Eradication of Neuroendocrine Cells Within Barrettʼs Esophagus Using Liquid Nitrogen Spray Cryotherapy

Abstract

Purpose: Barrett's esophagus (BE) is a pre-malignant condition characterized by goblet cell metaplasia. Case reports demonstrate the presence of neuroendocrine (NE) cells within both Barrett's metaplasia and esophageal adenocarcinoma (EAC). NE cells also can proliferate to form their own tumors within the GI tract, or be present on histologic evaluation of other tumors such as gastric or colonic carcinoma. The association of NE cells with progression to carcinoma is uncharacterized, but their presence is theorized to increase malignant potential. A 48 year old Caucasian male presented for evaluation of heartburn, regurgitation, nocturnal cough and dysphagia to a local gastroenterologist. He was diagnosed with GERD and BE, and was started on a proton pump inhibitor (PPI). Due to persistent symptoms, he was referred to our center. 48 hour wireless esophageal pH monitoring off PPI confirmed upright and supine acid reflux. High resolution manometry demonstrated reduced lower esophageal sphincter resting pressure with normal relaxation and peristalsis. A 2.2 cm hiatal hernia was appreciated and confirmed on endoscopy, during which additional biopsies of long segment BE (C0M4 by Prague classification) were obtained. Histologic evaluation was notable for goblet cell metaplasia, as well as diffuse NE cell hyperplasia (positive chromogranin stain) with focal proliferation of NE cells, consistent with micronodular hyplasia of enterochromaffin-like (ECL) cells. Despite high dose PPI, the patient had persistent nocturnal cough and regurgitation. Nissen fundoplication was planned. The presence of long segment Barrett's, along with NE cells of unknown malignant potential, generated sufficient concern to recommend pre-surgical endoscopic ablation before altering the esophagogastric junction. The patient underwent 7 total sessions of liquid nitrogen spray cryotherapy (CSA Medical, Baltimore MD) every 6 weeks. During each procedure, all salmon-colored mucosa received 3 cycles of 20 seconds of treatment, per the standard ablation protocol. Repeat endoscopy 6 weeks after the final treatment revealed no visual evidence of residual BE. Therefore, 4 quadrant surveillance biopsies were taken throughout the original segment length. On these and all subsequent surveillance biopsies, histologic evaluation has confirmed the absence of both goblet cell metaplasia and NE cells. The patient has undergone successful Nissen fundoplication, and is doing well off PPI. To our knowledge, this is the first demonstration of successful eradication of NE cells in the gastrointestinal tract with use of liquid nitrogen spray cryotherapy. Further studies are needed to evaluate the role of NE cells in progression of BE to EAC. Disclosure: Dr. Smith - Consultant, CSA Medical, Inc.