Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Ann Surg Oncol. 2022 Nov;29(12):7619-7630. doi: 10.1245/s10434-022-12107-w. Epub 2022 Jul 18.
This study aimed to comprehensively investigate the clinicopathologic characteristics and therapeutic situations of gallbladder neuroendocrine neoplasms (GB-NENs) in the real world via a multicenter, large-scale cohort study.
The study searched for patients in 143 hospitals in China and enrolled 154 patients with GB-NENs diagnosed in 40 hospitals between 2004 and 2021. Clinicopathologic characteristics and therapeutic approaches were analyzed retrospectively.
The median age at the initial diagnosis of the patients with GB-NENs was 63 years (range 33-83 years), and 61.7% of the patients were women. Tumor-node-metastasis staging classified 92 patients as stage 3 or above. Based on the 2019 World Health Organization classification, 96 cases (62.3%) were confirmed pathologically as poorly differentiated neuroendocrine carcinomas, 13 cases (8.4%) as well-differentiated neuroendocrine tumors, and 45 cases as mixed neuroendocrine-non-neuroendocrine neoplasms. The liver was the most frequent metastatic site. Immunohistochemistry showed that synaptophysin was most frequently positive (80.4%), followed by chromogranin A (61.7%), and CD56 (58.4%). Computed tomography and magnetic resonance imaging showed more common clear boundaries (25/39 cases) and invasive growth features (27 cases). None of these cases had an accurate diagnosis before surgery, with a misdiagnosis rate of 100%. Surgical resection is the main treatment, and platinum-based chemotherapeutic regimens were preferred as adjuvant therapies for patients with GB-NENs. The available survival data for 74 patients showed an overall survival rate of 59% at 1 year, 33% at 3 years, and 29% at 5 years. No significant difference was found between the patients treated with and those treated without adjuvant chemotherapy.
Gallbladder neuroendocrine neoplasms have high malignancy and a poor prognosis. Importantly, this large-scale cohort study significantly improves our understanding of GB-NENs and will benefit the exploration of its mechanism and treatment modes. Further investigation is necessary to explore the management of this disease.
本研究通过多中心、大规模队列研究，全面探讨了胆囊神经内分泌肿瘤（GB-NENs）的临床病理特征和治疗情况。
本研究在中国 143 家医院中进行检索，纳入了 2004 年至 2021 年期间 40 家医院诊断的 154 例 GB-NENs 患者。回顾性分析了临床病理特征和治疗方法。
GB-NENs 患者的中位初诊年龄为 63 岁（范围 33-83 岁），61.7%为女性。肿瘤-淋巴结-转移分期将 92 例患者分为 3 期或以上。根据 2019 年世界卫生组织分类，96 例（62.3%）病理证实为低分化神经内分泌癌，13 例（8.4%）为高分化神经内分泌肿瘤，45 例为混合性神经内分泌-非神经内分泌肿瘤。肝脏是最常见的转移部位。免疫组化显示突触素最常阳性（80.4%），其次是嗜铬粒蛋白 A（61.7%）和 CD56（58.4%）。计算机断层扫描和磁共振成像显示更常见的清晰边界（25/39 例）和侵袭性生长特征（27 例）。这些病例在术前均无准确诊断，误诊率为 100%。手术切除是主要治疗方法，铂类化疗方案是 GB-NENs 患者辅助治疗的首选。对 74 例患者的生存数据进行了分析，发现 1 年、3 年和 5 年的总生存率分别为 59%、33%和 29%。接受和未接受辅助化疗的患者之间的生存率无显著差异。
胆囊神经内分泌肿瘤恶性程度高，预后差。重要的是，这项大规模队列研究显著提高了我们对 GB-NENs 的认识，有助于探索其发病机制和治疗模式。需要进一步研究来探讨这种疾病的治疗方法。
