Central neuromodulators for patients with functional esophageal disorders: A systematic review and meta-analysis.

BACKGROUD: The use of neuromodulators is prevalent in various functional gastrointestinal disease. However, data concerning the outcomes of these treatments in functional esophageal disorders (FED) remains limited and inadequate. AIMS: The aim of the present study is to examine the efficacy of central neuromodulators in FED. METHODS: We searched PubMed, EMBASE, and the Cochrane library databases from inception to April 2023. Randomized controlled trials that compared the effects of neuromodulators and placebos on FED are included. Primary outcome is the symptom improvement, and Rome IV criteria is used to assess eligible studies. RESULTS: Eleven randomized controlled studies (three for functional chest pain, four for reflux hypersensitivity/functional heartburn, three for globus, and one for functional dysphagia) were included in the final analysis. Neuromodulators reduced chest pain by 52%-71% in patients with functional chest pain, and alleviated symptom by 46%-75% in patients with globus (n = 3, Odds ratio 6.30, 95% confidence interval 4.17-9.50). However, the results were inconsistent for reflux hypersensitivity and functional heartburn. There was a lack of convincing evidence to support the use of neuromodulators for functional dysphagia. The use of neuromodulators did not have a significant impact on the quality of life. CONCLUSIONS: Functional chest pain and globus may potentially benefit from the use of neuromodulators, but their effectiveness for functional dysphagia, functional heartburn and reflux hypersensitivity remains controversial. More controlled trials are needed to confirm the therapeutic effects on these conditions.

Administration of oral prednisolone to prevent esophageal stricture after balloon-type radiofrequency ablation for ultralong-segment esophageal neoplasia.

BACKGROUND AND AIMS: Endoscopic radiofrequency ablation (RFA) has shown good efficacy and safety in eradicating flat-type early esophageal squamous cell neoplasia (ESCN). However, post-RFA stricture is still a major concern, especially when treating ultralong-segment ESCNs. The aim of this study was to investigate the efficacy and safety of oral prednisolone to prevent post-RFA stricture. METHODS: We prospectively enrolled 48 patients treated with balloon-type RFA who had Lugol-unstained or mosaic-like flat-type ESCNs with an expected treatment area of >10 cm. Oral prednisolone was started at a dose of 30 mg/day on the third day after RFA and continued for 4 weeks. The results were compared with an historical control group of 25 patients who received RFA without oral steroids. The primary endpoint was the frequency of post-RFA stricture. Secondary endpoints were the number of balloon dilation sessions and adverse event rate. RESULTS: No significant differences were found in the worst pathology grade at baseline and length of unstained lesions between the 2 groups. The complete response rates after 1 session of RFA were 73% and 72%, respectively. Compared with the control group, the oral prednisolone group had a significantly lower stricture rate (4% [2/48 patients] vs 44% [11/25 patients]; P < .0001) and a lower number of balloon dilation sessions (median, 0 [range, 0-4] vs 6 [range, 0-10]). Two cases of asymptomatic candida esophagitis occurred in the study group, but no severe adverse effects. CONCLUSIONS: Oral prednisolone may offer a useful and safe preventive option for post-RFA stricture in ultralong ESCNs. (Clinical trial registration number: NCT05768282.).

A Noninferiority Trial Comparing 2 Days vs 5 Days of Terlipressin and Ceftriaxone in Terms of 5-Day Rebleeding for Patients With Acute Gastroesophageal Variceal Hemorrhage.

INTRODUCTION: This trial was to shorten the duration of both vasoconstrictors and prophylactic antibiotics to only 2 days in the therapy of acute gastroesophageal variceal hemorrhage. METHODS: After successful endoscopic hemostasis of gastroesophageal variceal hemorrhage, eligible patients were randomized to receive terlipressin infusion 1 mg per 6 hours and ceftriaxone 1 g daily for 5 days (group A) or a similar regimen for 2 days (group B). Primary end points were very early rebleeding at 5 days, and secondary end points included 48-hour hemostasis, 42-day rebleeding, and hospitalization days. RESULTS: Group A comprised 48 patients, and group B comprised 52 patients. Both groups were comparable in the severity of liver disease. Forty-eight-hour initial hemostasis was 95.8% in group A and 100% in group B ( P = 0.13). Very early rebleeding between 3 and 5 days occurred in 1 patient (2.1%) in group A and 2 patients (3.8%) in group B ( P = 0.60). The difference was 1.8% and the 95% confidence interval was -1.31% to 2.08%, which demonstrated noninferiority. Forty-two-day rebleeding occurred in 5 patients (10.4%) in group A and 4 patients (7.7%) in group B ( P = 0.63). The median hospitalization days were 8.5 ± 3.8 days in group A vs 5.6 ± 2.6 days in group B ( P < 0.001). DISCUSSION: After successful endoscopic hemostasis of acute variceal bleeding, combination of 2-day terlipressin infusion and ceftriaxone therapy was not inferior to the 5-day regimen in terms of very early rebleeding, with the advantage of shortening hospitalization stay.

