Prognostic impact and reasons for variability by tumor location in gastric cancer

BACKGROUND Gastric cancer(GC)is a highly prevalent gastrointestinal tract tumor.Several trials have demonstrated that the location of GC can affect patient prognosis.However,the factors determining tumor location remain unclear.AIM To investigate the tumor location of patients,we went on to study the influencing factors that lead to changes in the location of GC.METHODS A retrospective evaluation was carried out on 3287 patients who underwent gastrectomy for GC in Zhejiang Cancer Hospital.The patients were followed up post-diagnosis and post-gastrectomy.The clinicopathological variables and overall survival of the patients were recorded.By analyzing the location of GC,the tumor location was divided into four categories:“Upper”,“middle”,“lower”,and“total”.Statistical software was utilized to analyze the relationship of each variable with the location of GC.RESULTS A total of 3287 patients were included in this study.The clinicopathological indices of gender,age,serum levels of carcinoembryonic antigen(CEA),carbohydrate antigen(CA19-9)and CA72-4 levels,were significantly associated with tumor location in patients with GC.In addition,there was a strong correlation between GC location and the prognosis of postoperative patients.Specifically,patients with“lower”and“middle”GC demonstrated a better prognosis than those with tumors in other categories.CONCLUSION The five clinicopathological indices of gender,age,CEA,CA19-9 and CA72-4 levels exhibit varying degrees of influence on the tumor location.The tumor location correlates with patient prognosis following surgery.

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.

Early gastric composite tumor comprising signet-ring cell carcinoma and mucosa-associated lymphoid tissue lymphoma:A case report

BACKGROUND Composite tumors are neoplasms comprising two distinct,yet intermingling,cell populations.This paper reports a rare phenomenon where early gastric signet-ring cell carcinoma(SRCC)and gastric mucosa-associated lymphoid tissue(MALT)lymphoma coexist within the same lesion.CASE SUMMARY A 40-year-old woman presented to the West China Hospital for examination,which revealed a whitish,shallow,and uneven mucosal lesion in the stomach.The lesion was diagnosed as a poorly differentiated adenocarcinoma,including SRCC with atypical lymphoid hyperplasia associated with Helicobacter pylori infection,based on histopathological examination of the biopsy specimen.The lesion was excised using segmental gastrectomy.However,histological exami-nation of the surgical specimen confirmed that it was a poorly differentiated gastric adenocarcinoma with features of SRCC and MALT lymphoma.These two entities were stage I and coexisted in the same lesion.CONCLUSION It is uncommon for gastric SRCC and MALT lymphoma to coexist without distinct borders.Surgical resection is effective for these lesions.

Roles of the tumor microenvironment in the resistance to programmed cell death protein 1 inhibitors in patients with gastric cancer

Despite the continuous developments and advancements in the treatment of gastric cancer(GC),which is one of the most prevalent types of cancer in China,the overall survival is still poor for most patients with advanced GC.In recent years,with the progress in tumor immunology research,attention has shifted toward immunotherapy as a therapeutic approach for GC.Programmed cell death protein 1(PD-1)inhibitors,as novel immunosuppressive medications,have been widely utilized in the treatment of GC.However,many patients are still resistant to PD-1 inhibitors and experience recurrence in the advanced stages of PD-1 immunotherapy.To reduce the occurrence of drug resistance and recurrence in GC patients receiving PD-1 immunotherapy,to maximize the clinical activity of immunosuppressive drugs,and to elicit a lasting immune response,it is essential to research the tumor microenvironment mechanisms leading to PD-1 inhibitor resistance in GC patients.This article reviews the progress in studying the factors influencing the resistance to PD-1 inhibitors in the GC tumor microenvironment,aiming to provide insights and a basis for reducing resistance to PD-1 inhibitors for GC patients in the future.

Impact of oxaliplatin and trastuzumab combination therapy on tumor markers and T lymphocyte subsets for advanced gastric cancer

