Clinical Application and Research Progress of Accelerated Rehabilitation Surgery in Perioperative Period of Advanced Gastric Cancer in the Elderly

Enhanced recovery after surgery (ERAS) has been used in various surgical professions in recent years and is widely accepted by doctors. This concept not only helps patients speed up postoperative recovery, reduce the incidence of related complications and shorten hospital stays, but also has been proved to be effective and safe in the perioperative application of gastric cancer. This article reviews the clinical application and research progress of enhanced recovery after surgery in the perioperative period of advanced gastric cancer in the elderly.

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.

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.

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.

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.

Evaluation of oxaliplatin and tigio combination therapy in locally advanced gastric cancer

BACKGROUND Locally advanced gastric cancer(LAGC)is a common malignant tumor.In recent years,neoadjuvant chemotherapy has gradually become popular for the treatment of LAGC.AIM To investigate the efficacy of oxaliplatin combined with a tigio neoadjuvant chemotherapy regimen vs a conventional chemotherapy regimen for LAGC.METHODS Ninety patients with LAGC were selected and randomly divided into control and study groups with 45 patients in each group,according to the numerical table method.The control group was treated with conventional chemotherapy,and the study group was treated with oxaliplatin combined with tigio-neoadjuvant che-motherapy.The primary outcome measures were the clinical objective response rate(ORR)and surgical resection rate(SRR),whereas the secondary outcome measures were safety and Karnofsky Performance Status score.RESULTS The ORR in the study group was 80.00%,which was significantly higher than that of the control group(57.78%).In the study group,SRR was 75.56%,which was significantly higher than that of the control group(57.78%).There were 15.56%adverse reactions in the study group and 35.56%in the control group.These differences were statistically significant between the two groups.CONCLUSION The combination of oxaliplatin and tigio before surgery as neoadjuvant chemotherapy for patients with LAGC can effectively improve the ORR and SRR and is safe.

Efficacy evaluation and survival analysis of the combination of oxaliplatin plus Teysuno (SOX) with immune checkpoint inhibitors in the conversion therapy of locally advanced gastric cancer

Background:The efficacy of combining immune checkpoint inhibitors(ICIs)with chemotherapy in neoadjuvant therapy for locally advanced gastric cancer has been explored.However,limited research exists on its effectiveness in conversion therapy,and its superiority over standalone chemotherapy remains to be elucidated.This study aims to investigate the efficacy and survival outcomes of patients treated with ICIs in combination with conversion therapy for locally advanced gastric cancer.Methods:Retrospective data from patients with locally advanced gastric cancer treated with either oxaliplatin+S-1(SOX)alone or in combination with ICIs in conversion therapywere collected.Clinical andpathological characteristics,disease-free survival,andefficacy assessments in nonoperable patients were compared between the 2 treatment groups.Efficacy was further evaluated through dynamic changes in serum markers,and patients’quality of life was assessed using the QLQ-STO22(Gastric Cancer–Specific Quality of Life Questionnaire)quality-of-life measurement scale.Results:A total of 140 patients underwent conversion therapy:80 in the SOX alone group and 60 in the SOX combined with the ICIs group.There were no significant differences in baseline characteristics between the 2 groups.Compared with the SOX alone group,the SOX combined with ICIs group exhibited a higher conversion rate(83.3%vs 75%,P=0.23),R0 resection rate(90.0%vs 83.3%,P=0.31),pathological complete response(pCR)rate(18%vs 5%,P=0.02),median disease-free survival(21.4 vs 16.9 months,P=0.007),the objective response rate in nonoperable patients(60%vs 40%,P=0.301),and median progression-free survival time(7.9 vs 5.7 months,P=0.009).The QLQ-STO22 quality-of-life assessment revealed statistically significant improvements in pain,swallowing difficulties,and dietary restrictions in the combination therapy group compared with those in the monotherapy group.The enhanced efficacy of immune combination with SOX is evident,as demonstrated by the significantly prolonged surgical duration in operated patients(206.6±26.6 min vs 197.8±19.8 min,P=0.35)and intraoperative blood loss(158.9±21.2 mL vs 148.9±25.1 mL,P=0.59).No significant differences were observed in postoperative complications.Conclusions:Compared with the SOX conversion therapy regimen,SOX combined with ICIs demonstrated higher conversion rates,R0 resection rates,pathological response rates,and disease-free survival without increasing surgical difficulty or complications.Nonoperable patients also experienced longer progression-free survival and objective response rates.

