Citations

Objective Surveillance interval protocols after complete remission of intestinal metaplasia (CRIM) post radiofrequency ablation (RFA) in Barrett’s oesophagus (BE) are currently empiric and not based on substantial evidence. We aimed to assess the timeline, location and patterns of recurrence following CRIM to inform these guidelines. Design Data on patients undergoing RFA for BE were obtained from prospectively maintained databases of five (three USA and two UK) tertiary referral centres. RFA was performed until CRIM was confirmed on two consecutive endoscopies. Results 594 patients achieved CRIM as of 1 May 2017. 151 subjects developed recurrent BE over a median (IQR) follow-up of 2.8 (1.4–4.4) years. There was 19% cumulative recurrence risk of any BE within 2 years and an additional 49% risk over the next 8.6 years. There was no evidence of a clinically meaningful change in the recurrence hazard rate of any BE, dysplastic BE or high-grade dysplasia/cancer over the duration of follow-up, with an estimated 2% (95% CI −7% to 12%) change in recurrence rate of any BE in a doubling of follow-up time. 74% of BE recurrences developed at the gastro-oesophageal junction (GOJ) (24.1% were dysplastic) and 26% in the tubular oesophagus. The yield of random biopsies from the tubular oesophagus, in the absence of visible lesions, was 1% (BE) and 0.2% (dysplasia). Conclusions BE recurrence risk following CRIM remained constant over time, suggesting that lengthening of follow-up intervals, at least in the first 5 years after CRIM, may not be advisable. Sampling the GOJ is critical to detecting recurrence. The requirement for random biopsies of the neosquamous epithelium in the absence of visible lesions may need to be re-evaluated.

Abstract Background Post-surgical complications such as leaks are the source of considerable morbidity and mortality. Success of conservative interventions is highly variable. Recurrence after surgical repair is also not uncommon. Our aim was to develop novel endoscopic strategies to maximize negative intracavitary pressure to manage leaks in cases where conventional management either failed or were not feasible. Methods We have used transluminal locking loop drains with low intermittent suction in the management of non-healing leaks in various areas. An example presented here illustrates this concept where a 68-year-old male patient underwent paraesophageal hernia repair with Nissen fundoplication. Patient presented 3 weeks later with fistula leading to a 13 cm meditational abscess. Patient developed right hemiparesis requiring tissue plasminogen activator (tPA). Post-tPA patient developed hemoptysis and hematemesis requiring emergency intubation. The defect in the esophagus was 6–8 mm. Endoscopic repair with stitching or clipping would have left a large undrained cavity with a potential to expand. Endoscopic repair with transcutaneous drain placement was challenging due to recent tPA and a difficult location. Moreover there was potential to develop esophago- pleural- broncho- cutaneous fistula. Endoscopic vacuum therapy was felt to be a suboptimal choice. Patient was high-risk surgical candidate as it would have required radical surgery in the setting of tPA.Upper endoscopy was performed and the cavity was debrided. No direct communication with bronchopulmonary tree noted. A transnasal guidewire assisted 16 Fr, 60 cm locking loop drain was placed and connected to low intermittent suction that was switched to bulb based suction. Results The output from naso-cavity drain decreased nearly 100 cc per day in the first 5 days and the size reduced by 30, 50 and 80% by day 5, 9 and 12 respectively. Near complete elimination of the cavity was observed on day 15. Esophagogram showed complete resolution of the leak and computerized tomography revealed no residual cavity Conclusion Developing transluminal endoscopic strategies to maximize negative intracavitary pressure helps expedite the healing of resistant postsurgical leaks. This technique avoids the need for frequent drain changes that remains a challenge for vacuum therapy. Disclosure All authors have declared no conflicts of interest.

Abstract Background The neo-squamous epithelium that replaces columnar epithelium after successful endoscopic ablation of Barrett's esophagus (BE) has not been fully characterized in regard to its structural and functional integrity. Intercellular space is a surrogate marker for epithelial structural integrity and mucosal impedance (MI) is a surrogate for transepithelial resistance and thus epithelial functional integrity. Impairment of the structural and functional integrity may influence recurrence following successful ablation. We aimed to measure the esophageal epithelial intercellular space diameter and MI in the neo-squamous and normal squamous epithelium of patients who underwent successful radiofrequency ablation for dysplastic BE. Methods Forty patients with complete remission of intestinal metaplasia (CRIM) (defined as two negative surveillance endoscopies for intestinal metaplasia) were prospectively recruited. Patients were excluded if they had endoscopic evidence of esophagitis. MI measurements were taken at 1 cm above the GE junction and 2 cm above the prior BE segment (targeting uninvolved squamous epithelium), using a novel through the scope MI probe. Endoscopic biopsies were also taken at these corresponding sites to assess intercellular space diameter using transmission electron microscopy (TEM) using standard techniques. Results 80% of patients were male with a mean age of 69 years. Mean follow since achieving CRIM was 30 months. 39 patients underwent RFA for dysplasia. The mean intercellular space diameter was higher in the neo-squamous epithelium (1.01 μm) when compared to the untreated native squamous epithelium (0.96 μm) [Difference of 0.056 μm, 95% CI of -0.036 to 0.148, P = 0.228]. The mean MI was significantly lower in the neosquamous epithelium (4001.3 Ω) when compared to the untreated native epithelium (5168.1 Ω) [Difference of 1166.7 Ω, 95% CI 418.8 to 1914.6, P = 0.003]. Conclusion Neo-squamous epithelium that replaces BE epithelium following successful endoscopic therapy for BE appears to be functionally and likely structurally deficient with regards to acid reflux barrier function, when compared to native squamous esophageal epithelium. This impairment may be associated with recurrence following successful ablation. Disclosure All authors have declared no conflicts of interest.

