Endoscopic Resections for Barrett's Neoplasia: A Long-Term, Single-Center Follow-Up Study.

Background and Objectives: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are both well-established and effective treatments for dysplasia and early cancer in Barrett's esophagus (BE). This study aims to compare the short- and long-term outcomes associated with these procedures in treating Barrett's neoplasia. Materials and Methods: This single-center retrospective cohort study included 95 patients, either EMR (n = 67) or ESD (n = 28), treated for Barrett's neoplasia at Sahlgrenska University Hospital between 2004 and 2019. The primary outcome was the complete (en-bloc) R0 resection rate. Secondary outcomes included the curative resection rate, additional endoscopic resections, adverse events, and overall survival. Results: The complete R0 resection rate was 62.5% for ESD compared to 16% for EMR (p < 0.001). The curative resection rate for ESD was 54% versus 16% for EMR (p < 0.001). During the follow-up, 22 out of 50 patients in the EMR group required additional endoscopic resections (AERs) compared to 3 out of 21 patients in the ESD group (p = 0.028). There were few adverse events associated with both EMR and ESD. In both the stratified Kaplan-Meier survival analysis (Log-rank test, Chi-square = 2.190, df = 1, p = 0.139) and the multivariate Cox proportional hazards model (hazard ratio of 0.988; 95% CI: 0.459 to 2.127; p = 0.975), the treatment group (EMR vs. ESD) did not significantly impact the survival outcomes. Conclusions: Both EMR and ESD are effective and safe treatments for BE neoplasia with few adverse events. ESD resulted in higher curative resection rates with fewer AERs, indicating its potential as a primary treatment modality. However, the survival analysis showed no difference between the methods, highlighting their comparable long-term outcomes.

Expert assessment of infiltration depth and recommendation of endoscopic resection technique in early Barrett cancer.

BACKGROUND: Early Barrett cancer can be curatively treated by endoscopic resection. The choice of the resection technique, however-endoscopic mucosal resection (EMR) or submucosal dissection (ESD)-largely depends on the assumed infiltration depth as judged by the endoscopist. However, the accuracy of endoscopic diagnosis of the degree of cancer infiltration is not known. METHODS: Three to four high-quality images (both in overview and close-up) from 202 of early Barrett esophagus cancer cases (82% men, mean age 66.9 years) were selected from our endoscopy database (73.3% stage T1a and 26.7% in stage T1b). Images were shown to 9 Barrett esophagus experts, with patients' clinical data (age, sex, Barrett esophagus length) and biopsy results. The experts were asked to predict infiltration depth (T1b vs. T1a), and to suggest the appropriate endoscopic resection technique (EMR or ESD, or surgery). Interobserver variability (kappa values) was also determined for these parameters. RESULTS: Overall positive (PPV) and negative predictive values (NPV) to diagnose T1b versus T1a infiltration were 40.7% (95% CI: 36.7, 44.8) and 79.8% (95% CI: 77.5, 81.9), respectively; kappa value was 0.41. Paris classification (kappa 0.51) and suggested treatment also varied between experts. In a post hoc analysis, only the correlation between lesions classified as invisible or flat according to the Paris classification (IIB; 25% of all cases) and the suggested resection technique was better: In this subgroup, EMR was recommended in >80% of cases, with a high complete (basal R0) resection rate (mean of 88.1%). CONCLUSIONS: Precise endoscopic distinction between mucosal and submucosal involvement of Barrett esophagus cancer by experts as a basis for choosing the resection technique has limited predictive values and high interobserver variability. It seems that mainly invisible/flat lesions may result in good resection outcomes when treated by EMR, but this stratification strategy has to be assessed in further studies.

Significant and distinct impacts of sleeve gastrectomy and Roux-en-Y gastric bypass on esophageal acid exposure, esophageal motility, and endoscopic findings: a systematic review and meta-analysis.

