Prognostic analysis of related factors of adverse reactions to immunotherapy in advanced gastric cancer and establishment of a nomogram model

BACKGROUND Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years.However,the adverse reactions of immunotherapy and its relationship with patient prognosis still need further study.In order to determine the association between adverse reaction factors and prognosis,the aim of this study was to conduct a systematic prognostic analysis.By comprehensively evaluating the clinical data of patients with advanced gastric cancer treated by immunotherapy,a nomogram model will be established to predict the survival status of patients more accurately.AIM To explore the characteristics and predictors of immune-related adverse reactions(irAEs)in advanced gastric cancer patients receiving immunotherapy with programmed death protein-1(PD-1)inhibitors and to analyze the correlation between irAEs and patient prognosis.METHODS A total of 140 patients with advanced gastric cancer who were treated with PD-1 inhibitors in our hospital from June 2021 to October 2023 were selected.Patients were divided into the irAEs group and the non-irAEs group according to whether or not irAEs occurred.Clinical features,manifestations,and prognosis of irAEs in the two groups were collected and analyzed.A multivariate logistic regression model was used to analyze the related factors affecting the occurrence of irAEs,and the prediction model of irAEs was established.The receiver operating characteristic(ROC)curve was used to evaluate the ability of different indicators to predict irAEs.A Kaplan-Meier survival curve was used to analyze the correlation between irAEs and prognosis.The Cox proportional risk model was used to analyze the related factors affecting the prognosis of patients.RESULTS A total of 132 patients were followed up,of whom 63(47.7%)developed irAEs.We looked at the two groups’clinical features and found that the two groups were statistically different in age≥65 years,Ki-67 index,white blood cell count,neutrophil count,and regulatory T cell(Treg)count(all P<0.05).Multivariate logistic regression analysis showed that Treg count was a protective factor affecting irAEs occurrence(P=0.030).The ROC curve indicated that Treg+Ki-67+age(≥65 years)combined could predict irAEs well(area under the curve=0.753,95%confidence interval:0.623-0.848,P=0.001).Results of the Kaplan-Meier survival curve showed that progressionfree survival(PFS)was longer in the irAEs group than in the non-irAEs group(P=0.001).Cox proportional hazard regression analysis suggested that the occurrence of irAEs was an independent factor for PFS(P=0.006).CONCLUSION The number of Treg cells is a separate factor that affects irAEs in advanced gastric cancer patients receiving PD-1 inhibitor immunotherapy.irAEs can affect the patients’PFS and result in longer PFS.Treg+Ki-67+age(≥65 years old)combined can better predict the occurrence of adverse reactions.

Nomogram model including LATS2 expression was constructed to predict the prognosis of advanced gastric cancer after surgery

BACKGROUND Gastric cancer is a leading cause of cancer-related deaths worldwide.Prognostic assessments are typically based on the tumor-node-metastasis(TNM)staging system,which does not account for the molecular heterogeneity of this disease.LATS2,a tumor suppressor gene involved in the Hippo signaling pathway,has been identified as a potential prognostic biomarker in gastric cancer.AIM To construct and validate a nomogram model that includes LATS2 expression to predict the survival prognosis of advanced gastric cancer patients following ra-dical surgery,and compare its predictive performance with traditional TNM staging.METHODS A retrospective analysis of 245 advanced gastric cancer patients from the Fourth Hospital of Hebei Medical University was conducted.The patients were divided into a training group(171 patients)and a validation group(74 patients)to deve-lop and test our prognostic model.The performance of the model was determined using C-indices,receiver operating characteristic curves,calibration plots,and decision curves.RESULTS The model demonstrated a high predictive accuracy with C-indices of 0.829 in the training set and 0.862 in the validation set.Area under the curve values for three-year and five-year survival prediction were significantly robust,suggesting an excellent discrimination ability.Calibration plots confirmed the high concordance between the predictions and actual survival outcomes.CONCLUSION We developed a nomogram model incorporating LATS2 expression,which significantly outperformed conven-tional TNM staging in predicting the prognosis of advanced gastric cancer patients postsurgery.This model may serve as a valuable tool for individualized patient management,allowing for more accurate stratification and im-proved clinical outcomes.Further validation in larger patient cohorts will be necessary to establish its generaliza-bility and clinical utility.

