Recurrent Intestinal Metaplasia Research Articles

Rates of Recurrent Intestinal Metaplasia and Dysplasia After Successful Endoscopic Therapy of Barrett's Neoplasia by Endoscopic Mucosal Resection vs Endoscopic Submucosal Dissection and Ablation: A Large North American Multicenter Cohort.

Endoscopic eradication therapy (EET) combining endoscopic resection (ER) with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) followed by ablation is the standard of care for the treatment of dysplastic Barrett's esophagus (BE). We have previously shown comparable rates of complete remission of intestinal metaplasia (CRIM) with both approaches. However, data comparing recurrence after CRIM are lacking. We compared rates of recurrence after CRIM with both techniques in a multicenter cohort. Patients undergoing EET achieving CRIM at 3 academic institutions were included. Demographic and clinical data were abstracted. Outcomes included rates and predictors of any BE and dysplastic BE recurrence in the 2 groups. Cox-proportional hazards models and inverse probability treatment weighting (IPTW) analysis were used for analysis. A total of 621 patients (514 EMR and 107 ESD) achieving CRIM were included in the recurrence analysis. The incidence of any BE (15.7, 5.7 per 100 patient-years) and dysplastic BE recurrence (7.3, 5.3 per 100 patient-years) were comparable in the EMR and ESD groups, respectively. On multivariable analyses, the chances of BE recurrence were not influenced by ER technique (hazard ratio 0.87; 95% confidence interval 0.51-1.49; P = 0.62), which was also confirmed by IPTW analysis (ESD vs EMR: hazard ratio 0.98; 95% confidence interval 0.56-1.73; P = 0.94). BE length, lesion size, and history of cigarette smoking were independent predictors of BE recurrence. Patients with BE dysplasia/neoplasia achieving CRIM, initially treated with EMR/ablation, had comparable recurrence rates to ESD/ablation. Randomized trials are needed to confirm these outcomes between the 2 ER techniques.

Novel histologic score predicts recurrent intestinal metaplasia after successful endoscopic eradication therapy.

Endoscopic eradication therapy (EET) is an effective treatment for Barrett's esophagus (BE); however, disease recurrence remains problematic requiring surveillance post-treatment. While data regarding predictors of recurrence are limited, uncontrolled reflux may play a significant role. Our aim was to develop a scoring system based on histopathologic reflux in surveillance biopsies following EET to identify patients at high risk for recurrence of BE. Patients were identified from two centers in the treatment with resection and endoscopic ablation techniques for BE consortium. Hematoxylin and eosin-stained slides of surveillance biopsies post-EET were assessed for histologic changes associated with reflux from a cohort of patients who also underwent pH-metry (derivation cohort). We developed a novel scoring system (Recurrent Epithelial Changes from Uncontrolled Reflux [RECUR]) composed of dilated intercellular spaces, epithelial ballooning, basal cell hyperplasia, and parakeratosis, to identify patients with abnormal esophageal acid exposure. This scoring system was then used to grade surveillance biopsies from patients with or without recurrence of BE following EET (validation cohort). Of 41 patients in the derivation cohort, 19.5% had abnormal acid exposure times (AET) while on proton pump inhibitor therapy. The mean (SD) RECUR score for patients with AET <4% was 4.0 (1.6), compared with 5.5 (0.9) for AET ≥4% (P = 0.015). In the validation cohort consisting of 72 patients without recurrence and 64 patients with recurrence following EET, the RECUR score was the only significant predictor of recurrence (odds ratio: 1.36, 95% confidence interval: 1.10-1.69, P = 0.005). Histologic grading of surveillance biopsies using the RECUR scoring system correlates with BE recurrence following EET.

Outcomes of endoscopic submucosal dissection (ESD) plus radiofrequency ablation (RFA) for nodular Barrett’s esophagus