BACKGROUND: The lack of standardized objective assessment of esophageal physiology and anatomy contributes to controversies regarding the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on gastroesophageal reflux disease. This study aimed to investigate esophageal acid exposure, esophageal motility, and endoscopic findings before and after SG and RYGB. METHODS: This was a systematic review and meta-analysis of studies reporting at least 1 objective measure of esophageal physiology and/or esophagogastroduodenoscopy (EGD) at baseline and after SG or RYGB. The changes in pH test, manometry, and EGD parameters were summarized. RESULTS: Acid exposure time (AET) and DeMeester score (DMS) significantly increased after SG (mean difference [MD]: 2.1 [95% CI, 0.3-3.9] and 8.6 [95% CI, 2.0-15.2], respectively). After RYGB, both AET and DMS significantly decreased (MD: -4.2 [95% CI, -6.1 to -2.3] and -16.6 [95% CI, -25.4 to -7.8], respectively). Lower esophageal sphincter resting pressure and length significantly decreased after SG (MD: -2.8 [95% CI, -4.6 to -1.1] and -0.1 [95% CI, -0.2 to -0.02], respectively). There were no significant changes in esophageal manometry after RYGB. The relative risks of erosive esophagitis were 2.3 (95% CI, 1.5-3.5) after SG and 0.4 (95% CI, 0.2-0.8) after RYGB. The prevalence rates of Barrett esophagus changed from 0% to 3.6% after SG and from 2.7% to 1.4% after RYGB. CONCLUSION: SG resulted in the worsening of all objective parameters, whereas RYGB resulted in the improvement in AET, DMS, and EGD findings. Determining the risk factors associated with these outcomes can help in surgical choice.

Long- vs short-segment Barrett's esophagus-derived adenocarcinoma: clinical features and outcomes of endoscopic submucosal dissection.

BACKGROUND: The incidence of Barrett's esophageal adenocarcinoma (BEA) is increasing, and endoscopic submucosal dissection (ESD) has been frequently performed for its treatment. However, the differences between the characteristics and ESD outcomes between short- and long-segment BEA (SSBEA and LSBEA, respectively) are unclear. We compared the clinicopathological characteristics and short- and long-term outcomes of ESD between both groups. METHODS: We retrospectively reviewed 155 superficial BEAs (106 SSBEAs and 49 LSBEAs) treated with ESD in 139 patients and examined their clinicopathological features and ESD outcomes. SSBEA and LSBEA were classified based on whether the maximum length of the background mucosa of BEA was < 3 cm or ≥ 3 cm, respectively. RESULTS: Compared with SSBEA, LSBEA showed significantly higher proportions of cases with the macroscopically flat type (36.7% vs. 5.7%, p < 0.001), left wall location (38.8% vs. 11.3%, p < 0.001), over half of the tumor circumference (20.4% vs. 1.9%, p < 0.001), and synchronous lesions (17.6% vs. 0%, p < 0.001). Compared with SSBEA, regarding ESD outcomes, LSBEA showed significantly longer resection duration (91.0 min vs. 60.5 min, p < 0.001); a lower proportion of submucosal invasion (14.3% vs. 29.2%, p = 0.047), horizontal margin negativity (79.6% vs. 94.3%, p = 0.0089), and R0 resection (69.4% vs. 86.8%, p = 0.024); and a higher proportion of post-procedural stenosis cases (10.9% vs. 1.9%, p = 0.027). The 5-year cumulative incidence of metachronous cancer in patients without additional treatment was significantly higher for LSBEA than for SSBEA (25.0% vs. 0%, p < 0.001). CONCLUSIONS: The clinicopathological features of LSBEA and SSBEA and their treatment outcomes differed in many aspects. As LSBEAs are difficult to diagnose and treat and show a high risk of metachronous cancer development, careful ESD and follow-up or eradication of the remaining BE may be required.

Comparison of interventions for Barrett's esophagus: A network meta-analysis.

