Complete Eradication Of Neoplasia Research Articles

Predictors of recurrence of dysplasia or cancer in patients with dysplastic Barrett's esophagus following complete eradication of dysplasia: a single-center retrospective cohort study.

Endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) for Barrett's esophagus (BE)-related high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) are considered effective treatments for eradication of BE. Little is known about the impact of achieving complete eradication of intestinal metaplasia (CE-IM) following the complete eradication of neoplasia (CE-N), specifically if CE-IM reduces the risk of recurrent dysplasia. Retrospective cohort study of consecutive patients with BE and HGD or intramucosal cancer (IMC)-treated endoscopically at a tertiary referral center between 2001 and 2019. Association between CE-IM and recurrent dysplasia after CE-N was evaluated. A total of 433 patients treated with EMR and/or RFA were included. Of these, 381 (88%) achieved CE-N, of which 345 (80%) had adequate follow-up for inclusion in the analysis. A total of 266 (77%) patients achieved CE-IM; with a median follow-up since initial treatment for HGD/IMC of 45.9months (IQR 25.9, 93.1); 20 patients (5.8%) had recurrent dysplasia after achieving CE-N. Kaplan Meier survival curves revealed that time free of recurrence in those who achieved CE-IM was significantly higher (p = 0.002). In the multivariable analysis, CE-IM was associated with a significant lower hazard of recurrence (HR 0.2, 95% CI 0.1, 0.6), whereas the number of endoscopic treatments to achieve CE-N was associated with a significant higher hazard of recurrence (HR 1.1, 95% CI 1.0, 1.2). Achieving CE-IM following CE-N reduces the risk of recurrent dysplasia and should be considered a treatment target among patients with BE undergoing endoscopic therapies for HGD or EAC.

Systematic review with meta-analysis: the long-term efficacy of Barrett's endoscopic therapy-stringent selection criteria and a proposal for definitions.

Barrett's endoscopic therapy (BET) is well established for neoplasia in Barrett's oesophagus using a concept of complete eradication of all Barrett's. However, long-term efficacy is not known. To perform a systematic review and meta-analysis to examine long-term efficacy of BET for Barrett's neoplasia. Electronic databases were searched for studies meeting stringent criteria: (a) subjects with high-grade dysplasia and/or superficial adenocarcinoma who underwent BET (ablation±endoscopic mucosal resection); (b) BET completion by confirmation of complete eradication of neoplasia (CE-N) and intestinal metaplasia (CE-IM) with systematic sampling and (c) clearly defined follow-up (endoscopy and biopsy) protocol of ≥2years thereafter for detection of recurrence. Pooled estimates of CE-N and CE-IM after BET completion and follow-up were analysed. Eight studies met the stringent criteria (n=794, males 89%, age 64.6years). Despite high efficacy of BET at therapy completion (CE-N: 95.9 [91.7-98.7]%; CE-IM: 90.9 [83-96.6]%), this declined (CE-N: 89 [73.4-98.2]%; CE-IM: 77.8 [65.6-88]%) over 3.4years of follow-up. There was considerable heterogeneity. Only two studies reported a post-BET follow-up of >5years (CE-IM 50 [41.5%-58.5]%). Higher person years of follow-up seem to correlate with decrease in BET efficacy. Using stringent criteria for appropriate study selection with sufficient follow-up, a lack of high-quality controlled intervention trials becomes evident for assessment of long-term durable remission rates of BET despite initial high success rates. We plea for a uniform documentation of study details which could be used in future trials.