BACKGROUND Advanced gastric cancer(AGC)remains a challenging malignancy with poor prognosis.The combination of oxaliplatin and trastuzumab has shown promising results in AGC treatment.This study aimed to investigate the effects of oxaliplatin and trastuzumab combination therapy on serum tumor markers and T lymphocyte subsets in patients with AGC and to explore their potential as predictive biomarkers for treatment response.AIM To investigate the impact of oxaliplatin and trastuzumab combination therapy on serum markers and T cell subsets in patients with AGC.METHODS This prospective study enrolled 60 patients with AGC.All patients received oxaliplatin(130 mg/m^(2),every 3 weeks)and trastuzumab(8 mg/kg loading dose,followed by 6 mg/kg every 3 weeks)for six cycles.Serum carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9),and cancer antigen 72-4(CA72-4)were measured before and after treatment.T-lymphocyte subsets,including CD3+,CD4+,CD8+,and CD4+/CD8+ratios,were also evaluated.The clinical response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1.RESULTS After six cycles of treatment,the CEA,CA19-9,and CA72-4 serum levels significantly decreased compared to baseline levels(P<0.001).The percentages of CD3+and CD4+T lymphocytes increased significantly(P<0.05),whereas the percentage of CD8+T lymphocytes decreased(P<0.05).The CD4+/CD8+ratio also significantly increased after treatment(P<0.05).Patients with a higher decrease in serum tumor markers(≥50%reduction)and a higher increase in CD4+/CD8+ratio(≥1.5-fold)showed better clinical response rates(P<0.05).CONCLUSION Oxaliplatin and trastuzumab combination therapy effectively reduced serum tumor marker levels and modulated T lymphocyte subsets in patients with AGC.Combination therapy not only has a direct antitumor effect,but also enhances the immune response in patients with AGC.Serum tumor markers and T lymphocyte subsets may serve as potential predictive biomarkers for treatment response in patients with AGC receiving combination therapy.

Endoscopic“calabash”ligation and resection for small gastric mesenchymal tumors

BACKGROUND Gastric mesenchymal tumors(GMT)are identified as soft tissue neoplasms that arise from mesenchymal stem cells within the gastrointestinal tract.GMT pri-marily encompass gastric stromal tumors(GST),gastric leiomyomas,and gastric schwannomas.Although most GMT are benign,there are still potential malignant changes,especially GST.Thus,early surgical intervention is the primary treat-ment for GMT.We have designed a simple endoscopic“calabash”ligation and resection(ECLR)procedure to treat GMT.Its efficacy and safety need to be com-pared with those of traditional endoscopic techniques,such as endoscopic sub-mucosal excavation(ESE).AIM To assess the safety and effectiveness of ECLR in managing small GMT(sGMT)with a maximum diameter≤20 mm by comparing to ESE.METHODS This retrospective analysis involved patients who were hospitalized in our institution between November 2021 and March 2023,underwent endoscopic resection,and received a pathological diagnosis of GMT.Cases with a tumor diameter≤20 mm were chosen and categorized into two cohorts:Study and control groups.The study group was composed of patients treated with ECLR,whereas the control group was composed of those treated with ESE.Data on general clinical characteristics(gender,age,tumor diameter,tumor growth direction,tumor pathological type,and risk grade),surgery-related information(complete tumor resection rate,operation duration,hospitalization duration,hospitalization cost,and surgical complications),and postoperative follow-up were collected for both groups.The aforementioned data were subsequently analyzed and compared.RESULTS Five hundred and eighty-nine individuals were included,with 297 cases in the control group and 292 in the study group.After propensity score matching,the final analysis incorporated 260 subjects in each cohort.The findings indicated that the study group exhibited shorter operation duration and lowered medical expenses relative to the control group.Furthermore,the study group reported less postoperative abdominal pain and had a lower incidence of intraoperative perforation and postoperative electrocoagulation syndrome than the control group.There were no substantial variations observed in other parameters among the two cohorts.CONCLUSION ECLR is a viable and effective approach for managing sGMT.

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.

Prognostic value and predictive model of tumor markers in stageⅠtoⅢgastric cancer patients

BACKGROUND Preoperative serum tumor markers have been widely used in the diagnosis and treatment of gastric cancer patients.However,few studies have evaluated the prognosis of gastric cancer patients by establishing statistical models with multiple serum tumor indicators.AIM To explore the prognostic value and predictive model of tumor markers in stage I and III gastric cancer patients.METHODS From October 2018 to April 2020,a total of 1236 patients with stage I to III gastric cancer after surgery were included in our study.The relationship between serum tumor markers and clinical and pathological data were analyzed.We established a statistical model to predict the prognosis of gastric cancer based on the results of COX regression analysis.Overall survival(OS)was also compared across different stages of gastric cancer.RESULTS The deadline for follow-up was May 31,2023.A total of 1236 patients were included in our study.Univariate analysis found that age,clinical stage,T and N stage,tumor location,differentiation,Borrmann type,size,and four serum tumor markers were prognostic factors of OS(P<0.05).It was shown that clinical stage,tumor size,alpha foetoprotein,carcinoembryonic antigen,CA125 and CA19-9(P<0.05)were independent prognostic factors for OS.According to the scoring results obtained from the statistical model,we found that patients with high scores had poorer survival time(P<0.05).Furthermore,in stage I patients,the 3-year OS for scores 0-3 ranged from 96.85%,95%,85%,and 80%.In stage II patients,the 3-year OS for scores 0-4 were 88.6%,76.5%,90.5%,65.5%and 60%.For stage III patients,3-year OS for scores 0-6 were 70.9%,68.3%,64.1%,50.9%,38.4%,18.5%and 5.2%.We also analyzed the mean survival of patients with different scores.For stage I patients,the mean OS was 55.980 months.In stage II,the mean OS was 51.550 months.The mean OS for stage III was 39.422 months.CONCLUSION Our statistical model can effectively predict the prognosis of gastric cancer patients.

