Prediction,prevention and management of gastroesophageal reflux after per-oral endoscopic myotomy:An update

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.

Early adenocarcinoma mixed with a neuroendocrine carcinoma component arising in the gastroesophageal junction: A case report

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.

Prognostic nutritional index in predicting survival of patients with gastric or gastroesophageal junction adenocarcinoma: A systematic review

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.

Causal associations between gastroesophageal reflux disease and essential hypertension: A bidirectional Mendelian randomization study

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.

Contemporary concepts of prevention and management of gastroesophageal variceal bleeding in liver cirrhosis patients

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.

Epidemiological, Clinical Aspects and Factors Associated with Typical Gastroesophageal Reflux Disease in the General Population of Parakou, Republic of Benin

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.

Gastroesophageal reflux disease in children: What’s new right now?

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.

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

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

Evaluating the causal relationship between human blood metabolites and gastroesophageal reflux disease

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.

Impact of preoperative therapy on surgical outcomes of laparoscopic total gastrectomy for gastric/gastroesophageal junction cancer

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.

Dental evaluation is helpful in the differentiation of functional heartburn and gastroesophageal reflux disease

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.

Ineffective esophageal motility is associated with acute rejection after lung transplantation independent of gastroesophageal reflux

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.

Left lateral decubitus sleeping position is associated with improved gastroesophageal reflux disease symptoms: A systematic review and meta-analysis

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.

Systematic Review and Meta-analysis of Randomized Controlled Trials on Manual Therapy for the Treatment of Gastroesophageal Reflux Disease

Objective The objective of our study was to systematically evaluate the clinical efficacy and safety of manual therapy in the treatment of gastroesophageal reflux disease(GERD),providing a reference value for clinical decision-making.Method Studies of randomized controlled trials(RCTs)evaluating the efficacy of manual therapy in patients with GERD were searched through Chinese National Knowledge Infrastructure,Wanfang,ViP China Science and Technology Journal Database,China Biology Medicine Database,PubMed,The Cochrane Library,OviD Medline,and Embase.Two researchers independently reviewed the literature,extracted data,and performed a risk of bias analysis using the Cochrane risk of bias assessment tool,and conducted meta-analysis analysis and publication bias evaluation,the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)tool 26 was used to rate the caliber of the data in this meta-analysis.Results This study included 11 RCTs.Meta-analysis showed that the manual therapy group had a higher total effective rate(odds ratio[OR]=4.63,95%confidence interval[Cl;3.01,7.14],p<0.00001)and better Reflux Disease Questionnaire scores[weighted mean difference(WMD)=-1.59,95%CI[-2.85,-0.33],p=0.01]than the control group.The subgroup analysis showed significant differences in improving the total effective rate in manual therapy versus Western medicine,manual therapy versus Chinese medicine decoction,manual therapy+Western medicine versus Western medicine,and manual therapy+conventional treatment versus conventional treatment groups.Among the 11 trials,5 reported adverse events,and all RCTs had the possibility of publication bias.Subgroup analysis shows that the differences in age could significantly influence heterogeneity;The GRADE analysis revealed that the overall quality of evidence for all outcome indicators was low and did not support our recommendation for the outcome.Conclusion Manual therapy is more effective than medication therapy alone in relieving GERD symptoms.Furthermore,conventional therapy combined with manual therapy was found to be even more effective.Hence,it is crucial to consider these findings when applying manual therapy to GERD patients to enhance treatment outcomes.Future studies must address issues such as study quality,treatment duration,and generalizability.

Pre-Lung transplant reflux testing demonstrates high prevalence of gastroesophageal reflux in cystic fibrosis and reduces chronic rejection risk

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.

Rifaximin in the Treatment of Gastroesophageal Reflux Disease: A New Idea Based on the Relationship between Intestinal Microecology and Gastroesophageal Reflux Disease

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.

Prevalence of gastroesophageal reflux disease in children with extraesophageal manifestations using combined-video,multichannel intraluminal impedance-pH study

BACKGROUND Gastroesophageal reflux disease(GERD)might be either a cause or comorbidity in children with extraesophageal problems especially as refractory respiratory symptoms,without any best methods or criterion for diagnosing it in children.AIM To evaluate the prevalence of extraesophageal GERD using conventional and combined-video,multichannel intraluminal impedance-pH(MII-pH),and to propose novel diagnostic parameters.METHODS The study was conducted among children suspected of extraesophageal GERD at King Chulalongkorn Memorial Hospital between 2019 and 2022.The children underwent conventional and/or combined-video MII-pH.The potential parameters were assessed and receiver operating characteristic was used for the significant parameters.RESULTS Of 51 patients(52.9%males),aged 2.24 years were recruited.The common problems were cough,recurrent pneumonia,and hypersecretion.Using MII-pH,35.3%of the children were diagnosed with GERD by reflux index(31.4%),total reflux events(3.9%),and symptom indices(9.8%)with higher symptom recorded in the GERD group(94 vs 171,P=0.033).In the video monitoring group(n=17),there were more symptoms recorded(120 vs 220,P=0.062)and more GERD(11.8%vs 29.4%,P=0.398)by symptom indices.Longest reflux time and mean nocturnal baseline impedance were significant parameters for diagnosis with receiver operating characteristic areas of 0.907(P=0.001)and 0.726(P=0.014).CONCLUSION The prevalence of extraesophageal GERD in children was not high as expected.The diagnostic yield of symptom indices increased using video monitoring.Long reflux time and mean nocturnal baseline impedance are novel parameters that should be integrated into the GERD diagnostic criteria in children.