Prognostic significances of systemic inflammatory response markers in patients with synchronous esophageal and head and neck cancers.

BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) frequently develop synchronous esophageal cancer (ESCC), but there is a lack of clinical predictors. The neutrophil to lymphocyte (NLR), platelet to lymphocyte (PLR), and lymphocyte to monocyte ratios (LMRs), reflect the balance between pro-cancer inflammation and anti-cancer immune responses, but their role in HNSCC and synchronous cancer remain uncertain. METHOD: The study consecutively enrolled a total of 717 patients with newly diagnosed HNSCC who received pre-treatment esophageal endoscopic screening. The pretreatment NLR, LMR and PLRs were calculated and analyzed in comparison with the clinical factors. RESULTS: A total of 103 patients (14.4%) were found to have synchronous ESCCs, and were associated with a significantly lower absolute lymphocyte count (p < 0.001), higher NLRs (p = 0.044) and lower LMRs (p = 0.001), but not PLRs (p = 0.49). The ROC curve for the presence of synchronous ESCC verified the optimal cutoff value as 2.5 for NLRs and 4.0 for LMRs. Multivariable logistic regression revealed that a LMR <4 (OR 2.22; 95% CI 1.27-3.88, p = 0.005), alcohol consumption (OR 4.19; 95% CI 1.47-11.91, p = 0.007), tumor location over the pharynx (OR 1.68; 95% CI 1.07-2.64, p = 0.025), and low body mass index (OR 0.94; 95% CI 0.88-0.99, p = 0.039) were risk factors for developing synchronous ESCC. A low-LMR was significantly associated with decreases in overall survival (p < 0.0001), in both synchronous and non-synchronous groups. Multivariate analysis demonstrated that LMR <4 (HR 1.97; 95% CI 1.38-2.81, p < 0.001), a low-BMI (HR 0.96; 95% CI 0.93-0.99, p = 0.044) and presence of synchronous ESCC (HR 1.56; 95% CI 1.10-2.22, p = 0.013) were independent prognostic factors for HNSCC patients. CONCLUSION: Incorporation of LMR into other identified risk factors, such as alcohol consumption, tumor location over pharynx, and low-BMI, may establish a more efficient screening program for esophageal exploration in HNSCC patients. The significances of LMR also suggest that anti-cancer immunity may play a role in the filed cancerization to initiate multiple cancers, and the immunotherapy may have potentials for prevention or as an adjuvant treatment for synchronous SCC in the future.

Feasibility of new-generation endocytoscopy for the real-time diagnosis of ampullary lesions: A pilot study (with video).

BACKGROUND AND AIM: An early and accurate diagnosis of ampullary neoplasia is crucial; however, sampling bias is still a major concern. New-generation endocytoscopy enables real-time visualization of cellular structures and enables an accurate pathological prediction; however, its feasibility for small ampullary lesions has never been investigated. METHODS: We developed a novel endocytoscopic (EC) classification system for ampullary lesions after an expert review and agreement from five experienced endoscopists and one pathologist. We then consecutively enrolled a total of 43 patients with an enlarged ampulla (< 3 cm), all of whom received an endocytoscopic examination. The feasibility of endocytoscopy was evaluated, and the performance of the EC classification system was then correlated with the final histopathology. RESULTS: In five cases (11.6%), the endocytoscope could not approach the ampulla, and these cases were defined as technical failure. Among the remaining 38 patients, 8 had histopathology-confirmed adenocarcinoma, 15 had adenoma, and 15 had non-neoplastic lesions. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the EC classification system to diagnose ampullary neoplasias were 95.7%, 86.7%, 91.7%, 92.9%, and 92.1%, respectively. Moreover, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the EC classification to diagnose ampullary cancer were 62.5%, 100%, 100%, 90.9%, and 92.1%, respectively. One case with intra-ampullary papillary-tubular carcinoma was classified as having a non-neoplastic lesion by endocytoscopy. CONCLUSIONS: Endocytoscopy and the novel EC classification system demonstrated good feasibility to discriminate ampullary neoplasias from non-neoplastic lesions and may be useful for optical biopsies of clinically suspicious ampullary lesions.