Background Although Endoscopic Submucosal Dissection (ESD) was proven superior to Endoscopic Mucosal Resection (EMR) in achieving higher complete remission rates for neoplastic Barrett’s Esophagus (BE), its safety with Radiofrequency Ablation (RFA) remains unstudied. We share our experience with ESD + RFA for nodular BE eradication. Methods A retrospective study of all patients ≥18-years with nodular BE who underwent ESD + RFA between September 2015 and December 2020 at our tertiary center. Patients with advanced adenocarcinoma requiring esophagectomy were excluded. Primary outcomes included adverse events (AE) rates and complete eradication rates for adenocarcinoma (CE-EAC), dysplasia (CE-D), and intestinal metaplasia (CE-IM). Secondary outcomes included local recurrence rates following eradication. Results Eighteen patients were included with a total of 22 ESDs performed and a median of 2 RFA sessions-per-patient [IQR: 1.25, 3]. Sixteen patients were males and/or white (88.9%) with a median BMI of 29.75 kg/m2 [IQR: 26.9, 31.5]. Fourteen patients had long-segment BE (77.7%) while 16 had hiatal hernias (88.9%). Median resection size was 12.1 cm2 [IQR: 5.6, 20.2]. AEs included one intraprocedural micro-perforation (4.5%) and 4 strictures (22.2%), only one of which developed post-RFA. All AEs were successfully treated endoscopically. Over a median of 42.5 months [IQR: 28, 59.25], CE-EAC was achieved in 13 patients (100%), CE-D in 15 patients (100%), and CE-IM in 14 patients (77.8%). Following eradication, 2 patients had recurrent dysplasia (2/15, 13.3%) and one had recurrent intestinal metaplasia (1/14, 7.1%). Conclusion In high-risk patients with long-segment neoplastic BE requiring extensive endoscopic resection, ESD + RFA offers excellent complete eradication rates with rare additional adverse events by RFA. Standard endoscopic surveillance following eradication remains important.

Intestinal Metaplasia in the Esophageal Remnant Is Rare After Ivor Lewis Esophagectomy

BackgroundMost patients undergoing esophagectomy will experience intermittent reflux of gastric and biliary content into the remnant esophagus postoperatively. The incidence of new or recurrent intestinal metaplasia following chemoradiation and surgery has not been well-described. Furthermore, post-resection guidelines do not exist regarding surveillance for metaplasia in the esophageal remnant. MethodsPatients undergoing Ivor Lewis esophagectomy after concurrent chemoradiation for a diagnosis of esophageal adenocarcinoma from 2006 to 2018 were identified. Pathology records were reviewed for the presence of intestinal metaplasia on pretreatment biopsies, surgical specimen, or post-resection biopsies. ResultsIn total, 619 patients met inclusion criteria, including 267 (43%) who had intestinal metaplasia noted either prior to or at the time of esophagectomy. The median duration of metaplastic disease prior to resection was 4.4 months. During a median follow-up time of 28 months (interquartile range, 12–60), intestinal metaplasia was noted in the remnant esophagus in 12 (2%) patients, 7 of whom had a prior history of metaplasia. Local recurrence of adenocarcinoma was also uncommon, and occurred in 37/577 (6%) of patients with complete resections, with similar event rates among those with and without a prior history of metaplasia (14/249 [6%] vs. 23/328 [7%], p = 0.614). ConclusionsOur findings suggest that despite several factors predisposing to mucosal damage following esophagectomy, occurrence of new intestinal metaplasia after trimodality therapy in our patient population appears to be rare, even among patient with a previous history of this pathologic finding, which may have significant implications for surveillance and cost-savings after resection.

Clinical significance of recurrent gastroesophageal junction intestinal metaplasia after endoscopic eradication of Barrett’s esophagus

After endoscopic eradication of Barrett's esophagus (BE), recurrence of intestinal metaplasia at the gastroesophageal junction (GEJIM) is common. The clinical significance of this finding is unclear. We assessed whether recurrent GEJIM is associated with increased risk of subsequent dysplasia and whether endoscopic treatment lowers this risk. A retrospective, multicenter, cohort study was performed of treated BE patients who achieved complete eradication of intestinal metaplasia (IM). Postablation follow-up was performed at standard intervals. Recurrent GEJIM was defined as nondysplastic IM on gastroesophageal junction biopsy specimens without endoscopic evidence of BE. Patients were categorized as "never-GEJIM," "GEJIM-observed," or "GEJIM-treated." Endoscopic treatment for recurrent GEJIM was at the endoscopists' discretion. The primary outcome was dysplasia recurrence. Analyses were performed using log-rank tests and Cox proportional hazards modeling. Six hundred thirty-three patients were analyzed; median follow-up was 47 months (interquartile range, 24-69). Most patients (81%) had high-grade dysplasia or intramucosal adenocarcinoma before treatment. Dysplasia recurrence was 2.2% per year. GEJIM-observed patients had the lowest rate of recurrence (.6%/y) followed by GEJIM-treated (2.2%/y) and never-GEJIM (2.6%/y) (log-rank P= .07). In multivariate analyses, compared with never-GEJIM, the risk of dysplasia recurrence was significantly lower in GEJIM-observed patients (adjusted hazard ratio, .19; 95% confidence interval, .05-.81) and not different in GEJIM-treated patients (adjusted hazard ratio, .81; 95% confidence interval, .39-1.67). Older age and longer initial BE length were independently associated with recurrence. Recurrent GEJIM after endoscopic eradication of BE was not associated with an increased risk of subsequent dysplasia. Future studies are warranted to determine if observation is appropriate for this finding.