Development of a clinical nomogram for prediction of response to neoadjuvant chemotherapy in patients with advanced gastric cancer

BACKGROUND The efficacy of neoadjuvant chemotherapy(NAC)in advanced gastric cancer(GC)is still a controversial issue.AIM To find factors associated with chemosensitivity to NAC treatment and to provide the optimal therapeutic strategies for GC patients receiving NAC.METHODS The clinical information was collected from 230 GC patients who received NAC treatment at the Central South University Xiangya School of Medicine Affiliated Haikou Hospital from January 2016 to December 2020.Least absolute shrinkage and selection operator logistic regression analysis was used to find the possible predictors.A nomogram model was employed to predict the response to NAC.RESULTS In total 230 patients were finally included in this study,including 154 males(67.0%)and 76 females(33.0%).The mean age was(59.37±10.60)years,ranging from 24 years to 80 years.According to the tumor regression grade standard,there were 95 cases in the obvious response group(grade 0 or grade 1)and 135 cases in the poor response group(grade 2 or grade 3).The obvious response rate was 41.3%.Least absolute shrinkage and selection operator analysis showed that four risk factors significantly related to the efficacy of NAC were tumor location(P<0.001),histological differentiation(P=0.001),clinical T stage(P=0.008),and carbohydrate antigen 724(P=0.008).The C-index for the prediction nomogram was 0.806.The calibration curve revealed that the predicted value exhibited good agreement with the actual value.Decision curve analysis showed that the nomogram had a good value in clinical application.CONCLUSION A nomogram combining tumor location,histological differentiation,clinical T stage,and carbohydrate antigen 724 showed satisfactory predictive power to the response of NAC and can be used by gastrointestinal surgeons to determine the optimal treatment strategies for advanced GC patients.

Research progress of integrated traditional Chinese and Western medicine in the treatment of advanced gastric cancer

Gastric cancer(GC)is a malignant tumor originating from the gastric epithelium,and its incidence and mortality rates rank third among all malignant tumors worldwide.It is also one of the most common cancers in China and is treated predominantly by Western medicine in clinical practice.However,with the advancements in medical technology and informatics,the values of traditional Chinese medicine(TCM)in preventing and treating GC and improving prognosis have increasingly been recognized.According to TCM,clinical manifestations of GC can be divided into Yege(dysphagia),regurgitation,stomach pain,and Zhengxia(abdominal mass).Due to the unbalanced distribution of health care resources in China,most GC patients already have progressive or advanced-stage disease at the first diagnosis.As a result,most GC patients have poor physical function,and surgery or chemotherapy alone will aggravate the impairment to the immune function and seriously affect the quality of life.In contrast,TCM therapies have shown promising efficacy in the management of these patients.Here we review the role of the integrated TCM and Western medicine in treating advanced GC.

Short-term efficacy and influencing factors of conventional chemotherapy combined with irinotecan in patients with advanced gastric cancer

BACKGROUND Gastric cancer is one of the most common cancers worldwide, with a 5-year survival rate of only 20%. The age of onset of gastric cancer is in line with the general rule of cancer. Most of them occur after middle age, mostly between 40and 60 years old, with an average age of about 50 years old, and only 5% of patients are under 30 years old. The incidence of male is higher than that of female.AIM To investigate the short-term efficacy and influencing factors of chemotherapy combined with irinotecan in patients with advanced gastric cancer.METHODS Eighty patients with advanced gastric cancer who were treated in our hospital from January 2019 to January 2022 were selected. The patients were divided into an observation group(n = 40) and control group(n = 40) by the envelope method.The control group was given preoperative routine chemotherapy. The observation group was treated with irinotecan in addition to the chemotherapy given to the control group. The short-term efficacy of treatment in the two groups, as well as tumor marker levels and quality of life before and after treatment were evaluated.RESULTS The short-term treatment effect in the observation group was better than that in the control group(P < 0.05), and the total effective rate was 57.50%. The age and proportion of tumor node metastasis(TNM) stage IV patients with ineffective chemotherapy in the observation group were(65.12 ± 5.71) years and 52.94%,respectively, which were notably higher than those of patients with effective chemotherapy(P < 0.05), while the Karnofsky Performance Scale score was(67.70± 3.83) points, which was apparently lower than that of patients with effective chemotherapy(P <0.05). After 3 mo of treatment, the SF-36 scale scores of physiological function, energy, emotional function, and mental health in the observation group were 65.12 ± 8.14, 54.76 ± 6.70, 47.58 ± 7.22,and 66.16 ± 8.11 points, respectively, which were considerably higher than those in the control group(P < 0.05). The incidence rates of grade Ⅲ-Ⅳ diarrhea and grade Ⅲ-Ⅳ thrombocytopenia in the observation group were 32.50% and 25.00%, respectively, which were markedly higher than those in the control group(P < 0.05).CONCLUSION Chemotherapy combined with irinotecan in patients with advanced gastric cancer has a good short-term efficacy and can significantly reduce serum tumor markers and improve the quality of life of patients. The efficacy may be affected by the age and TNM stage of the patients, and its long-term efficacy needs further study.