Clinical and pathological predictors of failure of endoscopic therapy for Barrett’s related high-grade dysplasia and early esophageal adenocarcinoma

Multimodal endoscopic treatment for Barrett's esophagus (BE) related high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) is safe and effective. However, there is a paucity of data to predict the response to endoscopic treatment. This study aimed to identify predictors of failure to achieve complete eradication of neoplasia (CE-N) and complete eradication of intestinal metaplasia (CE-IM). We performed a retrospective analysis of prospectively collected data of all HGD/EAC cases treated endoscopically at a tertiary referral center. Only patients with confirmed HGD/EAC from initial endoscopic mucosal resection (EMR) were included. Potential predictive variables including clinical characteristics, endoscopic features, and index histologic parameters of the EMR specimens were evaluated using multivariate Cox regression. A total of 457 patients were diagnosed with HGD/EAC by initial EMR from January 2008 to January 2019. Of these, 366 patients who underwent subsequent endoscopic treatment with or without RFA were included. Cumulative incidence rates at 3 years for CE-N and CE-IM were 91.4% (95% CI 87.8-94.2%) and 66.8% (95% CI 61.2-72.3%), respectively during a median follow-up period of 35months. BE segment of 3-10cm (HR 0.45; 95% CI 0.36-0.57) and > 10cm (HR 0.25; 95% CI 0.15-0.40) were independent clinical predictors associated with failure to achieve CE-N. With respect to CE-IM, increasing age (HR 0.88; 95% CI 0.78-1.00) was another predictor along with BE segment of 3-10cm (HR 0.37; 95% CI 0.28-0.49) and > 10cm (HR 0.15; 95% CI 0.07-0.30). Lymphovascular invasion increased the risk of CE-N and CE-IM failure in EAC cases. Failure to achieve CE-N and CE-IM is associated with long-segment BE and other clinical variables. Patients with these predictors should be considered for a more intensive endoscopic treatment approach at expert centers.

Clinical characteristics of young patients with early Barrett's neoplasia.

BACKGROUNDEsophageal adenocarcinoma (EAC) and high-grade dysplasia (HGD) may appear in young patients with Barrett’s esophagus (BE). However, characteristics of Barrett’s-related neoplasia in this younger population remain unknown.AIMTo identify clinical characteristics that differ between young and old patients with early-stage Barrett’s-related neoplasia.METHODSWe conducted a retrospective analysis of a prospectively maintained database comprised of consecutive patients with early-stage EAC (pT1) and HGD at a tertiary-referral center between 2001 and 2017. Baseline characteristics, drug and risk factor exposures, clinicopathological staging of EAC/HGD and treatment outcomes [complete eradication of neoplasia (CE-N), complete eradication of intestinal metaplasia (CE-IM), recurrence of neoplasia and recurrence of intestinal metaplasia] were retrieved. Multivariate analyses were performed to identify factors that differed significantly between older and younger (≤ 50 years) patients.RESULTSWe identified 450 patients with T1 EAC and HGD (74% and 26%, respectively); 45 (10%) were ≤ 50 years. Compared to the older group, young patients were more likely to present with ongoing gastroesophageal reflux disease (GERD) symptoms (55% vs 38%, P = 0.04) and to be obese (body mass index > 30, 48% vs 32%, P = 0.04). Multivariate logistic regression analysis showed that young patients were significantly more likely to have ongoing GERD symptoms [odds ratio (OR) 2.00, 95% confidence interval (CI) 1.04-3.85, P = 0.04] and to be obese (OR 2.06, 95%CI 1.07-3.98, P = 0.03) whereas the young group was less likely to have a smoking history (OR 0.39, 95%CI 0.20-0.75, P < 0.01) compared to the old group. However, there were no significant differences regarding tumor histology, CE-N, CE-IM, recurrence of neoplasia and recurrence of intestinal metaplasia (mean follow-up, 44.3 mo).CONCLUSIONWhile guidelines recommend BE screening in patients > 50 years of age, younger patients should be considered for screening endoscopy if they suffer from obesity and GERD symptoms.