78 INTESTINAL METAPLASIA IN THE ESOPHAGEAL REMNANT IS RARE AFTER IVOR LEWIS ESOPHAGECTOMY

Abstract Most patients undergoing esophagectomy will experience intermittent reflux of gastric and biliary content into the remnant esophagus over the course of their lives. The incidence of new or recurrent intestinal metaplasia (IM) following chemoradiation and surgery has not been well-described. Furthermore, post-resection guidelines do not exist regarding surveillance for IM in the esophageal remnant. We hypothesized that the incidence of IM in patients who underwent active post-treatment surveillance would be low. Methods Patients undergoing Ivor Lewis esophagectomy after concurrent chemoradiation for a diagnosis of esophageal adenocarcinoma at a single institution from 2006–2018 were identified. Pathology records were reviewed for the presence of IM on pretreatment biopsies, surgical specimen, or post-resection biopsies. Categorical variables were compared using Pearson’s chi-square test or Fisher’s exact test, where appropriate, and continuous variables were compared using Kruskal-Wallis test. Time-to-event outcomes were assessed using the Kaplan–Meier method. Results 621 patients were included, and 242 (39%) were known to have had IM prior to esophagectomy. An additional 26 (4%) patients without a preexisting diagnosis of IM were found to have IM in the surgical specimen. During a median follow-up of 62 months, development of new IM was rare, occurring only in 12 (2%) patients, 7 of whom had a prior history of IM(Table); incidence was 0.6 cases per patient-years. Of these 12, 3 (25%) developed local adenocarcinoma recurrence. Overall, local recurrence of adenocarcinoma was uncommon, and occurred at similar rates in patients with and without a history of IM(p = 0.774). Conclusion Despite several factors predisposing to mucosal damage following esophagectomy, occurrence of new IM after trimodality therapy in our patient population appears to be rare, even among patient with a previous history of metaplasia.

Mo1257 NITROUS OXIDE CRYOBALLOON ABLATION IS A SAFE, EFFECTIVE AND DURABLE ENDOSCOPIC TREATMENT FOR DYSPLASTIC TREATMENT-NAÏVE AND PREVIOUSLY-ABLATED BARRETT’S ESOPHAGUS

Nitrous oxide cryoballoon (CB) ablation can effectively and safely eradicate dysplasia and intestinal metaplasia (IM) in patients with dysplastic BE but the durability of treatment effect is unknown. We evaluated the safety, efficacy, and durability of CB ablation for complete eradication of dysplasia and IM. We analyzed the outcomes of consecutive BE patients treated with CB at a single academic medical center for dysplastic BE from 2015 to 2018. We excluded patients with invasive adenocarcinoma, those treated primarily with radiofrequency ablation (RFA), and those enrolled in ongoing clinical trials. CB ablation was applied to all the gastric cardia and all visible BE using the CB focal ablation system and default cryogen dose of 10 seconds, after eradication of neoplastic-type lesions with endoscopic mucosal resection (EMR). “Touch-up” ablation was performed using CB or argon plasma coagulation for small residual columnar islands. Primary endpoints were complete eradication of dysplasia (CE-D) and intestinal metaplasia (CE-IM) at 1, 2, 3, 4 years. Secondary endpoints were adverse events, disease progression, recurrence rate, time to recurrence, treatment success after recurrence. Patients who achieved CE-IM were included for the durability analysis. Kaplan-Meir analysis was performed to assess durability where any recurrence was considered a failure. 70 patients (mean age 67.6 years, 88.6% male, mean BE Prague C 2.5+/- 4.3 cm, Prague M 4.3 +/- 4.6 cm), HGD=64%, LGD 36%) were studied. 65.7% of the patients were treatment naïve, the rest had prior EMR (n=6), RFA (n=13) or both (n=5). Median follow-up was 27.4 months (IQR 16.1-43.4). CE-D and CE-IM at 1 year were 96.7% and 73.8%, respectively. The median number of CB sessions to achieve CE-IM at 1 year was 3 (IQR 2-3.5). Table 1 shows the rates of CE-D and CE-IM for years 1-4, allowing for re-treatment with CB or “touch-up” APC. The rate of CE-IM was above 90% at 2, 3 and 4 years, with no difference between treatment-naïve and previously-ablated The durability (rates of CE-D and CE-IM) of CB response in 45 patients who achieved CE-D or CE-IM at 1 year followed until last follow-up or recurrence of dysplasia or IM are presented in Figure 1. One patient had an LGD recurrence at 21.7 months and 3(4.3%) patients had a recurrence of IM; all were successfully re-treated with CB ablation. The median time to recurrence was 18.6 months (Figure 1). No patient progressed beyond their baseline dysplasia grade or developed cancer. The incidence of stricture requiring dilation was 7.1%. 1 patient (1.4 %) developed self-limited bleeding. Recurrence rate of IM after initial CB eradication is low. CB ablation has high efficacy, safety, and durability for eradicating dysplasia and intestinal metaplasia in dysplastic BE as a primary or rescue therapy.Figure 1Kaplan-Meier analysis of the durability of complete eradication of dysplasia and intestinal metaplasia. All subjects in this analysis achieved either complete eradication of dysplasia (n=58) or intestinal metaplasia (n=45) at 12 months. Time 0 for this analysis is the first finding of complete eradication of dysplasia or intestinal metaplasia at 12 months. Any recurrent dysplasia (n=1 LGD) or IM (n=3; 2 HGD, 1 LGD) noted after achieving CE-D or CE-IM was considered a failure, even if it was subsequently successfully eradicated by cryoballoon ablation.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Mo1265 WATS TESTING INCREASES DETECTION OF RECURRENT INTESTINAL METAPLASIA FOLLOWING COMPLETE ERADICATION OF INTESTINAL METAPLASIA IN TREATED BARRETT’S ESOPHAGUS WITH LOW-GRADE DYSPLASIA, HIGH-GRADE DYSPLASIA, OR INTRAMUCOSAL ADENOCARCINOMA