BACKGROUND AND OBJECTIVE: Barrett's esophagus (BE) is a precancerous condition that has the potential to develop into esophageal cancer (EC). Currently, there is a wide range of management options available for individuals at different pathological stages in Barrett's esophagus (BE). However, there is currently a lack of knowledge regarding their comparative efficacy. To address this gap, we conducted a network meta-analysis of published randomized controlled trials to examine the comparative effectiveness of all regimens. METHODS: Data extracted from eligible randomized controlled trials were utilized in a Bayesian network meta-analysis to examine the relative effectiveness of BE's treatment regimens and determine their ranking in terms of efficacy. The ranking probability for each regimen was assessed using the surfaces under cumulative ranking values. The outcomes under investigation were complete ablation of BE, neoplastic progression of BE, and complete eradication of dysplasia. RESULTS: We identified twenty-three RCT studies with a total of 1675 participants, and ten different interventions. Regarding complete ablation of non-dysplastic BE, the comparative effectiveness ranking indicated that argon plasma coagulation (APC) was the most effective regimen, with the highest SUCRA value, while surveillance and PPI/H2RA were found to be the least efficacious regimens. For complete ablation of BE with low-grade dysplasia, high-grade dysplasia, or esophageal cancer, photodynamic therapy (PDT) had the highest SUCRA value of 94.1%, indicating it as the best regimen. Additionally, for complete eradication of dysplasia, SUCRA plots showed a trend in ranking PDT as the highest with a SUCRA value of 91.2%. Finally, for neoplastic progression, radiofrequency ablation (RFA) and surgery were found to perform significantly better than surveillance. The risk of bias assessment revealed that 6 studies had an overall high risk of bias. However, meta-regression with risk of bias as a covariate did not indicate any influence on the model. In terms of the Confidence in Network Meta-Analysis evaluation, a high level of confidence was found for all treatment comparisons. CONCLUSION: Endoscopic surveillance alone or PPI/H2RA alone may not be sufficient for managing BE, even in cases of non-dysplastic BE. However, APC has shown excellent efficacy in treating non-dysplastic BE. For cases of BE with low-grade dysplasia, high-grade dysplasia, or esophageal cancer, PDT may be the optimal intervention as it can induce regression of BE metaplasia and prevent future progression of BE to dysplasia and EC.

AGA Clinical Practice Guideline on Endoscopic Eradication Therapy of Barrett's Esophagus and Related Neoplasia.

BACKGROUND & AIMS: Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Endoscopic eradication therapy (EET) can be effective in eradicating BE and related neoplasia and has greater risk of harms and resource use than surveillance endoscopy. This clinical practice guideline aims to inform clinicians and patients by providing evidence-based practice recommendations for the use of EET in BE and related neoplasia. METHODS: The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients, conducted an evidence review, and used the Evidence-to-Decision Framework to develop recommendations regarding the use of EET in patients with BE under the following scenarios: presence of (1) high-grade dysplasia, (2) low-grade dysplasia, (3) no dysplasia, and (4) choice of stepwise endoscopic mucosal resection (EMR) or focal EMR plus ablation, and (5) endoscopic submucosal dissection vs EMR. Clinical recommendations were based on the balance between desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 5 recommendations for the use of EET in BE and related neoplasia. Based on the available evidence, the panel made a strong recommendation in favor of EET in patients with BE high-grade dysplasia and conditional recommendation against EET in BE without dysplasia. The panel made a conditional recommendation in favor of EET in BE low-grade dysplasia; patients with BE low-grade dysplasia who place a higher value on the potential harms and lower value on the benefits (which are uncertain) regarding reduction of esophageal cancer mortality could reasonably select surveillance endoscopy. In patients with visible lesions, a conditional recommendation was made in favor of focal EMR plus ablation over stepwise EMR. In patients with visible neoplastic lesions undergoing resection, the use of either endoscopic mucosal resection or endoscopic submucosal dissection was suggested based on lesion characteristics. CONCLUSIONS: This document provides a comprehensive outline of the indications for EET in the management of BE and related neoplasia. Guidance is also provided regarding the considerations surrounding implementation of EET. Providers should engage in shared decision making based on patient preferences. Limitations and gaps in the evidence are highlighted to guide future research opportunities.

Treatment of esophageal adenocarcinoma in patients with a history of bariatric surgery.

BACKGROUND: The relationship among obesity, bariatric surgery, and esophageal adenocarcinoma (EAC) is complex, given that some bariatric procedures are thought to be associated with increased incidence of reflux and Barrett's esophagus. Previous bariatric surgery may complicate the use of the stomach as a conduit for esophagectomy. In this study, we presented our experience with patients who developed EAC after bariatric surgery and described the challenges encountered and the techniques used. METHODS: We conducted a retrospective review of our institutional database to identify all patients at our institution who were treated for EAC after previously undergoing bariatric surgery. RESULTS: In total, 19 patients underwent resection with curative intent for EAC after bariatric surgery, including 10 patients who underwent sleeve gastrectomy. The median age at diagnosis of EAC was 63 years; patients who underwent sleeve gastrectomy were younger (median age, 56 years). The median time from bariatric surgery to EAC was 7 years. Most patients had a body mass index (BMI) score of >30 kg/m2 at the time of diagnosis of EAC; approximately 40% had class III obesity (BMI score > 40 kg/m2). Six patients (32%) had known Barrett's esophagus before undergoing a reflux-increasing bariatric procedure. Sleeve gastrectomy patients underwent esophagectomy with gastric conduit, colonic interposition, or esophagojejunostomy. Only 1 patient had an anastomotic leak (after esophagojejunostomy). CONCLUSION: Endoscopy should be required both before (for treatment selection) and after all bariatric surgical procedures. Resection of EAC after bariatric surgery requires a highly individualized approach but is safe and feasible.

