Chatura Jayasekera

Added value of narrow band imaging and confocal laser endomicroscopy in detecting Barrett’s esophagus neoplasia

BACKGROUND AND STUDY AIMS Advances in endoscopic imaging techniques have enabled more accurate identification of subtle mucosal abnormalities. The aim of the study was to assess the accuracy of predicting high grade dysplasia (HGD) and intramucosal cancer (IMC) in mucosa predicted as being nondysplastic vs. dysplastic by high definition white light endoscopy (HD-WLE), narrow band imaging (NBI), and confocal laser endomicroscopy (CLE). PATIENTS AND METHODS A cross-sectional study was performed in a tertiary referral setting between February 2010 and September 2011. A total of 50 consecutive patients who were referred to St Vincents Hospital for management of dysplastic Barretts esophagus were included. A prediction of likely histology was made for each mucosal point (four-quadrant every 1 cm and any visible mucosal abnormality), first with HD-WLE, followed by NBI, and finally CLE. Biopsies were taken at all of these points. RESULTS A total of 1190 individual biopsy points were assessed. At histology, 39 biopsy points were found to harbor HGD and 52 biopsy points harbored IMC. For the detection of HGD/IMC the sensitivity, specificity, and accuracy were: HD - WLE, 79.1 %, 83.1 %, and 82.8 %; NBI, 89.0 %, 80.1 %, and 81.4 %; and CLE, 75.7 %, 80.0 %, and 79.9 %, respectively. All mucosal points with IMC and all patients with HGD were detected by targeted biopsies guided by HD-WLE and NBI without the need for random Seattle protocol biopsies. CONCLUSIONS HD-WLE in combination with NBI is highly accurate in the detection of HGD/IMC. Performing targeted biopsies in the surveillance of Barretts esophagus is possible in expert centers.

Cluster of 4 cases of esophageal squamous cell cancer developing in adults with surgically corrected esophageal atresia—time for screening to start

BACKGROUND Currently, no recommendations exist for the endoscopic screening of patients in adulthood, with surgically corrected esophageal atresia (EA), for the development of esophageal cancer. A small number of individual case reports in the literature have raised concern that these cancers pose an increased risk (2 adenocarcinoma and 3 squamous cell carcinoma). METHODS St Vincents hospital has set up an EA clinic to review adult patients previously operated on for correction of EA. These patients underwent clinical review and were offered endoscopic evaluation if they had symptoms of dysphagia or gastroesophageal reflux. Among those patients, 3 have developed esophageal squamous cell carcinoma (SCC). A retrospective review of the EA database from the Royal Childrens Hospital (798 patients [309 patients older than 40 years]) was then performed to identify any other cases of esophageal cancer developing in this cohort. One further patient was identified. RESULTS To date, 4 of 309 patients have developed esophageal SCC over the age of 40 years. The cumulative incidence of esophageal SCC in this age group was 50 times that expected in the general population. CONCLUSIONS (1) This cluster provides strong evidence that there is a substantial risk of SCC in these adults with surgically repaired EA. (2) We believe that long-term surveillance endoscopy enhanced by advanced imaging techniques is indicated in all adults from the age of 20 years who have had surgical repair of EA.

Detection and staging of esophageal cancers within Barrett's esophagus is improved by assessment in specialized Barrett's units

BACKGROUND Identification and resection of mucosal abnormalities are critical in managing dysplastic Barretts esophagus (BE) because these areas may harbor esophageal adenocarcinoma (EAC). OBJECTIVES To compare mucosal lesion and EAC detection rates in dysplastic BE in the community versus a BE unit and assess the impact of EMR on disease staging and management. DESIGN Prospective cohort study. SETTING Tertiary referral center. PATIENTS Patients with dysplastic BE. INTERVENTIONS Reassessment with high-definition white-light endoscopy (HD-WLE), narrow-band imaging (NBI), and Seattle protocol biopsies. EMR performed in lesions thought to harbor neoplasia. Review of referral histology and endoscopies. MAIN OUTCOME MEASUREMENTS Mucosal lesion and EAC detection rates in a BE unit versus the community. Impact of EMR on management. RESULTS Sixty-nine patients were referred (88% male; median age, 69 years). At referral, HD-WLE/NBI use was 57%/14%, and Seattle protocol adherence was 20%. Eighteen patients had intramucosal cancer. Lesions were detected in 65 patients in the BE unit versus 29 patients at referral (P < .001). EMR was performed in 47 patients. BE unit assessment confirmed EAC in all 18 patients and identified 10 additional patients (56% increased cancer detection, P = .036); all 10 had lesions identified in the BE unit (vs 3 identified at referral). EMR in these patients found submucosal cancer (n = 4) and intramucosal cancer (n = 6), resulting in esophagectomy (n = 4) and chemoradiotherapy (n = 1). LIMITATION Academic center. CONCLUSION BE assessment at a BE unit resulted in increased lesion and EAC detection. EMR of early cancers was critical in optimizing patient management. These data suggest that BE unit referral be considered in patients with dysplastic BE.

