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.

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.

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.

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.

Application of neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy in curative surgery for esophageal cancer:A metaanalysis

BACKGROUND The effectiveness of neoadjuvant therapy in esophageal cancer(EC)treatment is still a subject of debate.AIM To compare the clinical efficacy and toxic side effects between neoadjuvant chemoradiotherapy(nCRT)and neoadjuvant chemotherapy(nCT)for locally advanced EC(LAEC).METHODS A comprehensive search was conducted using multiple databases,including PubMed,EMBASE,MEDLINE,Science Direct,The Cochrane Library,China National Knowledge Infrastructure,Wanfang Database,Chinese Science and Technology Journal Database,and Chinese Biomedical Literature Database Article.Studies up to December 2022 comparing nCRT and nCT in patients with EC were selected.RESULTS The analysis revealed significant differences between nCRT and nCT in terms of disease-free survival.The results indicated that nCRT provided better outcomes in terms of the 3-year overall survival rate(OSR)[odds ratio(OR)=0.95],complete response rate(OR=3.15),and R0 clearance rate(CR)(OR=2.25).However,nCT demonstrated a better 5-year OSR(OR=1.02)than nCRT.Moreover,when compared to nCRT,nCT showed reduced risks of cardiac complications(OR=1.15)and pulmonary complications(OR=1.30).CONCLUSION Overall,both nCRT and nCT were effective in terms of survival outcomes for LAEC.However,nCT exhibited better performance in terms of postoperative complications.

Effects of neoadjuvant chemotherapy vs chemoradiotherapy in the treatment of esophageal adenocarcinoma:A systematic review and meta-analysis

BACKGROUND Neoadjuvant therapy is an essential modality for reducing the clinical stage of esophageal cancer;however,the superiority of neoadjuvant chemotherapy(nCT)or neoadjuvant chemoradiotherapy(nCRT)is unclear.Therefore,a discussion of these two modalities is necessary.AIM To investigate the benefits and complications of neoadjuvant modalities.METHODS To address this concern,predefined criteria were established using the PICO protocol.Two independent authors performed comprehensive searches using predetermined keywords.Statistical analyses were performed to identify significant differences between groups.Potential publication bias was visualized using funnel plots.The quality of the data was evaluated using the Risk of Bias Tool 2(RoB2)and the GRADE approach.RESULTS Ten articles,including 1928 patients,were included for the analysis.Significant difference was detected in pathological complete response(pCR)[P<0.001;odds ratio(OR):0.27;95%CI:0.16-0.46],30-d mortality(P=0.015;OR:0.4;95%CI:0.22-0.71)favoring the nCRT,and renal failure(P=0.039;OR:1.04;95%CI:0.66-1.64)favoring the nCT.No significant differences were observed in terms of survival,local or distal recurrence,or other clinical or surgical complications.The result of RoB2 was moderate,and that of the GRADE approach was low or very low in almost all cases.CONCLUSION Although nCRT may have a higher pCR rate,it does not translate to greater long-term survival.Moreover,nCRT is associated with higher 30-d mortality,although the specific cause for postoperative complications could not be identified.In the case of nCT,toxic side effects are suspected,which can reduce the quality of life.Given the quality of available studies,further randomized trials are required.

Latest insights into the global epidemiological features,screening,early diagnosis and prognosis prediction of esophageal squamous cell carcinoma

As a highly invasive carcinoma,esophageal cancer(EC)was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020.Esophageal squamous cell carcinoma(ESCC)is the major histological subtype of EC,and its incidence and mortality rates are decreasing globally.Due to the lack of specific early symptoms,ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis,and the incidence and mortality rates are still high in many countries,especially in China.Therefore,enormous challenges still exist in the management of ESCC,and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC.Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated,certain promising biomarkers are being investigated to facilitate clinical decision-making.With the advent and advancement of highthroughput technologies,such as genomics,proteomics and metabolomics,valuable biomarkers with high sensitivity,specificity and stability could be identified for ESCC.Herein,we aimed to determine the epidemiological features of ESCC in different regions of the world,especially in China,and focused on novel molecular biomarkers associated with ESCC screening,early diagnosis and prognosis prediction.

