Molecular evaluation of ablative therapy of Barrett's oesophagus

Abstract

Barrett's oesophagus is a major risk factor for developing oesophageal adenocarcinoma. Ablation by argon plasma coagulation (APC) and photodynamic therapy (PDT) is currently under investigation for the removal of metaplastic and dysplastic Barrett's oesophagus. This study examined the effect of ablative therapy on Barrett's oesophagus at cell-cycle and genetic levels. The premalignant potential of residual or recurring Barrett's oesophagus was assessed by p53 immunohistochemistry, Ki67-related proliferative capacity, and DNA ploidy status (ie an abnormal chromosome 1 number) as measured by interphase in situ hybridization. Twenty-nine patients with Barrett's oesophagus (23 male and 6 female, mean age 58 years, mean length of Barrett's oesophagus 4 cm) were treated with APC or PDT. Intestinal metaplasia without dysplasia was present in 16 patients, low-grade dysplasia in five, and high-grade dysplasia in eight patients. Biopsy samples were obtained at regular intervals (mean follow-up 20 months, range 6-36 months). One month after the first ablation, Barrett's oesophagus was no longer identified, either endoscopically or histologically, in nine patients (32%). At this time point, significant down-grading was achieved for abnormal chromosome 1 numbers (p = 0.020) and Ki67-defined proliferation (p = 0.002). Patients with residual Barrett's oesophagus were additionally treated with APC, resulting in the elimination of Barrett's oesophagus in 76% of all patients. However, at the last follow-up endoscopy, metaplasia without dysplasia was still present in five patients, and low- and high-grade dysplasia were each present in one patient. An abnormal chromosome 1 number and p53 protein overexpression were detected only in the high-grade dysplastic lesion, but increased proliferation was still present in the majority of these persisting cases. Although endoscopic removal of Barrett's oesophagus by ablative therapies is possible in the majority of patients, histologically complete elimination cannot be achieved in all cases. Persistent Barrett's oesophagus may still harbour molecular aberrations and must therefore be considered still to be at risk of progression to adenocarcinoma.

Genomic analysis of Barrett's esophagus after ablative therapy: Persistence of genetic alterations at tumor suppressor loci

“…In a previous study, we investigated cellular proliferation, aneuploidy and p53 protein overexpression in BE patients after PDT and APC treatment. 45 After an initial downgrading of cell biologic abnormalities, i.e., aneuploidy and increased cellular proliferation, both ablative methods were not able to remove BE completely in a subset of patients. In these patients, biologic abnormalities persisted in both dysplastic and nondysplastic Barrett's epithelium.…”

Diagnostic and therapeutic endoscopy

“…However, complete ablation was obtained in 76% of patients with combined treatment without stricture formation. Residual Barretts epithelium may still harbor molecular aberrations and must, therefore, be considered to be at risk of progression to adenocarcinoma and, therefore, receive further treatment or adequate follow-up [34].…”

A Systematic Review and Meta-Analysis of the Treatment for Barrett’s Esophagus

“…In contrast to PDT, there is no need for patients treated with APC and MPEC to receive a photosensitizing drug, and systemic photosensitization is avoided. Accumulating evidence suggests that APC and MPEC have satisfying safety profiles, with significant complications (e.g., stricture, perforation, bleeding) in fewer than 15% of patients [13,14,[22][23][24][25][26][27][28][29]. This may, in part, be because of the limited depth of coagulation of the techniques compared with other ablative methods [28].…”

“…We extracted the results at 6 weeks post-treatment with APC or PDT, respectively. Another study by Hage et al [26] examined the effect of ablative therapy on BE at the cell-cycle and genetic levels; we included this study in our analysis because the endpoints of ablation of BE by histopathology were reported separately. Ragunath et al [27] discovered that APC and porfirmer sodium-induced PDT were equally effective in eradicating Barrett's mucosa but that PDT was more effective in eradicating dysplasia.…”