Tu1566 Efficacy of Endoscopic Mucosal Resection (EMR) in Eradication of Barrett's Esophagus Related Neoplasia: a Meta-Analysis and Systematic Review

Tu1566 Efficacy of Endoscopic Mucosal Resection (EMR) in Eradication of Barrett’s Esophagus Related Neoplasia: a Meta-Analysis and Systematic Review Madhav Desai*, Neil Gupta, Prashanth Vennalaganti, Ajay Bansal, Abhishek Choudhary, Mohammad A. Titi, Cesare Hassan, Prateek Sharma, Alessandro Repici Internal Medicine, Division of Gastroenterology, University of Kansas Medical Center, Kansas City, KS; Gastroenterology and Hepatology, Loyola University Medical Center, Maywood, IL; Gastroenterology and hepatology, Veteran Affairs Medical Center, Kansas City, Kansas City, MO; Gastroenterology and Digestive Endoscopy Unit, Nuovo Regina Margherita Hospital, Rome, Italy; Department of Gastroenterology, IRCCS Istituto Clinico Humanitas, Milan, Italy Background: Complete endoscopic mucosal resection [EMR] is an established approach for complete eradication of Barrett’s esophagus [BE] related neoplasia: high-grade dysplasia [HGD] and early adenocarcinoma [EAC]. However, efficacy rates in a large cohort of BE patients undergoing EMR as the primary eradication modality are not known. Methods: Two investigators independently identified potentially relevant studies through a search of MEDLINE and ISI Web of Knowledge (1980-2014), Cochrane Central Register of Controlled Trials, clinicaltrials.gov and bibliographic review of secondary sources. Search terms were: “Barrett’s e/oesophagus”, “Endoscopic mucosal resection” (EMR), “endoscopic resection”, dysplasia, adenocarcinoma. Inclusion criteria were: complete or step wise EMR, human studies, patient age 18 years or greater, prospective and retrospective studies, high grade dysplasia [HGD], superficial esophageal adenocarcinoma, sample size of 10 patients or greater and follow up of greater than 1 year. Exclusion criteria were: case reports, conference or symposium abstracts, abstract form only, review articles, Non English language articles, editorials, letters to editors, studies without biopsy proven BE, studies not reporting either efficacy or recurrence, duplicate reports of study samples. Primary outcome was complete eradication of neoplasia [CE-N (HGD/ EAC)]. Secondary outcomes were: 1) Complete eradication of intestinal metaplasia (CE-IM), 2) adverse events and 3) recurrence rates of -EAC, D and IM. Results: The initial composite search identified 22 studies; 10 studies met all the criteria and were included in the final analysis. This included a total of 620 patients, 83% males with a mean age of 66 years. The average follow up duration was 25.6 months [range 15 to 40.6 months]. Sustained CE-N was achieved in 95.7% [530/554] of the patients with CE-IM in 78% [397/508]. The major adverse events reported were: perforation 1.8% (11/620), symptomatic strictures 36.5% (226/620) and significant bleeding 8.2% (51/ 620). The estimated recurrence was: EAC 1.7% (10/574), Dysplasia 3.9% (22/565) and IM 14.3% (75/524). No deaths related to the procedure were reported. Conclusion: EMR, as the primary therapy for eradication of BE related neoplasia, appears to be a highly effective strategy. However, recurrence of intestinal metaplasia and neoplasia occurs in approximately 20% of the treated patients after initial successful eradication. Strictures related to therapy are reported in up to a 1/3 of the patients.

Multimodality endoscopic eradication for neoplastic Barrett oesophagus: results of an European multicentre study (EURO-II)

ObjectiveFocal endoscopic resection (ER) followed by radiofrequency ablation (RFA) safely and effectively eradicates Barrett's oesophagus (BO) containing high-grade dysplasia (HGD) and/or early cancer (EC) in smaller studies with limited follow-up....

Long-term recurrence of neoplasia and Barrett's epithelium after complete endoscopic resection

BackgroundCurrent endoscopic therapy for neoplastic Barrett's oesophagus (BO) consists of complete resection/ablation of all Barrett's tissue including neoplastic lesions. Recurrence seems to be frequent after thermal therapy, such as radiofrequency...