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.

Immunosuppressive tumor microenvironment in gastric signet-ring cell carcinoma

Gastric signet-ring cell carcinoma(GSRCC)is a subtype of gastric cancer with distinct phenotype and high risk of peritoneal metastasis.Studies have shown that early GSRCC has a good prognosis,while advanced GSRCC is insensitive to radiotherapy,chemotherapy or immune checkpoint blockade therapy.With technological advancement of single-cell RNA sequencing analysis and cytometry by time of flight mass cytometry,more detailed atlas of tumor microenvironment(TME)in GSRCC and its association with prognosis could be investigated extensively.Recently,two single-cell RNA sequencing studies revealed that GSRCC harbored a unique TME,manifested as highly immunosuppressive,leading to high immune escape.The TME of advanced GSRCC was enriched for immunosuppressive factors,including the loss of CXCL13+-cluster of differentiation 8+-Tex cells and declined clonal crosstalk among populations of T and B cells.In addition,GSRCC was mainly infiltrated by follicular B cells.The increased proportion of SRCC was accompanied by a decrease in mucosaassociated lymphoid tissue-derived B cells and a significant increase in follicular B cells,which may be one of the reasons for the poor prognosis of GSRCC.By understanding the relationship between immunosuppressive TME and poor prognosis in GSRCC and the underlying mechanism,more effective immunotherapy strategies and improved treatment outcomes of GSRCC can be anticipated.

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.

Evaluation of epithelial-mesenchymal transitioned circulating tumor cells in patients with resectable gastric cancer: Relevance to therapy response

AIM: To evaluate the epithelial-to-mesenchymal transition(EMT) of circulating tumor cells(CTCs) in gastric cancer patients.METHODS: We detected tumor cells for expression of four epithelial(E^+) transcripts(keratins 8, 18, and 19 and epithelial cell adhesion molecule) and two mesenchymal(M^+) transcripts(Vimentin and Twist) by a quantifiable, dual-colorimetric RNA-in situ hybridization assay. Between July 2014 and October 2014, 44 patients with gastric cancer were recruited for CTC evaluation. Blood samples were obtained from selected patients during the treatment course [before surgery, after surgery and at the 6^(th) cycle of XELOX based chemotherapy(about 6 mo postoperatively)].RESULTS: We found the EMT phenomenon in which there were a few biphenotypic E^+/M^+ cells in primary human gastric cancer specimens. Of the 44 patients, the presence of CTCs was reported in 35(79.5%) patients at baseline. Five types of cells including from exclusively E^+ CTCs to intermediate CTCs and exclusively M^+ CTCs were identified(4 patients with M^+ CTCs and 10 patients with M^+ or M^+ > E^+ CTCs). Further, a chemotherapy patient having progressive disease showed a proportional increase of mesenchymal CTCs in the post-treatment blood specimens. We used NCI-N87 cells to analyze the linearity and sensitivity of Can Patrol^(TM) system and the correlation coefficient(R^2) was 0.999.CONCLUSION: The findings suggest that the EMT phenomenon was both in a few cells of primary tumors and abundantly in CTCs from the blood of gastric cancer patients, which might be used to monitor therapy response.

Role of the tumor microenvironment in the pathogenesis of gastric carcinoma

Gastric carcinoma (GC) is the 4th most prevalent cancer and has the 2nd highest cancer-related mortality rate worldwide. Despite the incidence of GC has decreased over the past few decades, it is still a serious health problem. Chronic inflammatory status of the stomach, caused by the infection of Helicobacter pylori (H. pylori) and through the production of inflammatory mediators within the parenchyma is suspected to play an important role in the initiation and progression of GC. In this review, the correlation between chronic inflammation and H. pylori infection as an important factor for the development of GC will be discussed. Major components, including tumor-associated macrophages, lymphocytes, cancer-associated fibroblasts, angiogenic factors, cytokines, and chemokines of GC microenvironment and their mechanism of action on signaling pathways will also be discussed. Increasing our understanding of how the components of the tumor microenviroment interact with GC cells and the signaling pathways involved could help identify new therapeutic and chemopreventive targets.

