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
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
HER2 is overexpressed in approximately 10%-20% of gastric and gastroesophageal junction carcinomas. In these types of cancer, accurate assessment of HER2 status is mandatory, for selecting patients who may benefit fro...HER2 is overexpressed in approximately 10%-20% of gastric and gastroesophageal junction carcinomas. In these types of cancer, accurate assessment of HER2 status is mandatory, for selecting patients who may benefit from targeted therapies with anti-HER2 drugs such as Trastuzumab. This manuscript focuses on HER2 in gastric carcinogenesis, on optimal evaluation of HER2 and on the possible causes which may contribute to inaccurate HER2 evaluation. Similarly to breast cancer HER2 evaluation, standardization of HER2 testing in gastric cancer is necessary in diagnostic practice. The three principle aspects which require consideration are:(1) the choice of sample with regards to cancer morphology- intestinal vs diffuse areas;(2) the choice of scoring criteria- use of HER2 scoring criteria specific for gastric cancer; and(3) the choice of HER2 evaluation methods- use of an algorithm in which both immunohistochemistry and in situ hybridization play a role. Problematic issues include:(1) pre-analytic variables with particular emphasis on fixation;(2) recommended methodology for HER2 assessment(immunohistochemistry vs in situ hybridization);(3) HER2 heterogeneity both within the primary tumor and between primary tumor and metastases;(4) reliability of biopsies in HER 2 evaluation; and(5) quantity of sample(FFPE blocks from surgical specimens or endoscopic biopsies) necessary for an adequate assessment.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
Achalasia cardia,the most prevalent primary esophageal motility disorder,is predominantly characterized by symptoms of dysphagia and regurgitation.The principal therapeutic approaches for achalasia encompass pneumatic...Achalasia cardia,the most prevalent primary esophageal motility disorder,is predominantly characterized by symptoms of dysphagia and regurgitation.The principal therapeutic approaches for achalasia encompass pneumatic dilatation(PD),Heller's myotomy,and the more recent per-oral endoscopic myotomy(POEM).POEM has been substantiated as a safe and efficacious modality for the management of achalasia.Although POEM demonstrates superior efficacy compared to PD and an efficacy parallel to Heller's myotomy,the incidence of gastroesophageal reflux disease(GERD)following POEM is notably higher than with the aforementioned techniques.While symptomatic reflux post-POEM is relatively infrequent,the significant occurrence of erosive esophagitis and heightened esophageal acid exposure necessitates vigilant monitoring to preclude long-term GERD-related complications.Contemporary advancements in the field have enhanced our comprehension of the risk factors,diagnostic methodologies,preventative strategies,and therapeutic management of GERD subsequent to POEM.This review focuses on the limitations inherent in the 24-h pH study for evaluating post-POEM reflux,potential modifications in the POEM technique to mitigate GERD risk,and the strategies for managing reflux following POEM.展开更多
Introduction: Gastroesophageal reflux disease (GERD) is a benign and chronic disease that can impair the quality of life. Objective: To study the epidemiological, clinical aspects and factors associated with typical G...Introduction: Gastroesophageal reflux disease (GERD) is a benign and chronic disease that can impair the quality of life. Objective: To study the epidemiological, clinical aspects and factors associated with typical GERD in the general population of Parakou in the Republic of Benin. Methods: This was a descriptive and analytical cross-sectional study with prospective data collection which took place from May 1, 2019 to June 30, 2019. The study population consisted of any subject aged at least 15 years and living in Parakou. Subjects aged at least 15 years, present on the day of the survey and having given their free and informed verbal consent were included. The Short form of QRS®(Reflux-Qual Short form) questionnaire and the “Hospital Anxiety and Depression” score were used to assess the quality of life and anxiety/depression, respectively. The sampling was probabilistic through a 2-stage cluster sampling. The variable of interest was the presence of GERD. Results: Out of 390 subjects surveyed, 28 had symptoms of typical GERD, representing a prevalence of 7.18%. The average age of these subjects was 27.11 ± 7.88 years. Fifteen subjects (53.57%) were male, giving a sex ratio of 1.15. Fourteen (50%) had a secondary level of education, 12 (42.86%) were pupils/students, 18 (64.29%) were single. The monthly income of 22 subjects (78.57%) was lower than the guaranteed interprofessional minimum wage (40,000 FCFA). The average duration of progression of symptoms was 15.89 ± 4.97 months. Symptoms occurred less than twice a week in 22 subjects (78.57%). The clinical manifestations were both diurnal and nocturnal in 12 subjects (42.86%). None of the 28 subjects with GERD had clinical warning signs. Asthma, diabetes, consumption of high fat or spice foods, carbonated drinks, non-steroidal anti-inflammatory drugs, alcoholic beverages and tobacco were statistically associated with the occurrence of GERD. Each of the 28 subjects had at least one associated factor. A significant impair in quality of life was observed in 27 patients (96.43%). Conclusion: Typical GERD is relatively common in the general population of Parakou in the Republic of Benin. It often affects young males. Among the risk factors identified, the most common are carbonated drinks, spicy meals and diabetes. GERD significantly impairs quality of life. Raising awareness about the disease and its associated factors is necessary among the general population.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