UBE1C is upregulated and promotes neddylation of p53 in lung cancer.

NEDDylation is a type of protein post-translational modification that has high similarity to ubiquitination. UBE1C encodes NEDDylation E1 enzyme, locates at chromatin region 3p14.1 and shows high gene dosage amplification frequency in both Asian and Caucasian lung cancer patients. However, its NEDDylation substrates and roles in tumorigenesis remain elucidated. In this study, we aim to investigate the oncogenic role of UBE1C and its involvement in how NEDDylation regulates p53 in lung cancer. We found that UBE1C mRNA overexpression and DNA amplification in most of the lung cell lines and cancer patients. Patients with UBE1C overexpression showed poor prognosis. Moreover, we demonstrated that overexpression of UBE1C and NEDD8, a NEDDylation moiety, resulted in the p53 NEDDylation with inhibition of p53 acetylation at K373 residue. Importantly, UBE1C-mediated NEDDylation downregulated the transcriptional activity of p53 by inhibiting p53 ability to target promoter regions of its downstream transcription targets, consequently inhibiting the promoter activities and the expression of mRNA and protein of the p53 downstream genes including p21 and PTEN. In addition, UBE1C and NEDD8 overexpression promoted migration, invasion, and proliferation of lung cancer cells. Our findings suggest that UBE1C acts as an oncogene with prognostic potential and highlight a potential role of UBE1C-mediated NEDDylation in downregulation of p53 transcriptional activity in lung cancer.

Performance of the Fecal Immunochemical Test in Detecting Advanced Colorectal Neoplasms and Colorectal Cancers in People Aged 40-49 Years: A Systematic Review and Meta-Analysis.

BACKGROUND: The incidence of early-onset colorectal cancer (CRC) is increasing. Many guidelines recommend initiating screening at 45 years. This study investigated the detection rate of advanced colorectal neoplasm (ACRN) by using fecal immunochemical tests (FITs) in individuals aged 40-49 years. METHODS: PubMed, Embase, and Cochrane Library databases were searched from inception to May 2022. The primary outcomes were the detection rates and positive predictive values of FITs for ACRN and CRC in people aged 40-49 (younger age group) and ≥50 years (average risk group). RESULTS: Ten studies with 664,159 FITs were included. The FIT positivity rate was 4.9% and 7.3% for the younger age and average risk groups, respectively. Younger individuals with positive FIT results had significantly higher risks of ACRN (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.79-3.73) or CRC (OR 2.86, 95% CI 1.59-5.13) than did individuals in the average-risk group, regardless of FIT results. Individuals aged 45-49 years with positive FIT results had a similar risk of ACRN (OR 0.80, 95% CI 0.49-1.29) to that of people aged 50-59 years with positive FIT results, although significant heterogeneity was observed. The positive predictive values of the FIT were 10-28.1% for ACRN and 2.7-6.8% for CRC in the younger age group. CONCLUSION: The detection rate of ACRN and CRC based on FITs in individuals aged 40-49 years is acceptable, and the yield of ACRN might be similar between individuals aged 45-49 and 50-59 years. Further prospective cohort and cost-effective analysis are warranted.

Prognostic significance of systemic inflammatory response markers in patients with superficial esophageal squamous cell carcinomas.

