AIM： To assess the use of capecitabine-based therapy and associated complication rates in patients with gastroesophageal cancer （GEC） in a real-world treat- ment setting. METHODS： Patients with claims between 2004...AIM： To assess the use of capecitabine-based therapy and associated complication rates in patients with gastroesophageal cancer （GEC） in a real-world treat- ment setting. METHODS： Patients with claims between 2004 and 2005 were identified from the Thomson Reuters MarketScan databases. Capecitabine regimens were compared with 5-fluorouracU （5-FU） and other chemotherapy regimens, and were stratified by treatment setting. RESULTS： We identified 1013 patients with GEC： approximately half had treatment initiated with a 5-FU regimen, whereas 11% had therapy initiated with a capecitabine regimen. The mean capecitabine dose overall was 2382 ± 1118 mg/d, and capecitabine was used as monotherapy more often than in combination. Overall, 5-FU regimens were the most common treat- ment option in neoadjuvant and adjuvant settings, while other non-capecitabine regimens were used more widely in first- and second-line settings. The overall unadjusted complication rate for capecitabine regimens was about half of that seen with 5-FU regimens. In multivariate analyses, capecitabine recipients had a 51% （95% CI： 26%-81%） lower risk of developing any complication than 5-FU recipients did. The risk of developing bone marrow, constitutional, gastrointestinal tract, infectious, or skin complications was lower with capecitabine therapy than with 5-FU.CONCLUSION： Capecitabine appeared to have a favorable side effect profile compared with 5-FU, which indicates that it may be a treatment option for GEC.展开更多
AIM:To investigate the effectiveness of 5-flurouracilbased neoadjuvant chemotherapy(NAC) for gastroesophageal and gastric cancer by meta-analysis.METHODS:MEDLINE and manual searches were performed to identify all publ...AIM:To investigate the effectiveness of 5-flurouracilbased neoadjuvant chemotherapy(NAC) for gastroesophageal and gastric cancer by meta-analysis.METHODS:MEDLINE and manual searches were performed to identify all published randomized controlled trials(RCTs) investigating the efficacy of the flurouracilbased NAC for gastroesophageal and gastric cancer,and RCTs of NAC for advanced gastroesophageal and gastric cancer vs no therapy before surgery.Studies that included patients with metastases at enrollment were excluded.Primary endpoint was the odds ratio(OR) for improving overall survival rate of patients with gastroesophageal and gastric cancer.Secondary endpoints were the OR of efficiency for down-staging tumor and increasing R0 resection in patients with gas-troesophageal and gastric cancer.Safety analyses were also performed.The OR was the principal measurement of effect,which was calculated as the treatment group(NAC plus surgery) vs control group(surgery alone) and was presented as a point estimate with 95% confidence intervals(CI).All calculations and statistical tests were performed using RevMan 5.1 software.RESULTS:Seven RCTs were included for the analysis.A total of 1249 patients with advanced gastroesophageal and gastric cancer enrolled in the seven trials were divided into treatment group(n = 620) and control group(n = 629).The quality scores of the RCTs were assessed according to the method of Jadad.The RCT quality scores ranged from 2 to 7(5-point scale),with a mean of 3.75.The median follow-up time in these studies was over 3 years.The meta-analysis showed that NAC improved the overall survival rate(OR 1.40,95%CI 1.11-1.76;P = 0.005),which was statistically significant.The 3-year progression-free survival rate was significantly higher in treatment group than in control group(37.7% vs 27.3%)(OR 1.62,95%CI 1.21-2.15;P = 0.001).The tumor down-stage rate was higher in treatment group than in control group(55.76% vs 41.38%)(OR 1.77,95%CI 1.27-2.49;P = 0.0009) and the R0 resection rate of the gastroesophageal and gastric cancer was higher in treatment group than in control group(75.11% vs 68.56%)(OR 1.38,95%CI 1.03-1.85;P = 0.03),with significant differences.No obvious safety concerns about mortality and complications were raised in these trials.There were no statistically significant differences in perioperative mortality(5.08% vs 4.86%)(OR 1.05,95%CI 0.57-1.94;P = 0.87 fixed-effect model) and in the complication rate between the two groups(13.25% vs 9.66%)(OR 1.40,95%CI 0.91-2.14;P = 0.12 fixed-effect model).Trials showed that patients from Western countries favored NAC compared with those from Asian countries(OR 1.40,95%CI 1.07-1.83).Monotherapy was inferior tomultiple chemotherapy(OR 1.40,95%CI 1.07-1.83).Intravenous administration of NAC was more advantageous than oral route(OR 1.41,95%CI 1.09-1.81).CONCLUSION:Flurouracil-based NAC can safely improve overall survival rate of patients with gastroesophageal/gastric cancer.Additionally,NAC can down the tumor stage and improve R0 resection.展开更多
The malfeasant role of the hypoxic tumour microenvironment(TME)in cancer progression was recognized decades ago but the exact mechanisms that augment the hallmarks of cancer and promote treatment resistance continue t...The malfeasant role of the hypoxic tumour microenvironment(TME)in cancer progression was recognized decades ago but the exact mechanisms that augment the hallmarks of cancer and promote treatment resistance continue to be elucidated.Gastroesophageal cancers(GOCs)represent a major burden of worldwide disease,responsible for the deaths of over 1 million people annually.Disentangling the impact of hypoxia in GOCs enables a better overall understanding of the disease pathogenesis while shining a light on novel therapeutic strategies and facilitating precision treatment approaches with the ultimate goal of improving outcomes for patients with these diseases.This review discusses the underlying principles and processes of the hypoxic response and the effect of hypoxia in promoting the hallmarks of cancer in the context of GOCs.We focus on its bidirectional influence on inflammation and how it drives angiogenesis,innate and adaptive immune evasion,metastasis,and the reprogramming of cellular bioenergetics.The contribution of the hypoxic GOC TME to treatment resistance is examined and a brief overview of the pharmacodynamics of hypoxiatargeted therapeutics is given.The principal methods that are used in measuring hypoxia and how they may enhance prognostication or provide rationale for individually tailored management in the case of tumours with significant hypoxic regions are also discussed.展开更多
BACKGROUND Laparoscopic gastrectomy for esophagogastric junction(EGJ)carcinoma enables the removal of the carcinoma at the junction between the stomach and esophagus while preserving the gastric function,thereby provi...BACKGROUND Laparoscopic gastrectomy for esophagogastric junction(EGJ)carcinoma enables the removal of the carcinoma at the junction between the stomach and esophagus while preserving the gastric function,thereby providing patients with better treatment outcomes and quality of life.Nonetheless,this surgical technique also presents some challenges and limitations.Therefore,three-dimensional reconstruction visualization technology(3D RVT)has been introduced into the procedure,providing doctors with more comprehensive and intuitive anatomical information that helps with surgical planning,navigation,and outcome evaluation.AIM To discuss the application and advantages of 3D RVT in precise laparoscopic resection of EGJ carcinomas.METHODS Data were obtained from the electronic or paper-based medical records at The First Affiliated Hospital of Hebei North University from January 2020 to June 2022.A total of 120 patients diagnosed with EGJ carcinoma were included in the study.Of these,68 underwent laparoscopic resection after computed tomography(CT)-enhanced scanning and were categorized into the 2D group,whereas 52 underwent laparoscopic resection after CT-enhanced scanning and 3D RVT and were categorized into the 3D group.This study had two outcome measures:the deviation between tumor-related factors(such as maximum tumor diameter and infiltration length)in 3D RVT and clinical reality,and surgical outcome indicators(such as operative time,intraoperative blood loss,number of lymph node dissections,R0 resection rate,postoperative hospital stay,postoperative gas discharge time,drainage tube removal time,and related complications)between the 2D and 3D groups.RESULTS Among patients included in the 3D group,27 had a maximum tumor diameter of less than 3 cm,whereas 25 had a diameter of 3 cm or more.In actual surgical observations,24 had a diameter of less than 3 cm,whereas 28 had a diameter of 3 cm or more.The findings were consistent between the two methods(χ^(2)=0.346,P=0.556),with a kappa consistency coefficient of 0.808.With respect to infiltration length,in the 3D group,23 patients had a length of less than 5 cm,whereas 29 had a length of 5 cm or more.In actual surgical observations,20 cases had a length of less than 5 cm,whereas 32 had a length of 5 cm or more.The findings were consistent between the two methods(χ^(2)=0.357,P=0.550),with a kappa consistency coefficient of 0.486.Pearson correlation analysis showed that the maximum tumor diameter and infiltration length measured using 3D RVT were positively correlated with clinical observations during surgery(r=0.814 and 0.490,both P<0.05).The 3D group had a shorter operative time(157.02±8.38 vs 183.16±23.87),less intraoperative blood loss(83.65±14.22 vs 110.94±22.05),and higher number of lymph node dissections(28.98±2.82 vs 23.56±2.77)and R0 resection rate(80.77%vs 61.64%)than the 2D group.Furthermore,the 3D group had shorter hospital stay[8(8,9)vs 13(14,16)],time to gas passage[3(3,4)vs 4(5,5)],and drainage tube removal time[4(4,5)vs 6(6,7)]than the 2D group.The complication rate was lower in the 3D group(11.54%)than in the 2D group(26.47%)(χ^(2)=4.106,P<0.05).CONCLUSION Using 3D RVT,doctors can gain a more comprehensive and intuitive understanding of the anatomy and related lesions of EGJ carcinomas,thus enabling more accurate surgical planning.展开更多