Prospects of polyglycolic acid sheets for the treatment of esophageal stricture after esophageal endoscopic submucosal dissection

Esophageal cancer is the seventh most common type of cancer and the sixth leading cause of cancer-related mortality worldwide.Endoscopic submucosal dissection(ESD)is widely used for the resection of early esophageal cancer.However,post-ESD esophageal stricture is a common long-term complication,which requires attention.Patients with post-ESD esophageal stricture often experience dysphagia and require multiple dilatations,which greatly affects their quality of life and increases healthcare costs.Therefore,to manage post-ESD esophageal stricture,researchers are actively exploring various strategies,such as pharmaceutical interventions,endoscopic balloon dilation,and esophageal stenting.Although steroids-based therapy has achieved some success,steroids can lead to complications such as osteoporosis and infection.Meanwhile,endoscopic balloon dilatation is effective in the short term,but is prone to recurrence and perforation.Additionally,esophageal stenting can alleviate the stricture,but is associated with discomfort during stenting and the complication of easy displacement also present challenges.Tissue engineering has evolved rapidly in recent years,and hydrogel materials have good biodegradability and biocompatibility.A novel type of polyglycolic acid(PGA)sheets has been found to be effective in preventing esophageal stricture after ESD,with the advantages of a simple operation and low complication rate.PGA membranes act as a biophysical barrier to cover the wound as well as facilitate the delivery of medications to promote wound repair and healing.However,there is still a lack of multicenter,large-sample randomized controlled clinical studies focused on the treatment of post-ESD esophageal strictures with PGA membrane,which will be a promising direction for future advancements in this field.

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.

Endoscopic treatment of extreme esophageal stenosis complicated with esophagotracheal fistula: A case report

BACKGROUND At present,there is no unified and effective treatment for extreme corrosive esophageal stenosis(CES)with esophagotracheal fistula(ETF).This case had extreme and severe esophageal stenosis(ES)and ETF after ingesting an enzyme-based chemical detergent,resulting in a serious pulmonary infection and severe malnutrition.Upper gastrointestinal imaging showed that he had an ETF,and endoscopy showed that he had extreme and severe esophageal stricture.This case was complex and difficult to treat.According to the domestic and foreign lite-rature,there is no universal treatment that is low-risk.CASE SUMMARY A patient came to our hospital with extreme ES,an ETF,and severe malnutrition complicated with pulmonary tuberculosis 1 mo after the consumption of an enzy-me-based detergent.The ES was serious,and the endoscope was unable to pass through the esophagus.We treated him by endoscopic incision method(EIM),esophageal stent placement(ESP),and endoscopic balloon dilation(EBD)by using the bronchoscope and gastroscope.This treatment not only closed the ETF,but also expanded the esophagus,with minimal trauma,greatly reducing the pain of the patient.According to the literature,there are no similar reported cases.CONCLUSION We report,for the first time,a patient with extreme CES complicated with ETF,where the endoscope could not be passed through his esophagus but he could be examined by bronchoscopy and treated by EIM,ESP,and EBD.

Intra-thyroid esophageal duplication cyst:A case report

BACKGROUND Esophageal cysts are relatively rare in clinical practice,with most of the literature comprising case reports.Esophageal cysts protruding into the thyroid gland are easily misdiagnosed as thyroid tumors.No such cases have been reported so far.CASE SUMMARY This article reports the case of a 31-year-old adult male diagnosed with thyroid nodules before admission.The patient underwent left thyroidectomy and isthmusectomy.During the surgery,esophageal cysts were identified in the esophageal muscle and thyroid glands.The pathology results confirmed a nodular goiter combined with esophageal cysts.Postoperatively,the patient developed a neck infection and underwent another operation and broad-spectrum antibiotic treatment for recovery.CONCLUSION We report the first clinical case of an esophageal cyst located within the thyroid gland that was successfully treated surgically.Esophageal cyst located within the thyroid gland cause difficulties in diagnosis.In the present study,the contents of the esophageal cysts were calcified foci,and a small amount of fluid mixture,which were easily misdiagnosed as thyroid nodules and misled the surgical methods.