Abstract Background Endoscopic mucosal resection (EMR) can be performed en-bloc in Barrett's esophagus (BE) lesions that are ≤2 cm in size. The true size of a BE lesion may be underestimated under white light endoscopy, limiting the rate of en-bloc resection. Volumetric laser endomicroscopy (VLE) provides high-resolution cross-sectional imaging of BE. A greater number of VLE glands are associated with BE dysplasia and may help predict lesion size. The aim of this study was to determine the association between VLE gland count and outcome of resection. Methods EMR specimens from patients with a history of dysplastic BE were imaged with VLE. EMRs performed on BE lesions ≤2cm in size with intent at en-bloc resection were included. Manual quantification of epithelial glands was performed in blinded fashion. Image visualization enhancement software was used to quantify the surface area occupied by epithelial glands on en-face VLE. Histologic en-bloc (R0) and incomplete (R1) resection of the targeted lesion was defined by the absence and presence of dysplasia and/or cancer at the specimen margins respectively. Results The study sample consisted of 37 EMRs from 31 patients. The mean (SD) size of EMRs was 1.04 (0.37) cm. Pathology showed low-grade dysplasia (N = 12), high-grade dysplasia (N = 19), and intramucosal cancer (N = 6). The en-bloc resection rate was 37.8% (R0: N = 14; R1: N = 23). The mean (SD) number of epithelial glands was 13.0 (6.7) and 28.8 (23.9) for R0 and R1 specimens, respectively, with a statistically significant mean difference of 15.8 glands (95% CI: 2–29, P = 0.02) between the two groups. A gland count of 28 or higher per EMR specimen predicted R1 with 100% sensitivity and 39% specificity (ROC: 0.69). The mean (SD) surface area occupied by epithelial glands in R0 and R1 specimens was 0.98 (1.1) mm2 and 2.3 (2.4) mm2, respectively. There was strong correlation between manual gland counts and epithelial gland surface area (R2: 0.81, P < 0.001). Conclusion A higher number of VLE glands in EMR specimens is associated with a lower en-bloc resection rate suggesting that white-light endoscopy underestimates lesion size and that VLE may have a potential role in lesion margin assessment. Disclosure All authors have declared no conflicts of interest.

AbstractBackground and AimVolumetric laser endomicroscopy (VLE) is used to identify Barrett's esophagus (BE) dysplasia. Selection of a dysplastic region of interest (ROI) can be challenging due to feature variability across a large amount of data. The degree of agreement among VLE users in selecting a ROI has not been studied.MethodsHigh‐definition videos that divided a VLE scan from 18 patients with biopsy‐proven BE dysplasia into 1‐cm segments were reviewed using a four‐quadrant grid superimposed for systematic interpretation. VLE scans were selected based on image quality and appropriate visualization of BE epithelium. Four experienced VLE users rated each quadrant as dysplastic or non‐dysplastic. For quadrants rated as dysplastic, reviewers selected a single timeframe with representative features. A high‐degree of agreement among reviewers was defined as ≥75% agreement on the quadrant diagnosis and ≥50% agreement on selected timeframe (±2 s).ResultsThirty‐one videos, each 32 s in length, comprising 124 quadrants were reviewed. There was high‐agreement among reviewers in 99 (80%) quadrants, of which 68 (69%) were rated as dysplastic. Compared with quadrants rated as non‐dysplastic, ROIs of quadrants rated as dysplastic contained a higher number of epithelial glands (12.7 vs 1.2, P < 0.001) with atypical architecture (54 vs 1, P < 0.001). A statistically significant difference was observed between the signal intensity profiles of quadrants rated as dysplastic and quadrants rated as non‐dysplastic (P = 0.004).ConclusionThis study highlights that experienced VLE users can identify ROIs with high‐degree of agreement. Selected ROIs contained VLE features associated with BE dysplasia.