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...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.展开更多
Objective: As laparoscopic surgery is widely applied for primarily treated gastric cancer(GC)/gastroesophageal junction cancer(GEJC) and gains many advantages, the feasibility of laparoscopic total gastrectomy(LTG) fo...Objective: As laparoscopic surgery is widely applied for primarily treated gastric cancer(GC)/gastroesophageal junction cancer(GEJC) and gains many advantages, the feasibility of laparoscopic total gastrectomy(LTG) for GC/GEJC patients who have received preoperative therapy(PT) has come to the fore. This study aims to analyze the safety and feasibility of LTG after PT for GC/GEJC patients.Methods: We retrospectively analyzed the data of 511 patients with GC/GEJC undergoing LTG, of which 405received LTG(LTG group) and 106 received PT+LTG(PT-LTG group) at Nanfang Hospital between June 2018and September 2022. The surgical outcomes were compared between the two groups.Results: The surgical duration was significantly longer in the PT-LTG group(P<0.001), while the incidence of intraoperative complications(P=1.000), postoperative complications(LTG group vs. PT-LTG group: 26.2% vs.23.6%, P=0.587), the classification of complication severity(P=0.271), and postoperative recovery was similar between two groups. Notably, the incidence of anastomotic complications of esophagojejunostomy was also comparable between the two groups(LTG group vs. PT-LTG group: 5.9% vs. 5.7%, P=0.918). The univariate and multivariate analysis confirmed that positive proximal margin [positive vs. negative: odds ratio(OR)=14.094, 95%confidence interval(95% CI): 2.639-75.260, P=0.002], rather than PT, has an impact on anastomotic complications after LTG(OR=0.945, 95% CI: 0.371-2.408, P=0.905).Conclusions: PT did not increase the surgical risk of LTG for GC/GEJC. Therefore, considering the positive effect of PT on long-term survival, the broader application of PT and LTG for GC/GEJC is supported by our findings.展开更多
BACKGROUND Gastric cancer is the third most common cause of cancer related death worldwide.Surgery with or without chemotherapy is the most common approach with curative intent;however,the prognosis is poor as mortali...BACKGROUND Gastric cancer is the third most common cause of cancer related death worldwide.Surgery with or without chemotherapy is the most common approach with curative intent;however,the prognosis is poor as mortality rates remain high.Several indexes have been proposed in the past few years in order to estimate the survival of patients undergoing gastrectomy.The preoperative nutritional status of gastric cancer patients has recently gained attention as a factor that could affect the postoperative course and various indexes have been developed.The aim of this systematic review was to assess the role of the prognostic nutritional index(PNI)in predicting the survival of patients with gastric or gastroesophageal adenocarcinoma who underwent gastrectomy with curative intent.AIM To investigate the role of PNI in predicting the survival of patients with gastric or gastroesophageal junction adenocarcinoma.METHODS A thorough literature search of PubMed and the Cochrane library was performed for studies comparing the overall survival(OS)of patients with gastric or gastroesophageal cancer after surgical resection depending on the preoperative PNI value.The PRISMA algorithm was used in the screening process and finally 16 studies were included in this systematic review.The review protocol was registered in the International Prospective Register of Systematic Reviews(PRO) RESULTS Sixteen studies involving 14551 patients with gastric or esophagogastric junction adenocarcinoma undergoing open or laparoscopic or robotic gastrectomy with or without adjuvant chemotherapy were included in this systematic review.The patients were divided into high-and low-PNI groups according to cut-off values that were set according to previous reports or by using receiver operating characteristic curve analysis in each individual study.The 5-year OS of patients in the low-PNI groups ranged between 39%and 70.6%,while in the high-PNI groups,it ranged between 54.9%and 95.8%.In most of the included studies,patients with high preoperative PNI showed statistically significant better OS than the low PNI groups.In multivariate analyses,low PNI was repeatedly recognised as an independent prognostic factor for poor survival.CONCLUSION According to the present study,low preoperative PNI seems to be an indicator of poor OS of patients undergoing gastrectomy for gastric or gastroesophageal cancer.展开更多
BACKGROUND Hemorrhage,which is not a rare complication in patients with gastric cancer(GC)/gastroesophageal junction cancer(GEJC),can lead to a poor prognosis.However,no study has examined the effectiveness and safety...BACKGROUND Hemorrhage,which is not a rare complication in patients with gastric cancer(GC)/gastroesophageal junction cancer(GEJC),can lead to a poor prognosis.However,no study has examined the effectiveness and safety of chemotherapy as an initial therapy for GC/GEJC patients with overt bleeding(OB).AIM To investigate the impact of OB on the survival and treatment-related adverse events(TRAEs)of GC/GEJC patients.METHODS Patients with advanced or metastatic GC/GEJC who received systematic treatment at Peking University Third Hospital were enrolled in this study.Propensity score matching(PSM)analysis was performed.RESULTS After 1:2 PSM analysis,93 patients were assessed,including 32 patients with OB before treatment(OBBT)and 61 patients without OBBT.The disease control rate was 90.6%in the group with OBBT and 88.5%in the group without OBBT,and this difference was not statistically significant.There was no difference in the incidence of TRAEs between the group with OBBT and the group without OBBT.The median overall survival(mOS)was 15.2 months for patients with OBBT and 23.7 months for those without OBBT[hazard ratio(HR)=1.101,95%confidence interval(CI):0.672-1.804,log rank P=0.701].The mOS was worse for patients with OB after treatment(OBAT)than for those without OBAT(11.4 months vs 23.7 months,HR=1.787,95%CI:1.006-3.175,log rank P=0.044).CONCLUSION The mOS for GC/GEJC patients with OBBT was similar to that for those without OBBT,but the mOS for patients with OBAT was worse than that for those without OBAT.展开更多
Despite the application of conventional therapies,the prognosis of advanced gastric cancer(GC)or gastroesophageal junction cancer(GEJC)is still poor.In recent years,immune checkpoint inhibitors(ICIs)have reshaped the ...Despite the application of conventional therapies,the prognosis of advanced gastric cancer(GC)or gastroesophageal junction cancer(GEJC)is still poor.In recent years,immune checkpoint inhibitors(ICIs)have reshaped the paradigm of cancer therapy.Emerging evidence support the feasibility of programmed cell death-1(PD-1)and its ligand(PD-L1)inhibition in chemo-refractory GC/GEJC.Nivolumab and pembrolizumab have initially been approved in Japan and United States,respectively for the third-line treatment of progressive GC or GEJC.In March 2020,nivolumab has also been licensed in China for treating advanced GC/GEJC who received≥2 lines of systemic therapies.Current studies are moving forward to the first-line application or focusing on combination strategies,though data are insufficient and disputable.In this review,we summarize the recently reported and ongoing clinical trials in ICIs for advanced GC/GEJC.Molecular characteristics and clinical implications of different tumor subtypes are also reviewed.We further discuss the safety profile and biomarkers for predicting the response of ICIs,which has guiding values in clinical practice.展开更多