Recurrent intestinal metaplasia at the gastroesophageal junction following endoscopic eradication of dysplastic Barrett’s esophagus may not be benign

Background and study aims: Radiofrequency ablation (RFA) combined with endoscopic mucosal resection (EMR) is effective for eradicating dysplastic Barrett’s esophagus. The durability of response is reported to be variable. We aimed to determine the effectiveness and durability of RFA with or without EMR for patients with dysplastic Barrett’s esophagus. Patients and methods: Patients with dysplastic Barrett’s esophagus referred to two academic hospitals were assessed with high definition white-light endoscopy, narrow-band imaging, and Seattle protocol biopsies. EMR was performed in visible lesions. RFA was performed at 3-month intervals until complete remission of dysplasia (CR-D) and intestinal metaplasia (CR-IM) was achieved. Results: In total, 137 patients received RFA (78 with EMR); 75 with over 12 months follow-up since commencing RFA. Pretreatment histology was intramucosal cancer (IMC) 21 %, high grade dysplasia (HGD) 54 %, low grade dysplasia (LGD) 25 %. CR-D rates were 88 %, 92 %, and 100 % at 1, 2, and 3 years; CR-IM rates were 69 %, 74 %, and 81 %. Kaplan–Meier analysis showed increasing probability of achieving CR-D/CR-IM over time. Of 26 patients maintaining CR-IM for > 12 months, five relapsed with intestinal metaplasia (19 %), and three with dysplasia (12 %). Recurrences occurred in patients with prior HGD/IMC, predominantly at the gastroesophageal junction (GEJ). None relapsed with cancer. Adverse events occurred in 4 % of RFA and 6.5 % of EMR procedures. Conclusions: RFA combined with EMR is effective in achieving CR-D/CR-IM in the majority of patients with dysplastic Barrett’s esophagus, with an incremental response over time. While durable in the majority, recurrent intestinal metaplasia and dysplasia, frequently occurring at the GEJ, suggest long-term surveillance is warranted in high risk groups.

Changes in gene expression of neo-squamous mucosa after endoscopic treatment for dysplastic Barrett’s esophagus and intramucosal adenocarcinoma

Background Endoscopic therapy, including by radiofrequency ablation (RFA) or endoscopic mucosal resection (EMR), is first line treatment for Barrett’s esophagus (BE) with high-grade dysplasia (HGD) or intramucosal cancer (IMC) and may be appropriate for some patients with low-grade dysplasia (LGD). Objective The purpose of this study was to investigate the molecular effects of endotherapy. Methods mRNA expression of 16 genes significantly associated with different BE stages was measured in paired pre-treatment BE tissues and post-treatment neo-squamous biopsies from 36 patients treated by RFA (19 patients, 3 IMC, 4 HGD, 12 LGD) or EMR (17 patients, 4 IMC, 13 HGD). EMR was performed prior to RFA in eight patients. Normal squamous esophageal tissues were from 20 control individuals. Results Endoscopic therapy resulted in significant change towards the normal squamous expression profile for all genes. The neo-squamous expression profile was significantly different to the normal control profile for 11 of 16 genes. Conclusion Endotherapy results in marked changes in mRNA expression, with replacement of the disordered BE dysplasia or IMC profile with a more “normal” profile. The neo-squamous mucosa was significantly different to the normal control squamous mucosa for most genes. The significance of this finding is uncertain but it may support continued endoscopic surveillance after successful endotherapy.