Prognostic and predictive blood biomarkers in gastric cancer and the potential application of circulating tumor cells

Gastric cancer(GC), with its high incidence and mortality rates, is a highly fatal cancer that is common in East Asia particularly in China. Its recurrence and metastasis are the main causes of its poor prognosis. Circulating tumor cells(CTCs) or other blood biomarkers that are released into the circulating blood stream by tumors are thought to play a crucial role in the recurrence and metastasis of gastric cancer. Therefore, the detection of CTCs and other blood biomarkers has an important clinical significance; in fact, they can help predict the prognosis, assess the staging, monitor the therapeutic effects and determine the drug susceptibility. Recent research has identified many blood biomarkers in GC, such as various serum proteins, autoantibodies against tumor associated antigens, and cell-free DNAs. The analysis of CTCs and circulating cell-free tumor DNA(ctDNA) in the peripheral blood of patients with gastric cancer is called as liquid biopsy. These blood biomarkers provide the disease status for individuals and have clinical meaning. In this review, we focus on the recent scientific advances regarding CTCs and other blood biomarkers, and discuss their origins and clinical meaning.

Prognostic significance of tumor immune microenvironment and immunotherapy:Novel insights and future perspectives in gastric cancer

Despite a decrease in gastric cancer incidence, the development of novel biologic agents and combined therapeutic strategies, the prognosis of gastric cancer remains poor. Recently, the introduction of modern immunotherapy, especially using immune checkpoint inhibitors, led to an improved prognosis in many cancers. The use of immunotherapy was also associated with manageable adverse event profiles and promising results in the treatment of patients with gastric cancer, especially in heavily pretreated patients. These data have led to an accelerated approval of some checkpoint inhibitors in this setting. Understanding the complex relationship between the host immune microenvironment and tumor and the immune escape phenomenon leading to cancer occurrence and progression will subsequently lead to the identification of prognostic immune markers. Furthermore, this understanding will result in the discovery of both new mechanisms for blocking tumor immunosuppressive signals and pathways to stimulate the local immune response by targeting and modulating different subsets of immune cells. Due to the molecular heterogeneity of gastric cancers associated with differentclinico-biologic parameters, immune markers expression and prognosis, novel immunotherapy algorithms should be personalized and addressed to selected subsets of gastric tumors, which have been proven to elicit the best clinical responses. Future perspectives in the treatment of gastric cancer include tailored dual immunotherapies or a combination of immunotherapy with other targeted agents with synergistic antitumor effects.

Classification,clinicopathologic features and treatment of gastric neuroendocrine tumors

Gastric neuroendocrine tumors (GNETs) are rare lesions characterized by hypergastrinemia that arise from enterochromaffin-like cells of the stomach. GNETs consist of a heterogeneous group of neoplasms comprising tumor types of varying pathogenesis, histomorphologic characteristics, and biological behavior. A classification system has been proposed that distinguishes four types of GNETs; the clinicopathological features of the tumor, its prognosis, and the patient&#x02019;s survival strictly depend on this classification. Thus, correct management of patients with GNETs can only be proposed when the tumor has been classified by an accurate pathological and clinical evaluation of the patient. Recently developed cancer therapies such as inhibition of angiogenesis or molecular targeting of growth factor receptors have been used to treat GNETs, but the only definitive therapy is the complete resection of the tumor. Here we review the literature on GNETs, and summarize the classification, clinicopathological features (especially prognosis), clinical presentations and current practice of management of GNETs. We also present the latest findings on new gene markers for GNETs, and discuss the effective drugs developed for the diagnosis, prognosis and treatment of GNETs.

New-style laparoscopic and endoscopic cooperative surgery for gastric stromal tumors

AIM: To evaluate the feasibility and safety of a new style of laparoscopic and endoscopic cooperative surgery (LECS), an improved method of laparoscopic intragastric surgery (LIGS) for the treatment of gastric stromal tumors (GSTs). METHODS: Six patients were treated with the newstyle LECS. Surgery was performed according to the following procedures: (1) Exposing and confirming the location of the tumor with gastroscopy; (2) A laparoscopy light was placed in the cavity using the trocar at the navel, and the other two trocars penetrated both the abdominal and stomach walls; (3) With gastroscopy monitoring, the operation was carried out in the gastric lumen using laparoscopic instruments and the tumor was resected; and (4) The tumor tissue was removed orally using a gastroscopy basket, and puncture holes and perforations were sutured using titanium clips. RESULTS: Tumor size ranged from 2.0 to 4.5 cm (average 3.50 ± 0.84 cm). The operative time ranged from 60 to 130 min (average 83.33 ± 26.58 min). Blood loss was less than 20 mL and hospital stay ranged from 6 to 8 d (average 6.67 ± 0.82 d). The patients were allowed out of bed 12 h later. A stomach tube was inserted for 72 h after surgery, and a liquid diet was then taken. All cases had single tumors which were completely resected using the new-style LECS. No postoperative complications occurred. Pathology of all resected specimens showed GST: no cases of implantation or metastasis were found.CONCLUSION: New-style LECS for GSTs is a quick, optimized, fast recovery, safe and effective therapy.