Efficacy of continuous gastric artery infusion chemotherapy in relieving digestive obstruction in advanced gastric cancer

BACKGROUND Obstruction or fullness after feeding is common in gastric cancer(GC)patients,affecting their nutritional status and quality of life.Patients with digestive obstruction are generally in a more advanced stage.Existing methods,including palliative gastrectomy,gastrojejunostomy,endoluminal stent,jejunal nutrition tube and intravenous chemotherapy,have limitations in treating these symptoms.AIM To analyze the efficacy of continuous gastric artery infusion chemotherapy(cGAIC)in relieving digestive obstruction in patients with advanced GC.METHODS This study was a retrospective study.Twenty-nine patients with digestive obstruction of advanced GC who underwent at least one cycle of treatment were reviewed at The Second Affiliated Hospital of Zhejiang University School of Medicine.The oxaliplatin-based intra-arterial infusion regimen was applied in all patients.Mild systemic chemotherapy was used in combination with local treatment.The clinical response was evaluated by contrast-enhanced computed tomography using Response Evaluation Criteria In Solid Tumors(RECIST)criteria.Digestive tract symptoms and toxic effects were analyzed regularly.A comparison of the Karnofsky Performance Status(KPS)score and Stooler’s Dysphagia Score before and after therapy was made.Univariate survival analysis and multivariate survival analysis were also performed to explore the key factors affecting patient survival.RESULTS All patients finished cGAIC successfully without microcatheter displacement,as confirmed by arteriography.The median follow-up time was 24 mo(95%CI:20.24-27.76 mo).The overall response rate was 89.7%after cGAIC according to the RECIST criteria.The postoperative Stooler’s Dysphagia Score was significantly improved.Twentytwo(75.9%)of the 29 patients experienced relief of digestive obstruction after the first two cycles,and 13(44.8%)initially unresectable patients were then considered radically resectable.The median overall survival time(mOS)was 16 mo(95%CI:9.32-22.68 mo).Patients who received radical surgery had a significantly longer mOS than other patients(P value<0.001).Multivariate Cox regression analysis indicated that radical resection after cGAIC,intravenous chemotherapy after cGAIC,and immunotherapy after cGAIC were independent predictors of mOS.None of the patients stopped treatment because of adverse events.CONCLUSION cGAIC was effective and safe in relieving digestive obstruction in advanced GC,and it could improve surgical conversion possibility and survival time.

Laparoscopy-assisted gastrectomy for advanced gastric cancer patients with situs inversus totalis: Two case reports and review of literature