One-step circumferential endoscopic mucosal cap resection of Barrett's esophagus with early neoplasia

Focal endoscopic mucosal resection (EMR) of visible intraepithelial lesions arising within Barrett's esophagus (BE) may miss synchronous lesions that are not endoscopically apparent. Stepwise radical endoscopic resection would obviate this concern by removing all BE; however, it requires repeated endoscopy which may increase the risk of complications, particularly for patients with circumferential BE. The aim of the study was to evaluate the safety and efficacy of one-step complete circumferential resection of BE by cap-assisted EMR (EMR-C) among patients with circumferential BE and high-grade dysplasia or intramucosal carcinoma. Between January 2003 and March 2010, 47 patients with circumferential BE and biopsy-proven high-grade dysplasia or intramucosal cancer underwent EMR-C. We evaluated: (1) complete eradication of neoplasia, (2) complete eradication of metaplasia, and (3) complications including bleeding and esophageal stricture. Complete eradication of neoplasia and complete eradication of metaplasia were achieved after a median follow-up of 18.4 months in 91% (43/47) of patients. After EMR-C, two patients (one IMC, one invasive cancer) underwent esophagectomy. Histology of the resected specimens showed no residual disease and a T1bN0 lesion, respectively. Two patients had progression of neoplasia. A stenosis occurred in 18 out of 45 patients (40%). All stenoses were treated with dilations and two required temporary placement of a covered stent. One-step complete EMR-C is a safe and effective technique which can be considered in patients with early neoplastic lesions. Although 40% of patients developed dysphagia, this could well be managed endoscopically.

282 Radiofrequency Ablation Combined With Endoscopic Resection Is Highly Effective for Eradication of Early Barrett's Neoplasia: Final Results of a Large Prospective European Multicenter Study (EURO-II)

Radiofrequency Ablation Combined With Endoscopic Resection Is Highly Effective for Eradication of Early Barrett’s Neoplasia: Final Results of a Large Prospective European Multicenter Study (EURO-II) Nadine Phoa*, Roos E. Pouw, Raf Bisschops, Oliver Pech, Krish Ragunath, Bas L. Weusten, Brigitte Schumacher, Bjorn Rembacken, Alexander Meining, Helmut Messmann, Erik J. Schoon, Liebwin Gossner, Jayan Mannath, Cees a. Seldenrijk, Mike Visser, Antoon E. Lerut, Thomas RoSch, Stefan Seewald, Fiebo J. Ten Kate, Christian Ell, Horst Neuhaus, Jacques J. Bergman Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands; University Hospital Leuven, Leuven, Belgium; Dr. Horst-Schmidt-Kliniken, Wiesbaden, Germany; Nottingham Digestive Diseases Centre, Nottingham University Hospital, Nottingham, United Kingdom; Gastroenterology and Hepatology, St Antonius Hospital, Nieuwegein, Netherlands; Evangelisches Krankenhaus Dusseldorf, Dusseldorf, Germany; The General Infirmary at Leeds, Leeds, United Kingdom; Technical University of Munich, Munich, Germany; Klinikum Augsburg, Augsburg, Germany; Catharina Hospital, Eindhoven, Netherlands; Klinikum Karlsruhe, Karlsruhe, Germany; Pathology, St Antonius Hospital, Nieuwegein, Netherlands; Pathology, Academic Medical Center, Amsterdam, Netherlands; Universitatsklinikum HamburgEppendorf, Hamburg, Germany Background: Radiofrequency ablation (RFA) after prior endoscopic resection (ER) of focal lesions, has proven highly effective for Barrett’s esophagus (BE) containing high-grade dysplasia (HGD) or early cancer (EC), in a number of small-sized single center studies. Aim: To prospectively evaluate the efficacy of RFA combined with ER in case of focal lesions, for BE with HGD/EC in 13 European centers with expertise in BE neoplasia. Methods: Patients with BE 12 cm and HGD/EC on 2 separate endoscopies were included. Visible lesions ( 2cm length; 50% circumference) were removed with ER, residual EC was excluded on 2 mapping endoscopies post-ER. Subsequent RFA was scheduled every 3 months until clearance of BE was achieved, with max 5 RFA sessions allowed. Escape treatment was permitted for residual BE after RFA (max 2 APC sessions for islands 5mm, ER for islands 5mm or suspicious lesions). Followup (FU) endoscopy was scheduled at 3 9 mo after last treatment and annually thereafter, with 4Q/2cm biopsies from neosquamous epithelium and gastric cardia. Endpoints: complete eradication of neoplasia (CE-neo) and intestinal metaplasia (CE-IM); durability of CE-neo/CE-IM. To ensure uniformity and protocol compliance, investigators were trained at the coordinating site and a study monitor attended all treatments and first FU on-site. Central pathology review of all ER/biopsies was performed at the coordinating site. Results: 132 patients (107M, mean 65yrs, median BE C3M6) underwent en-bloc (n 63) or piecemeal ER (n 56); or no-ER (n 13). Worst ER histology: EC (n 78), HGD (n 31), LGD (n 7), no dysplasia (n 3). Worst grade post-ER/pre-RFA: HGD (n 36), LGD (n 45), no dysplasia (n 51). 124 pts completed the treatment phase, 8 discontinued due to unrelated causes. After a median of 3 (IQR 3-4) treatments, including ER (n 14) or APC (n 14), per intention-to-treat analysis (counting drop-outs as failures) CE-neo was reached in 122/132 (92%) and CEIM in 115/132 (87%) pts. In a per-protocol analysis (censoring for drop-outs) CEneo/CE-IM were achieved in 98% and 93%, respectively. Of 2 CE-neo failures, 1 was referred for surgery (T1bN0M0), 1 patient was treated endoscopically (offprotocol). Of 115 pts who reached CE-neo/CE-IM per-protocol, CE-neo was maintained in 112/115 (97%) pts during median 25 (IQR 18-34) mo FU since last treatment, with median 4 (2-5) FU endoscopies and 41 biopsies per patient. 3 pts with recurrent neoplasia (EC n 1; HGD n 2) were effectively re-treated by ER or APC. Conclusion: This is the largest prospective multicenter trial on RFA combined with ER for treatment of BE with HGD/EC. Our outcomes suggest that if performed by trained, expert endoscopists in carefully selected patients, this combined approach is highly effective, and appears durable in the majority (97%) of patients once complete eradication of neoplasia and IM is established. Fig 1. Inflammation score (range 0-13) of inflamed pediatric Crohn’s disease ileum increased compared to both non-inflammed Crohn’s diseae and control. Results expressed as mean SEM (*P 0.001).