Wide area transepithelial sample biopsy with three-dimensional computer-assisted analysis (WATS, CDx Diagnostics, Suffern, NY) uses brush sampling to evaluate histologic features of a wide area of mucosa. A limited literature describes its yield for intestinal metaplasia (IM) in surveillance after successfully treated dysplastic Barrett’s esophagus (BE). To determine the additional yield for IM of WATS testing in addition to forceps biopsy (FB) in surveillance of BE following endoscopic treatment achieving complete eradication of intestinal metaplasia (CEIM). The WATS Registry is an ongoing multicenter U.S. study enrolling subjects undergoing WATS as part of usual care at 13 sites. Patients are aged 18 to 80 and are enrolled in one of three categories: diagnostic endoscopy for heartburn or regurgitation symptoms without a history of BE, surveillance endoscopy for already-diagnosed BE without prior endoscopic eradication therapy, or surveillance endoscopy for BE following eradication therapy. We analyzed all surveillance endoscopy visits for treated BE following CEIM. CEIM was defined as an endoscopy with negative FB for IM, negative WATS for IM (if taken), and no treatment given. We plotted product-limit estimates and Poisson models of the rate of recurrence of intestinal metaplasia using only the FB results to define recurrence compared with using both the FB and WATS testing results to define recurrence. In total, 384 endoscopies were performed for follow-up of treated Barrett’s esophagus with low-grade dysplasia, high-grade dysplasia, or intramucosal adenocarcinoma. Of these 384, 318 had CEIM, and 252 had one or more surveillance endoscopies at risk for recurrence (Table). The addition of WATS to FB increased the estimated rate of recurrence by rate ratio of 3.6 (95% confidence limits 2.0 – 6.0) (Figure). Among the 38 recurrences detected first or only on WATS, an irregular z-line was described in 9, one or more centimeters of columnar mucosa in 4, and a targeted FB was collected in 20. There were 16 recurrences detected on FB. Among the 38 WATS recurrences, concurrent cardia brushings or biopsies were available for 10, of which, 3 had IM of the cardia. The addition of WATS testing to FB substantially increased the detection of recurrent IM after eradication of BE with dysplasia or intramucosal carcinoma. Errant detection of cardia IM is not the likely source for most of these brushes, given that only 30% of those with cardia sampled separately showed IM of the cardia. The clinical implications and mechanisms of detecting recurrence on WATS testing versus FB remain uncertain, however, this increased detection of IM could have important implications for surveillance of treated BE.FigureProduct-limit estimate of the proportion of participants with recurrence of intestinal metaplasia detected by forceps biopsy alone compared to forceps biopsy and wide area transepithelial sample biopsy with three-dimensional computer-assisted analysis by time in years after the first registry visit with complete eradication of intestinal metaplasia.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

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.