BACKGROUND Early adenocarcinoma mixed with a neuroendocrine carcinoma(NEC)component arising in the gastroesophageal junctional(GEJ)region is rare and even rarer in young patients.Here,we report such a case in a 29-yea...BACKGROUND Early adenocarcinoma mixed with a neuroendocrine carcinoma(NEC)component arising in the gastroesophageal junctional(GEJ)region is rare and even rarer in young patients.Here,we report such a case in a 29-year-old Chinese man.CASE SUMMARY This patient presented to our hospital with a 3-mo history of dysphagia and regurgitation.Upper endoscopy revealed an elevated nodule in the distal esophagus 1.6 cm above the GEJ line,without Barrett’s esophagus or involvement of the gastric cardia.The nodule was completely resected by endoscopic submu-cosal dissection(ESD).Pathological examination confirmed diagnosis of intra-mucosal adenocarcinoma mixed with an NEC component,measuring 1.5 cm.Immunohistochemically,both adenocarcinoma and NEC components were positive for P53 with a Ki67 index of 90%;NEC was positive for synaptophysin and chromogranin.Next-generation sequencing of 196 genes demonstrated a novel germline mutation of the ERCC3 gene in the DNA repair pathway and a germline mutation of the RNF43 gene,a common gastric cancer driver gene,in addition to pathogenic somatic mutations in P53 and CHEK2 genes.The patient was alive without evidence of the disease 36 mo after ESD.CONCLUSION Early adenocarcinoma with an NEC component arising in the distal esophageal side of the GEJ region showed evidence of gastric origin.展开更多
BACKGROUND Clinical studies have reported that patients with gastroesophageal reflux disease(GERD)have a higher prevalence of hypertension.AIM To performed a bidirectional Mendelian randomization(MR)analysis to invest...BACKGROUND Clinical studies have reported that patients with gastroesophageal reflux disease(GERD)have a higher prevalence of hypertension.AIM To performed a bidirectional Mendelian randomization(MR)analysis to investi-gate the causal link between GERD and essential hypertension.METHODS Eligible single nucleotide polymorphisms(SNPs)were selected,and weighted median,inverse variance weighted(IVW)as well as MR egger(MR-Egger)re-gression were used to examine the potential causal association between GERD and hypertension.The MR-Pleiotropy RESidual Sum and Outlier analysis was used to detect and attempt to reduce horizontal pleiotropy by removing outliers SNPs.The MR-Egger intercept test,Cochran’s Q test and“leave-one-out”sen-sitivity analysis were performed to evaluate the horizontal pleiotropy,heterogen-eities,and stability of single instrumental variable.RESULTS IVW analysis exhibited an increased risk of hypertension(OR=1.46,95%CI:1.33-1.59,P=2.14E-16)in GERD patients.And the same result was obtained in replication practice(OR=1.002,95%CI:1.0008-1.003,P=0.000498).Meanwhile,the IVW analysis showed an increased risk of systolic blood pressure(β=0.78,95%CI:0.11-1.44,P=0.021)and hypertensive heart disease(OR=1.68,95%CI:1.36-2.08,P=0.0000016)in GERD patients.Moreover,we found an decreased risk of Barrett's esophagus(OR=0.91,95%CI:0.83-0.99,P=0.043)in essential hypertension patients.CONCLUSION We found that GERD would increase the risk of essential hypertension,which provided a novel prevent and therapeutic perspectives of essential hypertension.展开更多
This editorial describes the contemporary concepts of prevention and management of gastroesophageal variceal bleeding in liver cirrhosis(LC)patients according to the current guidelines.Gastroesophageal variceal bleedi...This editorial describes the contemporary concepts of prevention and management of gastroesophageal variceal bleeding in liver cirrhosis(LC)patients according to the current guidelines.Gastroesophageal variceal bleeding is the most dangerous complication of portal hypertension in LC patients.Risk stratification and determination of an individual approach to the choice of therapeutic measures aimed at their prevention and management has emerged as one of the top concerns in modern hepatology.According to the current guidelines,in the absence of clinically significant portal hypertension,etiological and nonetiological therapies of LC is advisable for the primary preventing gastroesophageal variceal bleeding,whereas its presence serves as an indication for the administration of non-selectiveβ-blockers,among which carvedilol is the drug of choice.Non-selectiveβ-blockers,as well as endoscopic variceal ligation and transjugular intrahepatic portosystemic shunt can be used to prevent recurrence of gastroesophageal variceal bleeding.Pharmacotherapy with vasoactive drugs(terlipressin,somatostatin,octreotide),endoscopic variceal ligation,endovascular techniques and transjugular intrahepatic portosystemic shunt are recommended for the treatment of acute gastroesophageal variceal bleeding.Objective and accurate risk stratification of gastroesophageal variceal bleeding will allow developing individual strategies for their prevention and management,avoiding the first and further decompensation in LC,which will improve the prognosis and survival of patients suffering from it.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
BACKGROUND Heartburn is identically the key symptom of both,gastroesophageal reflux disease(GERD)and functional heartburn(FHB),making the differential diagnosis resource-intensive.Oral manifestations of GERD can be ea...BACKGROUND Heartburn is identically the key symptom of both,gastroesophageal reflux disease(GERD)and functional heartburn(FHB),making the differential diagnosis resource-intensive.Oral manifestations of GERD can be easily examined;therefore,their exploration might be a cheap,widely available,and useful tool in the differentiation of GERD and FHB.AIM To evaluate the prevalence of dental erosions(DE)and periodontal diseases(PD)in patients with heartburn and their association with GERD and FHB.METHODS A total of 116[M/F:51/65,mean age:54(17-80)years]consecutive patients with heartburn were enrolled for detailed esophageal function and orodental examinations.RESULTS Dental disorders were detected in 89%(103/116).Patients with PD+DE had significantly more often pathologic reflux(90.0%vs 27.8%;P<0.05),higher esophagitis scores(1.8 vs 0.9;P<0.05),and a significantly different mean impedance curve(P=0.04)than those without any dental diseases.The opposite approach established that patients with GERD had significantly higher prevalence of DE and PD,especially if both were present(28.9%vs 2.0%;P<0.01),more severe PD(1.5 vs 1.0;P<0.01),and longer history of heartburn(15 years vs 9 years;P<0.01)than those with FHB.CONCLUSION The dental evaluation of patients with heartburn seems to be useful in the differential diagnosis of GERD and FHB.Among the studied parameters,the co-appearance of DE and PD seems to be the best predictor of GERD,whereas the absence of dental disorders was mostly observed in FHB.展开更多
