Clinical Analysis of 15 Cases of Gallbladder Neuroendocrine Carcinoma and Comparison with Gallbladder Adenocarcinoma Using a Propensity Score Matching

Shida Yan,1,* Yingyi Wang,2,* Xiao Chen,1,* Yefan Zhang,1 Zhen Huang,1 Jianjun Zhao,1 Jianguo Zhou,1 Zhiyu Li,1 Xinyu Bi,1 Zhiwen Luo,1 Jianqiang Cai,1 Hong Zhao1 1Department of Hepatobiliary Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianqiang Cai; Hong ZhaoDepartment of Hepatobiliary Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, People’s Republic of ChinaEmail caijianqiang188@sina.com; zhaohong@cicams.ac.cnPurpose: This study aimed to investigate the clinicopathological features and prognosis of gallbladder neuroendocrine carcinoma (GB-NEC).Patients and Methods: Fifteen patients with GB-NEC and 171 patients with gallbladder adenocarcinoma (GB-ADC) treated in two tertiary medical centers between 2009 and 2015 were included. The clinicopathological features and prognostic risk factors of GB-NEC were analyzed retrospectively. A propensity score matching in a 1:2 ratio was used to compare the prognosis of GB-NEC and GB-ADC.Results: For patients with GB-NEC, the median age of patients was 58.4 years (range 26– 75), with a M:F ratio of 7:8. Based on 2010 WHO classification, ten cases were pathologically confirmed as NECs and five cases as MANECs. For TNM staging, eleven patients were stage III or above; while for Nevin staging, seven patients were stage IV or above. The 1-, 2-, and 3-year overall survival (OS) of GB-NEC were 60.0%, 38.8% and 31.1%, respectively, and the median survival time was 20.4 months. Patients with lymph node metastasis had significantly shorter survival than those without (OS: 10.4 vs 26.0 months, p< 0.05). Accordingly, patients of Nevin stage III had better OS than those of Nevin stage IV (p< 0.05), but other potential risk factors including gender, age, clinical symptoms, TNM stage, histopathologic subtype and treatment showed no significance. After the propensity score matching, the baseline variables had no significant difference between 15 patients with GB-NEC and 30 patients with GB-ADC, survival analysis showed GB-NEC had worse prognosis (3-year overall survival rate: 31.1% vs 63.8%, p< 0.01).Conclusion: Nevin staging helps classify patients of GB-NEC with different prognosis and the lymph node metastasis is a strong negative prognostic factor for OS. The propensity score analysis revealed even with the similar stage and treatment, GB-NEC still had worse OS than GB-ADC.Keywords: gallbladder, neuroendocrine carcinoma, adenocarcinoma, survival, propensity score matching