Neuroendocrine Carcinoma of Gallbladder: A Step Beyond Palliative Therapy, Experience of 25 Cases

Abstract

Published literature on gall bladder neuroendocrine tumors (GB NETs) is limited with none reporting the role of multimodal therapy. Patients with histologically confirmed GB NETs treated at Tata Memorial Hospital, Mumbai, from January 2010 to June 2017 were analyzed. Staging was done by contrast-enhanced computed tomography (CECT) of abdomen and chest or a positron emission topography (PET) scan. Tumor marker (CA19-9) was measured. WHO-2017 guideline was used to classify GB NETs. GB NETs were categorized as early disease (ED) (T1, T2, N0, i.e., stages I and II); locally advanced disease (LAD) (T3, T4, or N+, i.e., stage III); and metastatic disease (MD). Response to treatment was assessed with RECIST1.1 criteria. Twenty-five patients of GB NETs were identified; 19 with neuroendocrine carcinomas (NECs) and 6 with mixed adenoneuroendocrine carcinomas (MANECs). Two patients (8%) presented with ED, 9 (36%) with LAD, and 14 (56%) had MD. Those with ED underwent open revision radical cholecystectomy. Both received adjuvant chemotherapy (ACT) with six cycles of carboplatin-etoposide and were disease-free at 3months of follow-up. Of the nine patients with LAD, six received three cycles of neoadjuvant chemotherapy (NACT) (carboplatin-etoposide) and three operated upfront. All six patients showed partial response to NACT and five underwent open radical cholecystectomy with R0 resection. All patients operated after NACT received three cycles of ACT. Their median follow-up was 7months (range 3-22months). Three patients with LAD developed metastasis after median disease-free survival of 5months. The median survival in patients with MD was 12 (range 6-23) months. In carefully selected patients of GB NECs, downsizing with NACT facilitates radical resection with negative margins.