Receptor of advanced glycation end-products axis and gallbladder cancer:A forgotten connection that we should reconsider

Compelling evidence derived from clinical and experimental research has demonstrated the crucial contribution of chronic inflammation in the development of neoplasms,including gallbladder cancer.In this regard,data derived from clinical and experimental studies have demonstrated that the receptor of advanced glycation end-products(RAGE)/AGEs axis plays an important role in the onset of a crucial and long-lasting inflammatory milieu,thus supporting tumor growth and development.AGEs are formed in biological systems or foods,and food-derived AGEs,also known as dietary AGEs are known to contribute to the systemic pool of AGEs.Once they bind to RAGE,the activation of multiple and crucial signaling pathways are triggered,thus favoring the secretion of several proinflammatory cytokines also involved in the promotion of gallbladder cancer invasion and migration.In the present review,we aimed to highlight the relevance of the association between high dietary AGEs intakes and high risk for gallbladder cancer,and emerging data supporting that dietary intervention to reduce gallbladder cancer risk is a very attractive approach that deserves much more research efforts.

Effects of cytoreductive surgery combined with hyperthermic perfusion chemotherapy on prognosis of patients with advanced gallbladder cancer

BACKGROUND Gallbladder cancer(GC)is a common malignant tumor and one of the leading causes of cancer-related death worldwide.It is typically highly invasive,difficult to detect in the early stages,and has poor treatment outcomes,resulting in high mortality rates.The available treatment options for GC are relatively limited.One emerging treatment modality is hyperthermic intraperitoneal chemotherapy(HIPEC).HIPEC involves delivering heated chemotherapy directly into the abdominal cavity.It combines the strategies of surgical tumor resection and localized chemotherapy administration under hyperthermic conditions,aiming to enhance the concentration and effectiveness of drugs within the local tumor site while minimizing systemic toxicity.AIM To determine the effects of cytoreductive surgery(CRS)combined with HIPEC on the short-term prognosis of patients with advanced GC.METHODS Data from 80 patients treated at the Punan Branch of Renji Hospital,Shanghai Jiao Tong University School of Medicine between January 2018 and January 2020 were retrospectively analyzed.The control group comprised 44 patients treated with CRS,and the research group comprised 36 patients treated with CRS combined RESULTS The baseline data of the research and control groups were similar(P>0.05).Six days after surgery,the alanine aminotransferase,aspartate aminotransferase,total bilirubin,and direct bilirubin levels significantly decreased compared to the preoperative levels in both groups(P<0.05).However,the values did not differ between the two groups six days postoperatively(P>0.05).Similarly,the postoperative creatinine and blood urea nitrogen levels were significantly lower than the preoperative levels in both groups(P<0.05),but they did not differ between the groups six days postoperatively(P>0.05).Furthermore,the research group had fewer postoperative adverse reactions than the control group(P=0.027).Finally,a multivariate Cox analysis identified the tumor stage,distant metastasis,and the treatment plan as independent factors affecting prognosis(P<0.05).The three-year survival rate in the study group was higher than that in the control group(P=0.002).CONCLUSION CRS combined with HIPEC lowers the incidence of adverse reactions and improves survival in patients with advanced GC.

A Modified Surgical Approach of Hepatopancreatoduodenectomy for Advanced Gallbladder Cancer:Report of Two Cases and Literature Review

Gallbladder cancer（GBC） is the most common cancer of the biliary tract, constituting 80%–95% of malignant biliary tract tumors. Surgical resection is currently regarded as the sole curative treatment for GBC. Hepatopancreatoduodenectomy（HPD） has been adopted to remove the advanced gallbladder tumor together with the infiltrated parts within the liver, lower biliary tract and the peripancreatic region of GBC patients. However, patients who underwent HPD were reported to have a distinctly higher postoperative morbidity（71.4%, ranging from 30.8% to 100%） and mortality（13.2%, ranging from 2.4% to 46.9%） than those given pancreatoduodenectomy（PD） alone. We present two patients with advanced GBC who underwent a modified surgical approach of HPD： PD with microwave ablation（MWA） of adjacent liver tissues and the technique of intraductal cooling of major bile ducts. No serious complications like bile leakage, pancreatic fistula, hemorrhage and organ dysfunction, etc. occurred in the two patients. They had a rapid recovery with postoperative hospital stay being 14 days. Application of this approach effectively eliminated tumor-infiltrated adjacent tissues, and maximally reduced the postoperative morbidity and mortality. This modified surgical method is secure and efficacious for the treatment of locally advanced GBC.

