The approach to high grade dysplasia in Barrett’s esophagus

Abstract

Buttar et al. at the Mayo Clinic performed a study whose aim was to determine whether patients who have Barrett’s esophagus with focal high-grade dysplasia (HGD) have the same risk of developing adenocarcinoma as those with diffuse high grade dysplasia. Barrett’s esophagus is a change in the normal esophageal squamous epithelial lining to specialized columnar epithelium, which is typically seen in patients with gastroesophageal reflux disease (1). Of the patients who develop Barrett’s esophagus, approximately 5–10% will be at risk of developing adenocarcinoma (2). Currently, the best predictor for the development of cancer is histological classification of dysplasia on biopsy. Patients who have biopsy-proven HGD have an increased risk of progressing to adenocarcinoma (3). Surgical resection is typically the therapeutic recommendation for operative candidates who are diagnosed with HGD (4). However, it is not known whether the extent of HGD has any correlation with the risk of developing adenocarcinoma. This study involved a retrospective cohort of 100 consecutive patients who had histology-proven HGD on esophageal biopsy with no obvious adenocarcinoma. Slides were reviewed and results confirmed by two expert pathologists. Thirty-three patients were categorized as having focal HGD, in which histological features were limited to a single focus of five or fewer crypts, and 67 were categorized as having diffuse HGD, in which histological features involved more than five crypts in a single biopsy specimen or more than one biopsy fragment. The endpoint of the study was the histological diagnosis of esophageal adenocarcinoma, with the index point being the first endoscopic biopsy diagnosis of HGD at the Mayo Clinic. Cancer-free survival was determined by the interval between the index date and the diagnosis of cancer/esophagectomy or the date of the last cancer-free endoscopic surveillance. Nine of the patients with focal HGD and 25 of the patients with diffuse HGD were managed surgically. The remaining patients were carefully observed undergoing endoscopic surveillance every 3 months by the same endoscopist utilizing an intensive biopsy protocol involving four quadrant biopsy specimens taken at 1 cm intervals. The results showed that cancer-free survival rates at 1 and 3 yr were 93% and 86%, respectively, for focal HGD versus 62% and 44% for diffuse HGD ( p < 0.001). Within the 8-yr follow-up, 32 of the 100 patients developed adenocarcinoma (four patients categorized as focal HGD and 28 patients categorized with diffuse HGD). Nineteen of these 32 patients were diagnosed with adenocarcinoma within 6 months of their diagnosis with HGD (two patients with focal HGD and 17 with diffuse HGD). Fifteen of the 34 patients who underwent esophagectomy as therapy were found to have adenocarcinoma not previously recognized by biopsy samples (one in a patient with focal and 14 in patients with diffuse). The remaining 66 patients not undergoing esophagectomy underwent endoscopic surveillance alone or combined with photodynamic therapy. Of these 66 patients, three of the focal and 17 of the diffuse were diagnosed with adenocarcinoma. Their conclusion was that the patients with diffuse HGD were more likely to develop cancer during the 1st yr after diagnosis and on continuing follow-up than were patients with focal HGD.