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.

Esophageal cancer screening,early detection and treatment:Current insights and future directions

Esophageal cancer ranks among the most prevalent malignant tumors globally,primarily due to its highly aggressive nature and poor survival rates.According to the 2020 global cancer statistics,there were approximately 604000 new cases of esophageal cancer,resulting in 544000 deaths.The 5-year survival rate hovers around a mere 15%-25%.Notably,distinct variations exist in the risk factors associated with the two primary histological types,influencing their worldwide incidence and distribution.Squamous cell carcinoma displays a high incidence in specific regions,such as certain areas in China,where it meets the cost-effect-iveness criteria for widespread endoscopy-based early diagnosis within the local population.Conversely,adenocarcinoma(EAC)represents the most common histological subtype of esophageal cancer in Europe and the United States.The role of early diagnosis in cases of EAC originating from Barrett's esophagus(BE)remains a subject of controversy.The effectiveness of early detection for EAC,particularly those arising from BE,continues to be a debated topic.The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses.In areas with higher incidences,such as China and Japan,early diagnosis is more common,which has led to the advancement of endoscopic methods as definitive treatments.These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality.Early screening,prompt diagnosis,and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.

Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

As a highly invasive malignancy,esophageal cancer(EC)is a global health issue,and was the eighth most prevalent cancer and the sixth leading cause of cancerrelated death worldwide in 2020.Due to its highly immunogenic nature,emerging immunotherapy approaches,such as immune checkpoint blockade,have demonstrated promising efficacy in treating EC;however,certain limitations and challenges still exist.In addition,tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment(TIME);thus,understanding the TIME is urgent and crucial,especially given the importance of an immunosuppressive microenvironment in tumor progression.The aim of this review was to better elucidate the mechanisms of the suppressive TIME,including cell infiltration,immune cell subsets,cytokines and signaling pathways in the tumor microenvironment of EC patients,as well as the downregulated expression of major histocompatibility complex molecules in tumor cells,to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of immunotherapies.Therefore,personalized treatments could be developed to maximize the advantages of immunotherapy.

Microbiome changes in esophageal cancer:implications for pathogenesis and prognosis

Esophageal cancer(EC)is an aggressive malignancy with a poor prognosis.Various factors,including dietary habits,and antacid and antibiotic use,have been shown to influence the esophageal microbiome.Conversely,enrichment and diversity of the esophageal microbiome can also impact its function.Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC,thus suggesting the potential contribution of the esophageal microbiome to EC development.Additionally,distinct microbiome compositions have been observed in patients with different responses to radiotherapy and chemotherapy,indicating the role of the esophageal microbiome in modulating treatment outcomes.In this review,we have examined previous studies on the esophageal microbiome in healthy individuals and patients with EC or other esophageal diseases,with a focus on identifying microbial communities associated with EC pathogenesis and prognosis.Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies,ultimately leading to better outcomes for patients.

Lipid metabolism analysis in esophageal cancer and associated drug discovery

Esophageal cancer is an upper gastrointestinal malignancy with a bleak prognosis.It is still being explored in depth due to its complex molecular mechanisms of occurrence and development.Lipids play a crucial role in cells by participating in energy supply,biofilm formation,and signal transduction processes,and lipid metabolic reprogramming also constitutes a significant characteristic of malignant tumors.More and more studies have found esophageal cancer has obvious lipid metabolism abnormalities throughout its beginning,progress,and treatment resistance.The inhibition of tumor growth and the enhancement of antitumor therapy efficacy can be achieved through the regulation of lipid metabolism.Therefore,we reviewed and analyzed the research results and latest findings for lipid metabolism and associated analysis techniques in esophageal cancer,and comprehensively proved the value of lipid metabolic reprogramming in the evolution and treatment resistance of esophageal cancer,as well as its significance in exploring potential therapeutic targets and biomarkers.

