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Background This study evaluated the proportion of patients with residual neoplasia after endoscopic resection (ER) for Barrett's neoplasia with confirmed tumor-positive vertical resection margin (R1v). Methods This retrospective cohort study included patients undergoing ER for Barrett's neoplasia with histologically documented R1v since 2008 in the Dutch Barrett Expert Centers. We defined R1v as cancer cells touching vertical resection margins and Rx as nonassessable margins. Reassessment of R1v specimens was performed by experienced pathologists until consensus was reached regarding vertical margins. Results 101/110 included patients had macroscopically complete resections (17 T1a, 84 T1b), and 99/101 (98%) ER specimens were histologically reassessed, with R1v confirmed in 74 patients (75%), Rx in 16%, and R0 in 9%. Presence/absence of residual neoplasia could be assessed in 66/74 patients during endoscopic reassessment (52) and/or in the surgical resection specimen (14), and 33/66 (50%) had residual neoplasia. Residual neoplasia detected during endoscopy was always endoscopically visible and biopsies from a normal-appearing ER scar did not detect additional neoplasia. Of 25 patients who underwent endoscopic follow-up (median 37 months [interquartile range 12–50]), 4 developed local recurrence (16.0%), all detected as visible abnormalities. Conclusions After ER with R1v, 50% of patients had no residual neoplasia. Histological evaluation of ER margins appears challenging, as in this study 75% of documented R1v cases were confirmed during reassessment. Endoscopic reassessment 8–12 weeks after ER seems to accurately detect residual neoplasia and can help to determine the most appropriate strategy for patients with R1v. [ABSTRACT FROM AUTHOR]

Background: The use of endoscopic submucosal dissection (ESD) is gradually expanding for treatment of neoplasia in Barrett's esophagus (BE). We aimed to report outcomes of all ESDs for BE neoplasia performed in the Netherlands.Methods: Retrospective assessment of outcomes, using treatment and follow-up data from a joint database.Results: 130/138 patients had complete ESDs, with 126/130 (97 %) en bloc resections. Median (interquartile range (IQR)) procedure time was 121 minutes (90-180). Pathology findings were high grade dysplasia (HGD) (5 %) or esophageal adenocarcinoma (EAC) T1a (43 %) or T1b (52 %; 19 % sm1, 33 % ≥ sm2). Among resections of HGD or T1a EAC lesions, 87 % (95 %CI 75 %-92 %) were both en bloc and R0; the corresponding value for T1b EAC lesions was 49 % (36 %-60 %). Among R1 resections, 10/34 (29 %) showed residual cancer, all detected at first endoscopic follow-up. The remaining 24 patients (71 %) showed no residual neoplasia. Six of these patients underwent surgery with no residual tumor; the remaining 18 underwent endoscopic follow-up during median 31 months with 1 local recurrence (annual recurrence rate 2 %). Among R0 resections, annual local recurrence rate during median 27 months was 0.5 %.Conclusion: In expert hands, ESD allows safe removal of bulky intraluminal neoplasia and submucosal cancer. ESD of the latter showed R1 resection margins in 50 %, yet only one third had persisting neoplasia at follow-up. To better stratify R1 patients with an indication for additional surgery, repeat endoscopy after healing of the ESD might be a helpful possible prognostic factor for residual cancer. [ABSTRACT FROM AUTHOR]

Background: Endoscopic eradication therapy with radiofrequency ablation (RFA) is effective in most patients with Barrett's esophagus (BE). However, some patients experience poor healing and/or poor squamous regeneration. We evaluated incidence and treatment outcomes of poor healing and poor squamous regeneration.Methods: We included all patients treated with RFA for early BE neoplasia from a nationwide Dutch registry based on a joint treatment protocol. Poor healing (active inflammatory changes or visible ulcerations ≥ 3 months post-RFA), poor squamous regeneration (< 50 % squamous regeneration), and treatment success (complete eradication of BE [CE-BE]) were evaluated.Results: 1386 