Survival benefit of concurrent chemoradiotherapy for advanced ampulla of Vater cancer

BACKGROUND Currently,there is no standard adjuvant therapy for patients with resected ampulla of Vater(AoV)cancer.AIM To evaluate the effectiveness of adjuvant concurrent chemoradiotherapy(CCRT)in patients with advanced AoV cancer who underwent curative resection.METHODS This single-centered,retrospective study included 29 patients with advanced AoV cancer who underwent pancreaticoduodenectomy between 2006 and 2018.The impact of CCRT on advanced AoV cancer was analyzed.RESULTS The 1-,3-,and 5-yr recurrence-free survival(RFS)rates for patients with advanced AoV cancer were 82.8%,48.3%,and 40.8%,respectively,and the overall survival(OS)rates were 89.7%,62.1%,and 51.7%,respectively.Lymphovas-cular invasion was found to be a significant risk factor for RFS and OS in patients with advanced AoV cancer in the univariate analysis,whereas T stage and lymph node metastasis were significantly associated with OS in the multivariate analysis.Compared to the patients who did not receive adjuvant CCRT,those who received adjuvant CCRT did not show statistically significant improvements in the RFS and OS,although they had a significantly lower average age and significantly higher platelet-to-lymphocyte ratio.CONCLUSION Adjuvant CCRT did not improve survival outcomes in patients with advanced AoV cancer.These findings contribute to existing knowledge on the effectiveness of CCRT in this patient population and provide important insights for clinical decision-making.

A phase Ⅰ study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer

Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics,tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer patients.Methods: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day cycles.Pharmacokinetic samples were obtained on d 1 and d 28. Clinical responses were assessed every eight weeks.Results: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea(85.7%), vomiting(28.6%), nausea(25.0%) and decreased appetite(17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response(CR), and three achieved partial response(PR). The objective response rate(ORR) and disease control rate(DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival(PFS) was3.98 months.Conclusions: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase Ⅲ trial(No. NCT05122494).

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.

Clinical efficacy and safety of erlotinib combined with chemotherapy in the treatment of advanced pancreatic cancer:A meta-analysis

BACKGROUND Advanced pancreatic cancer is resistant to chemotherapeutic drugs,resulting in limited treatment efficacy and poor prognosis.Combined administration of the chemotherapeutic gemcitabine and erlotinib is considered a potential first-line treatment for advanced pancreatic cancer.However,their comparative benefits and potential risks remain unclear.AIM To assess the clinical efficacy and safety of erlotinib combined with other chemotherapy regimens for the treatment of advanced pancreatic cancer.METHODS Literature on the clinical efficacy and safety of erlotinib combined with chemotherapy for advanced pancreatic cancer was retrieved through an online search.The retrieved literature was subjected to a methodological qualitative assessment and was analyzed using the RevMan 5.3 software.Ten randomized controlled trials involving 2444 patients with advanced pancreatic cancer were included in the meta-analysis.RESULTS Compared with chemotherapeutic treatment,erlotinib combined with chemotherapy significantly prolonged the progression-free survival time of pancreatic cancer patients[hazard ratio(HR)=0.78,95%CI:0.66-0.92,P=0.003].Meanwhile,the overall survival(HR=0.99,95%CI:0.72-1.37,and P=0.95)and disease control rate(OR=0.93,95%CI:0.45-0.91,P=0.84)were not significantly favorable.In terms of safety,the erlotinib and chemotherapy combination was associated with a significantly higher risk of diarrhea(OR=3.59,95%CI:1.63-7.90,P<0.05)and rash(OR=3.63,95%CI:1.64-8.01,P<0.05)compared with single-agent chemotherapy.Moreover,the risk of vomiting(OR=1.27,95%CI:0.62-2.59,P=0.51),regurgitation/anorexia(OR=1.61,95%CI:0.25-10.31,P=0.62),and infection(OR=0.72,95%CI:0.28-1.87,P=0.50)were not significant in either group.CONCLUSION Compared with a single chemotherapeutic modality,erlotinib combined with gemcitabine can prolong progression-free survival in pancreatic cancer,but does not improve survival benefit or disease control rate,and can increase the risk of diarrhea and rash.

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.