Update on applications of endoscopic cryotherapy in the gastrointestinal tract.

PURPOSE OF REVIEW: Endoscopic cryotherapy has emerged as a minimally invasive procedure for targeted tissue ablation within the gastrointestinal tract. This review aims to provide a comprehensive overview of current clinical applications of EC with a review of the pertinent literature. RECENT FINDINGS: Endoscopic cryotherapy has demonstrated safety and efficacy for various gastrointestinal conditions. Recent studies have highlighted the efficacy of endoscopic cryotherapy, including both liquid nitrogen-based spray cryotherapy and the novel cryoballoon focal ablation system, in achieving complete eradication of dysplasia and neoplasia in Barrett's esophagus. Endoscopic cryotherapy has also shown promise as a second-line treatment option for patients with dysplastic Barrett's esophagus refractory to radiofrequency ablation and as an alternative to surgical resection for duodenal adenomas, when endoscopic resection is not feasible. Innovative applications for the treatment of gastrointestinal bleeding and management of benign refractory esophageal strictures have also been reported. SUMMARY: Endoscopic cryotherapy represents a safe, effective, and well tolerated therapeutic option for various clinical scenarios in gastrointestinal endoscopy, including challenging disease states such as refractory Barrett's esophagus and advanced esophageal cancer. Advancements in cryotherapy technology and ongoing research continue to explore additional clinical indications and expand the role of endoscopic cryotherapy in patient care with an aim toward improved patient outcomes.

Safety and efficacy of salvage endoscopic submucosal dissection for Barrett's neoplasia recurrence after radiofrequency ablation.

BACKGROUND: This study evaluated the safety and efficacy of salvage endoscopic submucosal dissection (ESD) for Barrett's neoplasia recurrence after radiofrequency ablation (RFA). METHODS: Data from patients at 16 centers were collected for a multicenter retrospective study. Patients who underwent at least one RFA treatment for Barrett's esophagus and thereafter underwent further esophageal ESD for neoplasia recurrence were included. RESULTS: Data from 56 patients who underwent salvage ESD between April 2014 and November 2022 were collected. Immediate complications included one muscular tear (1.8%) treated with stent (Agree classification: grade IIIa). Two transmural perforations (3.6%; treated with clips) and five muscular tears (8.9%; two treated with clips) had no clinical impact and were not considered as adverse events. Seven patients (12.5%) developed strictures (grade IIIa), which were treated with balloon dilation. Histological analysis showed 36 adenocarcinoma, 17 high grade dysplasia, and 3 low grade dysplasia. En bloc and R0 resection rates were 89.3% and 66.1%, respectively. Resections were curative in 33 patients (58.9%), and noncurative in 22 patients (39.3%), including 11 "local risk" (19.6%) and 11 "high risk" (19.6%) resections. At the end of follow-up with a median time of 14 (0-75) months after salvage ESD, and with further endoscopic treatment if necessary (RFA, argon plasma coagulation, endoscopic mucosal resection, ESD), neoplasia remission ratio was 37/53 (69.8%) and the median remission time was 13 (1-75) months. CONCLUSION: In expert hands, salvage ESD was a safe and effective treatment for recurrence of Barrett's neoplasia after RFA treatment.

The use of a real-time computer-aided detection system for visible lesions in the Barrett's esophagus during live endoscopic procedures: a pilot study (with video).

