Volume 120, Issue 7, Pages 1607-1619 (June 2001) Long-term nonsurgical management of Barrett's esophagus with high-grade dysplasia  Thomas G. Schnell, Stephen J. Sontag, Gregorio Chejfec, Gerard Aranha, Adrienne Metz, Susan O'Connell, Ulla J. Seidel, Amnon Sonnenberg  Gastroenterology  Volume 120, Issue 7, Pages 1607-1619 (June 2001) DOI: 10.1053/gast.2001.25065 Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 1 (A) Negative for dysplasia: Intestinal epithelium overgrowing an island of squamous mucosa. Glands have a single, basally oriented layer of nuclei. (Hematoxylin-eosin × 800). (B) Low-grade dysplasia: Intestinal epithelium with villous differentiation. Compared with (A) the nuclei are enlarged, hyperchromatic, crowded, and stratified, often extending up onto the mucosal surface. (Hematoxylin-eosin × 800). (C) High-grade dysplasia: Intestinal epithelium with branching glands. Compared with (B) the glandular architecture is more distorted. The irregularly stretched nuclei that project onto the mucosal surface are now more hyperchromatic, larger, and rounder due to loss of polarity. Mitoses are easily seen. (Hematoxylin-eosin × 800). (D) Adenocarcinoma: Intestinal epithelium with infiltrative, well-differentiated mucin-producing adenocarcinoma. The dysplastic cells with the abnormal nuclei have invaded the lamina propria. (Hematoxylin-eosin × 160). Gastroenterology 2001 120, 1607-1619DOI: (10.1053/gast.2001.25065) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 2 The entire high-risk population: Hines Veterans Affairs. Distribution of the 1125 patients at their current most advanced dysplasia. Of the 1125 patients, 1099 had Barrett's epithelium. The group of 79 patients include patients with prevalent HGD (n = 34) and patients with incident HGD (n = 45). The rectangular box shows the fate of the 79 patients: 63 progressed no further than HGD, 12 progressed to cancer from HGD or through HGD, and 4 had unsuspected cancer discovered during the 1-year intensive search. The following three groups are not included in the overall study population: *prevalent Barrett's cancer (n = 42); **LGD that bypassed HGD and progressed directly to cancer (n = 10); and ***GEJ cancer without evidence of Barrett's (n = 26). Patients in these groups had never been diagnosed with HGD existing alone. Gastroenterology 2001 120, 1607-1619DOI: (10.1053/gast.2001.25065) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 3 Incidence of esophageal cancer in 79 patients with HGD. Four of 34 patients with prevalent HGD had unsuspected cancer diagnosed during the first year of searching. Two additional patients with prevalent HGD and 10 of the 45 patients with incident HGD developed esophageal cancer during surveillance. The time interval between first diagnosis of LGD and HGD and the diagnosis of cancer is shown for all 12 patients with cancer. *Died of noncancer causes. **Died of esophageal cancer. AdCa, adenocarcinoma. Gastroenterology 2001 120, 1607-1619DOI: (10.1053/gast.2001.25065) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 4 Representative examples of the histological course of (A) patients with prevalent and incident HGD and (B) some of the patients with HGD who developed cancer. Many patients had only 1 or 2 episodes of HGD and eventually died with their esophagus in tact; some showed reemergence of HGD after many years of LGD or no dysplasia. Two of the 3 patients who died had deaths that were unrelated to cancer. Patient 2 had the 10-year hiatus without endoscopy follow up. During the 10 years of no surveillance, the patient developed dysphagia and returned with a large unresectable tumor. Nine of the 12 patients (8 shown) remain alive since the diagnosis of cancer. AdCa, adenocarcinoma; RS, resected at surgery; US, unresectable; NS, no surgery; C, electrocoagulation. (arrow), Alive; (X), died; (●), biopsy. Gastroenterology 2001 120, 1607-1619DOI: (10.1053/gast.2001.25065) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 4 Representative examples of the histological course of (A) patients with prevalent and incident HGD and (B) some of the patients with HGD who developed cancer. Many patients had only 1 or 2 episodes of HGD and eventually died with their esophagus in tact; some showed reemergence of HGD after many years of LGD or no dysplasia. Two of the 3 patients who died had deaths that were unrelated to cancer. Patient 2 had the 10-year hiatus without endoscopy follow up. During the 10 years of no surveillance, the patient developed dysphagia and returned with a large unresectable tumor. Nine of the 12 patients (8 shown) remain alive since the diagnosis of cancer. AdCa, adenocarcinoma; RS, resected at surgery; US, unresectable; NS, no surgery; C, electrocoagulation. (arrow), Alive; (X), died; (●), biopsy. Gastroenterology 2001 120, 1607-1619DOI: (10.1053/gast.2001.25065) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 5 Kaplan–Maier Survival Curves. (A) Time to development of cancer. Cumulative survival of patients with HGD remaining free of esophageal cancer. (B) Time to death. Cumulative survival of patients with HGD who developed esophageal cancer compared with those who remained free of cancer. Gastroenterology 2001 120, 1607-1619DOI: (10.1053/gast.2001.25065) Copyright © 2001 American Gastroenterological Association Terms and Conditions