Goals: To investigate factors predictive of progression from nondysplastic Barrett esophagus (NDBE) or low-grade dysplasia (LGD) to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) using a large, prospective cohort of patients, wherein all esophageal biopsies undergo expert gastrointestinal pathologist review. Background: Efficacy and cost-effectiveness of endoscopic surveillance to detect incident EAC in the setting of Barrett esophagus (BE), particularly in NDBE patients, is questioned. Previous studies have reported factors predictive of progression to EAC to guide surveillance intervals, but their strength is limited by small sample size and absence of expert gastrointestinal pathologist involvement in esophageal biopsy review. Study: NDBE and LGD subjects were identified from a prospective registry in a tertiary care center. “Progressors” were BE subjects who developed HGD/EAC>12 months after the initial NDBE or LGD diagnosis. Cox proportional hazards model were used to identify predictors of progression. Results: In total, 318 with NDBE and 301 with BE-LGD (mean age, 62.6 y, 85% male) were included. The mean follow-up was 5.3 years. The 7 NDBE and 21 LGD subjects progressed to HGD/EAC. BE length [hazards ratio (HR), 1.16; 95% confidence interval (CI), 1.03-1.29], presence of nodularity (HR, 4.98; 95% CI, 1.80-11.7), and baseline LGD (HR, 2.57; 95% CI, 1.13-6.57) were significant predictors of progression on multivariate analysis. Conclusions: In this well-defined cohort of NDBE and BE-LGD subjects, BE length, presence of LGD, and nodularity were independent predictors of progression to HGD/EAC. These factors may aid in identifying high-risk patients who may benefit from closer endoscopic surveillance/therapy.

1 Background: Endoscopic resection (ER) is used to treat early esophageal cancers (EAC). With the advent of techniques such as ESD that can remove large lesions en bloc, it is important to determine if performing piecemeal resections of intramucosal cancers is detrimental. Aim: To evaluate the response rates in patients with esophageal intramucosal adenocarcinoma (IMC) who had a single ER (SR) compared to those treated with piecemeal resection (PR). Methods: This is a cohort study of patients being followed in our BE unit. Patients in a prospectively maintained database with EAC from Jan 1998 to Apr 2012 were assessed. IMC was defined as lesions that were intramucosal without extension into the submucosa. All T1a cancers were verified by two expert gastrointestinal pathologists. We compared the tumor characteristics and recurrence rate between the two groups of SR and PR of IMC. Results: A total of 197 IMC (T1a) lesions in 138 patients were identified. 88(44.7%) lesions were performed SR and 109(55.3%) were PR. Mean follow up time were 45 months (IQR 24-70.5) in SR and 39 months (IQR 26-52, P=0.067) in PR. Complete remission were found of 92.1% (81) in SR and of 93.6% (102) in PR (P=0.788) patients. The recurrence rate was 7.9% in the SR patients, and 6.4% in the PR patients (P=0.699). Median time to progression was 12 months in the SR group (IQR 8-23.5) and 11 months in the PR (IQR 8-22) (P=0.765) group. The mean survival duration was 116.3 months in the SR and 89 months in the PR (P=0.079). No statistical difference in 5-year survival rates was found between SR (83.2%) and PR (80.9%) (P=0.082). Cox proportional hazard model analysis showed local recurrence after EMR was not related to number of specimen resected or technique. Conclusions: PR appears to be as effective a therapy as en bloc for esophageal IMC. Using PR does not appear to affect clinical outcomes.

ABSTRACTThe rapid increase and poor survival of esophageal adenocarcinoma (EAC) have led to significant efforts to promote early detection. Given that the premalignant lesion of Barrett's esophagus (BE) is the major known risk factor for EAC, multiple investigators have studied biomarker signatures that can predict malignant progression of BE to EAC. MicroRNAs, a novel class of gene regulators, are small non‐coding RNAs and have been associated with carcinogenesis. MicroRNAs are ideal biomarkers because of their remarkable stability in fixed tissues, a common method for collection of clinical specimens, and in blood either within exosomes or as microRNA‐protein complexes. Multiple studies show potential of microRNAs as tissue and blood biomarkers for diagnosis and prognosis of EAC but the results need confirmation in prospective studies. Although head‐to‐head comparisons are lacking, microRNA panels require less genes than messenger RNA panels for diagnosis of EAC in BE. MicroRNA diagnostic panels will need to be compared for accuracy against global measures of genome instability that were recently shown to be good predictors of progression but require sophisticated analytic techniques. Early studies on blood microRNA panels are promising but have found microRNA markers to be inconsistent among studies. MicroRNA expression in blood is different between various microRNA sub‐compartments such as exosomes and microRNA‐protein complexes and could affect blood microRNA measurements. Further standardization is needed to yield consistent results. We have summarized the current understanding of the tissue and blood microRNA signatures that may predict the development and progression of EAC. J. Cell. Biochem. 117: 1288–1295, 2016. © 2016 Wiley Periodicals, Inc.