Rifaximin in the Treatment of Gastroesophageal Reflux Disease (GERD) is a common clinical disorder, the most common symptom of which is a burning sensation behind the breastbone (heartburn) or reflux of stomach conten...Rifaximin in the Treatment of Gastroesophageal Reflux Disease (GERD) is a common clinical disorder, the most common symptom of which is a burning sensation behind the breastbone (heartburn) or reflux of stomach contents into the upper pharynx (acid reflux). The prevalence in China is increasing year by year, which can affect the quality of life of patients and also increase the economic burden on families and society. The pathogenesis of GERD is still unclear, and some studies suggest that intestinal microecology may be closely related to the development of GERD. Rifaximin is not readily absorbed orally and acts locally in the intestine, so it has mild adverse effects and good safety, and can be used to treat gastrointestinal diseases such as irritable bowel syndrome, traveler’s diarrhea, small intestinal bacterial overgrowth, diverticulosis, inflammatory bowel disease and hepatic encephalopathy. Therefore, this paper focuses on intestinal microecology as a possible pathogenesis of GERD and further explores the feasibility of rifaximin for the treatment of GERD.展开更多
Gastroesophageal reflux(GER)in children is very common and refers to the involuntary passage of gastric contents into the esophagus.This is often physiological and managed conservatively.In contrast,GER disease(GERD)i...Gastroesophageal reflux(GER)in children is very common and refers to the involuntary passage of gastric contents into the esophagus.This is often physiological and managed conservatively.In contrast,GER disease(GERD)is a less common pathologic process causing troublesome symptoms,which may need medical management.Apart from abnormal transient relaxations of the lower esophageal sphincter,other factors that play a role in the pathogenesis of GERD include defects in esophageal mucosal defense,impaired esophageal and gastric motility and clearance,as well as anatomical defects of the lower esophageal reflux barrier such as hiatal hernia.The clinical manifestations of GERD in young children are varied and nonspecific prompting the necessity for careful diagnostic evaluation.Management should be targeted to the underlying aetiopathogenesis and to limit complications of GERD.The following review focuses on up-to-date information regarding of the pathogenesis,diagnostic evaluation and management of GERD in children.展开更多
BACKGROUND Triplet chemotherapy,with docetaxel-5FU-oxaliplatin FLOT regimen recently became the standard perioperative treatment for localized gastric cancer(GC).An adapted regimen called TeFOX was recently tested in ...BACKGROUND Triplet chemotherapy,with docetaxel-5FU-oxaliplatin FLOT regimen recently became the standard perioperative treatment for localized gastric cancer(GC).An adapted regimen called TeFOX was recently tested in metastatic setting and gave promising results.AIM To determine safety and efficacy of TeFOX perioperative regimen.METHODS This monocentric retrospective study aims to test efficacy and safety of the perioperative TeFOX regimen given alone or in combination with trastuzumab in patients with localized GC.TeFOX consist in docetaxel(50 mg/m^2)with oxaliplatin 85 mg/m^2 and and leucovorin(400mg/m^2^)5 FU bolus(400mg/m^2)on day 1,followed by continuous infusion of 5FU for 46h(2400mg/m^2)every 2 wk.RESULTS Thirty-three consecutive patients were included in this retrospective study.Eighteen patients have a gastroesophageal junction cancer and 11 have a GC.Median follow-up of surviving patients was 32 mo.R0 resection was obtained in 30(91)patients.Twelve patients(36)had a pathological complete response and 8(24)patients a nearly complete pathological response.Median OS and PFS were not reached at data base lock.We have observed 6 metastatic relapses and 1 localized relapse.No relapse was observed in patients with pathological complete responses.The most common grade 3-4 adverse events were peripheral neuropathy(21)and asthenia(20).CONCLUSION TeFOX regimen could be safely administrated in perioperative treatment of localized GC.TeFOX and the FLOT regimen have comparable efficacy and safety profiles.展开更多
BACKGROUND Gastroesophageal reflux disease(GERD)affects approximately 13% of the global population.However,the pathogenesis of GERD has not been fully elucidated.The development of metabolomics as a branch of systems ...BACKGROUND Gastroesophageal reflux disease(GERD)affects approximately 13% of the global population.However,the pathogenesis of GERD has not been fully elucidated.The development of metabolomics as a branch of systems biology in recent years has opened up new avenues for the investigation of disease processes.As a powerful statistical tool,Mendelian randomization(MR)is widely used to explore the causal relationship between exposure and outcome.AIM To analyze of the relationship between 486 blood metabolites and GERD.METHODS Two-sample MR analysis was used to assess the causal relationship between blood metabolites and GERD.A genome-wide association study(GWAS)of 486 metabolites was the exposure,and two different GWAS datasets of GERD were used as endpoints for the base analysis and replication and meta-analysis.Bonferroni correction is used to determine causal correlation features(P<1.03×10^(-4)).The results were subjected to sensitivity analysis to assess heterogeneity and pleiotropy.Using the MR Steiger filtration method to detect whether there is a reverse causal relationship between metabolites and GERD.In addition,metabolic pathway analysis was conducted using the online database based MetaboAnalyst 5.0 software.RESULTS In MR analysis,four blood metabolites are negatively correlated with GERD:Levulinate(4-oxovalerate),stearate(18:0),adrenate(22:4n6)and p-acetamidophenylglucuronide.However,we also found a positive correlation between four blood metabolites and GERD:Kynurenine,1-linoleoylglycerophosphoethanolamine,butyrylcarnitine and guanosine.And bonferroni correction showed that butyrylcarnitine(odd ratio 1.10,95% confidence interval:1.05-1.16,P=7.71×10^(-5))was the most reliable causal metabolite.In addition,one significant pathways,the"glycerophospholipid metabolism"pathway,can be involved in the pathogenesis of GERD.CONCLUSION Our study found through the integration of genomics and metabolomics that butyrylcarnitine may be a potential biomarker for GERD,which will help further elucidate the pathogenesis of GERD and better guide its treatment.At the same time,this also contributes to early screening and prevention of GERD.However,the results of this study require further confirmation from both basic and clinical real-world studies.展开更多