Prevalence and Incidence of Intestinal Metaplasia and Dysplasia of Gastric Cardia in Patients With Barrett’s Esophagus After Endoscopic Therapy

Endoscopic eradication therapy (EET) for Barrett's esophagus (BE) has unclear effects on the gastric cardia. We investigated the prevalence of intestinal metaplasia (IM) and dysplasia in the cardia after complete eradication of IM (CEIM) and the incidence of newly diagnosed cardia IM or dysplasia after EET. We performed a prospective study, from 2013 through 2016, of patients with previously successful EET undergoing surveillance after CEIM (cross-sectional group) and treatment-naïve patients with BE undergoing EET (longitudinal group). Standard biopsies were collected from multiple levels in the cardia and analyzed histologically. We calculated the prevalence (cross-sectional group) and the incidence (longitudinal group) of cardia IM or dysplasia after EET. Of the 116 patients in the cross-sectional group, 17 (15%) had cardia IM or dysplasia after CEIM: 12 patients had IM, 2 patients were indefinite for dysplasia, and 3 patients had low-grade dysplasia. Cardia IM or dysplasia were most commonly found at the tops of gastric folds. Among 42 subjects in the longitudinal group, the pre-treatment prevalence of cardia IM or dysplasia was 28.5% (3 with non-dysplastic IM, 9 with dysplastic IM, 1 indefinite for dysplasia, 2 with low-grade dysplasia, 3 with high-grade dysplasia, and 3 with intramucosal cancer). All achieved CEIM. The incidence of cardia IM or dysplasia was 11.9% after 18 months of follow up. IM or dysplasia was more higher in the cardia after CEIM than in the tubular esophagus (P < .01). In a prospective study, we found that cardia dysplasia becomes less, not more, common, after successful EET; recurrence of IM or dysplasia was more frequent in the cardia than the esophagus. Patients with BE undergoing EET should have careful examination of the cardia, with a single set of surveillance biopsies at the top of the gastric folds.

Endoscopic therapy for Barrett's esophagus and early esophageal cancer: Where do we go from here?

Since Barrett’s esophagus is a precancerous condition, efforts have been made for its eradication by various ablative techniques. Initially, laser ablation was attempted in non-dysplastic Barrett’s esophagus and subsequently, endoscopic ablation using photodynamic therapy was used in Barrett’s patients with high-grade dysplasia who were poor surgical candidates. Since then, various ablative therapies have been developed with radiofrequency ablation having the best quality of evidence. Resection of dysplastic areas only without complete removal of entire Barrett’s segment is associated with high risk of developing metachronous neoplasia. Hence, the current standard of management for Barrett’s esophagus includes endoscopic mucosal resection of visible abnormalities followed by ablation to eradicate remaining Barrett’s epithelium. Although endoscopic therapy cannot address regional lymph node metastases, such nodal involvement is present in only 1% to 2% of patients with intramucosal adenocarcinoma in Barrett esophagus and therefore is useful in intramucosal cancers. Post ablation surveillance is recommended as recurrence of intestinal metaplasia and dysplasia have been reported. This review includes a discussion of the technique, efficacy and complication rate of currently available ablation techniques such as radiofrequency ablation, cryotherapy, argon plasma coagulation and photodynamic therapy as well as endoscopic mucosal resection. A brief discussion of the emerging technique, endoscopic submucosal dissection is also included.

PS02.062: CONFOCAL LASER ENDOMICROSCOPY IN THE ASSESSMENT OF PERSISTENT/RECURRENT INTESTINAL METAPLASIA/NEOPLASIA AFTER ENDOSCOPIC TREATMENT OF BORN

Abstract Background Patients after endoscopic treatment of Barrett's esophagus related neoplasia (BORN) should undergo regular endoscopic surveillance with biopsies to detect recurrent intestinal metaplasia (IM) or neoplasia (N). Probe-based confocal laser endomicroscopy (pCLE) offers detailed examination of cellular structures and may examine larger areas compared to standard biopsy. Methods A single center, prospective, controlled and pathologist-blinded (still ongoing) study in patients undergoing surveillance endoscopy after endoscopic treatment of BORN. pCLE images were obtained from the neo-Z-line (in few cases including macroscopically visible tongues), the cardia and the esophagus. Thereafter, standard biopsies were taken and sent for histopathological analysis (minimally 4 biopsies from macroscopically normal neo-Z-line, 2 biopsies from the cardia and the esophagus and targeted biopsies from visible abnormalities, if present). Results We examined 34 patients, from these 14 patients (41%) had the initial diagnosis of low-grade intraepithelial neoplasia (LGIN), 8 patients (24%) had high-grade intraepithelial neoplasia (HGIN) and 12 patients (35%) had an early adenocarcinoma (EAC). Three patients (9%) underwent endoscopic resection (ER), in 18 patients (53%) we performed ER or dissection of all visible lesions followed by radiofrequency ablation (RFA), and 13 patients (38%) had RFA as a single treatment modality. Persistent/recurrent IM was detected only at the level of neo-Z-line in 8 patients (24%, 8/34 pts) by both methods. pCLE but not biopsies detected persistent/recurrent IM in 2 patients (6%, 2/34), another 2 patients had IM present in biopsies but not in pCLE. pCLE diagnosed one patient with recurrent LGIN in a macroscopic visible tongue arising from neo-Z-line, which was not confirmed in biopsies (there was only agreement in persistent IM detected by both methods). Sensitivity and specificity of pCLE in detection of persistent/recurrent IM was 80% (95% CI 44–98) and 92% (95% CI 73–99), respectively, with a positive predictive value of 80% (95% CI 51–94) and a negative predictive value of 92% (95% CI 76–98). Agreement of pCLE and histopathological findings was 88%. Conclusion pCLE seems comparable to standard biopsies in detection of persistent/recurrent IM after endoscopic treatment of BORN. Nevertheless, these results need to be confirmed in a larger cohort of patients. Disclosure All authors have declared no conflicts of interest.