Efficacy and safety of endoscopic submucosal dissection for early gastric cancer and precancerous lesions in elderly patients

BACKGROUND With advancements in the development of endoscopic technologies,the endo-scopic submucosal dissection(ESD)has been one of the gold-standard therapies for early gastric cancer.AIM To investigate the efficacy and safety ESD in the treatment of early gastric cancer and precancerous lesions in the elderly patients.METHODS Seventy-eight elderly patients with early gastric cancer and precancerous lesions admitted to the Third Affiliated Hospital of Qiqihar Medical University were se-lected and classified into two groups according to the different surgical therapies they received between January 2021 and June 2022.Among them,39 patients treated with ESD were included in an experimental group,and 39 patients treated with endoscopic mucosal resection(EMR)were included in a control group.We compared the basic intraoperative conditions,postoperative short-term recovery,long-term recovery effects and functional status of gastric mucosa between the two groups;the basic intraoperative conditions included lesion resection,intra-operative bleeding and operation time;the postoperative short-term recovery assessment indexes were length of hospital stay and incidence of surgical complic-ations;and the long-term recovery assessment indexes were the recurrence rate at 1 year postoperatively and the survival situation at 1 year and 3 years postoper-atively;and we compared the preoperative and predischarge serum pepsinogen I(PG I)and PG II levels and PG I/PG II ratio in the two groups before surgery and discharge.RESULTS The curative resection rate and the rate of en bloc resection were higher in the experimental group than in the control group.The intraoperative bleeding volume was higher in the experimental group than in the control group.The operation time was longer in the experimental group than that in the control group,and the rate for base residual focus was lower in the experimental group than that of the control group,and the differences were all statistically significant(all P<0.05).The length of hospital stay was longer in the experi-mental group than in the control group,and the incidence of surgical complications,1-year postoperative recu-rrence rate and 3-year postoperative survival rate were lower in the experimental group than in the control group,and the differences were statistically significant(all P<0.05).However,the difference in the 1-year postoperative survival rate was not statistically significant between the two groups(P>0.05).Before discharge,PG I and PG I/PG II ratio were elevated in both groups compared with the preoperative period,and the above indexes were higher in the experimental group than those in the control group,and the differences were statistically significant(both P<0.05).Moreover,before discharge,PG II level was lower in both groups compared with the preoperative period,and the level was lower in the experimental group than in the control group,and the differences were all statistically significant(all P<0.05).CONCLUSION Compared with EMR,ESD surgery is more thorough.It reduces the rate of base residual focus,recurrence rate,surgical complications,and promotes the recovery of gastric cells and glandular function.It is safe and suitable for clinical application.

Clinical significance of preoperative nutritional status in elderly gastric cancer patients undergoing radical gastrectomy:A singlecenter retrospective study

BACKGROUND The population of elderly patients with gastric cancer is increasing,which is a major public health issue in China.Malnutrition is one of the greatest risk factors for adverse clinical outcomes in elderly patients with gastric cancer.AIM To investigate the preoperative nutritional status and its association with delayed discharge of elderly gastric cancer patients following radical gastrectomy.METHODS A total of 783 patients aged 65 years and older harboring gastric adenocarcinoma and following radical gastrectomy were retrospectively analyzed from the prospectively collected database of Zhongshan Hospital of Fudan University between January 2018 and May 2020.RESULTS The overall rate of malnutrition was 31.8%.The incidence of postoperative complications was significantly higher in the malnourished group compared to the well-nourished group(P<0.001).Nutritional characteristics in the malnourished group,including body mass index,prognostic nutritional index(PNI),albumin,prealbumin,and hemoglobin,were all significantly lower than those in the well-nourished group.The percentage of patients who received postoperative total nutrient admixture was lower in the malnourished group compared to the wellnourished group(22.1%vs 33.5%,P=0.001).Age≥70 years(HR=1.216,95%CI:1.048-1.411),PNI<44.5(HR=1.792,95%CI:1.058-3.032),operation time≥160 minutes(HR=1.431,95%CI:1.237-1.656),and postoperative complications grade III or higher(HR=2.191,95%CI:1.604-2.991)were all recognized as independent risk factors associated with delayed discharge.CONCLUSION Malnutrition is relatively common in elderly patients undergoing gastrectomy.Low PNI is an independent risk factor associated with delay discharge.More strategies are needed to improve the clinical outcome of these patients.

