Supplementary Material for: Comparison of Clinicopathological Features of Biliary Neuroendocrine Carcinoma with Adenocarcinoma

<b><i>Objective:</i></b> This study aimed to demonstrate the clinical features and postoperative outcomes of extrahepatic bile duct (EHBD) neuroendocrine carcinoma (NEC) and compared with those of adenocarcinoma. <b><i>Methods:</i></b> We retrospectively analyzed patients with EHBD cancer operated in our institution between 1995 and 2015. <b><i>Results:</i></b> Of 475 patients, 468 had adenocarcinoma, while 7 had NEC/mixed adenoneuroendocrine carcinoma (MANEC) in this study. There were no notable preoperative and pathological features in patients with NEC/MANEC. However, patients with NEC/MANEC had a higher recurrence rate (51.8 vs. 100%, <i>p</i> = 0.016), poorer relapse-free survival (RFS) time (the median RFS time: 35 vs. 12 months, <i>p</i> = 0.006), and poorer overall survival (OS) time (the median OS time: 60 vs. 19 months, <i>p</i> = 0.078) than those with adenocarcinoma. Furthermore, patients with NEC/MANEC had higher rates of liver metastasis (11.9 vs. 85.7%, <i>p</i> &lt; 0.001) than those with adenocarcinoma. In multivariable regression analysis, pathological type with NEC/MANEC was a risk factor for poorer RFS (<i>p</i> = 0.022, hazard ratio: 6.09). <b><i>Conclusions:</i></b> Patients with NEC/MANEC have high malignant potential and poor outcomes. It is necessary to develop an effective approach and postoperative adjuvant treatment for patients with NEC/MANEC.