BACKGROUND Faced with limited and inadequate treatment options for patients with advanced gastric cancer or gastroesophageal junction cancer(GC/GEJC), researchers have turned toward, with the support of promising clin...BACKGROUND Faced with limited and inadequate treatment options for patients with advanced gastric cancer or gastroesophageal junction cancer(GC/GEJC), researchers have turned toward, with the support of promising clinical trials, anti-PD-1/anti-PD-L1 antibody therapy. But there are also different clinical trial results. To better assess its efficacy and safety, we integrated data from 13 eligible studies for a systematic review and meta-analysis.AIM To comprehensively evaluate the efficacy and safety of anti-PD-1/anti-PD-L1 antibody therapy in the treatment of advanced GC/GEJC patients.METHODS PubMed, Web of Science, Cochrane Library,and EMBASE databases were searched to identify eligible articles with outcomes including objective response rate(ORR), disease control rate(DCR), overall survival(OS), progression-free survival(PFS), and adverse events(AEs) of anti-PD-1/anti-PD-L1 antibody therapy.RESULTS Our study encompassed a total of 13 trials totaling 1618 patients. The outcomes showed a pooled ORR and DCR of 15%(95% confidence interval [CI]: 14%-18%) and 40%(95%CI: 33%-46%), respectively. The pooled 6-mo OS and PFS were 54%(95%CI: 45%-64%) and 26%(95%CI: 20%-32%), respectively, and the 12-mo OS and PFS were 42%(95%CI: 21%-62%) and 11%(95%CI: 8%-13%), respectively. In addition, the incidence of any-grade AEs and grade ≥ 3 AEs was 64%(95%CI: 54%-73%) and 18%(95%CI: 16%-20%), respectively. Most importantly, PD-L1 positive patients exhibited a higher ORR rate than PD-L1 negative patients(odds ratio = 2.54, 95%CI: 1.56-4.15).CONCLUSION Anti-PD-1/anti-PD-L1 antibody therapy has shown promising anti-tumor efficacy with manageable AEs in advanced GC/GEJC patients, with PD-L1 overexpressing patients exhibiting a higher ORR. What is more, the clinical efficacy of anti-PD-1/PD-L1 combined with traditional chemotherapy drugs is even better, although the occurrence of AEs still causes considerate concerns.展开更多
Gastric and gastroesophageal junction(GEJ)cancers represent an aggressive group of malignancies with poor prognosis even when diagnosed in relatively early stage,with an increasing incidence both in Asia and in Wester...Gastric and gastroesophageal junction(GEJ)cancers represent an aggressive group of malignancies with poor prognosis even when diagnosed in relatively early stage,with an increasing incidence both in Asia and in Western countries.These cancers are characterized by heterogeneity as a result of different pathogenetic mechanisms as shown in recent molecular analyses.Accordingly,the understanding of phenotypic and genotypic correlations/classifications has been improved.Current therapeutic strategies have also advanced and moved beyond surgical extirpation alone,with the incorporation of other treatment modalities,such as radiation and chemotherapy(including biologics).Chemoradiotherapy has been used as postoperative treatment after suboptimal gastrectomy to ensure local disease control but also improvement in survival.Preoperative chemoradiotherapy/chemotherapy has been employed to increase the chance of a successful R0 resection and pathologic complete response rate,which is associated with improved long-term outcomes.Several studies have defined various chemotherapy regimens to accompany radiation(before and after surgery).Recently,addition of immunotherapy after trimodality of gastroesophageal cancer has produced an advantage in disease-free interval.Targeted agents used in the metastatic setting are being investigated in the early setting with mixed results.The aim of this review is to summarize the existing data on trimodality approaches for gastric and GEJ cancers,highlight the remaining questions and present the current research effort addressing them.展开更多
Objective Esophageal and gastric lesions are effectively managed with minimally invasive upper endoscopic procedures such as endoscopic mucosa resection(EMR)and endoscopic submucosal dissection(ESD),offering patients ...Objective Esophageal and gastric lesions are effectively managed with minimally invasive upper endoscopic procedures such as endoscopic mucosa resection(EMR)and endoscopic submucosal dissection(ESD),offering patients alternatives to invasive interventions.While ESD is well established in Eastern Asia,its adoption in Denmark for superficial esophageal cancer is recent.This study presents real-world data on the feasibility,safety,and hospitalization duration associated with ESD and EMR for esophageal and gastric lesions.Methods A retrospective analysis was conducted on patients who underwent ESD or EMR at a specialized center in Denmark from October 2016 to June 2022.Data on treatment,indication,lesion location,hospitalization duration,procedure duration,specimen size,complications,recurrence,and one-year overall survival were collected.Statistical comparisons utilized the Mann-Whitney U test,independent sample median test,and chi-squared test.Results The study included 130 patients(144 procedures):72 underwent ESD and 58 underwent EMR.Compared with EMR,ESD resulted in greater percentages of en bloc and R0 resections(98.8%vs.64.1%,p<0.001;and 83.9%vs.23.8%,p<0.001),greater complication rates(28.7%vs.3.1%,p<0.001)and longer procedure times(119.5 min vs.37.0 min,p<0.001).The ESD procedure time significantly decreased over time(p=0.01).The local recurrence rates were 14.5%for ESD and 23.8%for EMR(p=0.767).The one-year overall survival rates were similar between the groups(95.8%vs.94.8%,p=0.553).Conclusion Both ESD and EMR are safe and viable for treating esophageal and gastric lesions.ESD offers advantages but requires more time and skill.These findings support the literature,emphasizing the importance of considering patient-specific factors and surgeon proficiency in selecting the appropriate procedure.展开更多
BACKGROUND Faecal immunochemical test(FIT)has been recommended to assess symptomatic patients for colorectal cancer(CRC)detection.Nevertheless,some conditions could theoretically favour blood originating in proximal a...BACKGROUND Faecal immunochemical test(FIT)has been recommended to assess symptomatic patients for colorectal cancer(CRC)detection.Nevertheless,some conditions could theoretically favour blood originating in proximal areas of the gastrointestinal tract passing through the colon unmetabolized.A positive FIT result could be related to other gastrointestinal cancers(GIC).AIM To assess the risk of GIC detection and related death in FIT-positive symptomatic patients(threshold 10μg Hb/g faeces)without CRC.METHODS Post hoc cohort analysis performed within two prospective diagnostic test studies evaluating the diagnostic accuracy of different FIT analytical systems for CRC and significant colonic lesion detection.Ambulatory patients with gastrointestinal symptoms referred consecutively for colonoscopy from primary and secondary healthcare,underwent a quantitative FIT before undergoing a complete colonoscopy.Patients without CRC were divided into two groups(positive and negative FIT)using the threshold of 10μg Hb/g of faeces and data from follow-up were retrieved from electronic medical records of the public hospitals involved in the research.We determined the cumulative risk of GIC,CRC and upper GIC.Hazard rate(HR)was calculated adjusted by age,sex and presence of significant colonic lesion.RESULTS We included 2709 patients without CRC and a complete baseline colonoscopy,730(26.9%)with FIT≥10μgr Hb/gr.During a mean time of 45.5±20.0 mo,a GIC was detected in 57(2.1%)patients:An upper GIC in 35(1.3%)and a CRC in 14(0.5%).Thirty-six patients(1.3%)died due to GIC:22(0.8%)due to an upper GIC and 9(0.3%)due to CRC.FIT-positive subjects showed a higher CRC risk(HR 3.8,95%CI:1.2-11.9)with no differences in GIC(HR 1.5,95%CI:0.8-2.7)or upper GIC risk(HR 1.0,95%CI:0.5-2.2).Patients with a positive FIT had only an increased risk of CRC-related death(HR 10.8,95%CI:2.1-57.1)and GIC-related death(HR 2.2,95%CI:1.1-4.3),with no differences in upper GIC-related death(HR 1.4,95%CI:0.6-3.3).An upper GIC was detected in 22(0.8%)patients during the first year.Two variables were independently associated:anaemia(OR 5.6,95%CI:2.2-13.9)and age≥70 years(OR 2.7,95%CI:1.1-7.0).CONCLUSION Symptomatic patients without CRC have a moderate risk increase in upper GIC,regardless of the FIT result.Patients with a positive FIT have an increased risk of post-colonoscopy CRC.展开更多