BACKGROUND Gastroesophageal reflux is associated with poorer outcomes after lung transplant,likely through recurrent aspiration and allograft injury.Although prior studies have demonstrated a relationship between impe...BACKGROUND Gastroesophageal reflux is associated with poorer outcomes after lung transplant,likely through recurrent aspiration and allograft injury.Although prior studies have demonstrated a relationship between impedance-pH results and transplant outcomes,the role of esophageal manometry in the assessment of lung transplant patients remains debated,and the impact of esophageal dysmotility on transplant outcomes is unclear.Of particular interest is ineffective esophageal motility(IEM)and its associated impact on esophageal clearance.AIM To assess the relationship between pre-transplant IEM diagnosis and acute rejection after lung transplantation.METHODS This was a retrospective cohort study of lung transplant recipients at a tertiary care center between 2007 and 2018.Patients with pre-transplant anti-reflux surgery were excluded.Manometric and reflux diagnoses were recorded from pre-transplant esophageal function testing.Time-to-event analysis using Cox proportional hazards model was applied to evaluate outcome of first episode of acute cellular rejection,defined histologically per International Society of Heart and Lung Transplantation guidelines.Subjects not meeting this endpoint were censored at time of post-transplant anti-reflux surgery,last clinic visit,or death.Fisher’s exact test for binary variables and student’s t-test for continuous variables were performed to assess for differences between groups.RESULTS Of 184 subjects(54%men,mean age:58,follow-up:443 person-years)met criteria for inclusion.Interstitial pulmonary fibrosis represented the predominant pulmonary diagnosis(41%).During the follow-up period,60 subjects(33.5%)developed acute rejection.The all-cause mortality was 16.3%.Time-to-event univariate analyses demonstrated significant association between IEM and acute rejection[hazard ratio(HR):1.984,95%CI:1.03-3.30,P=0.04],confirmed on Kaplan-Meier curve.On multivariable analysis,IEM remained independently associated with acute rejection,even after controlling for potential confounders such as the presence of acid and nonacid reflux(HR:2.20,95%CI:1.18-4.11,P=0.01).Nonacid reflux was also independently associated with acute rejection on both univariate(HR:2.16,95%CI:1.26-3.72,P=0.005)and multivariable analyses(HR:2.10,95%CI:1.21-3.64,P=0.009),adjusting for the presence of IEM.CONCLUSION Pre-transplant IEM was associated with acute rejection after transplantation,even after controlling for acid and nonacid reflux.Esophageal motility testing may be considered in lung transplant to predict outcomes.展开更多
BACKGROUND A limited number of studies have demonstrated that sleeping in the left lateral decubitus(LLD)decreases nocturnal reflux in patients with gastroesophageal reflux disease(GERD)compared to right lateral decub...BACKGROUND A limited number of studies have demonstrated that sleeping in the left lateral decubitus(LLD)decreases nocturnal reflux in patients with gastroesophageal reflux disease(GERD)compared to right lateral decubitus(RLD)and supine.AIM This systematic review summarizes the association between sleeping in the LLD position and nocturnal reflux in patients with GERD.METHODS Studies published up to July 17,2023,in MEDLINE,EMBASE,and CENTRAL were searched.Eligible studies were randomized and nonrandomized studies assessing the effect of sleeping in LLD compared to RLD and supine in reducing nocturnal reflux in GERD patients.Outcomes include the acid exposure time(AET)(%time in pH<4),acid clearance time(ACT)(in sec/episode),number of reflux episodes,and improvement in N-GSSIQ scores.RESULTS Two nonrandomized studies showed decreased AET and ACT in LLD sleep position in comparison to RLD(mean difference[MD]-2.03[95%CI:-3.62 to-0.45];-81.84[95%CI:-127.48 to-36.20],respectively)and supine position(MD-2.71[95%CI:-4.34 to-1.09];-74.47[95%CI:-116.26 to-32.69],respectively).There was no difference in AET and ACT between RLD sleep position and supine.Furthermore,one randomized controlled trial investigating the use of electronic sleep positional therapy,which increased the duration of LLD sleep and decreased the duration of RLD sleep compared to sham,showed nocturnal symptoms improvement(improved N-GSSIQ score,increased reflux-free nights,and resolution of nocturnal reflux symptoms).CONCLUSION Current evidence suggests that sleeping on the left side could reduce nocturnal reflux and improve GERD-related quality of life,therefore warranting interventions that promote LLD sleep position.展开更多
BACKGROUND Gastroesophageal reflux(GER)has been associated with poor outcomes after lung transplantation for chronic lung disease,including increased risk of chronic rejection.GER is common in cystic fibrosis(CF),but ...BACKGROUND Gastroesophageal reflux(GER)has been associated with poor outcomes after lung transplantation for chronic lung disease,including increased risk of chronic rejection.GER is common in cystic fibrosis(CF),but factors influencing the likelihood of pre-transplant pH testing,and the impact of testing on clinical management and transplant outcomes in patients with CF are unknown.AIM To evaluate the role of pre-transplant reflux testing in the evaluation of lung transplant candidates with CF.METHODS This was a retrospective study from 2007-2019 at a tertiary medical center that included all patients with CF undergoing lung transplant.Patients with pretransplant anti-reflux surgery were excluded.Baseline characteristics(age at transplantation,gender,race,body mass index),self-reported GER symptoms prior to transplantation,and pre-transplant cardiopulmonary testing results,were recorded.Reflux testing consisted of either 24-h pH-or combined multichannel intraluminal impedance and pH monitoring.Post-transplant care included a standard immunosuppressive regimen,and regular surveillance bronchoscopy and pulmonary spirometry in accordance with institutional practice as well as in symptomatic patients.The primary outcome of chronic lung allograft dysfunction(CLAD)was defined clinically and histologically per International Society of Heart and Lung Transplantation criteria.Statistical analysis was performed with Fisher’s exact test to assess differences between cohorts,and time-to-event Cox proportional hazards modeling.RESULTS After applying inclusion and exclusion criteria,a total of 60 patients were included in the study.Among all CF