Analysis of metabolic characteristics of metabolic syndrome in elderly patients with gastric cancer by non-targeted metabolomics

BACKGROUND The relationship between metabolic syndrome(MetS)and gastric cancer(GC),which is a common metabolic disease,has attracted much attention.However,the specific metabolic characteristics of MetS in elderly patients with GC remain unclear.AIM To investigate the differentially abundant metabolites and metabolic pathways between preoperative frailty and MetS in elderly patients with GC based on nontargeted metabolomics techniques.METHODS In this study,125 patients with nonfrail nonmeal GC were selected as the control group,and 50 patients with GC in the frail group were selected as the frail group.Sixty-five patients with GC combined with MetS alone were included in the MetS group,and 50 patients with GC combined with MetS were included in the MetS group.Nontargeted metabolomics techniques were used to measure plasma metabolite levels by ultrahigh-performance liquid chromatography-mass spectrometry.Multivariate statistical analysis was performed by principal component analysis,orthogonal partial least squares,pattern recognition analysis,cluster analysis,and metabolic pathway annotation.RESULTS A total of 125 different metabolites,including amino acids,glycerophospholipids,sphingolipids,fatty acids,sugars,nucleosides and nucleotides,and acidic compounds,were identified via nontargeted metabolomics techniques.Compared with those in the control group,there were 41,32,and 52 different metabolites in the MetS group,the debilitated group,and the combined group,respectively.Lipid metabolites were significantly increased in the MetS group.In the weak group,amino acids and most glycerol phospholipid metabolites decreased significantly,and fatty acids and sphingosine increased significantly.The combined group was characterized by significantly increased levels of nucleotide metabolites and acidic compounds.The alanine,aspartic acid,and glutamate metabolic pathways were obviously enriched in the asthenic group,and the glycerol and phospholipid metabolic pathways were obviously enriched in the combined group.CONCLUSION Elderly GC patients with simple frailty,simple combined MetS,and frailty combined with MetS have different metabolic characteristics,among which amino acid and glycerophospholipid metabolite levels are significantly lower in frail elderly GC patients,and comprehensive supplementation of fat and protein should be considered.Many kinds of metabolites,such as amino acids,lipids,nucleotides,and acidic compounds,are abnormally abundant in patients with MetS combined with fthenia,which may be related to tumor-related metabolic disorders.

Impact of nutritional support on immunity,nutrition,inflammation,and outcomes in elderly gastric cancer patients after surgery

BACKGROUND Postoperative rehabilitation of elderly patients with gastric cancer has always been the focus of clinical attention.Whether the intervention by a full-course nutritional support team can have a positive impact on the postoperative immune function,nutritional status,inflammatory response,and clinical outcomes of this special population has not yet been fully verified.AIM To evaluate the impact of full-course nutritional support on postoperative comprehensive symptoms in elderly patients with gastric cancer.METHODS This is a retrospective study,including 60 elderly gastric cancer patients aged 70 years and above,divided into a nutritional support group and a control group.The nutritional support group received full postoperative nutritional support,including individualized meal formulation,and intravenous and parenteral nutrition supplementation,and was regularly evaluated and adjusted by a professional nutrition team.The control group received routine postoperative care.RESULTS After intervention,the proportion of CD4+lymphocytes(25.3%±3.1%vs 21.8%±2.9%,P<0.05)and the level of immunoglobulin G(12.5 G/L±2.3 G/L vs 10.2 G/L±1.8 G/L,P<0.01)were significantly higher in the nutritional support group than in the control group;the changes in body weight(-0.5 kg±0.8 kg vs-1.8 kg±0.9 kg,P<0.05)and body mass index(-0.2±0.3 vs-0.7±0.4,P<0.05)were less significant in the nutritional support group than in the control group;and the level of C-reactive protein(1.2 mg/L±0.4 mg/L vs 2.5 mg/L±0.6 mg/L,P<0.01)and WBC count(7.2×10^(9)/L±1.5×10^(9)/L vs 9.8×10^(9)/L±2.0×10^(9)/L,P<0.01)were significantly lower in the nutritional support group than in the control group.In addition,patients in the nutritional support group had a shorter hospital stay(10.3 d±2.1 d vs 14.8 d±3.6 d,P<0.05)and lower incidence of infection(15%vs 35%,P<0.05)in those of the control group.CONCLUSION The intervention by the nutritional support team has a positive impact on postoperative immune function,nutritional status,inflammatory response,and clinical outcomes in elderly patients with gastric cancer.

Preoperative malnutrition in elderly gastric cancer patients and adverse postoperative outcomes of radical gastrectomy

Malnutrition is not only a prevalent condition among the elderly but also a common comorbidity in elderly people with gastric cancer(GC).Malnutrition is closely linked to high rates of postoperative complications and poor wound healing in elderly GC patients,which may lead to a higher incidence and mor-tality rate of GC.Malnutrition decreases the physical function of elderly GC patients after surgery,severely affecting their postoperative life quality and hindering subsequent treatments.This retrospective study was conducted by Zhao et al,focusing on the clinical baseline data,postoperative complications,and hospitalization times of elderly GC patients who underwent curative gastrectomy.Additionally,the underlying causes of poor outcomes for patients were discussed.This study may provide a solid basis for the clinical treatment of elderly GC patients in the future.Therefore,malnutrition can serve as a negative prognostic factor for curative surgery in GC patients.Addressing malnutrition and its adverse effects can benefit elderly GC patients from surgical treatment.

