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High-risk human papillomavirus (hr-HPV) infection is causal for almost all cervical malignancy (both squamous and adenocarcinoma), 90% of anal neoplasia, 70% of penile tumors, and 25% of head and neck cancers. The shared immunogenetics of cervical and esophageal malignancy suggests that HPV infection could well be a common denominator in the etiology of both cancers. In this regard, we have demonstrated that transcriptionally active hr-HPV (genotypes 16 and 18) is strongly associated with Barrett's dysplasia and esophageal adenocarcinoma. Increasing hr-HPV viral load and integration status has been linked with greater disease severity along the Barrett metaplasia–dysplasia–adenocarcinoma sequence as has been demonstrated in cervical intraepithelial neoplasia and cancer. HPV infections in both the cervix and esophagus are both focal, i.e. present in greater quantities at the squamocolumnar junction (SCJ). HPV affinity is to junctional tissue, as basal cells are particularly accessible at the squamocolumnar transformation zone and especially susceptible to this viral infection. We have postulated that progressive acid damage to the esophagus increases the likelihood of mucosal breaks enabling the virus to enter the basal layer of the transformation zone. The SCJ is the transformation zone of the esophagus and is strikingly similar to the transition zone (ectoendocervical SCJ) of the uterine cervix where almost all high-grade cervical lesions and cancers arise including 80% of adenocarcinomas. These transition zone cells exhibit features of squamous epithelium as well as glandular cells, which have been described in both Barrett's esophagus and cervical mucosa. Barrett's esophagus (BE) is derived from a discrete population of embryonic cells residing at the SCJ. There is loss of SCJ immune-phenotype following excision without regeneration at other junctional sites. Prevention of cervical cancer in up to 80–95% of patients with screen-detected CIN is dependent on the excision/ablation of the entire transformation zone. The persistence of hr-HPV 16/18 following eradication of CIN is a significant risk factor for recurrence. Similarly, we have demonstrated that persistent hr-HPV infection 16/18 and p53 overexpression are associated with treatment failure after endoscopic ablation of BD/EAC. Thus, we believe that excision/ablation of the SCJ in patients with BD/intramucosal EAC should be performed to reduce the potential malignant risk. We propose to test this hypothesis by a multicenter randomized controlled trial whereby patients (both HPV positive and those which are virus negative) will be allocated into two arms: complete excision of the SCJ via endoscopic mucosal resection (EMR) in addition to radiofrequency ablation (RFA) ± EMR of BD/intramucosal EAC (experimental arm) versus current standard of care (RFA ± EMR) of said lesions. Treatment efficacy in both groups will be evaluated by comparing disease elimination, regression/progression, and recurrence (if any). All patients would be entered into an intensive endoscopic surveillance protocol (biannually) for at least 2 years with lesional/neosquamous biopsies to compare the recurrence rate of both dysplasia/neoplasia in both arms. Viral (HPV DNA/p16INK4A/E6/E7 mRNA) and host biomarkers (e.g. p53) will be analyzed both at baseline and posttreatment intervals. A positive study would initiate development of tools best suited for SCJ destruction. [ABSTRACT FROM AUTHOR]

SUMMARY: Barrett's esophagus progresses to esophageal adenocarcinoma in a stepwise histological fashion of no dysplasia, low grade dysplasia, high grade dysplasia and cancer. Hence the progression to cancer from various histological stages is different. Progression to cancer from low grade dysplasia is highly variable in the literature due to high inter-observer variability between pathologists in diagnosing it. Studies have shown the utility of having confirmation of low grade dysplasia by expert pathologists or documenting its persistence on two subsequent endoscopies in order to unify the diagnosis. The treatment of low grade dysplasia is variable. In this article we summarize the diagnosis, evaluation and management of low grade dysplasia in Barrett's Esophagus [ABSTRACT FROM AUTHOR]

Patients with Barrett''s esophagus are frequently treated with radiofrequency ablation (RFA). Those that undergo this procedure have a low risk of developing subsquamous intestinal metaplasia, and none have been reported to develop subsquamous dysplasia or cancer. We report the development of subsquamous neoplasia in 3 patients who were treated with RFA for Barrett''s esophagus (2 developed adenocarcinoma and 1 developed high-grade dysplasia). The identification of these cases indicates the need for continued surveillance following RFA, even after complete eradication of intestinal metaplasia, and caution for widespread use of ablation, especially in patients with low-risk Barrett''s esophagus. [Copyright &y& Elsevier]

Background & Aims: Endoscopic mucosal resection (EMR) is an important diagnostic, staging, and therapeutic tool for patients with Barrett''s esophagus (BE)–associated neoplasia. We analyzed the histopathologic characteristics of specimens collected during EMR compared with biopsy specimens from patients with BE and assessed interobserver variability in pathologists'' assessment of EMR and biopsy specimens. Methods: We evaluated EMR (n = 251) and biopsy (n = 269) specimens collected from patients with BE at 2 tertiary referral centers. A detailed histologic analysis was performed for each EMR and biopsy specimen to determine the grade of dysplasia, depth of the specimen, proportion of specimen with dysplasia, and quality of samples. Interobserver agreement for both biopsy and EMR specimens (among 4 experienced pathologists) was calculated by using kappa statistics. Results: Histologic analysis showed that submucosa was present in the majority of EMRs, compared with biopsy specimens (88% vs 1%, P < .0001). Almost all biopsy specimens (99%) included lamina propria. However, the muscularis mucosa was observed in only 58% of biopsy specimens. For both EMR and biopsy specimens, the highest grade of dysplasia comprised ≤25% of the total area in >50% of the specimens. Interobserver agreement on the diagnosis of dysplasia was significantly greater for EMR specimens than biopsy specimens (low-grade dysplasia, 0.33 vs 0.22, P < .001; high-grade dysplasia, 0.43 vs 0.35, P = .018). Conclusions: Submucosa can be examined in most samples collected from EMR; the distribution of neoplasia is focal within biopsy and EMR specimens. There is more interobserver agreement among pathologists in the analysis of EMR samples than biopsy specimens for the diagnosis of dysplasia. [Copyright &y& Elsevier]