patients,41(68.3%)completed reflux monitoring as part of pre-lung transplant evaluation.Objective evidence of pathologic reflux,defined as acid exposure time>4%,was found in 24 subjects,representing 58%of the tested group.CF patients with pre-transplant reflux testing were older(35.8 vs 30.1 years,P=0.01)and more commonly reported typical esophageal reflux symptoms(53.7%vs 26.3%,P=0.06)compared to those without reflux testing.Other patient demographics and baseline cardiopulmonary function did not significantly differ between CF subjects with and without pre-transplant reflux testing.Patients with CF were less likely to undergo pre-transplant reflux testing compared to other pulmonary diagnoses(68%vs 85%,P=0.003).There was a decreased risk of CLAD in patients with CF who underwent reflux testing compared to those who did not,after controlling for confounders(Cox Hazard Ratio 0.26;95%CI:0.08-0.92).CONCLUSION Pre-transplant reflux testing revealed high prevalence of pathologic reflux in CF patients and was associated with decreased risk of CLAD.Systematic reflux testing may enhance outcomes in this patient population.展开更多
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HER2 is overexpressed in approximately 10%-20% of gastric and gastroesophageal junction carcinomas. In these types of cancer, accurate assessment of HER2 status is mandatory, for selecting patients who may benefit from targeted therapies with anti-HER2 drugs such as Trastuzumab. This manuscript focuses on HER2 in gastric carcinogenesis, on optimal evaluation of HER2 and on the possible causes which may contribute to inaccurate HER2 evaluation. Similarly to breast cancer HER2 evaluation, standardization of HER2 testing in gastric cancer is necessary in diagnostic practice. The three principle aspects which require consideration are:(1) the choice of sample with regards to cancer morphology- intestinal vs diffuse areas;(2) the choice of scoring criteria- use of HER2 scoring criteria specific for gastric cancer; and(3) the choice of HER2 evaluation methods- use of an algorithm in which both immunohistochemistry and in situ hybridization play a role. Problematic issues include:(1) pre-analytic variables with particular emphasis on fixation;(2) recommended methodology for HER2 assessment(immunohistochemistry vs in situ hybridization);(3) HER2 heterogeneity both within the primary tumor and between primary tumor and metastases;(4) reliability of biopsies in HER 2 evaluation; and(5) quantity of sample(FFPE blocks from surgical specimens or endoscopic biopsies) necessary for an adequate assessment.
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.
文摘Achalasia cardia,the most prevalent primary esophageal motility disorder,is predominantly characterized by symptoms of dysphagia and regurgitation.The principal therapeutic approaches for achalasia encompass pneumatic dilatation(PD),Heller's myotomy,and the more recent per-oral endoscopic myotomy(POEM).POEM has been substantiated as a safe and efficacious modality for the management of achalasia.Although POEM demonstrates superior efficacy compared to PD and an efficacy parallel to Heller's myotomy,the incidence of gastroesophageal reflux disease(GERD)following POEM is notably higher than with the aforementioned techniques.While symptomatic reflux post-POEM is relatively infrequent,the significant occurrence of erosive esophagitis and heightened esophageal acid exposure necessitates vigilant monitoring to preclude long-term GERD-related complications.Contemporary advancements in the field have enhanced our comprehension of the risk factors,diagnostic methodologies,preventative strategies,and therapeutic management of GERD subsequent to POEM.This review focuses on the limitations inherent in the 24-h pH study for evaluating post-POEM reflux,potential modifications in the POEM technique to mitigate GERD risk,and the strategies for managing reflux following POEM.
文摘Introduction: Gastroesophageal reflux disease (GERD) is a benign and chronic disease that can impair the quality of life. Objective: To study the epidemiological, clinical aspects and factors associated with typical GERD in the general population of Parakou in the Republic of Benin. Methods: This was a descriptive and analytical cross-sectional study with prospective data collection which took place from May 1, 2019 to June 30, 2019. The study population consisted of any subject aged at least 15 years and living in Parakou. Subjects aged at least 15 years, present on the day of the survey and having given their free and informed verbal consent were included. The Short form of QRS®(Reflux-Qual Short form) questionnaire and the “Hospital Anxiety and Depression” score were used to assess the quality of life and anxiety/depression, respectively. The sampling was probabilistic through a 2-stage cluster sampling. The variable of interest was the presence of GERD. Results: Out of 390 subjects surveyed, 28 had symptoms of typical GERD, representing a prevalence of 7.18%. The average age of these subjects was 27.11 ± 7.88 years. Fifteen subjects (53.57%) were male, giving a sex ratio of 1.15. Fourteen (50%) had a secondary level of education, 12 (42.86%) were pupils/students, 18 (64.29%) were single. The monthly income of 22 subjects (78.57%) was lower than the guaranteed interprofessional minimum wage (40,000 FCFA). The average duration of progression of symptoms was 15.89 ± 4.97 months. Symptoms occurred less than twice a week in 22 subjects (78.57%). The clinical manifestations were both diurnal and nocturnal in 12 subjects (42.86%). None of the 28 subjects with GERD had clinical warning signs. Asthma, diabetes, consumption of high fat or spice foods, carbonated drinks, non-steroidal anti-inflammatory drugs, alcoholic beverages and tobacco were statistically associated with the occurrence of GERD. Each of the 28 subjects had at least one associated factor. A significant impair in quality of life was observed in 27 patients (96.43%). Conclusion: Typical GERD is relatively common in the general population of Parakou in the Republic of Benin. It often affects young males. Among the risk factors identified, the most common are carbonated drinks, spicy meals and diabetes. GERD significantly impairs quality of life. Raising awareness about the disease and its associated factors is necessary among the general population.
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Changzhou High-level Medical Talents Training Project of the Health Commission of the Changzhou City,No.2022CZBJ079Changzhou Sci&Tech Program,No.CE20235064.