BACKGROUND Situs inversus totalis(SIT)is a rare condition in which the positions of abdominal and thoracic organs present a“mirror image”of the normal ones in the median sagittal plane.Although minimally invasive surgery has evolved to achieve laparoscopic gastrectomy for gastric cancer(GC)patients with SIT,it is difficult to perform lymphadenectomy(LND)in such a transposed anatomical condition.Herein,we report the cases of two patients with SIT who successfully underwent laparoscopy-assisted gastrectomy(LAG)with D2 LND.CASE SUMMARY Case 1:A 65-year-old man was admitted for intermittent abdominal pain and distension,occasional belching,and acid reflux for 4 mo.He was diagnosed with GC(cT3N1-2M0)with SIT.Before surgery,he had undergone four cycles of neoadjuvant chemotherapy and immunotherapy.Then,the patient was evaluated as having a partial response,and laparoscopy-assisted distal gastrectomy with D2 LND and Billroth II reconstruction were performed.The operation was performed successfully within 240 min with an estimated blood loss of 50 mL and no severe complications.The patient was discharged on postoperative day(POD)9.Case 2:A 55-year-old man was admitted for upper abdominal distension with pain and discomfort after eating for 3 mo.He was diagnosed with GC(cT3N1M0)with SIT.He had a history of hypertension for more than 10 years;however,his blood pressure was well-controlled via regular medication.We performed laparoscopy-assisted total gastrectomy with D2 LND and Roux-en-Y reconstruction.The operation was performed successfully within 168 min with an estimated blood loss of 50 mL and no severe complications.The patient was discharged on POD 10.CONCLUSION LAG with D2 LND could be considered an accessible,safe,and curative procedure for advanced GC patients with SIT.

Immunotherapy for advanced gastric cancer

Gastric cancer(GC)is believed to be the fifth most common cancer and the third most common cause of death worldwide.Treatment techniques include radiation,chemotherapy,gastrectomy,and targeted treatments are often employed.Some hopeful results from the development of GC immunotherapy have already changed treatment approaches.Along with previous combination medicines,new immunotherapies have been developed that target distinct molecules.Despite ongoing studies into the current therapeutic options and significant improvements in this field,the prognosis for the ailment is poor.Since there are few treatment options and a delay in detection,the illness actually advances,spreads,and metastasizes.The bulk of immunotherapies in use today rely on cytotoxic immune cells,monoclonal antibodies,and gene-transferred vaccines.Immune checkpoint inhibitors have become more popular.In this review,we sought to examine the viewpoint and development of several immunotherapy treatment modalities for advanced GC,as well as the clinical results thus far reported.Additionally,we outlined tumor immune escape and tumor immunosurveillance.

Efficacy and outcome of extensive intraoperative peritoneal lavage plus surgery vs surgery alone with advanced gastric cancer patients

BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors.After resection,one of the major problems is its peritoneal dissemination and recurrence.Some free cancer cells may still exist after resection.In addition,the surgery itself may lead to the dissemination of tumor cells.Therefore,it is necessary to remove residual tumor cells.Recently,some researchers found that extensive intraoperative peritoneal lavage(EIPL)plus intraperitoneal chemotherapy can improve the prognosis of patients and eradicate peritoneal free cancer for GC patients.However,few studies explored the safety and long-term outcome of EIPL after curative gastrectomy.AIM To evaluate the efficacy and long-term outcome of advanced GC patients treated with EIPL.METHODS According to the inclusion and exclusion criteria,a total of 150 patients with advanced GC were enrolled in this study.The patients were randomly allocated to two groups.All patients received laparotomy.For the non-EIPL group,peritoneal lavage was washed using no more than 3 L of warm saline.In the EIPL group,patients received 10 L or more of saline(1 L at a time)before the closure of the abdomen.The surviving rate analysis was compared by the Kaplan-Meier method.The prognostic factors were carried out using the Cox appropriate hazard pattern.RESULTS The basic information in the EIPL group and the non-EIPL group had no significant difference.The median follow-up time was 30 mo(range:0-45 mo).The 1-and 3-year overall survival(OS)rates were 71.0%and 26.5%,respectively.The symptoms of ileus and abdominal abscess appeared more frequently in the non-EIPL group(P<0.05).For the OS of patients,the EIPL,Borrmann classification,tumor size,N stage,T stage and vascular invasion were significant indicators.Then multivariate analysis revealed that EIPL,tumor size,vascular invasion,N stage and T stage were independent prognostic factors.The prognosis of the EIPL group was better than the non-EIPL group(P<0.001).The 3-year survival rate of the EIPL group(38.4%)was higher than the non-EIPL group(21.7%).For the recurrence-free survival(RFS)of patients,the risk factor of RFS included EIPL,N stage,vascular invasion,type of surgery,tumor location,Borrmann classification,and tumor size.EIPL and tumor size were independent risk factors.The RFS curve of the EIPL group was better than the non-EIPL group(P=0.004),and the recurrence rate of the EIPL group(24.7%)was lower than the non-EIPL group(46.4%).The overall recurrence rate and peritoneum recurrence rate in the EIPL group was lower than the non-EIPL group(P<0.05).CONCLUSION EIPL can reduce the possibility of perioperative complications including ileus and abdominal abscess.In addition,the overall survival curve and RFS curve were better in the EIPL group.

