Conversion surgery after extensive chemotherapy for stage IV mixed adenoneuroendocrine carcinoma (MANEC) of the gallbladder: clinical implications from the patterns of response and recurrence.

A 53-year-old woman who was diagnosed as having advanced gallbladder cancer (T3N1M1, Stage IVB) showed a dramatic response to chemotherapy using gemcitabine + cisplatin and surgery with curative intent was attempted. Histopathological examination revealed residual tumor limited to the perimuscular connective tissue of the gallbladder (T2bN0M0, Stage IIB) and a mixture of poorly differentiated adenocarcinoma and neuroendocrine carcinoma (NEC) components was confirmed. At 6 months after the surgery, a small peritoneal nodule was detected and chemotherapy was resumed with gemcitabine, cisplatin, and S-1. However, the recurrent lesion showed no response at all and gradually formed a mass with the liver and kidney. Considering the difficulty of intensive chemotherapy and the relatively indolent progression of the disease at 15 months after the recurrence was first detected, repeat resection was performed. Histopathology of the resected lesions revealed only a NEC components. Although surgical intervention may be effective in selected cases, given that the NEC component is often associated with progression and recurrence of the disease, the chemotherapy regimen would need to include drugs for the NEC component in cases where the histopathological diagnosis of MANEC has been established.