patients (median BE C2M5) underwent RFA with baseline low grade dysplasia (27 %), high grade dysplasia (30 %), or early cancer (43 %). In 134 patients with poor healing (10 %), additional time and acid suppression resulted in complete esophageal healing, and 67/134 (50 %) had normal squamous regeneration with 97 % CE-BE. Overall, 74 patients had poor squamous regeneration (5 %). Compared with patients with normal regeneration, patients with poor squamous regeneration had a higher risk for treatment failure (64 % vs. 2 %, relative risk [RR] 27 [95 % confidence interval [CI] 18-40]) and progression to advanced disease (15 % vs. < 1 %, RR 30 [95 %CI 12-81]). Higher body mass index, longer BE segment, reflux esophagitis, and < 50 % squamous regeneration after baseline endoscopic resection were independently associated with poor squamous regeneration in multivariable logistic regression.Conclusions: In half of the patients with poor healing, additional time and acid suppression led to normal squamous regeneration and excellent treatment outcomes. In patients with poor squamous regeneration, however, the risk for treatment failure and progression to advanced disease was significantly increased. [ABSTRACT FROM AUTHOR]

Background: Lymph node metastasis (LNM) is possible after endoscopic resection of early esophageal adenocarcinoma (EAC). This study aimed to develop and internally validate a prediction model that estimates the individual risk of metastases in patients with pT1b EAC.Methods: A nationwide, retrospective, multicenter cohort study was conducted in patients with pT1b EAC treated with endoscopic resection and/or surgery between 1989 and 2016. The primary end point was presence of LNM in surgical resection specimens or detection of metastases during follow-up. All resection specimens were histologically reassessed by specialist gastrointestinal pathologists. Subdistribution hazard regression analysis was used to develop the prediction model. The discriminative ability of this model was assessed using the c-statistic.Results: 248 patients with pT1b EAC were included. Metastases were seen in 78 patients, and the 5-year cumulative incidence was 30.9 % (95 % confidence interval [CI] 25.1 %-36.8 %). The risk of metastases increased with submucosal invasion depth (subdistribution hazard ratio [SHR] 1.08, 95 %CI 1.02-1.14, for every increase of 500 μm), lymphovascular invasion (SHR 2.95, 95 %CI 1.95-4.45), and for larger tumors (SHR 1.23, 95 %CI 1.10-1.37, for every increase of 10 mm). The model demonstrated good discriminative ability (c-statistic 0.81, 95 %CI 0.75-0.86).Conclusions: A third of patients with pT1b EAC experienced metastases within 5 years. The probability of developing post-resection metastases was estimated with a personalized predicted risk score incorporating tumor invasion depth, tumor size, and lymphovascular invasion. This model requires external validation before implementation into clinical practice. [ABSTRACT FROM AUTHOR]

BACKGROUND : Clinical tumor stage of esophageal adenocarcinoma (EAC) is determined by endoscopic ultrasound and/or computed tomography scan, which have low accuracy for stages T1 and T2, potentially leading to overtreatment. We aimed to assess the proportion of cT2 EACs downstaged to cT1 after endoscopic reassessment (ERA) by an experienced interventional endoscopist. METHODS : We performed a prospective multicenter cohort study. Patients with cT2N0M0 EAC were included and underwent ERA. The primary outcome was proportion of cT2 EACs downstaged to cT1 after ERA. RESULTS : 15/25 included patients (60 %) were downstaged from cT2 to cT1 EAC after ERA and underwent attempted endoscopic resection. Endoscopic resection was aborted in 3/15 patients because of tumor invasion into the muscle layer; all three underwent successful surgical resection. Endoscopic resection was successful in 12/15 patients (80 %), all of whom had pT1 tumors. Overall, 10/25 (40 %) were treated with endoscopic resection alone. CONCLUSIONS : ERA downstaged about half of the cT2 tumors to cT1, rendering them suitable for endoscopic resection. ERA had substantial clinical impact on therapeutic management, preventing overtreatment in 40 % of patients. [ABSTRACT FROM AUTHOR]