文摘BACKGROUND Early adenocarcinoma mixed with a neuroendocrine carcinoma(NEC)component arising in the gastroesophageal junctional(GEJ)region is rare and even rarer in young patients.Here,we report such a case in a 29-year-old Chinese man.CASE SUMMARY This patient presented to our hospital with a 3-mo history of dysphagia and regurgitation.Upper endoscopy revealed an elevated nodule in the distal esophagus 1.6 cm above the GEJ line,without Barrett’s esophagus or involvement of the gastric cardia.The nodule was completely resected by endoscopic submu-cosal dissection(ESD).Pathological examination confirmed diagnosis of intra-mucosal adenocarcinoma mixed with an NEC component,measuring 1.5 cm.Immunohistochemically,both adenocarcinoma and NEC components were positive for P53 with a Ki67 index of 90%;NEC was positive for synaptophysin and chromogranin.Next-generation sequencing of 196 genes demonstrated a novel germline mutation of the ERCC3 gene in the DNA repair pathway and a germline mutation of the RNF43 gene,a common gastric cancer driver gene,in addition to pathogenic somatic mutations in P53 and CHEK2 genes.The patient was alive without evidence of the disease 36 mo after ESD.CONCLUSION Early adenocarcinoma with an NEC component arising in the distal esophageal side of the GEJ region showed evidence of gastric origin.
基金Supported by National Natural Science Foundation of China(General Program),No.82070631.
文摘BACKGROUND Clinical studies have reported that patients with gastroesophageal reflux disease(GERD)have a higher prevalence of hypertension.AIM To performed a bidirectional Mendelian randomization(MR)analysis to investi-gate the causal link between GERD and essential hypertension.METHODS Eligible single nucleotide polymorphisms(SNPs)were selected,and weighted median,inverse variance weighted(IVW)as well as MR egger(MR-Egger)re-gression were used to examine the potential causal association between GERD and hypertension.The MR-Pleiotropy RESidual Sum and Outlier analysis was used to detect and attempt to reduce horizontal pleiotropy by removing outliers SNPs.The MR-Egger intercept test,Cochran’s Q test and“leave-one-out”sen-sitivity analysis were performed to evaluate the horizontal pleiotropy,heterogen-eities,and stability of single instrumental variable.RESULTS IVW analysis exhibited an increased risk of hypertension(OR=1.46,95%CI:1.33-1.59,P=2.14E-16)in GERD patients.And the same result was obtained in replication practice(OR=1.002,95%CI:1.0008-1.003,P=0.000498).Meanwhile,the IVW analysis showed an increased risk of systolic blood pressure(β=0.78,95%CI:0.11-1.44,P=0.021)and hypertensive heart disease(OR=1.68,95%CI:1.36-2.08,P=0.0000016)in GERD patients.Moreover,we found an decreased risk of Barrett's esophagus(OR=0.91,95%CI:0.83-0.99,P=0.043)in essential hypertension patients.CONCLUSION We found that GERD would increase the risk of essential hypertension,which provided a novel prevent and therapeutic perspectives of essential hypertension.
文摘This editorial describes the contemporary concepts of prevention and management of gastroesophageal variceal bleeding in liver cirrhosis(LC)patients according to the current guidelines.Gastroesophageal variceal bleeding is the most dangerous complication of portal hypertension in LC patients.Risk stratification and determination of an individual approach to the choice of therapeutic measures aimed at their prevention and management has emerged as one of the top concerns in modern hepatology.According to the current guidelines,in the absence of clinically significant portal hypertension,etiological and nonetiological therapies of LC is advisable for the primary preventing gastroesophageal variceal bleeding,whereas its presence serves as an indication for the administration of non-selectiveβ-blockers,among which carvedilol is the drug of choice.Non-selectiveβ-blockers,as well as endoscopic variceal ligation and transjugular intrahepatic portosystemic shunt can be used to prevent recurrence of gastroesophageal variceal bleeding.Pharmacotherapy with vasoactive drugs(terlipressin,somatostatin,octreotide),endoscopic variceal ligation,endovascular techniques and transjugular intrahepatic portosystemic shunt are recommended for the treatment of acute gastroesophageal variceal bleeding.Objective and accurate risk stratification of gastroesophageal variceal bleeding will allow developing individual strategies for their prevention and management,avoiding the first and further decompensation in LC,which will improve the prognosis and survival of patients suffering from it.
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.
基金the University of Szeged Open Access Fund,No.6373.
文摘BACKGROUND Heartburn is identically the key symptom of both,gastroesophageal reflux disease(GERD)and functional heartburn(FHB),making the differential diagnosis resource-intensive.Oral manifestations of GERD can be easily examined;therefore,their exploration might be a cheap,widely available,and useful tool in the differentiation of GERD and FHB.AIM To evaluate the prevalence of dental erosions(DE)and periodontal diseases(PD)in patients with heartburn and their association with GERD and FHB.METHODS A total of 116[M/F:51/65,mean age:54(17-80)years]consecutive patients with heartburn were enrolled for detailed esophageal function and orodental examinations.RESULTS Dental disorders were detected in 89%(103/116).Patients with PD+DE had significantly more often pathologic reflux(90.0%vs 27.8%;P<0.05),higher esophagitis scores(1.8 vs 0.9;P<0.05),and a significantly different mean impedance curve(P=0.04)than those without any dental diseases.The opposite approach established that patients with GERD had significantly higher prevalence of DE and PD,especially if both were present(28.9%vs 2.0%;P<0.01),more severe PD(1.5 vs 1.0;P<0.01),and longer history of heartburn(15 years vs 9 years;P<0.01)than those with FHB.CONCLUSION The dental evaluation of patients with heartburn seems to be useful in the differential diagnosis of GERD and FHB.Among the studied parameters,the co-appearance of DE and PD seems to be the best predictor of GERD,whereas the absence of dental disorders was mostly observed in FHB.