Efficacy and safety of laparoscopic vs open gastrectomy after neoadjuvant therapy for locally advanced gastric cancer

BACKGROUND Laparoscopic gastrectomy(LG)is widely accepted as a minimally invasive approach for the treatment of early gastric cancer.However,its role in locally advanced gastric cancer(LAGC)after neoadjuvant therapy(NAT)remains controversial.This study aimed to compare the efficacy and safety of LG vs open gastrectomy(OG)after NAT for the treatment of LAGC.AIM To compare the efficacy and safety of LG vs OG after NAT for LAGC.METHODS We conducted a prospective study of 76 patients with LAGC who underwent NAT followed by LG(n=38)or OG(n=38)between 2021 and 2023.The primary endpoint was overall survival(OS),and the secondary endpoints were diseasefree survival(DFS),surgical complications,and quality of life(QOL).RESULTS The two groups had comparable baseline characteristics,with a median follow-up period of 24 mo.The 3-year OS rates in the LG and OG groups were 68.4%and 60.5%,respectively(P=0.42).The 3-year DFS rates in the LG and OG groups were 57.9%and 50.0%,respectively(P=0.51).The LG group had significantly less blood loss(P<0.001),a shorter hospital stay(P<0.001),and a lower incidence of surgical site infection(P=0.04)than the OG group.There were no significant differences in other surgical complications between the groups,including anastomotic leakage,intra-abdominal abscess,or wound dehiscence.The LG group had significantly better QOL scores than the OG group regarding physical functioning,role functioning,global health status,fatigue,pain,appetite loss,and body image at 6 months postoperatively(P<0.05).CONCLUSION LG after NAT is a viable and safe alternative to OG for the treatment of LAGC,with similar survival outcomes and superior short-term recovery and QOL.LG patients had less blood loss,shorter hospitalizations,and a lower incidence of surgical site infections than OG patients.Moreover,the LG group had better QOL scores in multiple domains 6 mo postoperatively.Therefore,LG should be considered a valid option for patients with LAGC who undergo NAT,particularly for those who prioritize postoperative recovery and QOL.

Comparison between upfront surgery and neoadjuvant chemotherapy in patients with locally advanced gastric cancer:A systematic review

BACKGROUND Gastric cancer(GC)is a major health concern worldwide.Surgical resection and chemotherapy is the mainstay treatment for gastric carcinoma,however,the optimal approach remains unclear and should be different in each individual.Chemotherapy can be administered both pre-and postoperatively,but a multidisciplinary approach is preferred when possible.This is particularly relevant for locally advanced GC(LAGC),as neoadjuvant chemotherapy(NAT)could potentially lead to tumor downsizing thus allowing for a complete resection with curative intent.Even though the recent progress has been impressive,European and International guidelines are still controversial,thus attenuating the need for a more standardized approach in the management of locally advanced cancer.AIM To investigate the effects of NAT on the overall survival(OS),the disease-free survival(DFS),the morbidity and the mortality of patients with LAGC in comparison to upfront surgery(US).METHODS For this systematic review,a literature search was conducted between November and February 2023 in PubMed,Cochrane Library and clinicaltrials.gov for studies including patients with LAGC.Two independent reviewers conducted the research and extracted the data according to predetermined inclusion and exclusion criteria.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used to form the search strategy and the study protocol has been registered in the International Prospective Register of Systematic Reviews.RESULTS Eighteen studies with 4839 patients with LAGC in total were included in our systematic review.Patients were separated into two groups;one receiving NAT before the gastrectomy(NAT group)and the other undergoing upfront surgery(US group).The OS ranged from 41.6%to 74.2%in the NAT group and from 30.9%to 74%in the US group.The DFS was also longer in the NAT group and reached up to 80%in certain patients.The complications related to the chemotherapy or the surgery ranged from 6.4%to 38.1%in the NAT group and from 5%to 40.5%in the US group.Even though in most of the studies the morbidity was lower in the NAT group,a general conclusion could not be drawn as it seems to depend on multiple factors.Finally,regarding the mortality,the reported rate was higher and up to 5.3%in the US group.CONCLUSION NAT could be beneficial for patients with LAGC as it leads to better OS and DFS than the US approach with the same or even lower complication rates.However,patients with different clinicopathological features respond differently to chemotherapy,therefore currently the treatment plan should be individualized in order to achieve optimal results.