Background: Early detection of esophageal secondary primary tumors (SPTs) in head and neck squamous cell carcinoma (HNSCC) patients could increase patient survival. The purpose of this study was to determine the diagnostic yield of esophageal SPTs using Lugol chromoendoscopy. Methods: A systematic review of all available databases was performed to find all Lugol chromoendoscopy screening studies. Results: Fifteen studies with a total of 3386 patients were included. The average yield of esophageal‐SPTs in patients with HNSCC was 15%. The prevalence was the highest for patients with an index hypopharyngeal (28%) or oropharyngeal (14%) tumor. The esophageal‐SPTs were classified as high‐grade dysplasia in 49% of the cases and as invasive carcinoma's in 51%. Conclusion: Our results show that 15% of the patients with HNSCC that underwent Lugol chromoendoscopy were diagnosed with an esophageal‐SPT. Based on these results there is enough evidence to perform Lugol chromoendoscopy, especially in an Asian patient population. [ABSTRACT FROM AUTHOR]

Background and study aims  Retrospectively, minimally 5% of patients with esophageal squamous cell carcinoma (ESCC) and 11 % with head and neck squamous cell carcinoma (HNSCC) in Western countries developed a second primary tumor (SPT). SPT screening in ESCC and HNSCC patients is not implemented routinely in daily practice in many Western countries. This study aimed to assess medical specialist knowledge and opinions regarding screening for head and neck SPTs (HNSPTs) in ESCC patients and vice versa in the Netherlands. Methods  A nationwide survey among gastroenterologists and head and neck (HN) surgeons was conducted between December 2020 and March 2021. The survey consisted of 27 questions and focused on knowledge of medical specialists of the prevalence and opinions toward implementing screening for HNSPTs in ESCC patients and vice versa. Results  One hundred twenty-eight gastroenterologists (20.5 %) and 31 HN surgeons (50.0 %) completed the survey. The expected median prevalence of HNSPTs in ESCC was 7.0 % (interquartile range [IQR]: 5.0-15.0) among gastroenterologists and 5.0 % (IQR:3.0-8.0) among HN surgeons. For ESPTs in HNSCC, the expected median prevalence was 9.5 % (IQR: 5.0-12.0) among gastroenterologists and 4.0 % (IQR: 2.0-5.0) among HN surgeons. Screening for HNSPTs and ESPTs was considered promising by 35.2 % and 39.6 %, respectively, which increased to 54.7 % of the specialists after providing incidence data on SPTs. Of the HN surgeons, 41.3 % felt they were as capable as gastroenterologists of performing esophageal screening. Conclusions  This Dutch nationwide survey revealed a lack of knowledge and different perspectives among specialists about screening to detect SPTs in ESCC and HNSCC patients. Adequate education seems essential to increase awareness among specialists and improve SPT detection, independent of the need for implementation of screening for SPTs in ESCC and HNSCC patients., Competing Interests: Competing interests Dr. Bruno received research support from and is consultant for Boston Scientific, Cook Medical, InterScope, Mylan, 3 M and Pentax Medical. Dr. Spander received research support from Medtronics, Boston Scientific, Norgine, Informed, Sentinel and Sysmex. Dr. Koch received research support from DrFalk Pharma and consultancy fees from ERBE Elektromedizin and Pentax Medical., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background and Aims: After endoscopic resection (ER) of early esophageal adenocarcinoma (EAC), the optimal management of patients with high-risk histologic features for lymph node metastases (ie, submucosal invasion, poor differentiation grade, or lymphovascular invasion) remains unclear. We aimed to evaluate outcomes of endoscopic follow-up after ER for high-risk EAC., Methods: For this retrospective cohort study, data were collected from all Dutch patients managed with endoscopic follow-up (endoscopy, EUS) after ER for high-risk EAC between 2008 and 2019. We distinguished 3 groups: intramucosal cancers with high-risk features, submucosal