文摘Rifaximin in the Treatment of Gastroesophageal Reflux Disease (GERD) is a common clinical disorder, the most common symptom of which is a burning sensation behind the breastbone (heartburn) or reflux of stomach contents into the upper pharynx (acid reflux). The prevalence in China is increasing year by year, which can affect the quality of life of patients and also increase the economic burden on families and society. The pathogenesis of GERD is still unclear, and some studies suggest that intestinal microecology may be closely related to the development of GERD. Rifaximin is not readily absorbed orally and acts locally in the intestine, so it has mild adverse effects and good safety, and can be used to treat gastrointestinal diseases such as irritable bowel syndrome, traveler’s diarrhea, small intestinal bacterial overgrowth, diverticulosis, inflammatory bowel disease and hepatic encephalopathy. Therefore, this paper focuses on intestinal microecology as a possible pathogenesis of GERD and further explores the feasibility of rifaximin for the treatment of GERD.
基金Supported by the Research Grant Contract Allocated for Basic Research from the Chulalongkorn University,No.HEA663000047.
文摘Gastroesophageal reflux(GER)in children is very common and refers to the involuntary passage of gastric contents into the esophagus.This is often physiological and managed conservatively.In contrast,GER disease(GERD)is a less common pathologic process causing troublesome symptoms,which may need medical management.Apart from abnormal transient relaxations of the lower esophageal sphincter,other factors that play a role in the pathogenesis of GERD include defects in esophageal mucosal defense,impaired esophageal and gastric motility and clearance,as well as anatomical defects of the lower esophageal reflux barrier such as hiatal hernia.The clinical manifestations of GERD in young children are varied and nonspecific prompting the necessity for careful diagnostic evaluation.Management should be targeted to the underlying aetiopathogenesis and to limit complications of GERD.The following review focuses on up-to-date information regarding of the pathogenesis,diagnostic evaluation and management of GERD in children.
文摘BACKGROUND Triplet chemotherapy,with docetaxel-5FU-oxaliplatin FLOT regimen recently became the standard perioperative treatment for localized gastric cancer(GC).An adapted regimen called TeFOX was recently tested in metastatic setting and gave promising results.AIM To determine safety and efficacy of TeFOX perioperative regimen.METHODS This monocentric retrospective study aims to test efficacy and safety of the perioperative TeFOX regimen given alone or in combination with trastuzumab in patients with localized GC.TeFOX consist in docetaxel(50 mg/m^2)with oxaliplatin 85 mg/m^2 and and leucovorin(400mg/m^2^)5 FU bolus(400mg/m^2)on day 1,followed by continuous infusion of 5FU for 46h(2400mg/m^2)every 2 wk.RESULTS Thirty-three consecutive patients were included in this retrospective study.Eighteen patients have a gastroesophageal junction cancer and 11 have a GC.Median follow-up of surviving patients was 32 mo.R0 resection was obtained in 30(91)patients.Twelve patients(36)had a pathological complete response and 8(24)patients a nearly complete pathological response.Median OS and PFS were not reached at data base lock.We have observed 6 metastatic relapses and 1 localized relapse.No relapse was observed in patients with pathological complete responses.The most common grade 3-4 adverse events were peripheral neuropathy(21)and asthenia(20).CONCLUSION TeFOX regimen could be safely administrated in perioperative treatment of localized GC.TeFOX and the FLOT regimen have comparable efficacy and safety profiles.
基金Supported by National Natural Science Foundation of China,No.82174363.
文摘BACKGROUND Gastroesophageal reflux disease(GERD)affects approximately 13% of the global population.However,the pathogenesis of GERD has not been fully elucidated.The development of metabolomics as a branch of systems biology in recent years has opened up new avenues for the investigation of disease processes.As a powerful statistical tool,Mendelian randomization(MR)is widely used to explore the causal relationship between exposure and outcome.AIM To analyze of the relationship between 486 blood metabolites and GERD.METHODS Two-sample MR analysis was used to assess the causal relationship between blood metabolites and GERD.A genome-wide association study(GWAS)of 486 metabolites was the exposure,and two different GWAS datasets of GERD were used as endpoints for the base analysis and replication and meta-analysis.Bonferroni correction is used to determine causal correlation features(P<1.03×10^(-4)).The results were subjected to sensitivity analysis to assess heterogeneity and pleiotropy.Using the MR Steiger filtration method to detect whether there is a reverse causal relationship between metabolites and GERD.In addition,metabolic pathway analysis was conducted using the online database based MetaboAnalyst 5.0 software.RESULTS In MR analysis,four blood metabolites are negatively correlated with GERD:Levulinate(4-oxovalerate),stearate(18:0),adrenate(22:4n6)and p-acetamidophenylglucuronide.However,we also found a positive correlation between four blood metabolites and GERD:Kynurenine,1-linoleoylglycerophosphoethanolamine,butyrylcarnitine and guanosine.And bonferroni correction showed that butyrylcarnitine(odd ratio 1.10,95% confidence interval:1.05-1.16,P=7.71×10^(-5))was the most reliable causal metabolite.In addition,one significant pathways,the"glycerophospholipid metabolism"pathway,can be involved in the pathogenesis of GERD.CONCLUSION Our study found through the integration of genomics and metabolomics that butyrylcarnitine may be a potential biomarker for GERD,which will help further elucidate the pathogenesis of GERD and better guide its treatment.At the same time,this also contributes to early screening and prevention of GERD.However,the results of this study require further confirmation from both basic and clinical real-world studies.