Endoscopic resection or esophagectomy has becoming the standard treatment for superficial esophageal squamous cell carcinomas (SESCC), but some patients may develop disease progression or second primary cancers after the therapies. Neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), and platelet to lymphocyte ratio (PLR) reflect the balance between pro-cancer inflammatory and anti-cancer immune responses, however their roles in SESCC are still unknown. We consecutively enrolled patients with newly diagnosed SESCC (clinical stage Tis or T1N0M0) who were treated at our institute. Pre-treatment NLR, LMR and PLR were assessed and then correlated with clinical factors and long-term survival. A total of 156 patients were enrolled (152 males, 4 females; median age: 52.2 years), of whom 104 received endoscopic resection and 52 were treated with esophagectomy or chemoradiation.. During a mean follow-up period of 60.1 months, seventeen patients died of ESCCs, and 45 died of second primary cancers. The 5-year ESCC-specific survival and 5-year overall survival rate were 86% and 57%, respectively. LMR (P < 0.05) and NLR (P < 0.05), but not PLR were significantly correlated with overall survival. Receiver operating characteristic curve analysis showed optimal LMR and NLR cut-off values of 4 and 2.5, respectively, to predict a poor prognosis. Patients with a high NLR or low LMR tended to have longer tumor length, larger circumferential extension, and presence of second primary cancers. Multivariate Cox regression analysis showed that presence of second primary cancers (HR: 5.05, 95%CI: 2.75-9.28), low LMR (HR: 2.56, 95%CI: 1.09-6.03) were independent risk factors for poor survival. A low pre-treatment LMR may be a non-invasive pretreatment predictor of poor prognosis to guide the surveillance program, suggesting that anti-cancer immunity may play a role in the early events of esophageal squamous cancer.

Implementing precision medicine in endoscopy practice.

In contrast to the "one-size-fits-all" approach, precision medicine focuses on providing health care tailored to individual variabilities. Implementing precision medicine in endoscopy practice involves selecting the appropriate procedures among the endoscopic armamentarium in the diagnosis and management of patients in a logical sequence, jointly considering the pretest probabilities of possible diagnoses, patients' comorbidities and preference, and risk-benefit ratio of the individual procedures given the clinical scenario. The aim of this review is to summarize evidence-supported strategies and measures that may enhance precision medicine in general endoscopy practice.

Association of Heavy Alcohol Intake and ALDH2 rs671 Polymorphism With Hepatocellular Carcinoma and Mortality in Patients With Hepatitis B Virus-Related Cirrhosis.

Importance: The role of heavy alcohol intake, aldehyde dehydrogenase 2 gene (ALDH2) rs671 polymorphism, and hepatitis B virus (HBV) infection in hepatocellular carcinoma (HCC) development and mortality remains uncertain. Objective: To investigate the association of heavy alcohol intake, ALDH2 rs671 polymorphism, and HBV infection with HCC development and mortality in patients with cirrhosis. Design, Setting, and Participants: This retrospective cohort study enrolled patients with cirrhosis with heavy alcoholism or/and HBV infection from January 2005 to December 2020. Patients were followed up through June 30, 2021. The current data analysis was performed from August 2021 to April 2022. Patients from 3 tertiary hospitals in Taiwan were enrolled. Exposures: Heavy alcohol intake was defined as consuming more than 80 g of ethanol each day for at least 5 years. Main Outcomes and Measures: The primary end point was newly developed HCC. The secondary end point was overall mortality. Results: Of 1515 patients with cirrhosis (342 with concomitant heavy alcoholism and HBV infection, 796 with HBV infection alone, and 377 with heavy alcoholism alone), 1277 (84.3%) were men, and their mean (SD) age was 49.5 (10.2) years; 746 patients had blood samples collected for ALDH2 rs671 polymorphism analysis. The 10-year cumulative incidences of HCC and mortality were significantly higher in patients with cirrhosis with concomitant HBV infection and alcoholism than in those with HBV infection alone or alcoholism alone. Heavy alcohol intake and the ALDH2 rs671 genotype (GA/AA) were associated with significantly increased risk of HCC and mortality in patients with HBV-related cirrhosis. In patients with cirrhosis with concomitant HBV infection and alcoholism, factors associated with risk of HCC were baseline serum HBV DNA (adjusted hazard ratio [aHR], 3.24; 95% CI, 1.43-7.31), antiviral therapy (aHR, 0.15; 95% CI, 0.05-0.39), alcohol intake (aHR, 1.78; 95% CI, 1.02-3.12), abstinence (aHR, 0.32; 95% CI, 0.18-0.59), and ALDH2 rs671 polymorphism (aHR, 5.61; 95% CI, 2.42-12.90). Factors associated with increased risk of mortality were abstinence (aHR, 0.25; 95% CI, 0.16-0.32), ALDH2 rs671 polymorphism (aHR, 1.58; 95% CI, 1.09-2.26), Child-Pugh class B vs A (aHR, 1.43; 95% CI, 1.13-2.25) and class C vs A (aHR, 1.98; 95% CI, 1.18-3.31), serum albumin (aHR, 0.61; 95% CI, 0.43-0.86), and HCC development (aHR, 1.68; 95% CI, 1.12-2.89). Conclusions and Relevance: These findings suggest that heavy alcohol intake and ALDH2 rs671 polymorphism are associated with significantly increased risk of HCC development and mortality in patients with HBV-related cirrhosis. Patients with these risk factors should be monitored closely for HCC.