Prediction of pathological complete response and prognosis in locally advanced rectal cancer

BACKGROUND Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide.Neoadjuvant chemoradiotherapy(nCRT)is standard for locally advanced rectal cancer(LARC).Except for pathological examination after resection,it is not known exactly whether LARC patients have achieved pathological complete response(pCR)before surgery.To date,there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes.AIM To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC.METHODS Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed.Patients were categorized into pCR and non-pCR groups.Univariate analysis(using the χ^(2) test or Fisher’s exact test)and logistic multivariate regression analysis were used to study clinical predictors affecting pCR.The 5-year disease-free survival(DFS)and overall survival(OS)rates were calculated using Kaplan-Meier analysis,and differences in survival curves were assessed with the log-rank test.RESULTS Univariate analysis showed that pretreatment carcinoembryonic antigen(CEA)level,lymphocyte-monocyte ratio(LMR),time interval between neoadjuvant therapy completion and total mesorectal excision,and tumor size were correlated with pCR.Multivariate results showed that CEA≤5 ng/mL(P=0.039),LMR>2.73(P=0.023),and time interval>10 wk(P=0.039)were independent predictors for pCR.Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates(94.7%vs 59.7%,P=0.002)and 5-year OS rates(95.8%vs 80.1%,P=0.019)compared to the non-pCR group.Tumor deposits(TDs)were significantly correlated with shorter DFS(P=0.002)and OS(P<0.001).CONCLUSION Pretreatment CEA,LMR,and time interval contribute to predicting nCRT efficacy in LARC patients.Achieving pCR demonstrates longer DFS and OS.TDs correlate with poor prognosis.

Post-operative morbidity after neoadjuvant chemotherapy and resection for gallbladder cancer: A national surgical quality improvement program analysis

BACKGROUND Gallbladder cancer is the most common malignancy of the biliary tract.Neo-adjuvant chemotherapy(NACT)has improved overall survival by enabling R0 resection.Currently,there is no consensus of guidelines for neoadjuvant therapy in gallbladder cancer.As investigations continue to analyze the regimen and benefit of NACT for ongoing care of gallbladder cancer patients,we examined American College of Surgeons National Surgical Quality Improvement Program(NSQIP)database to determine if there was higher morbidity among the neo-adjuvant group within the 30-day post-operative period.We hypothesized patients who underwent NACT were more likely to have higher post-operative morbidity.AIM To investigate the 30-day post-operative morbidity outcomes between patients who received NACT and underwent surgery and patients who only had surgery.METHODS A retrospective analysis of the targeted hepatectomy NSQIP data between 2015 and 2019 was performed to determine if NACT in gallbladder cancer increased the risk for post-operative morbidity(bile leak,infection rate,rate of converting to open surgery,etc.)compared to the group who only had surgery.To calculate the odds ratio for the primary and secondary outcomes,a crude logistic regression was performed.RESULTS Of the 452 patients,52 patients received NACT prior to surgery.There were no statistically significant differences in the odds of morbidity between the two groups,including bile leak[odds ratio(OR),0.69;95%confidence interval(95%CI):0.16-2.10;P=0.55],superficial wound infection(OR,0.58;95%CI:0.03-3.02;P=0.61),and organ space wound infection(OR,0.63;95%CI:0.18-1.63;P=0.61).CONCLUSION There was no significant difference in the risk of 30-day post-operative morbidity between the NACT and surgery group and the surgery only group.

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.

Analysis of the Efficacy,Progression-Free Survival,and Safety of Anlotinib in Advanced Lung Cancer Treatment

Objective:To analyze the clinical efficacy,progression-free survival,and safety of anlotinib in the treatment of advanced lung cancer.Methods:A retrospective analysis was conducted using data from 60 patients with advanced lung cancer treated with anlotinib from May 2019 to May 2021.This analysis aimed to comprehensively evaluate the clinical efficacy,progression-free survival,and adverse reactions of anlotinib.Results:The median progression-free survival(PFS)for the 60 patients was 5.79 months,with an overall response rate(ORR)of 21%and a disease control rate(DCR)of 90%.In the first-line group,the median PFS was 6.20 months,ORR was 76.92%,and DCR was 84.61%.The second-line group showed a median PFS of 6.30 months,ORR of 28.57%,and DCR of 90.48%.In the third-line group,the median PFS was 5.34 months,ORR was 19.23%,and DCR was 92.30%.The single-agent group exhibited a median PFS of 5.09 months,ORR of 23.33%,and DCR of 76.67%.In the combination group,the median PFS was 6.53 months,ORR was 46.67%,and DCR was 100%.The combination group demonstrated a significantly higher medication effect than the single-drug group,and adverse drug reactions were mostly grade 1-2.Conclusion:Anlotinib exhibits a better disease control rate and survival benefit in the treatment of advanced lung cancer.The combination effect is superior to monotherapy,with relatively controllable adverse effects.