文摘BACKGROUND Gastroesophageal reflux is associated with poorer outcomes after lung transplant,likely through recurrent aspiration and allograft injury.Although prior studies have demonstrated a relationship between impedance-pH results and transplant outcomes,the role of esophageal manometry in the assessment of lung transplant patients remains debated,and the impact of esophageal dysmotility on transplant outcomes is unclear.Of particular interest is ineffective esophageal motility(IEM)and its associated impact on esophageal clearance.AIM To assess the relationship between pre-transplant IEM diagnosis and acute rejection after lung transplantation.METHODS This was a retrospective cohort study of lung transplant recipients at a tertiary care center between 2007 and 2018.Patients with pre-transplant anti-reflux surgery were excluded.Manometric and reflux diagnoses were recorded from pre-transplant esophageal function testing.Time-to-event analysis using Cox proportional hazards model was applied to evaluate outcome of first episode of acute cellular rejection,defined histologically per International Society of Heart and Lung Transplantation guidelines.Subjects not meeting this endpoint were censored at time of post-transplant anti-reflux surgery,last clinic visit,or death.Fisher’s exact test for binary variables and student’s t-test for continuous variables were performed to assess for differences between groups.RESULTS Of 184 subjects(54%men,mean age:58,follow-up:443 person-years)met criteria for inclusion.Interstitial pulmonary fibrosis represented the predominant pulmonary diagnosis(41%).During the follow-up period,60 subjects(33.5%)developed acute rejection.The all-cause mortality was 16.3%.Time-to-event univariate analyses demonstrated significant association between IEM and acute rejection[hazard ratio(HR):1.984,95%CI:1.03-3.30,P=0.04],confirmed on Kaplan-Meier curve.On multivariable analysis,IEM remained independently associated with acute rejection,even after controlling for potential confounders such as the presence of acid and nonacid reflux(HR:2.20,95%CI:1.18-4.11,P=0.01).Nonacid reflux was also independently associated with acute rejection on both univariate(HR:2.16,95%CI:1.26-3.72,P=0.005)and multivariable analyses(HR:2.10,95%CI:1.21-3.64,P=0.009),adjusting for the presence of IEM.CONCLUSION Pre-transplant IEM was associated with acute rejection after transplantation,even after controlling for acid and nonacid reflux.Esophageal motility testing may be considered in lung transplant to predict outcomes.
文摘BACKGROUND A limited number of studies have demonstrated that sleeping in the left lateral decubitus(LLD)decreases nocturnal reflux in patients with gastroesophageal reflux disease(GERD)compared to right lateral decubitus(RLD)and supine.AIM This systematic review summarizes the association between sleeping in the LLD position and nocturnal reflux in patients with GERD.METHODS Studies published up to July 17,2023,in MEDLINE,EMBASE,and CENTRAL were searched.Eligible studies were randomized and nonrandomized studies assessing the effect of sleeping in LLD compared to RLD and supine in reducing nocturnal reflux in GERD patients.Outcomes include the acid exposure time(AET)(%time in pH<4),acid clearance time(ACT)(in sec/episode),number of reflux episodes,and improvement in N-GSSIQ scores.RESULTS Two nonrandomized studies showed decreased AET and ACT in LLD sleep position in comparison to RLD(mean difference[MD]-2.03[95%CI:-3.62 to-0.45];-81.84[95%CI:-127.48 to-36.20],respectively)and supine position(MD-2.71[95%CI:-4.34 to-1.09];-74.47[95%CI:-116.26 to-32.69],respectively).There was no difference in AET and ACT between RLD sleep position and supine.Furthermore,one randomized controlled trial investigating the use of electronic sleep positional therapy,which increased the duration of LLD sleep and decreased the duration of RLD sleep compared to sham,showed nocturnal symptoms improvement(improved N-GSSIQ score,increased reflux-free nights,and resolution of nocturnal reflux symptoms).CONCLUSION Current evidence suggests that sleeping on the left side could reduce nocturnal reflux and improve GERD-related quality of life,therefore warranting interventions that promote LLD sleep position.
基金The study was reviewed and approved by the Mass General Brigham Healthcare Institutional Review Board(2011P001563).
文摘BACKGROUND Gastroesophageal reflux(GER)has been associated with poor outcomes after lung transplantation for chronic lung disease,including increased risk of chronic rejection.GER is common in cystic fibrosis(CF),but factors influencing the likelihood of pre-transplant pH testing,and the impact of testing on clinical management and transplant outcomes in patients with CF are unknown.AIM To evaluate the role of pre-transplant reflux testing in the evaluation of lung transplant candidates with CF.METHODS This was a retrospective study from 2007-2019 at a tertiary medical center that included all patients with CF undergoing lung transplant.Patients with pretransplant anti-reflux surgery were excluded.Baseline characteristics(age at transplantation,gender,race,body mass index),self-reported GER symptoms prior to transplantation,and pre-transplant cardiopulmonary testing results,were recorded.Reflux testing consisted of either 24-h pH-or combined multichannel intraluminal impedance and pH monitoring.Post-transplant care included a standard immunosuppressive regimen,and regular surveillance bronchoscopy and pulmonary spirometry in accordance with institutional practice as well as in symptomatic patients.The primary outcome of chronic lung allograft dysfunction(CLAD)was defined clinically and histologically per International Society of Heart and Lung Transplantation criteria.Statistical analysis was performed with Fisher’s exact test to assess differences between cohorts,and time-to-event Cox proportional hazards modeling.RESULTS After applying inclusion and exclusion criteria,a total of 60 patients were included in the study.Among all CF patients,41(68.3%)completed reflux monitoring as part of pre-lung transplant evaluation.Objective evidence of pathologic reflux,defined as acid exposure time>4%,was found in 24 subjects,representing 58%of the tested group.CF patients with pre-transplant reflux testing were older(35.8 vs 30.1 years,P=0.01)and more commonly reported typical esophageal reflux symptoms(53.7%vs 26.3%,P=0.06)compared to those without reflux testing.Other patient demographics and baseline cardiopulmonary function did not significantly differ between CF subjects with and without pre-transplant reflux testing.Patients with CF were less likely to undergo pre-transplant reflux testing compared to other pulmonary diagnoses(68%vs 85%,P=0.003).There was a decreased risk of CLAD in patients with CF who underwent reflux testing compared to those who did not,after controlling for confounders(Cox Hazard Ratio 0.26;95%CI:0.08-0.92).CONCLUSION Pre-transplant reflux testing revealed high prevalence of pathologic reflux in CF patients and was associated with decreased risk of CLAD.Systematic reflux testing may enhance outcomes in this patient population.