Prevalence of Helicobacter pylori infection among patients with esophageal carcinoma

BACKGROUND Helicobacter pylori(H.pylori)is a widespread microorganism related to gastric adenocarcinoma(AC).In contrast,it has been reported that an inverse association exists between H.pylori infection and esophageal carcinoma.The mechanisms underlying this supposedly protective effect remain controversial.AIM To determine the prevalence of H.pylori infection in esophageal carcinoma patients,we performed a retrospective observational study of esophageal tumors diagnosed in our hospital.METHODS We retrospectively reviewed the prevalence of H.pylori infection in a cohort of patients diagnosed with esophageal carcinoma.Concomitant or previous proton pump inhibitor(PPI)usage was also recorded.RESULTS A total of 89 patients with esophageal carcinoma(69 males,77.5%),with a mean age of 66 years(range,26-93 years)were included.AC was the most frequent pathological variant(n=47,52.8%),followed by squamous cell carcinoma(n=37,41.6%).Fourteen ACs(29.8%)originated in the gastroesophageal junction and 33(70.2%)in the esophageal body.Overall,54 patients(60.7%)presented at stages III and IV.Previous H.pylori infection occurred only in 4 patients(4.5%),3 with AC(6.3%of all ACs)and 1 with squamous cell carcinoma(2.7%of all squamous cell tumors).All patients with previous H.pylori infection had stage III-IV.Only one patient had received prior H.pylori eradication therapy,whereas 86(96.6%)had received previous or concomitant PPI treatment.CONCLUSION In our cohort of patients,and after histologic evaluation of paraffin-embedded primary tumors,we found a very low prevalence of previous H.pylori infection.We also reviewed the medical history of the patients,concluding that the majority had received or were on PPI treatment.The minimal prevalence of H.pylori infection found in this cohort of patients with esophageal carcinoma suggests a protective role.

Drug-induced mucosal alterations observed during esophagogastroduodenoscopy

Several features of drug-induced mucosal alterations have been observed in the upper gastrointestinal tract,i.e.,the esophagus,stomach,and duodenum.These include pill-induced esophagitis,desquamative esophagitis,worsening of gastroesophageal reflux,chemotherapy-induced esophagitis,proton pump inhibitor-induced gastric mucosal changes,medication-induced gastric erosions and ulcers,pseudomelanosis of the stomach,olmesartan-related gastric mucosal inflammation,lanthanum deposition in the stomach,zinc acetate hydrate tabletinduced gastric ulcer,immune-related adverse event gastritis,olmesartan-associated sprue-like enteropathy,pseudomelanosis of the duodenum,and lanthanum deposition in the duodenum.For endoscopists,acquiring accurate knowledge regarding these diverse drug-induced mucosal alterations is crucial not only for the correct diagnosis of these lesions but also for differential diag-nosis of other conditions.This minireview aims to provide essential information on druginduced mucosal alterations observed on esophagogastroduodenoscopy,along with representative endoscopic images.

Immunoglobulin G-mediated food intolerance and metabolic syndrome influence the occurrence of reflux esophagitis in Helicobacter pylori-infected patients

BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse symptoms.Identifying its risk factors is crucial to understanding the etiology,prevention,and management of the disease.The occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(H.pylori)infection,and metabolic syndromes.AIM To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,H.pylori infection,and metabolic syndrome on reflux esophagitis.METHODS Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively enrolled.The patients’basic information,test results,gastroscopy results,H.pylori test results,and IgG-mediated food intolerance results were collected.Multivariate logistic regression analysis was used to analyze risk factors for reflux esophagitis.Statistical mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on H.pylori infection affecting reflux esophagitis.RESULTS A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,H.pylori infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,respectively.Multivariate analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,P<0.00001)and metabolic syndrome(OR=1.165,95%CI:1.030-1.317,P=0.01484),and the independent protective factor for reflux esophagitis was H.pylori infection(OR=0.400,95%CI:0.351-0.456,P<0.00001).IgG-mediated food intolerance had a partially positive mediating effect on H.pylori infection as it was associated with reduced occurrence of reflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on H.pylori infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intolerance and metabolic syndrome were at higher risk of developing reflux esophagitis,while patients with H.pylori infection were at lower risk.IgG-mediated food intolerance reduced the risk of reflux esophagitis pathogenesis in patients with H.pylori infection;however,metabolic syndrome increased the risk of patients with H.pylori infection developing reflux esophagitis.