Optimizing postsurgical recovery for elderly patients with gastric cancer

Based on a recent study by Li et al,this editorial examines the significance of enhanced recovery after surgery(ERAS)protocols for elderly patients with gastric cancer.Cancer-related mortality,which is overwhelmingly caused by gastric cancer,calls for effective treatment strategies.Despite advances in the field of oncology,conventional postoperative care often results in prolonged hospital stays and increased complications.The aim of ERAS is to expedite recovery,reduce surgical stress,and improve patient satisfaction.The study of Li et al showed that,compared to traditional care,ERAS significantly reduces mortality risk,shortens hospital stays,and decreases postoperative complications.These findings support the widespread implementation of ERAS protocols in surgical practice to enhance patient outcomes and healthcare value.

Advanced glycation end products in gastric cancer:A promising future

In this editorial,we delve into the article and offer valuable insights into a crucial aspect of gastric cancer aetiology.Gastric cancer is a malignancy emanating from the epithelial lining of the gastric mucosa and one of the most prevalent forms of cancer worldwide.The development of gastric cancer is associated with multiple risk factors,including Helicobacter pylori infection,advanced age,a diet rich in salt,and suboptimal eating patterns.Despite notable reductions in morbidity and mortality rates,gastric cancer remains a formidable public health concern,impacting patients’lives.Advanced glycation end products(AGEs)are complex compounds arising from nonenzymatic reactions within living organisms,the accumulation of which is implicated in cellular and tissue damage;thus,the levels are AGEs are correlated with the risk of diverse diseases.The investigation of AGEs is of paramount importance for the treatment of gastric cancer and can provide pivotal insights into disease pathogenesis and preventive and therapeutic strategies.The reduction of AGEs levels and suppression of their accumulation are promising avenues for mitigating the risk of gastric cancer.This approach underscores the need for further research aimed at identifying innovative interventions that can effectively lower the incidence and mortality rates of this malignancy.

Neoadjuvant chemoradiotherapy followed by D2 gastrectomy in locally advanced gastric cancer

AIM:To investigate the efficacy of neoadjuvant chemoradiotherapy(NACRT) for resectability of locally advanced gastric cancer(LAGC).METHODS:Between November 2007 and January 2014,29 patients with LAGC(clinically T3 with distal esophagus invasion/T4 or bulky regional node metastasis) that were treated with NACRT followed by D2 gastrectomy were included in this study.Resectability was evaluated with radiologic and endoscopic exams before and after NACRT.Using threedimensional conformal radiotherapy,patients received 45 Gy,with a daily dose of 1.8 Gy.The entire tumor extent and the regional metastatic lymph nodes were included in the gross tumor volume.Patients presenting with a resectable tumor after NACRT received a total or subtotal gastrectomy with D2 dissection.The pathologic tumor response was evaluated using Japanese Gastric Cancer Association histologic evaluation criteria.Postoperative morbidity was evaluated using the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.0.Overall survival(OS) and progression-free survival(PFS) rates were estimated using a Kaplan-Meier analysis and compared using the log-rank test.RESULTS:All patients were assessed as unresectable cases.Twenty-four patients(24/29; 82.8%) showed LAGC on positron emission tomography-computed tomography(CT) and contrast-enhanced CT,whereas four patients(4/29; 13.8%) with vague invasion orabutment to an adjacent organ underwent diagnostic laparoscopy.One patient(1/29; 3.4%),initially assessed as a resectable case,underwent an "open and closure" after the tumor was found to be unresectable.Abutment to an adjacent organ(34.5%) was the most common reason for NACRT.The clinical response rate one month after NACRT was 44.8%.After NACRT,69%(20/29) of patients had a resectable tumor.Of the 20 patients with a resectable tumor,18 patients(62.1%) underwent a D2 gastrectomy.The R0 resection rate was 94.4% and two patients(2/18; 11.1%) showed a complete response.The median follow-up duration was 13.5 mo.The one-year OS and PFS rates were 72.4 and 48.9%,respectively.The one-year OS,PFS,local failure-free survival,and distant metastasis-free survival were higher in patients with a resectable tumor after NACRT(P < 0.001,P < 0.001,P < 0.001,and P =0.078,respectively).No grade 3-4 late treatment-related toxicities or postoperative mortalities were observed.CONCLUSION:NACRT with D2 gastrectomy showed a high rate of R0 resection and promising local control,which may increase the R0 resection opportunity resulting in survival benefit.