Management of cancers of the digestive system has progressed rapidly into the molecular era. Despite the significant recent achievements in the diagnosis and treatment of these patients, the number of deaths for these...Management of cancers of the digestive system has progressed rapidly into the molecular era. Despite the significant recent achievements in the diagnosis and treatment of these patients, the number of deaths for these tumors has currently plateaued. Many investigations have assessed the role of HER2 in tumors of the digestive system in both prognostic and therapeutic settings, with heterogeneous results. Novel testing and treatment guidelines are emerging, in particular in gastric and colorectal cancers. However, further advances are needed. In this review we provide a comprehensive overview of the current state-ofknowledge of HER2 alterations in the most common tumors of the digestive system and discuss the operational implications of HER2 testing.展开更多
Carcinoma of the gastroesophageal junction(GEJ) is defined as carcinoma that crosses the GEJ line,irrespective of where the tumor epicenter is located.This group of cancer is rare but controversial.Based on study resu...Carcinoma of the gastroesophageal junction(GEJ) is defined as carcinoma that crosses the GEJ line,irrespective of where the tumor epicenter is located.This group of cancer is rare but controversial.Based on study results from the majority of epidemiologic and clinicopathologic investigations carried out in Western countries,this cancer is believed to arise from Barrett's esophagus(BE) and includes both distal esophageal and proximal gastric carcinomas because of similar characteristics in epidemiology,clinicopathology,and molecular pathobiology in relation to BE.As such,the most recent American Joint Committee on Cancer staging manual requires staging all GEJ carcinomas with the rule for esophageal adenocarcinoma(EA).This mandate has been challenged recently by the data from several studies carried out mainly in Chinese patients.The emerging evidence derivedfrom those studies suggests:(1) both BE and EA are uncommon in the Chinese population;(2) almost all GEJ cancers in Chinese arise in the proximal stomach and show the features of proximal gastric cancer,not those of EA;(3) application of the new cancer staging rule to GEJ cancer of Chinese patients cannot stratify patients' prognosis effectively;and(4) prognostic factors of GEJ cancer in Chinese are similar,but not identical,to those of EA.In conclusion,the recent evidence suggests that GEJ cancer in Chinese shows distinct clinicopathologic characteristics that are different from EA.Further investigations in molecular pathology may help illustrate the underlying pathogenesis mechanisms of this cancer in Chinese patients and better manage patients with this fatal disease.展开更多
Objective:To explore the independent factors associated with the overall survival(OS)after D2/R0 resection and adjuvant chemoradiotherapy(CRT)for stage Ⅲ gastric cancer(GC)and gastroesophageal junction(GEJ)cancer,and...Objective:To explore the independent factors associated with the overall survival(OS)after D2/R0 resection and adjuvant chemoradiotherapy(CRT)for stage Ⅲ gastric cancer(GC)and gastroesophageal junction(GEJ)cancer,and establish and validate a nomogram model to predict the OS in this patient population.Methods:A total of 569 stage Ⅲ GC or GEJ cancer patients who underwent D2/R0 resection and adjuvant CRT at our center from January 2013 to May 2018 were retrospectively enrolled in this study.The patients were randomly divided into training and validation cohorts in a 3:1 ratio.In the training cohort,univariate and multivariate analysis were conducted to identify clinical factors associated with OS,and a nomogram model was established on the basis of the independent factors.The concordance index(C-index)and the calibration curve were used to validate the prediction power of the nomogram.Results:Overall,427 and 142 patients were enrolled in the training and validation cohorts,respectively.In the univariate and multivariate analyses,age,Lauren's classification,TNM stage,and administration of adjuvant CRT were independent factors for OS to construct the nomogram.The C-index values were 0.654 and 0.613 in the training and validation cohorts,respectively.The calibration curves were identical to the actual OS.Risk stratification based on the nomogram model showed good risk stratification for OS in both groups.Conclusion:Our study included adjuvant CRT as a predictive factor and established a nomogram model for predicting the OS in patients with stage III GC or GEJ after D2/R0 resection and adjuvant therapy.This nomogram could facilitate more individualized prediction of OS in clinical practice.展开更多
Background:The JACOB trial(NCT01774786)was a double-blinded,placebo-controlled,randomized,multicenter,international,phase III trial evaluating the efficacy and safety of adding pertuzumab to trastuzumab and chemo-ther...Background:The JACOB trial(NCT01774786)was a double-blinded,placebo-controlled,randomized,multicenter,international,phase III trial evaluating the efficacy and safety of adding pertuzumab to trastuzumab and chemo-therapy in first-line treatment of human epidermal growth factor receptor 2(HER2)-positive metastatic gastric cancer/gastroesophageal junction cancer(GEJC).The aim of this analysis was to investigate efficacy and safety outcomes in the Chinese subpopulation from the JACOB trial.Methods:This post hoc subpopulation analysis included all patients recruited in China's Mainland(n=163;20.9%)between June 2013 and January 2016.The patients were randomly assigned in a 1:1 ratio to receive pertuzumab plus trastuzumab and chemotherapy(pertuzumab group;n=82)or placebo plus trastuzumab and chemotherapy(con-trol group;n=81).Intravenous pertuzumab(840 mg)and trastuzumab(8 mg/kg loading and 6 mg/kg maintenance doses)were given every 3 weeks until disease progression or unacceptable toxicity.Chemotherapy was given as per standard regimens/doses of capecitabine or 5-fluorouracil plus cisplatin.The primary endpoint was overall survival(OS);secondary efficacy endpoints included progression-free survival(PFS),and overall objective response rate(ORR).Results:The median OS was 18.7 months in the pertuzumab group and 16.1 months in the control group(hazard ratio[HR]0.75;95%confidence interval[CI]0.49 to 1.14).The median PFS was 10.5 and 8.6 months in the pertuzumab and control groups,respectively(HR 0.85;95%CI 0.60 to 1.21),and the median ORRs were 68.9%and 55.7%,respectively.The treatment effect in this Chinese subpopulation showed consistency with that in the global ITT population with numerically lower HR for OS and PFS compared with the control group.The safety profiles of the pertuzumab and control groups in this Chinese subpopulation analysis were generally comparable.The most common grade 3-5adverse events were neutropenia,anemia,and leukopenia.However,due to the nature of being a post hoc subgroup analysis,the results presented here are descriptive only and need to be interpreted with caution.Conclusions:OS and PFS were numerically improved by adding pertuzumab to trastuzumab and chemotherapy as first-line treatment in Chinese HER2-positive gastric cancer/GEJC patients,and this regimen demonstrated an acceptable safety profile.展开更多
文摘AIM： To assess the use of capecitabine-based therapy and associated complication rates in patients with gastroesophageal cancer （GEC） in a real-world treat- ment setting. METHODS： Patients with claims between 2004 and 2005 were identified from the Thomson Reuters MarketScan databases. Capecitabine regimens were compared with 5-fluorouracU （5-FU） and other chemotherapy regimens, and were stratified by treatment setting. RESULTS： We identified 1013 patients with GEC： approximately half had treatment initiated with a 5-FU regimen, whereas 11% had therapy initiated with a capecitabine regimen. The mean capecitabine dose overall was 2382 ± 1118 mg/d, and capecitabine was used as monotherapy more often than in combination. Overall, 5-FU regimens were the most common treat- ment option in neoadjuvant and adjuvant settings, while other non-capecitabine regimens were used more widely in first- and second-line settings. The overall unadjusted complication rate for capecitabine regimens was about half of that seen with 5-FU regimens. In multivariate analyses, capecitabine recipients had a 51% （95% CI： 26%-81%） lower risk of developing any complication than 5-FU recipients did. The risk of developing bone marrow, constitutional, gastrointestinal tract, infectious, or skin complications was lower with capecitabine therapy than with 5-FU.CONCLUSION： Capecitabine appeared to have a favorable side effect profile compared with 5-FU, which indicates that it may be a treatment option for GEC.