A prognosis model for predicting immunotherapy response of esophageal cancer based on oxidative stress-related signatures

Oxidative stress(OS)is intimately associated with tumorigenesis and has been considered a potential therapeutic strategy.However,the OS-associated therapeutic target for esophageal squamous cell carcinoma(ESCC)remains unconfirmed.In our study,gene expression data of ESCC and clinical information from public databases were downloaded.Through LASSO-Cox regression analysis,a risk score(RS)signature map of prognosis was constructed and performed external verification with the GSE53625 cohort.The ESTIMATE,xCell,CIBERSORT,TIMER,and ImmuCellAI algorithms were employed to analyze infiltrating immune cells and generate an immune microenvironment(IM).Afterward,functional enrichment analysis clarified the underlying mechanism of the model.Nomogram was utilized for forecasting the survival rate of individual ESCC cases.As a result,we successfully constructed an OS-related genes(OSRGs)model and found that the survival rate of high-risk groups was lower than that of low-risk groups.The AUC of the ROC verified the strong prediction performance of the signal in these two cohorts further.According to independent prognostic analysis,the RS was identified as an independent risk factor for ESCC.The nomogram and follow-up data revealed that the RS possesses favorable predictive value for the prognosis of ESCC patients.qRT-PCR detection demonstrated increased expression of MPC1,COX6C,CYB5R3,CASP7,and CYCS in esophageal cancer patients.In conclusion,we have constructed an OSRGs model for ESCC to predict patients’prognosis,offering a novel insight into the potential application of the OSRGs model in ESCC.

Effectiveness of antibiotic prophylaxis for acute esophageal variceal bleeding in patients with band ligation: A large observational study

BACKGROUND Esophageal variceal bleeding is a severe complication associated with liver cirrhosis and typically necessitates endoscopic hemostasis.The current standard treatment is endoscopic variceal ligation(EVL),and Western guidelines recom-mend antibiotic prophylaxis following hemostasis.However,given the impro-vements in prognosis for variceal bleeding due to advancements in the management of bleeding and treatments of liver cirrhosis and the global concerns regarding the emergence of multidrug-resistant bacteria,there is a need to reassess the use of routine antibiotic prophylaxis after hemostasis.AIM To evaluate the effectiveness of antibiotic prophylaxis in patients treated for EVL.METHODS We conducted a 13-year observational study using the Tokushukai medical database across 46 hospitals.Patients were divided into the prophylaxis group(received antibiotics on admission or the next day)and the non-prophylaxis group(did not receive antibiotics within one day of admission).The primary outcome was composed of 6-wk mortality,4-wk rebleeding,and 4-wk spontaneous bacterial peritonitis(SBP).The secondary outcomes were each individual result and in-hospital mortality.A logistic regression with inverse probability of treatment weighting was used.A subgroup analysis was conducted based on the Child-Pugh classification to determine its influence on the primary outcome measures,while sensitivity analyses for antibiotic type and duration were also performed.RESULTS Among 980 patients,790 were included(prophylaxis:232,non-prophylaxis:558).Most patients were males under the age of 65 years with a median Child-Pugh score of 8.The composite primary outcomes occurred in 11.2%of patients in the prophylaxis group and 9.5%in the non-prophylaxis group.No significant differences in outcomes were observed between the groups(adjusted odds ratio,1.11;95%confidence interval,0.61-1.99;P=0.74).Individual outcomes such as 6-wk mortality,4-wk rebleeding,4-wk onset of SBP,and in-hospital mortality were not significantly different between the groups.The primary outcome did not differ between the Child-Pugh subgroups.Similar results were observed in the sensitivity analyses.CONCLUSION No significant benefit to antibiotic prophylaxis for esophageal variceal bleeding treated with EVL was detected in this study.Global reassessment of routine antibiotic prophylaxis is imperative.