Effect of treatment modality on the long-term survival of patients with early glottic squamous cancer: a retrospective cohort study based on the SEER database.

Background: The optimal treatment strategy for patients with early glottic (T1-2N0M0) squamous cancer remains unclear. Methods: A retrospective population-based analysis was performed using the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was used to balance treatment arms, and Cox regression analysis was used to determine prognostic factors for survival. Kaplan-Meier analysis, log-rank tests, and competing risk analysis were used to compare survival outcomes between treatment modalities (surgery vs. radiotherapy). Results: Among the 3,994 eligible patients in this study, surgery was associated with improved cancer-specific survival (CSS) and overall survival (OS) compared with radiotherapy (log-rank test, P<0.05). This survival trend favoring surgery was consistent in the T1a, well/moderately differentiated grade, male, and all age subgroups. However, after the baseline characteristics were balanced with PSM, the survival outcomes (CSS and OS) did not differ significantly between the surgery and radiotherapy groups. Interestingly, surgery was associated with a 39% reduced risk of cancer-related death compared with radiotherapy in patients aged ≥70 years (hazard ratio 0.61; 95% CI: 0.43-0.87; P=0.006). However, this survival trend favoring surgery was not observed in younger patients (age <70 years), T stage subgroups, male or female subgroups, or in any of the pathological grade subgroups. Conclusions: In patients with early glottic squamous cell carcinoma undergoing surgery or radiotherapy, there is no sufficient evidence favoring one method over another in terms of survival. However, surgery is recommended in patients aged ≥70 years because, in this group, it was associated with improved survival outcomes compared with radiotherapy.

Antireflux mucosal intervention (ARMI) procedures for refractory gastroesophageal reflux disease: a systematic review and meta-analysis.

Background: Endoscopic treatments are increasingly being offered for refractory gastroesophageal reflux disease (GERD). Three procedures have similar concepts and techniques: antireflux mucosectomy (ARMS), antireflux mucosal ablation (ARMA), and antireflux band ligation (ARBL); we have collectively termed them antireflux mucosal intervention (ARMI). Here, we systematically reviewed the clinical outcomes and technical aspects. Methods: The PubMed, Embase, and Cochrane Library databases were searched from inception to October 2021. The primary outcome was the clinical success rate. The secondary outcomes were acid exposure time, DeMeester score, need for proton pump inhibitors (PPIs), endoscopic findings, and adverse events. Results: Fifteen studies were included. The pooled clinical success rate was 73.8% (95% confidence interval (CI) = 69%-78%) overall, 68.6% (95% CI = 62.2%-74.4%) with ARMS, 86.7% (95% CI = 78.7%-91.9%) with ARMA, and 76.5% (95% CI = 65%-85.1%) with ARBL. ARMI resulted in significantly improved acid exposure time, DeMeester score, and degree of hiatal hernia. Furthermore, 10% of patients had dysphagia requiring endoscopic dilatation after ARMS or ARMA, and ARMS was associated with a 2.2% perforation rate. By contrast, no bleeding, perforation, or severe dysphagia was noted with ARBL. Severe hiatal hernia (Hill grade III) may predict treatment failure with ARMA. Conclusions: The three ARMI procedures were efficacious and safe for PPI-refractory GERD. ARMA and ARBL may be preferred over ARMS because of fewer adverse events and similar efficacy. Further studies are necessary to determine the optimal technique and patient selection.

Alcohol Consumption, ALDH2 Polymorphism as Risk Factors for Upper Aerodigestive Tract Cancer Progression and Prognosis.