Covering the Cover

Covering the Cover

Su1108 ONGOING GERD SYMPTOMS AND OBESITY ARE POTENTIAL RISK FACTORS FOR BARRETT'S ADENOCARCINOMA AND HIGH-GRADE DYSPLASIA AMONG PATIENTS UNDER 50 YEARS OF AGE

Recent guidelines recommend endoscopic screening for Barrett’s esophagus (BE) only in patients with multiple risk factors. While increased age (>50 years) is often considered the most important risk factor, esophageal adenocarcinoma (EAC) and/or high-grade dysplasia (HGD) continues to be observed in younger patients (≤50 years). However, it is unclear if this younger cohort differs regarding specific clinical characteristics from the more typical age category of BE neoplasia, and if so, whether these features could help guide screening recommendations. We conducted a retrospective analysis of a prospectively maintained database comprised of consecutive patients with early stage EAC (T1) and HGD at a single, tertiary-referral center from March 2001 to July 2017. Information regarding baseline clinical characteristics, drug and risk factor exposures, clinicopathological staging of EAC/HGD and follow-up status including treatment outcomes such as complete remission of dysplasia (CR-D), and complete remission of intestinal metaplasia (CR-IM) were determined. Univariate and multivariate analyses were performed to identify factors that differed significantly between patients older and younger than 50 years. We identified 511 patients with T1 EAC and HGD (383 and 128, respectively); 50 (10%) were age ≤50 years; 461 (90%) were age >50 years. Compared to the older age group, young patients were more likely to have ongoing GERD symptoms and to be obese (BMI >30) (55% vs. 39%, p=0.003; 47% vs. 32%, p=0.038, respectively) and less likely to have ever been smokers (57% vs. 76%, p=0.004) on univariate analysis, with the same pattern of differences maintained at an even greater magnitude of effect on multivariate analysis. However, there were no significant differences between young and old age groups in terms of tumor depth of invasion, differentiation, lymphovascular invasion or deep margin positivity. Furthermore, there were no significant differences between the groups regarding outcomes of endoscopic therapies with respect to CR-D, CR-IM, recurrence of dysplasia and recurrence of intestinal metaplasia with a mean follow-up period of 44.3 ± 30.2 months. Younger patients (≤50 years) with early stage EAC or HGD were more likely to have ongoing GERD symptoms and to be obese compared to older patients despite similar clinical outcomes with endoscopic therapies. While 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.

Natural History of the Post-ablation Esophagus.

Endoscopic ablative therapy including radiofrequency ablation (RFA) represents the preferred management strategy for dysplastic Barrett's esophagus (BE) and appears to diminish the risk of developing esophageal adenocarcinoma (EAC). Limited data describe the natural history of the post-ablation esophagus. Recent findings demonstrate that recurrent intestinal metaplasia (IM) following RFA is relatively frequent. However, dysplastic BE and EAC subsequent to the complete eradication of intestinal metaplasia (CEIM) are uncommon. Moreover, data suggest that the risk of recurrent disease is probably highest in the first year following CEIM. Recurrent IM and dysplasia are usually successfully eradicated with repeat RFA. Future studies may refine surveillance intervals and inform the length of time surveillance should be conducted following RFA with CEIM. Further data will also be necessary to understand the utility of chemopreventive strategies, including NSAIDs, in reducing the risk of recurrent disease.