Progress in the Study of Vonoprazan Fumarate vs. Proton Pump Inhibitors in the Treatment of Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disease, and proton pump inhibitors (PPIs) have been recommended as the first-line treatment for GERD. In recent years, studies on vonoprazan fumarate in the treatment of GERD have attracted widespread attention. In this paper, we review the research progress of vonoprazan fumarate and proton pump inhibitors in the treatment of GERD in recent years, and compare and analyze the efficacy, safety, tolerability, and advantages and disadvantages of long-term application of both. By reviewing the relevant literature, we found that vonoprazan fumarate has similar performance with proton pump inhibitors in terms of efficacy and safety, but has potential advantages in terms of tolerability and long-term application. Therefore, we believe that vonoprazan fumarate may become a new option for GERD treatment, helping clinicians to develop more appropriate treatment plans for patients and providing new ideas and directions for research in related fields.

Local inflammatory response to gastroesophageal reflux:Association of gene expression of inflammatory cytokines with esophageal multichannel intraluminal impedance-pH data

BACKGROUND Gene expression of inflammatory cytokines may take part in the pathophysiology of different forms of gastroesophageal reflux disease(GERD).AIM To explore gene expression of inflammatory cytokines in esophageal mucosa in patients with erosive esophagitis(EE)and non-erosive forms of GERD(NERD)and its association with data of esophageal multichannel intraluminal impedancepH(MII-pH)measurements.METHODS This was a single-center prospective study.Esophageal mucosa samples were taken from the lower part of the esophagus during endoscopy.Expression of interleukin(IL)-1β,IL-10,IL-18,tumor necrosis factorα(TNFA),toll-like receptor 4(TLR4),GATA binding protein 3(GATA3),differentiation cluster 68(CD68)andβ-2 microglobulin genes in esophageal mucosa was assessed with ImmunoQuantex assays.MII-pH measurements were performed on all the participants.Diagnosis of GERD was confirmed by the results of the MII-pH data.Based on the endoscopy,patients were allocated to the groups of EE and NERD.The control group consisted of non-symptomatic subjects with normal endoscopy and MII-pH results.We used nonparametric statistics to compare the differences between the groups.Association of expression of the mentioned genes with the results of the MII-pH data was assessed with Spearman’s rank method.RESULTS Data from 60 patients with GERD and 10 subjects of the control group were available for the analysis.Higher expression of IL-18(5.89±0.4 vs 5.28±1.1,P=0.04)and GATA3(2.92±0.86 vs 2.23±0.96,P=0.03)was found in the EE group compared to NERD.Expression of IL-1β,IL-18,TNFA,and TLR4 was lower(P<0.05)in the control group compared to EE and NERD.Esophageal acid exposure correlated with the expression of IL-1β(Spearman’s rank r=0.29),IL-18(r=0.31),TNFA(r=0.35),GATA3(r=0.34),TLR4(r=0.29),and CD68(r=0.37).Mean esophagealрНcorrelated inversely with the expression of IL-18,TNFA,GATA3,TLR4,and CD68.No association of gene expression with the number of gastroesophageal refluxes was found.CONCLUSION In patients with EE,local expression of IL-18 and GATA3 was higher compared to subjects with NERD.Esophageal acid exposure correlated directly with expression of IL-1β,IL-18,TNFA,TLR4,CD68,andβ-2 microglobulin genes.Inverse correlation was revealed between expression of IL-18,TNFA,GATA3,TLR4,and CD68 and mean esophageal pH.

Modified Xiaochaihu Decoction for gastroesophageal reflux disease:A randomized double-simulation controlled trial

BACKGROUND Gastroesophageal reflux disease(GERD)has a high prevalence worldwide,and its incidence is increasing annually.Modified Xiaochaihu Decoction(MXD)could relieve the symptoms of GERD,but the effects of MXD on GERD manifestations and relapse prevention need to be further explained.Therefore,we performed a prospective,double-blind,and double-simulation study.AIM To verify the efficacy of MXD for GERD and its effect on esophageal motility.METHODS Using randomization,double-blinding,and a simulation design,288 participants with GERD were randomized to the treatment group and control group and received herbs(MXD)plus omeprazole simulation and omeprazole plus herbs simulation,respectively,for 4 wk.The GERD-Q scale score and esophageal manometry were measured at baseline,after treatment,and at 1 mo and 3 mo follow-up visits when medication was complete to evaluate recurrence indicators.RESULTS The GERD-Q scale score in both groups decreased significantly compared to those before treatment(P<0.01).However,no significant difference was observed between the two groups(P>0.05).Esophageal manometry showed that participants with lower esophageal sphincter pressure reduction and the proportion of ineffective swallowing(more than 50%)improved in both groups from baseline(P<0.01),especially in the treatment group(P<0.05).The percentage of small intermittent contractions,large intermittent contractions,and increased pre-phase contractions in the treatment group significantly improved compared with baseline(P<0.05)but did not improve in the control group(P>0.05).There was no significant difference between the groups after treatment(P>0.05).The percentage of weak esophageal contractility(distal contractile integral<450 mmHg·s·cm),improved in both groups(P<0.01),but no significant difference was observed between the groups after treatment(P>0.05).The relapse rate in the treatment group was lower than that in the control group at the 1 mo(P<0.01)and 3 mo follow-up(P<0.05).CONCLUSION MXD has a similar therapeutic effect to omeprazole in mild-to-moderate GERD.The therapeutic effect may be related to increased pressure in the lower esophageal sphincter and reduced ineffective swallowing.