The upper aerodigestive tract (UADT) is highly susceptible to multiple primary cancers originated from squamous epithelia and constitutes a field of cancerization. Patients with head and neck cancer (head and neck squamous cell carcinoma, HNSCC) are at high risk of developing multiple cancers in the esophagus (esophageal squamous cell carcinoma, ESCC). Conversely, esophageal cancer patients are prone to develop multiple primary tumors in the head and neck region. The East Asian-specific dysfunctional ALDH2*2 missense mutation is a genetic risk factor for UADT cancer. It is not only associated with increased incidences of UADT cancer, but is also implicated in faster cancer progression and poorer prognosis. Alcohol use is a major lifestyle risk factor which causes UADT cancer among ALDH2*2 carriers. The accumulation of the immediate metabolite of alcohol, acetaldehyde, is likely the genotoxic agents that is involved in the process of tumorigenesis. This review summarizes recent publications on the risk and association of ALDH2*2 mutation, alcohol consumption in synchronous, metachronous UADT cancer. Possible molecular mechanisms involved in cancer initiation, progress and prognosis are discussed. The review also highlights a need for precision medicine-based preventive and therapeutic strategies by integrating lifestyle and genetic risk factors, such as alcohol consumption, genotypes of the alcohol metabolizing genes, ADH1B and ALDH2, into a risk assessment model for better screening, surveillance and treatment outcome.

Safety of cold snare polypectomy with periprocedural antithrombotic agents for colorectal polyps: a systematic review and meta-analysis.

BACKGROUND: We aimed to study the safety of cold snare polypectomy (CSP) for colorectal polyps in patients administered periprocedural antithrombotic agents. METHODS: We searched the PubMed, Embase, and Cochrane Library databases through June 2021. The primary outcomes were the rates of delayed and immediate bleeding (requiring endoscopic hemostasis). Secondary outcomes included thromboembolic events. Meta-analysis using odds ratios (ORs) and corresponding 95% confidence intervals (CIs) was performed to compare the outcomes. RESULTS: Seventeen studies, including five randomized trials, were included. Over 96% of polyps were ⩽1 cm. The pooled rates of delayed and immediate bleeding for patients receiving CSP and periprocedural antithrombotic agents were 1.6% and 10.5%, respectively. Both the delayed (OR = 4.02, 95% CI = 1.98-8.17) and immediate bleeding (OR = 5.85, 95% CI = 3.84-8.89) rates were significantly higher in patients using periprocedural antithrombotic agents than in non-users. Although both antiplatelet agents and anticoagulants increased the risk of delayed bleeding, the risks associated with the use of direct oral anticoagulants (DOACs; 2.5%) or multiple agents (3.9%) were particularly high. Compared to their counterparts, diminutive polyps and uncomplicated lesions not requiring hemoclipping were associated with lower risks of delayed bleeding (pooled estimates of 0.4% and 0.18%, respectively). Thromboembolic risk was similar among patients using and not using periprocedural antithrombotic agents. CONCLUSIONS: CSP with periprocedural antiplatelet agents and warfarin may be feasible, especially for diminutive polyps. However, drug discontinuation should be considered with the use of DOACs or multiple agents which entail higher bleeding risk even with hemoclipping.

Assessment of tumor extension to the ductal system of submucosal glands in patients with superficial esophageal squamous neoplasms: Implications for endoscopic resection.

BACKGROUND: Endoscopic submucosal dissection (ESD) has become the standard treatment for superficial esophageal squamous cell neoplasia (SESCN); however, local recurrence still occurs occasionally even in patients who meet the current curative criteria. Esophageal ducts of the submucosal gland may serve as a pathway for the spread of SESCN to a deeper layer. However, the clinical impact of ductal involvement (DI) in patients undergoing ESD has yet to be investigated. METHODS: We consecutively enrolled patients with SESCN who were treated with ESD. The resected specimens were meticulously reviewed in multiple section slices for the presence and resected margins of DI, and their correlations with clinical factors were evaluated. RESULTS: A total of 210 lesions were analyzed, of which 78 (37.1%) presented with DI. The presence of submucosal invasion, lymphovascular invasion (LVI), and DI were indicators of worse prognosis (P < .05). Deep extended DIs were misdiagnosed as deep submucosal invasive cancer in 4 cases (2%). Of the 185 patients who met the criteria for curative ESD (ie, R0 resection and no deep submucosal invasion or LVI), 11 (5.9%) developed local recurrence/metastasis during a mean follow-up of 55.2 months (range, 6 to 140) months. Compared with patients with without DI, patients with DI had worse recurrence-free survival (P = .008, log-rank test) and a higher local risk of recurrence (12.7% vs 2.5%) after curative ESD (hazard ratio, 4.20; P = .038). CONCLUSIONS: A precise histological assessment of DI in SESCN is crucial after ESD, given that DI is common and associated with worse outcome. Whether total removal of esophageal glands/ducts can improve outcome requires future study.