Effectiveness of Endoscopic Therapy in Patients With Barrettʼs Esophagus (BE) With Early Cancer Is Comparable to That of BE With High-Grade Dysplasia (HGD): Results From an International, Multi-center Consortium: 2017 Category Award (Esophagus)

Introduction: Endoscopic therapy, the current treatment of choice for BE patients with HGD, is also a noninvasive alternative to surgery for treatment of BE with intra-mucosal cancer (IMC). There are limited data comparing the outcomes of endoscopic therapy in BE patients with IMC and HGD. We aimed to compare the rates of complete eradication of intestinal metaplasia (CE-IM), complete eradication of dysplasia (CE-D) and recurrent IM (Re-IM) between the two groups -IMC and HGD.Table: Table. Baseline characteristics and outcomes of endoscopic therapy in IMC and HGDMethods: We reviewed all BE subjects with HGD and IMC who underwent endoscopic therapy in a multicenter prospective registry. Patients were treated with endoscopic mucosal resection if visible lesions were noted and/or mucosal ablation (RFA, cryotherapy, APC) for the flat BE. Patients who underwent at least four EGDs with endoscopic therapy were included in the study. CEIM and CED was defined as histologic absence of intestinal metaplasia (IM) and dysplasia respectively. Re-IM was defined as histologic evidence of BE (IM, dysplasia or esophageal adenocarcinoma (EAC)) after achieving CEIM. Rates of CEIM, CED and Re-IM were calculated for the two study groups - IMC and HGD. Cox proportional hazard models were used to compare the outcomes of endoscopic therapy between the two groups. Results: 276 subjects (70 with IMC and 206 with HGD) with BE who underwent endoscopic therapy were included in the study. The median (IQR) age was 66.0 (58.0, 73.0) years. 232 (84.1%) were males. There were no differences in baseline characteristics (age, sex and BE segment length) between the IMC and HGD groups (table 1). In the IMC group, 57 (81.4%) and 62 (88.6%) subjects achieved CE-IM and CE-D respectively. In the HGD group, 173 (84.0%) and 185 (89.8%) subjects achieved CE-IM and CE-D respectively. There was no statistical difference in the proportion of subjects who achieved CE-IM (P=0.62) and CE-D (P=0.77) in the two groups. On multivariate analysis adjusting for age, sex and BE length, there was no statistical difference in the CE-IM (IMC vs HGD; HR 1.15, 95% CI 0.38 - 3.51, P=0.81) and CE-D (IMC vs HGD; HR 1.21, 95% CI 0.31-4.66, P=0.79) rates between the two groups. There were 25 (43.9%) Re-IM in the IMC group and 60 (34.7%) Re-IM in the HGD group (P=0.21). Conclusion: In this large well-defined cohort of BE patients, effectiveness of endoscopic therapy in IMC is comparable to that of HGD. Consideration of endoscopic therapy in BE patients with early cancer could reduce the need for invasive surgery.

Esophageal Epithelial Intercellular Space Dilatation and Risk of Recurrent Intestinal Metaplasia Following Successful Endoscopic Ablative Therapy: 2017 Presidential Poster Award

Esophageal Epithelial Intercellular Space Dilatation and Risk of Recurrent Intestinal Metaplasia Following Successful Endoscopic Ablative Therapy: 2017 Presidential Poster Award

Recurrence of intestinal metaplasia and early neoplasia after endoscopic eradication therapy for Barrett's esophagus: a systematic review and meta-analysis.

Background Conflicting data exist with regard to recurrence rates of intestinal metaplasia (IM) and dysplasia after achieving complete eradication of intestinal metaplasia (CE-IM) in Barrett’s esophagus (BE) patients. Aim (i) To determine the incidence of recurrent IM and dysplasia achieving CE-IM and (ii) to compare recurrence rates between treatment modalities [radiofrequency ablation (RFA) with or without endoscopic mucosal resection (EMR) vs stepwise complete EMR (SRER)]. Methods A systematic search was performed for studies reporting on outcomes and estimates of recurrence rates after achieving CE-IM. Pooled incidence [per 100-patient-years (PY)] and risk ratios with 95 %CI were obtained. Heterogeneity was measured using the I 2 statistic. Subgroup analyses, decided a priori, were performed to explore heterogeneity in results. Results A total of 39 studies were identified (25-RFA, 13-SRER, and 2 combined). The pooled incidence of any recurrence was 7.5 (95 %CI 6.1 – 9.0)/100 PY with a pooled incidence of IM recurrence rate of 4.8 (95 %CI 3.8 – 5.9)/100 PY, and dysplasia recurrence rate of 2.0 (95 %CI 1.5 – 2.5)/100 PY. Compared to the SRER group, the RFA group had significantly higher overall [8.6 (6.7 – 10.5)/100 PY vs. 5.1 (3.1 – 7)/100 PY, P = 0.01] and IM recurrence rates [5.8 (4.3 – 7.3)/100 PY vs. 3.1 (1.7 – 4)/100 PY, P < 0.01] with no difference in recurrence rates of dysplasia. Significant heterogeneity between studies was identified. The majority of recurrences were amenable to repeat endoscopic eradication therapy (EET). Conclusion The results of this study demonstrate that the incidence rates of overall, IM, and dysplasia recurrence rates post-EET are not inconsiderable and reinforce the importance of close surveillance after achieving CE-IM.