Implications of receptor for advanced glycation end products for progression from obesity to diabetes and from diabetes to cancer

Obesity and type 2 diabetes mellitus(T2DM)are chronic pathologies with a high incidence worldwide.They share some pathological mechanisms,including hyperinsulinemia,the production and release of hormones,and hyperglycemia.The above,over time,affects other systems of the human body by causing tissue hypoxia,low-grade inflammation,and oxidative stress,which lay the pathophysiological groundwork for cancer.The leading causes of death globally are T2DM and cancer.Other main alterations of this pathological triad include the accumulation of advanced glycation end products and the release of endogenous alarmins due to cell death(i.e.,damage-associated molecular patterns)such as the intracellular proteins high-mobility group box protein 1 and protein S100 that bind to the receptor for advanced glycation products(RAGE)-a multiligand receptor involved in inflammatory and metabolic and neoplastic processes.This review analyzes the latest advanced reports on the role of RAGE in the development of obesity,T2DM,and cancer,with an aim to understand the intracellular signaling mechanisms linked with cancer initiation.This review also explores inflammation,oxidative stress,hypoxia,cellular senescence,RAGE ligands,tumor microenvironment changes,and the“cancer hallmarks”of the leading tumors associated with T2DM.The assimilation of this information could aid in the development of diagnostic and therapeutic approaches to lower the morbidity and mortality associated with these diseases.

Contributions of the receptor for advanced glycation end products axis activation in gastric cancer

Compelling shreds of evidence derived from both clinical and experimental research have demonstrated the crucial contribution of receptor for advanced glycation end products(RAGE)axis activation in the development of neoplasms,including gastric cancer(GC).This new actor in tumor biology plays an important role in the onset of a crucial and long-lasting inflammatory milieu,not only by supporting phenotypic changes favoring growth and dissemination of tumor cells,but also by functioning as a pattern-recognition receptor in the inflammatory response to Helicobacter pylori infection.In the present review,we aim to highlight how the overexpression and activation of the RAGE axis contributes to the proliferation and survival of GC cells as and their acquisition of more invasive phenotypes that promote dissemination and metastasis.Finally,the contribution of some single nucleotide polymorphisms in the RAGE gene as susceptibility or poor prognosis factors is also discussed.

Occult pancreaticobiliary reflux is a pathogenic factor of some benign biliary diseases and gallbladder cancer

Background:Pancreaticobiliary maljunction(PBM)is a well-known high-risk factor for biliary malignant tumors because of constant pancreaticobiliary reflux(PBR).However,the impact of occult pancreaticobiliary reflux(OPR),which is characterized by high bile amylase levels in individuals with anatomically normal pancreaticobiliary junction,on biliary diseases remains unclear.The aim of this study was to assess the correlation between OPR and biliary diseases.Methods:We enrolled 94 consecutive patients with normal pancreaticobiliary junction and primary biliary diseases confirmed by magnetic resonance cholangiopancreatography.We prospectively collected patients’bile samples and measured bile amylase levels.We investigated the incidence of OPR and the difference in bile amylase levels among these patients and assessed the correlation between high bile amylase levels(HBAL)and benign or malignant biliary diseases,as well as the OPR risk factors.Results:The incidence of OPR was 36.6%in patients with benign biliary diseases,26.7%in those with cholangiocarcinoma and 62.5%in those with gallbladder cancer.The median bile amylase level tended to be higher in patients with gallbladder cancer than in those with benign biliary diseases,but there was no significant difference(165.5 IU/L vs.23.0 IU/L,P=0.212).The prevalence of an HBAL with bile amylase levels of 1000-7500 IU/L was similar in patients with gallbladder cancer and benign biliary diseases.However,the incidence of HBAL with bile amylase levels greater than 7500 IU/L was significantly higher in patients with gallbladder cancer than in those with benign biliary diseases(37.5%vs.4.2%,P=0.012).Multivariate logistic regression analysis revealed that choledocholithiasis was an independent risk factor for OPR.Conclusions:OPR can occur in benign and malignant biliary diseases,and it may be a pathogenic factor for some benign biliary diseases and a high-risk factor for gallbladder cancer.There is a correlation between choledocholithiasis and OPR.