Plant-based dietary patterns and risk of esophageal cancer:A prospective cohort study spanning 17 years

Objective: Plant-based diets have multiple health benefits for cancers;however, little is known about the association between plant-based dietary patterns and esophageal cancer(EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of EC.Methods: We performed endoscopic screening for 15,709 participants aged 40-69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index(PDI), healthful plant-based diet index(h PDI), and unhealthful plant-based diet index(u PDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios(HRs) and 95% confidence intervals(95% CIs) of EC across 3plant-based diet indices and further stratified the analysis by subgroups.Results: The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50(95% CI, 0.32-0.77) for h PDI. In addition, the HR per 10-point increase in the h PDI score was 0.42(95% CI, 0.27-0.66) for ECs. Conversely, u PDI was positively associated with the risk of EC, and the HR was 1.80(95% CI, 1.16-2.82). The HR per 10-point increase in the u PDI score was 1.90(95% CI, 1.26-2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity analyses.Conclusions: A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.

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.

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.

Amlodipine inhibits the proliferation and migration of esophageal carcinoma cells through the induction of endoplasmic reticulum stress

BACKGROUND L-type calcium channels are the only protein channels sensitive to calcium channel blockers,and are expressed in various cancer types.The Cancer Genome Atlas database shows that the mRNA levels of multiple L-type calcium channel subunits in esophageal squamous cell carcinoma tumor tissue are significantly higher than those in normal esophageal epithelial tissue.Therefore,we hypothesized that amlodipine,a long-acting dihydropyridine L-type calcium channel blocker,may inhibit the occurrence and development of esophageal cancer(EC).AIM To investigate the inhibitory effects of amlodipine on EC through endoplasmic reticulum(ER)stress.METHODS Cav1.3 protein expression levels in 50 pairs of EC tissues and corresponding paracancerous tissues were examined.Subsequently,the inhibitory effects of amlodipine on proliferation and migration of EC cells in vitro were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and Transwell assays.In vivo experiments were performed using murine xenograft model.To elucidate the underlying mechanisms,in vitro cell studies were performed to confirm that ER stress plays a role in inhibition proliferation and migration of EC cells treated with amlodipine.RESULTS The expression level of Cav1.3 in esophageal carcinoma was 1.6 times higher than that in paracancerous tissues.Amlodipine treatment decreased the viability of esophageal carcinoma cells in a dose-and time-dependent manner.In vivo animal experiments also clearly indicated that amlodipine inhibited the growth of EC tumors in mice.Additionally,amlodipine reduces the migration of tumor cells by inhibiting epithelial-mesenchymal transition(EMT).Mechanistic studies have demonstrated that amlodipine induces ER stress-mediated apoptosis and suppresses EMT.Moreover,amlodipine-induced autophagy was characterized by an increase in autophagy lysosomes and the accumulation of light chain 3B protein.The combination of amlodipine with the ER stress inhibitor 4-phenylbutyric acid further confirmed the role of the ER stress response in amlodipine-induced apoptosis,EMT,and autophagy.Furthermore,blocking autophagy increases the ratio of apoptosis and migration.CONCLUSION Collectively,we demonstrate for the first time that amlodipine promotes apoptosis,induces autophagy,and inhibits migration through ER stress,thereby exerting anti-tumor effects in EC.

Prognosis value of heat-shock proteins in esophageal and esophagogastric cancer:A systematic review and meta-analysis

BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many cancers.The prognostic significance of HSPs and their regulatory factors,such as heat shock factor 1(HSF1)and CHIP,are poorly understood.AIM To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer.METHODS A systematic review was conducted in accordance with PRISMA recommend-ations(PROSPERO:CRD42022370653),on Embase,PubMed,Cochrane,and LILACS.Cohort,case-control,and cross-sectional studies of patients with eso-phagus or esophagogastric cancer were included.HSP-positive patients were compared with HSP-negative,and the endpoints analyzed were lymph node metastasis,tumor depth,distant metastasis,and overall survival(OS).HSPs were stratified according to the HSP family,and the summary risk difference(RD)was calculated using a random-effect model.RESULTS The final selection comprised 27 studies,including esophageal squamous cell carcinoma(21),esophagogastric adenocarcinoma(5),and mixed neoplasms(1).The pooled sample size was 3465 patients.HSP40 and 60 were associated with a higher 3-year OS[HSP40:RD=0.22;95%confidence interval(CI):0.09-0.35;HSP60:RD=0.33;95%CI:0.17-0.50],while HSF1 was associated with a poor 3-year OS(RD=-0.22;95%CI:-0.32 to-0.12).The other HSP families were not associated with long-term survival.HSF1 was associated with a higher probability of lymph node metastasis(RD=-0.16;95%CI:-0.29 to-0.04).HSP40 was associated with a lower probability of lymph node dissemination(RD=0.18;95%CI:0.03-0.33).The expression of other HSP families was not significantly related to tumor depth and lymph node or distant metastasis.CONCLUSION The expression levels of certain families of HSP,such as HSP40 and 60 and HSF1,are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.

MicroRNAs:A novel signature in the metastasis of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma(ESCC)is a malignant epithelial tumor,characterized by squamous cell differentiation,it is the sixth leading cause of cancer-related deaths globally.The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered,coupled with higher risk of metastasis,which is an exceedingly malignant charac-teristic of cancer,frequently leading to a high mortality rate.Unfortunately,there is currently no specific and effective marker to predict and treat metastasis in ESCC.MicroRNAs(miRNAs)are a class of small non-coding RNA molecules,approximately 22 nucleotides in length.miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence,progression,and prognosis of cancer.Here,we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis,and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors.This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis,with the ultimate aim of reducing the mortality rate among patients with ESCC.

Biopsy forceps are useful for measuring esophageal varices in vitro

BACKGROUND To avoid acute variceal bleeding in cirrhosis,current guidelines recommend screening for high-risk esophageal varices(EVs)by determining variceal size and identifying red wale markings.However,visual measurements of EV during routine endoscopy are often inaccurate.AIM To determine whether biopsy forceps(BF)could be used as a reference to improve the accuracy of binary classification of variceal size.METHODS An in vitro self-made EV model with sizes ranging from 2 to 12 mm in diameter was constructed.An online image-based survey comprising 11 endoscopic images of simulated EV without BF and 11 endoscopic images of EV with BF was assembled and sent to 84 endoscopists.The endoscopists were blinded to the actual EV size and evaluated the 22 images in random order.RESULTS The respondents included 48 academic and four private endoscopists.The accuracy of EV size estimation was low in both the visual(13.81%)and BF-based(20.28%)groups.The use of open forceps improved the ability of the endoscopists to correctly classify the varices by size(small≤5 mm,large>5 mm)from 71.85%to 82.17%(P<0.001).CONCLUSION BF may improve the accuracy of EV size assessment,and its use in clinical practice should be investigated.

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.

Role of deubiquitinase JOSD2 in the pathogenesis of esophageal squamous cell carcinoma

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is a DUB involved in con-trolling protein deubiquitination and influencing critical cellular processes in cancer.AIM To investigate the impact of JOSD2 on the progression of ESCC.METHODS Bioinformatic analyses were employed to explore the expression,prognosis,and enriched pathways associated with JOSD2 in ESCC.Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines(KYSE30 and RESULTS )Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues,which was associated with poor prognosis.Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells.JOSD2 knockdown inhibited ESCC cell activity,including proliferation and colony-forming ability.Moreover,JOSD2 knockdown decreased the drug resistance and migration of ESCC cells,while JOSD2 overexpression enhanced these phenotypes.In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC.Mechanistically,JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways.Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2,which identified the four primary proteins that bind to JOSD2,namely USP47,IGKV2D-29,HSP90AB1,and PRMT5.CONCLUSION JOSD2 plays a crucial role in enhancing the proliferation,migration,and drug resistance of ESCC,suggesting that JOSD2 is a potential therapeutic target in ESCC.