文摘AIM:To investigate the effectiveness of 5-flurouracilbased neoadjuvant chemotherapy(NAC) for gastroesophageal and gastric cancer by meta-analysis.METHODS:MEDLINE and manual searches were performed to identify all published randomized controlled trials(RCTs) investigating the efficacy of the flurouracilbased NAC for gastroesophageal and gastric cancer,and RCTs of NAC for advanced gastroesophageal and gastric cancer vs no therapy before surgery.Studies that included patients with metastases at enrollment were excluded.Primary endpoint was the odds ratio(OR) for improving overall survival rate of patients with gastroesophageal and gastric cancer.Secondary endpoints were the OR of efficiency for down-staging tumor and increasing R0 resection in patients with gas-troesophageal and gastric cancer.Safety analyses were also performed.The OR was the principal measurement of effect,which was calculated as the treatment group(NAC plus surgery) vs control group(surgery alone) and was presented as a point estimate with 95% confidence intervals(CI).All calculations and statistical tests were performed using RevMan 5.1 software.RESULTS:Seven RCTs were included for the analysis.A total of 1249 patients with advanced gastroesophageal and gastric cancer enrolled in the seven trials were divided into treatment group(n = 620) and control group(n = 629).The quality scores of the RCTs were assessed according to the method of Jadad.The RCT quality scores ranged from 2 to 7(5-point scale),with a mean of 3.75.The median follow-up time in these studies was over 3 years.The meta-analysis showed that NAC improved the overall survival rate(OR 1.40,95%CI 1.11-1.76;P = 0.005),which was statistically significant.The 3-year progression-free survival rate was significantly higher in treatment group than in control group(37.7% vs 27.3%)(OR 1.62,95%CI 1.21-2.15;P = 0.001).The tumor down-stage rate was higher in treatment group than in control group(55.76% vs 41.38%)(OR 1.77,95%CI 1.27-2.49;P = 0.0009) and the R0 resection rate of the gastroesophageal and gastric cancer was higher in treatment group than in control group(75.11% vs 68.56%)(OR 1.38,95%CI 1.03-1.85;P = 0.03),with significant differences.No obvious safety concerns about mortality and complications were raised in these trials.There were no statistically significant differences in perioperative mortality(5.08% vs 4.86%)(OR 1.05,95%CI 0.57-1.94;P = 0.87 fixed-effect model) and in the complication rate between the two groups(13.25% vs 9.66%)(OR 1.40,95%CI 0.91-2.14;P = 0.12 fixed-effect model).Trials showed that patients from Western countries favored NAC compared with those from Asian countries(OR 1.40,95%CI 1.07-1.83).Monotherapy was inferior tomultiple chemotherapy(OR 1.40,95%CI 1.07-1.83).Intravenous administration of NAC was more advantageous than oral route(OR 1.41,95%CI 1.09-1.81).CONCLUSION:Flurouracil-based NAC can safely improve overall survival rate of patients with gastroesophageal/gastric cancer.Additionally,NAC can down the tumor stage and improve R0 resection.
文摘The malfeasant role of the hypoxic tumour microenvironment(TME)in cancer progression was recognized decades ago but the exact mechanisms that augment the hallmarks of cancer and promote treatment resistance continue to be elucidated.Gastroesophageal cancers(GOCs)represent a major burden of worldwide disease,responsible for the deaths of over 1 million people annually.Disentangling the impact of hypoxia in GOCs enables a better overall understanding of the disease pathogenesis while shining a light on novel therapeutic strategies and facilitating precision treatment approaches with the ultimate goal of improving outcomes for patients with these diseases.This review discusses the underlying principles and processes of the hypoxic response and the effect of hypoxia in promoting the hallmarks of cancer in the context of GOCs.We focus on its bidirectional influence on inflammation and how it drives angiogenesis,innate and adaptive immune evasion,metastasis,and the reprogramming of cellular bioenergetics.The contribution of the hypoxic GOC TME to treatment resistance is examined and a brief overview of the pharmacodynamics of hypoxiatargeted therapeutics is given.The principal methods that are used in measuring hypoxia and how they may enhance prognostication or provide rationale for individually tailored management in the case of tumours with significant hypoxic regions are also discussed.