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.

Immune-related adverse events associated with immune checkpoint inhibitors for advanced gastric and gastroesophageal junction cancer:A meta-analysis

BACKGROUND Immune checkpoint inhibitors(ICIs)have shown promising efficacy in treatment and clinical management of advanced gastric and gastroesophageal junction cancer.However,the inhibitors also cause immune-related adverse events(irAEs).The current systematic review and meta-analysis study aimed to investigate the incidence and nature of irAEs caused by ICIs.AIM To investigate the incidence and nature of irAEs in advanced gastric and gastroesophageal junction cancer.METHODS This systematic review was registered with PROSPERO(Reg.number:CRD42020152291).Data included in this study were collected from patients diagnosed with advanced gastric cancer or gastroesophageal junction cancer and treated with ICIs.A systematic literature search was conducted using the PubMed,EMBASE,and Cochrane Library databases.Meta-analysis was carried out using the single sample rate method.Synthesis and analysis of the data was conducted using Stata/SE and Review Manager Software.RESULTS The patients enrolled in the present study included 14 patients from 14 case reports,326 patients from 6 case series,and 1249 patients from 8 clinical trials.It was found that the overall incidence of irAEs was 16%[95%confidence interval(CI):11-20]for all grades and 3%(95%CI:2-4)for the severe grade.It was evident that the incidence of irAEs varied with the type of inhibitor and organs.A comparative study of the anti-programmed cell death receptor-1(PD-1)and antiprogrammed death receptor-ligand 1(PD-L1)treatments showed that the antiPD-1 group had a higher overall incidence of irAEs(20%)as compared with that of the anti-PD-L1 group(13%).Results of this study showed that the endocrine system experienced the highest incidence of organ-specific irAEs(7.4%),including hypothyroidism,hyperthyroidism,thyroiditis,diabetes,and adrenal insufficiency,followed by gastroenterology(2.2%),pulmonology(1.8%),neurology(1.4%),dermatology(1.4%),hematology(0.8%),and hepatology(0.7%).In clinical trials,it was found that the incidence of death related to irAEs was 1%(95%CI:0-2.0),whereby colitis and interstitial lung diseases were the leading causes of death.CONCLUSION It was evident that the incidence and nature of irAEs are both organ-and inhibitor-specific.The anti-PD-1 group had the highest incidence of all irAEs grades including the severe grades of irAEs.Early identification and management of irAEs allows clinical oncologists to effectively consider the pros and cons and hence enables them to strike a balance.

Systemic treatment for advanced pancreatic cancer

Pancreatic cancer is a deadly disease with an extremely poor 5-year survival rate due to treatment resistance and late-stage detection.Despite numerous years of research and pharmaceutical development,these figures have not changed.Treatment options for advanced pancreatic cancer are still limited.This illness is typically detected at a late stage,making curative surgical resection impossible.Chemotherapy is the most commonly utilized technique for treating advanced pancreatic cancer but has poor efficacy.Targeted therapy and immunotherapy have made significant progress in many other cancer types and have been proven to have extremely promising possibilities;these therapies also hold promise for pancreatic cancer.There is an urgent need for research into targeted treatment,immunotherapy,and cancer vaccines.In this review,we emphasize the founda-tional findings that have fueled the therapeutic strategy for advanced pancreatic cancer.We also address current advancements in targeted therapy,immuno-therapy,and cancer vaccines,all of which continue to improve the clinical outcome of advanced pancreatic cancer.We believe that clinical translation of these novel treatments will improve the low survival rate of this deadly disease.

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.

Advances in translational therapy for locally advanced gastric cancer

Translational therapy refers to a combination of chemotherapy,radiotherapy,targeted therapy,and immunotherapy for patients with advanced gastric cancer who are initially unable to undergo R0 resection.This treatment can achieve partial or complete remission of the unresectable tumors to meet the criteria for R0 resection,thus enabling the patients to prolong their survival time and improve their quality of life.In gastric cancer,translational therapy has been tried and improved.At present,there are a large number of patients with locally advanced gastric cancer in China,and the selection of suitable patients for transla-tional therapy to prolong objective survival and improve survival quality is one of the hot spots in the field of gastric cancer research.