Present situation and prospect of immunotherapy for unresectable locally advanced esophageal cancer during peri-radiotherapy

Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.

Immunotherapy for esophageal cancer:Where are we now and where can we go

Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.

Is Helicobacter pylori infection protective against esophageal cancer?

Helicobacter pylori(H.pylori)infection affects a substantial proportion of the global population and causes various gastric disorders,including gastric cancer.Recent studies have found an inverse relationship between H.pylori infection and eso-phageal cancer(EC),suggesting a protective role against EC.This editorial focuses on the possible mechanisms underlying the role of H.pylori infection in EC and explores the role of gut microbiota in esophageal carcinogenesis and the prac-ticality of H.pylori eradication.EC has two major subtypes:Esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinoma(EAC),which have different etiologies and risk factors.Gut microbiota can contribute to EC via inflammation-induced carcinogenesis,immunomodulation,lactagenesis,and genotoxin production.H.pylori infection is said to be inversely related to EAC,protecting against EAC by inducing atrophic gastritis,altering serum ghrelin levels,and triggering cancer cell apoptosis.Though H.pylori infection has no significant association with ESCC,COX-2-1195 polymorphisms and endogenous nitrosamine production can impact the risk of ESCC in H.pylori-infected in-dividuals.There are concerns regarding a plausible increase in EC after H.pylori eradication treatments.However,H.pylori eradication is not associated with an increased risk of EC,making it safe from an EC perspective.

Analysis of the Effectiveness of Biling Weitong Granules Combined with Trimethoprim and Vonoprazan in The Treatment of Reflux Esophagitis

Objective:To analyze the effectiveness of Biling Weitong Granules(BLWTG)combined with trimethoprim and vonoprazan in treating reflux esophagitis.Methods:Sixty patients with reflux esophagitis admitted to our hospital from March 2020 to March 2023 were selected as study subjects and randomly divided into a control group and an experimental group,with 30 cases in each group.The control group received only the combination treatment of trimethoprim and vonoprazan,while the experimental group was treated with BLWTG based on the control group.The acid reflux and heartburn symptom scores,quality-of-life scores,clinical efficacy,Chinese medicine symptom incidences,and the occurrence of adverse reactions before and after treatment in the two groups were compared.Results:After treatment,the acid reflux and heartburn symptom scores of patients in the experimental group were lower than those of the treatment control group,and the quality-of-life scores were higher than those of the treatment control group(P<0.05).The total clinical efficacy of the experimental group was 96.66%,which was significantly higher than that of the control group(73.33%,P<0.05).After treatment,the incidence of Chinese medicine symptoms,such as nausea and vomiting,abdominal distension and abdominal pain,and loss of appetite of the patients in the experimental group were significantly lower than those of the control group(P<0.05).During the treatment period,there was no significant difference in the incidence of adverse reactions between the two groups,which indicated that the safety of the two treatments was comparable(P>0.05).Conclusion:BLWTG combined with trimethoprim and vonoprazan was safe and reliable in treating reflux esophagitis,effectively relieving the symptoms and improving its clinical efficacy.This treatment is worthy of popularization.

Nomograms and prognosis for superficial esophageal squamous cell carcinoma

In recent years,endoscopic resection,particularly endoscopic submucosal dis-section,has become increasingly popular in treating non-metastatic superficial esophageal squamous cell carcinoma(ESCC).In this evolving paradigm,it is crucial to identify factors that predict higher rates of lymphatic invasion and poorer outcomes.Larger tumor size,deeper invasion,poorer differentiation,more infiltrative growth patterns(INF-c),higher-grade tumor budding,positive lymphovascular invasion,and certain biomarkers have been associated with lymph node metastasis and increased morbidity through retrospective reviews,leading to the construction of comprehensive nomograms for outcome prediction.If validated by future prospective studies,these nomograms would prove highly applicable in guiding the selection of treatment for superficial ESCC.

Role of Helicobacter pylori in esophageal carcinogenesis:Friend or foe?