文摘BACKGROUND Laparoscopic gastrectomy for esophagogastric junction(EGJ)carcinoma enables the removal of the carcinoma at the junction between the stomach and esophagus while preserving the gastric function,thereby providing patients with better treatment outcomes and quality of life.Nonetheless,this surgical technique also presents some challenges and limitations.Therefore,three-dimensional reconstruction visualization technology(3D RVT)has been introduced into the procedure,providing doctors with more comprehensive and intuitive anatomical information that helps with surgical planning,navigation,and outcome evaluation.AIM To discuss the application and advantages of 3D RVT in precise laparoscopic resection of EGJ carcinomas.METHODS Data were obtained from the electronic or paper-based medical records at The First Affiliated Hospital of Hebei North University from January 2020 to June 2022.A total of 120 patients diagnosed with EGJ carcinoma were included in the study.Of these,68 underwent laparoscopic resection after computed tomography(CT)-enhanced scanning and were categorized into the 2D group,whereas 52 underwent laparoscopic resection after CT-enhanced scanning and 3D RVT and were categorized into the 3D group.This study had two outcome measures:the deviation between tumor-related factors(such as maximum tumor diameter and infiltration length)in 3D RVT and clinical reality,and surgical outcome indicators(such as operative time,intraoperative blood loss,number of lymph node dissections,R0 resection rate,postoperative hospital stay,postoperative gas discharge time,drainage tube removal time,and related complications)between the 2D and 3D groups.RESULTS Among patients included in the 3D group,27 had a maximum tumor diameter of less than 3 cm,whereas 25 had a diameter of 3 cm or more.In actual surgical observations,24 had a diameter of less than 3 cm,whereas 28 had a diameter of 3 cm or more.The findings were consistent between the two methods(χ^(2)=0.346,P=0.556),with a kappa consistency coefficient of 0.808.With respect to infiltration length,in the 3D group,23 patients had a length of less than 5 cm,whereas 29 had a length of 5 cm or more.In actual surgical observations,20 cases had a length of less than 5 cm,whereas 32 had a length of 5 cm or more.The findings were consistent between the two methods(χ^(2)=0.357,P=0.550),with a kappa consistency coefficient of 0.486.Pearson correlation analysis showed that the maximum tumor diameter and infiltration length measured using 3D RVT were positively correlated with clinical observations during surgery(r=0.814 and 0.490,both P<0.05).The 3D group had a shorter operative time(157.02±8.38 vs 183.16±23.87),less intraoperative blood loss(83.65±14.22 vs 110.94±22.05),and higher number of lymph node dissections(28.98±2.82 vs 23.56±2.77)and R0 resection rate(80.77%vs 61.64%)than the 2D group.Furthermore,the 3D group had shorter hospital stay[8(8,9)vs 13(14,16)],time to gas passage[3(3,4)vs 4(5,5)],and drainage tube removal time[4(4,5)vs 6(6,7)]than the 2D group.The complication rate was lower in the 3D group(11.54%)than in the 2D group(26.47%)(χ^(2)=4.106,P<0.05).CONCLUSION Using 3D RVT,doctors can gain a more comprehensive and intuitive understanding of the anatomy and related lesions of EGJ carcinomas,thus enabling more accurate surgical planning.
基金Supported by The National Natural Science Foundation of China,No.81960503.
文摘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.
基金supported by grants from the Clinical Research Program of Nanfang Hospital, Southern Medical University (No.2021CR001 and No.2021CR013)Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer (No.2020B 121201004)“Climbing Program”, Special Fund of Guangdong Province (No.pdjh2022a0093 and No.pdjh2023a0098)。
文摘Objective: As laparoscopic surgery is widely applied for primarily treated gastric cancer(GC)/gastroesophageal junction cancer(GEJC) and gains many advantages, the feasibility of laparoscopic total gastrectomy(LTG) for GC/GEJC patients who have received preoperative therapy(PT) has come to the fore. This study aims to analyze the safety and feasibility of LTG after PT for GC/GEJC patients.Methods: We retrospectively analyzed the data of 511 patients with GC/GEJC undergoing LTG, of which 405received LTG(LTG group) and 106 received PT+LTG(PT-LTG group) at Nanfang Hospital between June 2018and September 2022. The surgical outcomes were compared between the two groups.Results: The surgical duration was significantly longer in the PT-LTG group(P<0.001), while the incidence of intraoperative complications(P=1.000), postoperative complications(LTG group vs. PT-LTG group: 26.2% vs.23.6%, P=0.587), the classification of complication severity(P=0.271), and postoperative recovery was similar between two groups. Notably, the incidence of anastomotic complications of esophagojejunostomy was also comparable between the two groups(LTG group vs. PT-LTG group: 5.9% vs. 5.7%, P=0.918). The univariate and multivariate analysis confirmed that positive proximal margin [positive vs. negative: odds ratio(OR)=14.094, 95%confidence interval(95% CI): 2.639-75.260, P=0.002], rather than PT, has an impact on anastomotic complications after LTG(OR=0.945, 95% CI: 0.371-2.408, P=0.905).Conclusions: PT did not increase the surgical risk of LTG for GC/GEJC. Therefore, considering the positive effect of PT on long-term survival, the broader application of PT and LTG for GC/GEJC is supported by our findings.
文摘BACKGROUND Gastric cancer is the third most common cause of cancer related death worldwide.Surgery with or without chemotherapy is the most common approach with curative intent;however,the prognosis is poor as mortality rates remain high.Several indexes have been proposed in the past few years in order to estimate the survival of patients undergoing gastrectomy.The preoperative nutritional status of gastric cancer patients has recently gained attention as a factor that could affect the postoperative course and various indexes have been developed.The aim of this systematic review was to assess the role of the prognostic nutritional index(PNI)in predicting the survival of patients with gastric or gastroesophageal adenocarcinoma who underwent gastrectomy with curative intent.AIM To investigate the role of PNI in predicting the survival of patients with gastric or gastroesophageal junction adenocarcinoma.METHODS A thorough literature search of PubMed and the Cochrane library was performed for studies comparing the overall survival(OS)of patients with gastric or gastroesophageal cancer after surgical resection depending on the preoperative PNI value.The PRISMA algorithm was used in the screening process and finally 16 studies were included in this systematic review.The review protocol was registered in the International Prospective Register of Systematic Reviews(PRO) RESULTS Sixteen studies involving 14551 patients with gastric or esophagogastric junction adenocarcinoma undergoing open or laparoscopic or robotic gastrectomy with or without adjuvant chemotherapy were included in this systematic review.The patients were divided into high-and low-PNI groups according to cut-off values that were set according to previous reports or by using receiver operating characteristic curve analysis in each individual study.The 5-year OS of patients in the low-PNI groups ranged between 39%and 70.6%,while in the high-PNI groups,it ranged between 54.9%and 95.8%.In most of the included studies,patients with high preoperative PNI showed statistically significant better OS than the low PNI groups.In multivariate analyses,low PNI was repeatedly recognised as an independent prognostic factor for poor survival.CONCLUSION According to the present study,low preoperative PNI seems to be an indicator of poor OS of patients undergoing gastrectomy for gastric or gastroesophageal cancer.
基金approved by the Peking University Third Hospital Medical Science Research Ethics Committee(IRB00006761-M2023544).
文摘BACKGROUND Hemorrhage,which is not a rare complication in patients with gastric cancer(GC)/gastroesophageal junction cancer(GEJC),can lead to a poor prognosis.However,no study has examined the effectiveness and safety of chemotherapy as an initial therapy for GC/GEJC patients with overt bleeding(OB).AIM To investigate the impact of OB on the survival and treatment-related adverse events(TRAEs)of GC/GEJC patients.METHODS Patients with advanced or metastatic GC/GEJC who received systematic treatment at Peking University Third Hospital were enrolled in this study.Propensity score matching(PSM)analysis was performed.RESULTS After 1:2 PSM analysis,93 patients were assessed,including 32 patients with OB before treatment(OBBT)and 61 patients without OBBT.The disease control rate was 90.6%in the group with OBBT and 88.5%in the group without OBBT,and this difference was not statistically significant.There was no difference in the incidence of TRAEs between the group with OBBT and the group without OBBT.The median overall survival(mOS)was 15.2 months for patients with OBBT and 23.7 months for those without OBBT[hazard ratio(HR)=1.101,95%confidence interval(CI):0.672-1.804,log rank P=0.701].The mOS was worse for patients with OB after treatment(OBAT)than for those without OBAT(11.4 months vs 23.7 months,HR=1.787,95%CI:1.006-3.175,log rank P=0.044).CONCLUSION The mOS for GC/GEJC patients with OBBT was similar to that for those without OBBT,but the mOS for patients with OBAT was worse than that for those without OBAT.