Clinical management of advanced gastric cancer: The role of new molecular drugs

Gastric cancer is the fourth most common malignant neoplasm and the second leading cause of death for cancer in Western countries with more than 20000 new cases yearly diagnosed in the United States. Surgery represents the main approach for this disease but, notwithstanding the advances in surgical techniques, we observed a minimal improvement in terms of overall survival with a significant increasing of relapsing disease rates. Despite the development of new drugs has significantly improved the effectiveness of chemotherapy, the prognosis of patients with unresectable or metastatic gastric adenocarcinoma remains poor. Recently, several molecular target agents have been investigated; in particular, trastuzumab represents the first target molecule showing improvements in overall survival in human epithelial growth factor 2-positive gastric cancer patients. New molecules targeting vascular epithelial growth factor, mammalian target of rapamycin, and anti hepatocyte growth factor-c-Met pathway are also under investigation, with interesting results. Anyway, it seems necessary to select more accurately the population to treat with new agents by the identification of new biomarkers in order to optimize the results. In this paper we review the actual &#x0201c;scenario&#x0201d; of targeted treatments, also focusing on the new agents in development for gastric cancer and gastro-esophageal carcinoma, discussing their efficacy and potential applications in clinical practice.

S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer: A meta-analysis

AIM: To assess the efficacy and tolerability of S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer (AGC).

New perspectives in the treatment of advanced or metastatic gastric cancer

Metastatic gastric cancer remains an incurable disease,with a relative 5-year survival rate of 7%-27%.Chemotherapy,which improves overall survival(OS) and quality of life,is the main treatment option.Metaanalysis has demonstrated that the best survival results obtained in earlier randomized studies were achieved with three-drug regimens containing a fluoropyrimidine,an anthracycline,and cisplatin(ECF).Although there has been little progress in improving median OS times beyond the 9-mo plateau achievable with the standard regimens,the availability of newer agents has provided some measure of optimism.A number of new combinations incorporating docetaxel,oxaliplatin,capecitabine,and S-1 have been explored in randomized trials.Some combinations,such as epirubicin-oxaliplatin-capecitabine,have been shown to be as effective as(or perhaps more effective than) ECF,and promising early data have been derived for S-1 in combination with cisplatin.One factor that might contribute to extending median OS is the advancement whenever possible to second-line cytotoxic treatments.However,the biggest hope for signif icant survival advances in the near future would be the combination of new targeted biological agents with existing chemotherapy f irst-line regimens.

Cost-effectiveness analysis of chemotherapy for advancedgastric cancer in China

AIM： To assess the economics of various chemotherapeutic regimens for advanced gastric cancer （AGC）, and to select the best cost-effective regimen for the common Chinese patients. METHODS： Data source used in this study was the Chinese Biomedical Disk Database. Patients were diagnosed as AGC and any regimen was eligible. Outcome measures included median survival time （MST） and percentage of complete and partial response （CR＋PR）. Economic statistics was per capita direct medical cost （DMC） of a single cycle. TreeAge Pro Healthcare 2007 software was used to carry out costeffectiveness and incremental cost-effectiveness analysis. Sensitivity analyses were applied by altering willingness- to-pay and annual discount rate, and also re-analyzed by excluding the studies with apparent heterogeneity. RESULTS： Seven retrospective economics studies on 760 patients were included. S-fluorouracil-based regimens were universal, and also some new agents were involved, such as docetaxel, paclitaxel, andoxaliplatin. By processing analysis, we could recommend etoposide, leucovorin and 5-fluorouracil （ELF） regimen as preference, with a DMC/MST ratio of 2543 RBM/11.7 mo and a DMC/CR＋PR ratio of 2543 RMB/53.3%. Uraciltegafur, etoposide and cisplatin （FEP） or 5-fluorouracil, adrimycin/epirubin and mitomycin （FAM） regimens could be regarded as optional first-line chemotherapy for AGC in common Chinese patients. With no regard for willingness-to-pay, the docetaxel, cisplatin and 5-fluorouracil （DCF） regimen could be chosen as either a first- or a second-line chemotherapy, with a DMC/CR＋PR ratio of 9979 RMB/56.3%. CONCLUSION： 5-fluorouracial regimens are still considered the mainstream for AGC, while new agents such as taxanes are optional. More randomized clinical trials are required before any mandatory recommendation of certain regimens for patients with AGC in China is made.