Serum basic fibroblast growth factor and interleukin-1βpredict the effect of first-line chemotherapy in patients with advanced gastric cancer

BACKGROUND The incidence and mortality rates of gastric cancer in China are the second-highest in the world,and most patients with gastric cancer lose their chance of surgery by the time of their diagnosis.AIM To explore the predictive potential of serum basic fibroblast growth factor and interleukin-1βlevels for the effect of first-line chemotherapy in patients with advanced gastric cancer.METHODS From the gastric cancer patients admitted to our hospital from May 2019 to April 2023,84 patients were selected and randomly and equally assigned to the experimental or control group.The FLOT group received the FLOT chemotherapy regimen(composed of oxaliplatin+calcium folinate+fluorouracil+paclitaxel),while the SOX group received the SOX chemotherapy regimen(composed of oxaliplatin+tiga capsules).The clinical efficacy,tumor marker levels,adverse reactions,and survival rates of the two groups were compared 7 days after the end of the relevant treatments.RESULTS The target effective rate of the FLOT group was 54.76%,which was much higher than that of the SOX group(33.33%;P<0.05).After treatment,both the groups demonstrated lower levels of cancer antigen(CEA),carbohydrate antigen 199(CA199),and peptide tissue antigen(TPS).For several patients before treatment(P<0.05).Third and fourth grades.In terms of adverse reactions,the level of white blood cells in both the groups was lower.Moreover,the incidence of hand-foot skin reactions in these two study groups was lower(P<0.05),while those of peripheral neuritis,vomiting,diarrhea,and abnormal liver function were significant(P<0.05).No statistically significant difference was noted between the two groups(P<0.05).The 1-year survival rate was higher in the FLOT group(P<0.05).CONCLUSION The FLOT regimen was effective in reducing the serum CEA,CA199,and TPS levels as well as in improving the 1-year survival rate of patients with good tolerability,making it worthy of clinical promotion and application.

Large gastric hamartomatous inverted polyp accompanied by advanced gastric cancer:A case report

BACKGROUND Gastric hamartomatous inverted polyps(GHIPs)are benign polyps of the gastric submucosal layer.Currently there are 52 reported cases in the English literature.According to a literature review,approximately 27%of GHIPs show a coexisting carcinoma.CASE SUMMARY A 66-year-old man was referred to our institution with ulcerative lesions detected on esophagogastroduodenoscopy(EGD)during a regular check-up.Other medical findings were nonspecific.The lesions had borderline histologic features that could not exclude malignancy and were followed up with three EGDs and biopsies at intervals of 3 mo.The latest biopsy was revealed as an adenocarcinoma.A total gastrectomy was performed to remove the tumor.The surgical specimen revealed a 6.9 cm×4.5 cm sized GHIP with a coexisting 1.6 cm sized well-differentiated adenocarcinoma which extended to the muscularis propria.The malignancy did not originate from the GHIP but showed an overlap.CONCLUSION A large GHIP,which was unusually presented as an ulcerative lesion,was surgically removed,and was accompanied by advanced gastric cancer.Regular follow-up and thorough examinations of ulcerative lesions with equivocal biopsy have resulted in appropriate diagnosis and treatment.Therefore,aggressive intervention may be beneficial if GHIP is suspected.

Current Status and Research Progress of Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer

Gastric cancer is one of the most common malignant tumours worldwide, with a high degree of malignancy and a poor prognosis. While early gastric cancer can be cured by surgical treatment, locally advanced gastric cancer requires neoadjuvant therapy to shrink the tumour, suppress potential metastases, achieve down-staging, and provide patients with the opportunity for radical surgery to prolong their survival. This article reviews the current status and progress of neoadjuvant chemotherapy for locally advanced gastric cancer.

