injury on the anterior surface of the fundus/gastric body and a solid perigastric injury of 12 mm in the ecoendoscopy.The case is presented in the tumor committee deciding to perform a laparoscopic wedge resection.The histological diagnosis was a IMT.The diagnosis is based on imaging tests like the abdominal CT,abdominal ecography and the ecoendoscopy but to confirm the diagnosis a pathological study is necessary.CONCLUSION Due to the unpredictable nature of this tumor,surgical resection is the best therapeutic option.

Antitumor activity of miR-188-3p in gastric cancer is achieved by targeting CBL expression and inactivating the AKT/mTOR signaling

BACKGROUND Altered miR-188-3p expression has been observed in various human cancers.AIM To investigate the miR-188-3p expression,its roles,and underlying molecular events in gastric cancer.METHODS Fifty gastric cancer and paired normal tissues were collected to analyze miR-188-3p and CBL expression.Normal and gastric cancer cells were used to manipulate miR-188-3p and CBL expression through different assays.The relationship between miR-188-3p and CBL was predicted bioinformatically and confirmed using a luciferase gene reporter assay.A Kaplan-Meier analysis was used to associate miR-188-3p or CBL expression with patient survival.A nude mouse tumor cell xenograft assay was used to confirm the in vitro data.RESULTS MiR-188-3p was found to be lower in the plasma of gastric cancer patients,tissues,and cell lines compared to their healthy counterparts.It was associated with overall survival of gastric cancer patients(P<0.001),tumor differentiation(P<0.001),lymph node metastasis(P=0.033),tumor node metastasis stage(I/II vs III/IV,P=0.024),and American Joint Committee on Cancer stage(I/II vs III/IV,P=0.03).Transfection with miR-188-3p mimics reduced tumor cell growth and invasion while inducing apoptosis and autophagy.CBL was identified as a direct target of miR-188-3p,with its expression antagonizing the effects of miR-188-3p on gastric cancer(GC)cell proliferation by inducing tumor cell apoptosis and autophagy through the inactivation of the Akt/mTOR signaling pathway.The in vivo data confirmed antitumor activity via CBL downregulation in gastric cancer.CONCLUSION The current data provides ex vivo,in vitro,and in vivo evidence that miR-188-3p acts as a tumor suppressor gene or possesses antitumor activity in GC.

Novel classification of gastric polyps:The good,the bad and the ugly

Gastric polyps(GPs)are increasingly common.On upper endoscopy,they should be examined with white light and occasionally chromoendoscopy,and their morphology classified according to the Paris classification.Most GPs have a typical endoscopic appearance and can be associated with diseases like Helicobacter pylori infection.Histological examination is necessary for an accurate diagnosis.While most polyps are non-neoplastic and do not require treatment,some carry a risk of malignancy or are already malignant.Therefore,understanding the diagnosis,classification,and management of GPs is crucial for patient prognostication.Our new classification categorizes GPs into"good","bad",and"ugly"based on their likelihood of becoming malignant.We aim to provide descriptions of the endoscopic appearance,pathology,treatment,and follow-up for different GPs,as well as clinical management flowcharts.