基金the National Key Research and Development Program of China(No.2017YFC1308900)。
文摘Despite the application of conventional therapies,the prognosis of advanced gastric cancer(GC)or gastroesophageal junction cancer(GEJC)is still poor.In recent years,immune checkpoint inhibitors(ICIs)have reshaped the paradigm of cancer therapy.Emerging evidence support the feasibility of programmed cell death-1(PD-1)and its ligand(PD-L1)inhibition in chemo-refractory GC/GEJC.Nivolumab and pembrolizumab have initially been approved in Japan and United States,respectively for the third-line treatment of progressive GC or GEJC.In March 2020,nivolumab has also been licensed in China for treating advanced GC/GEJC who received≥2 lines of systemic therapies.Current studies are moving forward to the first-line application or focusing on combination strategies,though data are insufficient and disputable.In this review,we summarize the recently reported and ongoing clinical trials in ICIs for advanced GC/GEJC.Molecular characteristics and clinical implications of different tumor subtypes are also reviewed.We further discuss the safety profile and biomarkers for predicting the response of ICIs,which has guiding values in clinical practice.
基金Beijing Hospitals Authority Ascent Plan,No. DFL20190803Capital Science and Technology Leading Talent Training Project,No. Z191100006119017+1 种基金National Nature and Science Foundation of China,No. 81773778China Postdoctoral Science Foundation,No. 2019M650775。
文摘BACKGROUND Faced with limited and inadequate treatment options for patients with advanced gastric cancer or gastroesophageal junction cancer(GC/GEJC), researchers have turned toward, with the support of promising clinical trials, anti-PD-1/anti-PD-L1 antibody therapy. But there are also different clinical trial results. To better assess its efficacy and safety, we integrated data from 13 eligible studies for a systematic review and meta-analysis.AIM To comprehensively evaluate the efficacy and safety of anti-PD-1/anti-PD-L1 antibody therapy in the treatment of advanced GC/GEJC patients.METHODS PubMed, Web of Science, Cochrane Library,and EMBASE databases were searched to identify eligible articles with outcomes including objective response rate(ORR), disease control rate(DCR), overall survival(OS), progression-free survival(PFS), and adverse events(AEs) of anti-PD-1/anti-PD-L1 antibody therapy.RESULTS Our study encompassed a total of 13 trials totaling 1618 patients. The outcomes showed a pooled ORR and DCR of 15%(95% confidence interval [CI]: 14%-18%) and 40%(95%CI: 33%-46%), respectively. The pooled 6-mo OS and PFS were 54%(95%CI: 45%-64%) and 26%(95%CI: 20%-32%), respectively, and the 12-mo OS and PFS were 42%(95%CI: 21%-62%) and 11%(95%CI: 8%-13%), respectively. In addition, the incidence of any-grade AEs and grade ≥ 3 AEs was 64%(95%CI: 54%-73%) and 18%(95%CI: 16%-20%), respectively. Most importantly, PD-L1 positive patients exhibited a higher ORR rate than PD-L1 negative patients(odds ratio = 2.54, 95%CI: 1.56-4.15).CONCLUSION Anti-PD-1/anti-PD-L1 antibody therapy has shown promising anti-tumor efficacy with manageable AEs in advanced GC/GEJC patients, with PD-L1 overexpressing patients exhibiting a higher ORR. What is more, the clinical efficacy of anti-PD-1/PD-L1 combined with traditional chemotherapy drugs is even better, although the occurrence of AEs still causes considerate concerns.
文摘Gastric and gastroesophageal junction(GEJ)cancers represent an aggressive group of malignancies with poor prognosis even when diagnosed in relatively early stage,with an increasing incidence both in Asia and in Western countries.These cancers are characterized by heterogeneity as a result of different pathogenetic mechanisms as shown in recent molecular analyses.Accordingly,the understanding of phenotypic and genotypic correlations/classifications has been improved.Current therapeutic strategies have also advanced and moved beyond surgical extirpation alone,with the incorporation of other treatment modalities,such as radiation and chemotherapy(including biologics).Chemoradiotherapy has been used as postoperative treatment after suboptimal gastrectomy to ensure local disease control but also improvement in survival.Preoperative chemoradiotherapy/chemotherapy has been employed to increase the chance of a successful R0 resection and pathologic complete response rate,which is associated with improved long-term outcomes.Several studies have defined various chemotherapy regimens to accompany radiation(before and after surgery).Recently,addition of immunotherapy after trimodality of gastroesophageal cancer has produced an advantage in disease-free interval.Targeted agents used in the metastatic setting are being investigated in the early setting with mixed results.The aim of this review is to summarize the existing data on trimodality approaches for gastric and GEJ cancers,highlight the remaining questions and present the current research effort addressing them.
文摘Objective Esophageal and gastric lesions are effectively managed with minimally invasive upper endoscopic procedures such as endoscopic mucosa resection(EMR)and endoscopic submucosal dissection(ESD),offering patients alternatives to invasive interventions.While ESD is well established in Eastern Asia,its adoption in Denmark for superficial esophageal cancer is recent.This study presents real-world data on the feasibility,safety,and hospitalization duration associated with ESD and EMR for esophageal and gastric lesions.Methods A retrospective analysis was conducted on patients who underwent ESD or EMR at a specialized center in Denmark from October 2016 to June 2022.Data on treatment,indication,lesion location,hospitalization duration,procedure duration,specimen size,complications,recurrence,and one-year overall survival were collected.Statistical comparisons utilized the Mann-Whitney U test,independent sample median test,and chi-squared test.Results The study included 130 patients(144 procedures):72 underwent ESD and 58 underwent EMR.Compared with EMR,ESD resulted in greater percentages of en bloc and R0 resections(98.8%vs.64.1%,p<0.001;and 83.9%vs.23.8%,p<0.001),greater complication rates(28.7%vs.3.1%,p<0.001)and longer procedure times(119.5 min vs.37.0 min,p<0.001).The ESD procedure time significantly decreased over time(p=0.01).The local recurrence rates were 14.5%for ESD and 23.8%for EMR(p=0.767).The one-year overall survival rates were similar between the groups(95.8%vs.94.8%,p=0.553).Conclusion Both ESD and EMR are safe and viable for treating esophageal and gastric lesions.ESD offers advantages but requires more time and skill.These findings support the literature,emphasizing the importance of considering patient-specific factors and surgeon proficiency in selecting the appropriate procedure.
基金Supported by Instituto de Salud Carlos III through the project PI17/00837(Co-funded by European Regional Development Fund/European Social Fund"A way to make Europe"/"Investing in your future")
文摘BACKGROUND Faecal immunochemical test(FIT)has been recommended to assess symptomatic patients for colorectal cancer(CRC)detection.Nevertheless,some conditions could theoretically favour blood originating in proximal areas of the gastrointestinal tract passing through the colon unmetabolized.A positive FIT result could be related to other gastrointestinal cancers(GIC).AIM To assess the risk of GIC detection and related death in FIT-positive symptomatic patients(threshold 10μg Hb/g faeces)without CRC.METHODS Post hoc cohort analysis performed within two prospective diagnostic test studies evaluating the diagnostic accuracy of different FIT analytical systems for CRC and significant colonic lesion detection.Ambulatory patients with gastrointestinal symptoms referred consecutively for colonoscopy from primary and secondary healthcare,underwent a quantitative FIT before undergoing a complete colonoscopy.Patients without CRC were divided into two groups(positive and negative FIT)using the threshold of 10μg Hb/g of faeces and data from follow-up were retrieved from electronic medical records of the public hospitals involved in the research.We determined the cumulative risk of GIC,CRC and upper GIC.Hazard rate(HR)was calculated adjusted by age,sex and presence of significant colonic lesion.RESULTS We included 2709 patients without CRC and a complete baseline colonoscopy,730(26.9%)with FIT≥10μgr Hb/gr.During a mean time of 45.5±20.0 mo,a GIC was detected in 57(2.1%)patients:An upper GIC in 35(1.3%)and a CRC in 14(0.5%).Thirty-six patients(1.3%)died due to GIC:22(0.8%)due to an upper GIC and 9(0.3%)due to CRC.FIT-positive subjects showed a higher CRC risk(HR 3.8,95%CI:1.2-11.9)with no differences in GIC(HR 1.5,95%CI:0.8-2.7)or upper GIC risk(HR 1.0,95%CI:0.5-2.2).Patients with a positive FIT had only an increased risk of CRC-related death(HR 10.8,95%CI:2.1-57.1)and GIC-related death(HR 2.2,95%CI:1.1-4.3),with no differences in upper GIC-related death(HR 1.4,95%CI:0.6-3.3).An upper GIC was detected in 22(0.8%)patients during the first year.Two variables were independently associated:anaemia(OR 5.6,95%CI:2.2-13.9)and age≥70 years(OR 2.7,95%CI:1.1-7.0).CONCLUSION Symptomatic patients without CRC have a moderate risk increase in upper GIC,regardless of the FIT result.Patients with a positive FIT have an increased risk of post-colonoscopy CRC.