In this letter,we comment on the article by López-Gómez et al,which explores the prevalence of Helicobacter pylori(H.pylori)infection among patients with esophageal carcinoma(EC)in a cohort of Spain population.The relationship between H.pylori infection and EC is very complex.Previous research results are often contradictory due to the influence of dietary habits,age,region,and other factors.López-Gómez et al reported a very low prevalence of previous H.pylori infection in their cohort of patients with EC,and most of them had previously received or concomitantly received proton pump inhibitors treatment.These results are similar to previous results,which suggest that H.pylori infection is related to the low incidence of EC.Therefore,this study may provide a direction for preventing EC and eradicating H.pylori in Spain.

Helicobacter pylori,esophageal precancerous lesions,and proton pump inhibitor overuse

This article reviews the cohort study published in the World Journal of Gastroenterology,which reported low rates of Helicobacter pylori(H.pylori)infection among esophageal cancer(EC)patients,coupled with proton pump inhibitor(PPI)overuse.These findings suggest a potential protective role of H.pylori against EC and indicate a possible association between PPI use and increased cancer risk.In light of these findings,our article examines the complex relationship between H.pylori and esophageal precancerous lesions,exploring the potential underlying mechanisms.We also address growing concerns regarding PPI overuse,including its potential effects on cancer therapy efficacy and the risk of drug interactions.Ultimately,this article highlights the urgent need for further research to evaluate the safety and efficacy of PPIs in cancer patients and to better understand their broader implications.

Esophageal intramural pseudodiverticulosis

Esophageal intramural pseudodiverticulosis(EIPD)is a disease of unknown pathogenesis characterized by usually systemic,cystic dilatation of the excretory ducts of esophageal submucosal glands.In this article,I review the epidemiology,clinical manifestations,endoscopic findings,esophagographic findings,and histopathology of EIPD.I also discuss the etiology and possible pathogenesis of EIPD based on my experiences with this disease and a review of the literature.EIPD usually presents with dysphagia in middle-aged individuals.It is often complicated with secondary infections,most commonly candidiasis.On esophagography,EIPD is delineated as small,multiple,flask-shaped outward projections within the esophageal wall.In recent years,EIPD has been mainly diagnosed by endoscopic findings of multiple,localized,small mucosal depressions.The orifices of the“pseudodiverticula”periodically open and close,and excrete mucus onto the mucosal surface.On histopathological examination,the luminal surface of dilated ducts in EIPD is covered by multilayered,hyperplastic epithelial cells,but myoepithelial cells in the glandular acini are well preserved.Treatment of EIPD is usually symptomatic therapy,and prevention of the infectious complications is important.The etiology and pathogenesis of EIPD are largely unknown,but functional abnormalities of autonomic nerve fibers innervating the esophageal glands likely play an important role,since the structures of the glands are basically preserved in this disease.

Study on the Application of Refined Nursing Care in The Care for Elderly Patients with Reflux Esophagitis

Objective: To investigate the application effect of refined nursing care in the care for elderly patients with reflux esophagitis. Methods: Following the difference in nursing style, 84 cases of elderly patients with reflux esophagitis admitted to our hospital from May 2022 to May 2023 were randomly grouped into a control group and a research group, with 42 cases each. The control group was given conventional nursing care and the research group was given refined nursing care. The psychological state and treatment adherence of the two groups of patients after the nursing intervention were compared. Results: After the nursing intervention, the self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores of the research group were lower than those of the control group (P < 0.05). The treatment compliance of the research group was better than the control group (P < 0.05). Conclusion: The implementation of refined nursing care for elderly patients with reflux esophagitis exhibited a significant effect on improving the patient’s psychological state, treatment compliance, and rehabilitation.

Reducing the global cancer burden with gastrointestinal screening: China's 30 years practice

Gastrointestinal(GI) cancers include esophageal [EC(International Classification of Disease 10^(th) revision: C15)], gastric [GC(C16)], and colorectal [CRC(C18-C21)] cancers. China is a high-incidence country of GI cancers.