Risk evaluation of splenic hilar lymph node metastasis and survival analysis of patients with advanced gastric cancer

Background:There is no consensus regarding the influence of prophylactic no.10 lymph node(LN)dissection in patients with advanced gastric cancer(AGC).We aimed to evaluate whether patients with AGC could benefit from no.10 LN dissection and to explore the clinicopathological indicators of no.10 LN metastasis.Methods:We analyzed the data of 218 patients with AGC who underwent standard D2 lymphadenectomy(SD2;n=108)or modified D2 lymphadenectomy(MD2;n=110)between January 2017 and January 2021.In addition,we examined factors influencing no.10 LN metastasis in the SD2 group.Results:Differentiation,tumor location,and no.4 positive LNs were significantly correlated with no.10 LN metastasis(P<0.05).Borrmann classification,differentiation,depth of invasion,LN metastasis(N),and tumor size were found to correlate with survival in univariate analyses.Age,sex,extent of gastrectomy,tumor location,and extent of lymphadenectomy were not associated with survival(P>0.05).The median survival times were 72.23 and 68.56months for the SD2 andMD2 groups,respectively(P=0.635).Postoperative major morbidity and mortality rates were 37.96%and 3.70%in the SD2 group,and 23.64%and 1.82%in the MD2 group,respectively.Conclusions:Based on our findings,prophylactic no.10 lymphadenectomy may be recommended in patients with AGC who exhibit positive no.4 LN status,poor differentiation,and tumors located on the greater curvature.

The transition and current pattern of drug therapy for advanced gastric cancer

Gastric cancer is one of the most common malignant tumors in the world.Its incidence ranks fifth among all malignant tumors worldwide and is the third leading cause of death among cancer patients.Surgery is currently considered to be the only radical treatment.However,the low rate of early diagnosis means that most patients have an advanced-stage disease at diagnosis which lost the chance of surgery.Therefore,the main treatment for advanced gastric cancer includes chemotherapy,targeted therapy,immunotherapy.The purpose of this study is to review the transition and current patterns of drug therapy for advanced gastric cancer and to provide assistance for subsequent clinical studies in advanced gastric cancer.

Level of circulating PD-L1 expression in patients with advanced gastric cancer and its clinical implications

Objective：The programmed cell death-1 receptor/programmed cell death-1 ligand （PD-1/PD-L1） pathway plays a crucial role in tumor evasion from host immunity.This study was designed to evaluate the association between circulating PD-L1 expression and prognosis in patients with advanced gastric cancer.Methods：Totally 80 advanced gastric cancer patients and 40 health controls from Beijing Cancer Hospital were enrolled in the present study.Circulating PD-L1 expression was tested by enzymelinked immunosorbent assay （ELISA）.The associations between the expression level of PD-L1 and clinicopathological features and prognosis were analyzed statistically.Results：Expression of PD-L1 in advanced gastric cancer patients was significandy up-regulated compared with health people （P=0.006）.The expression of PD-L1 was significantly correlated with differentiation and lymph node metastasis （P=0.026 and P=0.041,respectively）.Although we didn＇t find significant difference in all advanced gastric cancer patients with different PD-L1 expression,the adenocarcinoma patients with higher up-regulated PD-L1 expression had much better prognosis than low expression patients （65.6％ vs.44.7％,P=0.028）.Conclusions：PD-L1 was elevated in advance gastric cancer patients and may play an important role in tumor immune evasion and patients prognosis.

Expressions of Thymidylate Synthase, Thymidine Phosphorylase, Class Ⅲ β-tubulin, and Excision Repair Cross-complementing Group 1 Predict Response in Advanced Gastric Cancer Patients Receiving Capecitabine Plus Paclitaxel or Cisplatin