Outcomes after liquid nitrogen spray cryotherapy in Barrett's esophagus–associated high-grade dysplasia and intramucosal adenocarcinoma: 5-year follow-up

Liquid nitrogen spray cryotherapy (LNSCT) has been shown to be a safe, well-tolerated, and effective therapy for Barrett's esophagus (BE)-associated high-grade dysplasia (BE-HGD) and intramucosal adenocarcinoma (IMC). Long-term follow-up is lacking. The aim of this study was to assess the efficacy, durability, and rate of neoplastic progression after LNSCT in BE-HGD/IMC at 3 and 5 years. In this single-center, retrospective study drawn from a prospective database, patients with BE-HGD/IMC of any length treated with LNSCT were followed with surveillance endoscopy with biopsy for 3 to 5 years. Patients with IMC completely removed by endoscopic resection were included. Outcome measures included complete eradication of HGD (CE-HGD), dysplasia, and intestinal metaplasia; incidence rates; durability of response; location of recurrent intestinal metaplasia and dysplasia; and rate of disease progression. A total of 50 and 40 patients were included in 3-year and 5-year analyses. Initial CE-HGD, dysplasia, and intestinal metaplasia achieved in 98%, 90%, and 60%, respectively. Overall CE-HGD, dysplasia, and intestinal metaplasia at 3 years were 96% (48/50), 94% (47/50), and 82% (41/50), and at 5 years were 93% (37/40), 88% (35/40), and 75% (30/40). Incidence rates of recurrent intestinal metaplasia, dysplasia, and HGD/esophageal adenocarcinoma per person-year of follow-up after initial complete eradication of intestinal metaplasia (CE-IM) were 12.2%, 4.0%, and 1.4% per person-year for the 5-year cohort. Most recurrences were found immediately below the neosquamocolumnar junction. Two of 7 HGD recurrences occurred later than 4 years after initial eradication, and 2 patients (4%) progressed to adenocarcinoma despite treatment. In patients with BE-HGD/IMC, LNSCT is effective in eliminating dysplasia and intestinal metaplasia. Progression to adenocarcinoma was uncommon, and recurrence of dysplasia was successfully treated in mostcases. Long-term surveillance is necessary to detect late recurrence of dysplasia.

Recurrence of Barrett's Esophagus is Rare Following Endoscopic Eradication Therapy Coupled With Effective Reflux Control.

Recent data suggest that effective control of gastroesophageal reflux improves outcomes associated with endoscopic eradication therapy (EET) for Barrett's esophagus (BE). However, the impact of reflux control on preventing recurrent intestinal metaplasia and/or dysplasia is unclear. The aims of the study were: (a) to determine the effectiveness and durability of EET under a structured reflux management protocol and (b) to determine the impact of optimizing anti-reflux therapy on achieving complete eradication of intestinal metaplasia (CE-IM). Consecutive BE patients referred for EET were enrolled and managed with a standardized reflux management protocol including twice-daily PPI therapy during eradication. Primary outcomes were rates of CE-IM and IM or dysplasia recurrence. Out of 221 patients enrolled (46.0% with high-grade dysplasia/intramucosal carcinoma, 34.0% with low-grade dysplasia, and 20.0% with non-dysplastic BE) an overall CE-IM of 93% was achieved within 11.6±10.2 months. Forty-eight patients did not achieve CE-IM in 3 sessions. After modification of their reflux management, 45 (93.7%) achieved CE-IM in a mean of 1.1 RFA sessions. Recurrence occurred in 13 patients (IM in 10(4.8%), dysplasia in 3 (1.5%)) during a mean follow-up of 44±18.5 months. The only significant predictor of recurrence was the presence of a hiatal hernia. Recurrence of IM was significantly lower than historical controls (10.9 vs. 4.8%, P=0.04). The current study highlights the importance of reflux control in patients with BE undergoing EET. In this setting, EET has long-term durability with low recurrence rates providing early evidence for extending endoscopic surveillance intervals after EET.