BACKGROUND AND AIMS: This pilot study evaluated the performance of a recently developed computer-aided detection (CADe) system for Barrett's neoplasia during live endoscopic procedures. METHODS: Fifteen patients with a visible lesion and 15 without were included in this study. A CAD-assisted workflow was used that included a slow pullback video recording of the entire Barrett's segment with live CADe assistance, followed by CADe-assisted level-based video recordings every 2 cm of the Barrett's segment. Outcomes were per-patient and per-level diagnostic accuracy of the CAD-assisted workflow, in which the primary outcome was per-patient in vivo CADe sensitivity. RESULTS: In the per-patient analyses, the CADe system detected all visible lesions (sensitivity 100%). Per-patient CADe specificity was 53%. Per-level sensitivity and specificity of the CADe-assisted workflow were 100% and 73%, respectively. CONCLUSIONS: In this pilot study, detection by the CADe system of all potentially neoplastic lesions in Barrett's esophagus was comparable to that of an expert endoscopist. Continued refinement of the system may improve specificity. External validation in larger multicenter studies is planned. (Clinical trial registration number: NCT05628441.).

Risk stratification for synchronous/metachronous recurrence after endoscopic submucosal dissection for Barrett's esophageal adenocarcinoma using the length of Barrett's esophagus.

BACKGROUND: In Japan, the standard management of Barrett's esophageal adenocarcinoma after endoscopic submucosal dissection involves follow-up; however, multifocal synchronous/metachronous lesions are sometimes observed after endoscopic submucosal dissection. Risk stratification of multifocal cancer facilitates appropriate treatment, including eradication of Barrett's esophagus in high-risk cases; however, no effective risk stratification methods have been established. Thus, we identified the risk factors for multifocal cancer and explored risk-stratified treatment strategies for residual Barrett's esophagus. METHODS: We retrospectively reviewed the data of 97 consecutive patients with superficial Barrett's esophageal adenocarcinomas who underwent curative resection with endoscopic submucosal dissection. Multifocal cancer was defined by the presence of synchronous/metachronous lesions during follow-up. We used Cox regression analysis to identify the risk factors for multifocal cancer and subsequently analyzed differences in cumulative incidences. RESULTS: The cumulative incidences of multifocal cancer at 1, 3, and 5 years were 4.4%, 8.6%, and 10.7%, respectively. Significant risk factors for multifocal cancer were increased circumferential and maximal lengths of Barrett's esophagus. The cumulative incidences of multifocal cancer at 3 years were lower for patients with circumferential length < 4 cm and maximal length < 5 cm (2.9% and 1.2%, respectively) than for patients with circumferential length ≥ 4 cm and maximal length ≥ 5 cm (51.5% and 49.1%, respectively). CONCLUSIONS: Risk stratification of multifocal cancer using length of Barrett's esophagus was effective. Further multicenter prospective studies are needed to substantiate our findings.

Incidence and Prediction of Unrelated Mortality After Successful Endoscopic Eradication Therapy for Barrett's Neoplasia.

BACKGROUND & AIMS: Follow-up (FU) strategies after endoscopic eradication therapy (EET) for Barrett's neoplasia do not consider the risk of mortality from causes other than esophageal adenocarcinoma (EAC). We aimed to evaluate this risk during long-term FU, and to assess whether the Charlson Comorbidity Index (CCI) can predict mortality. METHODS: We included all patients with successful EET from the nationwide Barrett registry in the Netherlands. Data were merged with National Statistics for accurate mortality data. We evaluated annual mortality rates (AMRs, per 1000 person-years) and standardized mortality ratio for other-cause mortality. Performance of the CCI was evaluated by discrimination and calibration. RESULTS: We included 1154 patients with a mean age of 64 years (±9). During median 59 months (p25-p75 37-91; total 6375 person-years), 154 patients (13%) died from other causes than EAC (AMR, 24.1; 95% CI, 20.5-28.2), most commonly non-EAC cancers (n = 58), cardiovascular (n = 31), or pulmonary diseases (n = 26). Four patients died from recurrent EAC (AMR, 0.5; 95% CI, 0.1-1.4). Compared with the general Dutch population, mortality was significantly increased for patients in the lowest 3 age quartiles (ie, age <71 years). Validation of CCI in our population showed good discrimination (Concordance statistic, 0.78; 95% CI, 0.72-0.84) and fair calibration. CONCLUSION: The other-cause mortality risk after successful EET was more than 40 times higher (48; 95% CI, 15-99) than the risk of EAC-related mortality. Our findings reveal that younger post-EET patients exhibit a significantly reduced life expectancy when compared with the general population. Furthermore, they emphasize the strong predictive ability of CCI for long-term mortality after EET. This straightforward scoring system can inform decisions regarding personalized FU, including appropriate cessation timing. (NL7039).