Objective: To evaluate the role of class III β-tubulin (TUBB3), thymidylate synthase (TS), thymidine phosphorylase (TP), and excision repair cross-complementing group 1 (ERCC1) in clinical outcome of advanced gastric cancer patients receiving capecitabine plus paclitaxel or cisplatin. Methods: The clinical data and tumor specimens from 57 advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel (cohort 1, n=36) and capecitabine plus cisplatin (cohort 2, n=21) were retrospectively collected, and TUBB3, TS, TP, and ERCC1 expressions were detected by real-time quantitative PCR. The associations between expressions of biomarkers and response or survival were analyzed statistically. Results: The median age of 57 patients was 57 years (range: 27–75 years) with 38 males and 19 females. Of all patients, the response rates of patients with high TP, low TP and high TS, low TS expressions were 57.1%, 27.6% (P=0.024), and 55.2%, 28.6% (P=0.042), respectively. Among cohort 1, the response rates and median overall survivals of patients with low and high TUBB3 expressions were 61.1% vs. 33.3% (P=0.095) and 13.8 months vs. 6.6 months (P=0.019), respectively; the response rate (87.5%) of patients with low TUBB3 and high TP expressions was higher than that (14.3%) of patients with high TUBB3 and low TP expressions (P=0.01). Among cohort 2, the response rates of patients with low ERCC1 and high ERCC1 expressions were 45.5% and 20.0% respectively (P=0.361). Conclusion: TUBB3, TS and TP expressions could predict the response of advanced gastric cancer patients receiving capecitabine-based and paclitaxel-based chemotherapy. These results will be further confirmed in future large samples.

Aneuploidy of chromosome 8 in circulating tumor cells correlates with prognosis in patients with advanced gastric cancer

Objective： Previous work indicated that aneuploidy of chromosome 8 in circulating tumor cells（CTCs）correlated with therapeutic efficacy for advanced gastric cancer（AGC） patients. In this follow-up study performed on the same population of AGC patients, we investigated whether and how aneuploidy of chromosome 8 in CTCs correlates with patients＇ clinical prognosis.Methods： The prospective study was performed on 31 patients with newly diagnosed AGC. Previously established integrated subtraction enrichment（SE） and immunostaining-fluorescence in situ hybridization（i FISH）platform was applied to identify, enumerate and characterize CTCs. Quantification of CTCs and analysis of their aneuploidy of chromosome 8 were performed on patients before and after therapy.Results： CTCs were measured in 93.5% of AGC patients, and two CTC subtypes with diverse threshold values were identified, multiploid CTCs with the threshold of ≥2 per 7.5 m L and multiploid plus triploid CTCs with the threshold of ≥4, which were found to significantly correlate with poor progression-free survival（PFS） and overall survival（OS）. In particular, patients with ≥10% increased multiploid CTCs after an initial 6 weeks of therapy had poor PFS and OS, whereas improved PFS and OS were observed on those who had ≥10% decreased multiploid CTCs. After adjusting for clinically significant factors, ≥10% increased post-therapy multiploid CTCs was the only independent predictor of PFS and OS.Conclusions： Aneuploidy of CTCs correlates with prognosis of AGC patients. Quantitative comparison monitoring multiploid CTCs before and after therapy may help predict improved or inferior prognosis and chemoresistance.

Nomogram for predicting pathological complete response to neoadjuvant chemotherapy in patients with advanced gastric cancer

BACKGROUND Survival benefit of neoadjuvant chemotherapy(NAC)for advanced gastric cancer(AGC)is a debatable issue.Studies have shown that the survival benefit of NAC is dependent on the pathological response to chemotherapy drugs.For those who achieve pathological complete response(pCR),NAC significantly prolonged prolapsed-free survival and overall survival.For those with poor response,NAC yielded no survival benefit,only toxicity and increased risk for tumor progression during chemotherapy,which may hinder surgical resection.Thus,predicting pCR to NAC is of great clinical significance and can help achieve individualized treatment in AGC patients.AIM To establish a nomogram for predicting pCR to NAC for AGC patients.METHODS Two-hundred and eight patients diagnosed with AGC who received NAC followed by resection surgery from March 2012 to July 2019 were enrolled in this study.Their clinical data were retrospectively analyzed by logistic regression analysis to determine the possible predictors for pCR.Based on these predictors,a nomogram model was developed and internally validated using the bootstrap method.RESULTS pCR was confirmed in 27 patients(27/208,13.0%).Multivariate logistic regression analysis showed that higher carcinoembryonic antigen level,lymphocyte ratio,lower monocyte count and tumor differentiation grade were associated with higher pCR.Concordance statistic of the established nomogram was 0.767.CONCLUSION A nomogram predicting pCR to NAC was established.Since this nomogram exhibited satisfactory predictive power despite utilizing easily available pretreatment parameters,it can be inferred that this nomogram is practical for the development of personalized treatment strategy for AGC patients.