Complete Barrett’s excision by stepwise endoscopic resection in short-segment disease: long term outcomes and predictors of stricture

Complete Barrett's excision (CBE) of short-segment Barrett's high grade dysplasia (HGD) and early esophageal adenocarcinoma by stepwise endoscopic resection is a precise staging tool, detects covert synchronous disease, and may produce a sustained treatment response. Esophageal stricture is the most commonly reported complication of CBE although risk factors have not yet been clearly defined. Data were recorded prospectively on patients with limited co-morbidity and age ≤ 80 years undergoing CBE for histologically proven HGD or esophageal adenocarcinoma within ≤ C3M5 segments. Endoscopic resection was performed by standardized protocol every 6 - 8 weeks until CBE was achieved. Esophageal dilation was performed when patients reported dysphagia. Dysphagia scores were recorded at scheduled endoscopic surveillance or by telephone interview. By intention-to-treat analysis, complete eradication of neoplasia and intestinal metaplasia was achieved in 95 % and 82 %, respectively, in 77 patients undergoing a median of 2 resection sessions (interquartile range [IQR] 1 - 3). Esophageal dilation was required in 33 % (median 3 dilations, IQR 1 - 3.5) at median follow-up of 20 months (IQR 6 - 40). Independent risk factors for dilation requirement were the number of mucosal resections at the index procedure (odds ratio [OR] 1.3 per resection, 95 % confidence interval [CI] 1.0 - 1.9; P = 0.043) and maximal extent of the Barrett's segment (OR 2.2 per cm, 95 %CI 1.2 - 3.9; P = 0.009). Although CBE is highly effective in the treatment of Barrett's HGD and esophageal adenocarcinoma, the risk of post-CBE dysphagia increases with the maximal extent of the Barrett's segment and the number of mucosal resections at the index procedure. These data could be used to inform treatment decisions and identify those patients who may benefit from prophylactic therapies such as dilation.