cancers with low-risk features, and submucosal cancers with high-risk features. The primary outcome was the annual risk for metastases during follow-up, stratified for baseline histology., Results: One hundred twenty patients met the selection criteria. Median follow-up was 29 months (interquartile range, 15-48). Metastases were observed in 5 of 25 (annual risk, 6.9%; 95% confidence interval [CI], 3.0-15) high-risk intramucosal cancers, 1 of 55 (annual risk, .7%; 95% CI, 0-4.0) low-risk submucosal cancers, and 3 of 40 (annual risk, 3.0%; 95% CI, 0-7.0) high-risk submucosal cancers., Conclusions: Whereas the annual metastasis rate for high-risk submucosal EAC (3.0%) was somewhat lower than expected in comparison with previous reported percentages, the annual metastasis rate of 6.9% for high-risk intramucosal EAC is new and worrisome. This calls for further prospective studies and suggests that strict follow-up of this small subgroup is warranted until prospective data are available., (Copyright © 2022 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Aim: To quantify lymphovascular invasion (LVI) and to assess the prognostic value in patients with pT1b esophageal adenocarcinoma., Methods: In this nationwide, retrospective cohort study, patients were included if they were treated with surgery or endoscopic resection for pT1b esophageal adenocarcinoma. Primary endpoint was the presence of metastases, lymph node metastases, or distant metastases, in surgical resection specimens or during follow-up. A prediction model to identify risk factors for metastases was developed and internally validated., Results: 248 patients were included. LVI was distributed as follows: no LVI (n = 196; 79.0%), 1 LVI focus (n = 16; 6.5%), 2-3 LVI foci (n = 21; 8.5%) and ≥4 LVI foci (n = 15; 6.0%). Seventy-eight patients had metastases. The risk of metastases was increased for tumors with 2-3 LVI foci [subdistribution hazard ratio (SHR) 3.39, 95% confidence interval (CI) 2.10-5.47] and ≥4 LVI foci (SHR 3.81, 95% CI 2.37-6.10). The prediction model demonstrated a good discriminative ability (c-statistic 0.81)., Conclusion: The risk of metastases is higher when more LVI foci are present. Quantification of LVI could be useful for a more precise risk estimation of metastases. This model needs to be externally validated before implementation into clinical practice., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background and Aims: In contrast to the adverse event (AE) risk of endoscopic resection (ER) of adenomas, the intra- and postprocedural AE risks of ER of T1 colorectal cancer (CRC) are scarcely reported in the literature. It is unclear whether ER of early CRCs, which grow into the submucosal layer and sometimes show incomplete lifting, is associated with an increased AE risk. We aimed to identify the AE rate after ER of T1 CRCs and to identify the risk factors associated with these AEs., Methods: Medical records of patients with T1 CRCs diagnosed between 2000 and 2014 in 15 hospitals in the Netherlands were reviewed. Patients who underwent primary ER were selected. The primary outcome was the occurrence of endoscopy-related AEs. The secondary outcome was the identification of risk factors. Multivariate logistic regression was performed., Results: Endoscopic AEs occurred in 59 of 1069 (5.5%) patients, among which 37.3% were classified as mild, 59.3% as moderate, and 3.4% as severe. AEs were postprocedural bleeding (n = 40, 3.7%), perforation (n = 13, 1.2%), and postpolypectomy electrocoagulation syndrome (n = 6, 0.6%). No fatal AEs were observed. Independent predictors for AEs were age >70 years (odds ratio, 2.11; 95% confidence interval, 1.12-3.96) and tumor size >20 mm (odds ratio, 2.22; 95% confidence interval, 1.05-4.69)., Conclusions: In this large multicenter retrospective cohort study, AE rates of ER of T1 CRC (5.5%) are comparable with reported AE rates for adenomas. Larger tumor size and age >70 years are independent predictors for AEs. This study suggests that endoscopic treatment of T1 CRCs is not associated with an increased periprocedural AE risk., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)