文摘Management of cancers of the digestive system has progressed rapidly into the molecular era. Despite the significant recent achievements in the diagnosis and treatment of these patients, the number of deaths for these tumors has currently plateaued. Many investigations have assessed the role of HER2 in tumors of the digestive system in both prognostic and therapeutic settings, with heterogeneous results. Novel testing and treatment guidelines are emerging, in particular in gastric and colorectal cancers. However, further advances are needed. In this review we provide a comprehensive overview of the current state-ofknowledge of HER2 alterations in the most common tumors of the digestive system and discuss the operational implications of HER2 testing.
基金Supported by Science and Technology Development Project of the Nanjing City in China,No. ZKX05013,No. ZKX07011a special grant from the Nanjing Drum Tower Hospital in Nan-jing,China
文摘Carcinoma of the gastroesophageal junction(GEJ) is defined as carcinoma that crosses the GEJ line,irrespective of where the tumor epicenter is located.This group of cancer is rare but controversial.Based on study results from the majority of epidemiologic and clinicopathologic investigations carried out in Western countries,this cancer is believed to arise from Barrett's esophagus(BE) and includes both distal esophageal and proximal gastric carcinomas because of similar characteristics in epidemiology,clinicopathology,and molecular pathobiology in relation to BE.As such,the most recent American Joint Committee on Cancer staging manual requires staging all GEJ carcinomas with the rule for esophageal adenocarcinoma(EA).This mandate has been challenged recently by the data from several studies carried out mainly in Chinese patients.The emerging evidence derivedfrom those studies suggests:(1) both BE and EA are uncommon in the Chinese population;(2) almost all GEJ cancers in Chinese arise in the proximal stomach and show the features of proximal gastric cancer,not those of EA;(3) application of the new cancer staging rule to GEJ cancer of Chinese patients cannot stratify patients' prognosis effectively;and(4) prognostic factors of GEJ cancer in Chinese are similar,but not identical,to those of EA.In conclusion,the recent evidence suggests that GEJ cancer in Chinese shows distinct clinicopathologic characteristics that are different from EA.Further investigations in molecular pathology may help illustrate the underlying pathogenesis mechanisms of this cancer in Chinese patients and better manage patients with this fatal disease.
基金funded by the Beijing Hope Run Special Fund of Cancer Foundation of China(No.LC2018L03)National Natural Science Foundation of China(82073352).
文摘Objective:To explore the independent factors associated with the overall survival(OS)after D2/R0 resection and adjuvant chemoradiotherapy(CRT)for stage Ⅲ gastric cancer(GC)and gastroesophageal junction(GEJ)cancer,and establish and validate a nomogram model to predict the OS in this patient population.Methods:A total of 569 stage Ⅲ GC or GEJ cancer patients who underwent D2/R0 resection and adjuvant CRT at our center from January 2013 to May 2018 were retrospectively enrolled in this study.The patients were randomly divided into training and validation cohorts in a 3:1 ratio.In the training cohort,univariate and multivariate analysis were conducted to identify clinical factors associated with OS,and a nomogram model was established on the basis of the independent factors.The concordance index(C-index)and the calibration curve were used to validate the prediction power of the nomogram.Results:Overall,427 and 142 patients were enrolled in the training and validation cohorts,respectively.In the univariate and multivariate analyses,age,Lauren's classification,TNM stage,and administration of adjuvant CRT were independent factors for OS to construct the nomogram.The C-index values were 0.654 and 0.613 in the training and validation cohorts,respectively.The calibration curves were identical to the actual OS.Risk stratification based on the nomogram model showed good risk stratification for OS in both groups.Conclusion:Our study included adjuvant CRT as a predictive factor and established a nomogram model for predicting the OS in patients with stage III GC or GEJ after D2/R0 resection and adjuvant therapy.This nomogram could facilitate more individualized prediction of OS in clinical practice.
基金This post hoc analysis was sponsored by Shanghai Roche Pharmaceuticals Ltd.,China.Shanghai Roche Pharmaceuticals Ltd.,China was involved in the data interpretation and writing of the report.F.Hoffmann-La Roche Ltd.was involved in the study design,data collection,and data analysis
文摘Background:The JACOB trial(NCT01774786)was a double-blinded,placebo-controlled,randomized,multicenter,international,phase III trial evaluating the efficacy and safety of adding pertuzumab to trastuzumab and chemo-therapy in first-line treatment of human epidermal growth factor receptor 2(HER2)-positive metastatic gastric cancer/gastroesophageal junction cancer(GEJC).The aim of this analysis was to investigate efficacy and safety outcomes in the Chinese subpopulation from the JACOB trial.Methods:This post hoc subpopulation analysis included all patients recruited in China's Mainland(n=163;20.9%)between June 2013 and January 2016.The patients were randomly assigned in a 1:1 ratio to receive pertuzumab plus trastuzumab and chemotherapy(pertuzumab group;n=82)or placebo plus trastuzumab and chemotherapy(con-trol group;n=81).Intravenous pertuzumab(840 mg)and trastuzumab(8 mg/kg loading and 6 mg/kg maintenance doses)were given every 3 weeks until disease progression or unacceptable toxicity.Chemotherapy was given as per standard regimens/doses of capecitabine or 5-fluorouracil plus cisplatin.The primary endpoint was overall survival(OS);secondary efficacy endpoints included progression-free survival(PFS),and overall objective response rate(ORR).Results:The median OS was 18.7 months in the pertuzumab group and 16.1 months in the control group(hazard ratio[HR]0.75;95%confidence interval[CI]0.49 to 1.14).The median PFS was 10.5 and 8.6 months in the pertuzumab and control groups,respectively(HR 0.85;95%CI 0.60 to 1.21),and the median ORRs were 68.9%and 55.7%,respectively.The treatment effect in this Chinese subpopulation showed consistency with that in the global ITT population with numerically lower HR for OS and PFS compared with the control group.The safety profiles of the pertuzumab and control groups in this Chinese subpopulation analysis were generally comparable.The most common grade 3-5adverse events were neutropenia,anemia,and leukopenia.However,due to the nature of being a post hoc subgroup analysis,the results presented here are descriptive only and need to be interpreted with caution.Conclusions:OS and PFS were numerically improved by adding pertuzumab to trastuzumab and chemotherapy as first-line treatment in Chinese HER2-positive gastric cancer/GEJC patients,and this regimen demonstrated an acceptable safety profile.
