van Beek Dirk-Jan, Nell Sjoerd, Verkooijen Helena M, Borel Rinkes Inne H M, Valk Gerlof D, Vriens Menno R
Department of Endocrine Surgical Oncology, University Medical Center Utrecht, Utrecht, the Netherlands.
Department of Endocrine Surgical Oncology, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, the Netherlands.
Surgery. 2021 Apr;169(4):963-973. doi: 10.1016/j.surg.2020.09.037. Epub 2020 Nov 19.
Metastasized pancreatic neuroendocrine tumors are the leading cause of death in patients with multiple endocrine neoplasia type 1. Aside from tumor size, prognostic factors of pancreatic neuroendocrine tumors are largely unknown. The present study aimed to assess whether the prognosis of patients with resected multiple endocrine neoplasia type 1-related nonfunctioning pancreatic neuroendocrine tumors differs from those with resected multiple endocrine neoplasia type 1-related insulinomas and assessed factors associated with prognosis.
Patients who underwent resection of a multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors between 1990 and 2016 were identified in 2 databases: the DutchMEN Study Group and the International MEN1 Insulinoma Study Group databases. Cox regression was performed to compare liver metastases-free survival of patients with a nonfunctioning pancreatic neuroendocrine tumors versus those with an insulinoma and to identify factors associated with liver metastases-free survival.
Out of 153 patients with multiple endocrine neoplasia type 1, 61 underwent resection for a nonfunctioning pancreatic neuroendocrine tumor and 92 for an insulinoma. Of the patients with resected lymph nodes, 56% (18/32) of nonfunctioning pancreatic neuroendocrine tumors had lymph node metastases compared to 10% (4/41) of insulinomas (P = .001). Estimated 10-year liver metastases-free survival was 63% (95% confidence interval 42%-76%) for nonfunctioning pancreatic neuroendocrine tumors and 87% (72%-91%) for insulinomas. After adjustment for size, World Health Organization tumor grade, and age, nonfunctioning pancreatic neuroendocrine tumors had an increased risk for liver metastases or death (hazard ratio 3.04 [1.47-6.30]). In pancreatic neuroendocrine tumors ≥2 cm, nonfunctioning pancreatic neuroendocrine tumors (2.99 [1.22-7.33]) and World Health Organization grade 2 (2.95 [1.02-8.50]) were associated with liver metastases-free survival.
Patients with resected multiple endocrine neoplasia type 1-related nonfunctioning pancreatic neuroendocrine tumors had a significantly lower liver metastases-free survival than patients with insulinomas. Postoperative counseling and follow-up regimens should be tumor type specific and at least consider size and World Health Organization grade.
转移性胰腺神经内分泌肿瘤是1型多发性内分泌腺瘤患者的主要死因。除肿瘤大小外，胰腺神经内分泌肿瘤的预后因素大多未知。本研究旨在评估切除的1型多发性内分泌腺瘤相关无功能胰腺神经内分泌肿瘤患者的预后是否与切除的1型多发性内分泌腺瘤相关胰岛素瘤患者不同，并评估与预后相关的因素。
在两个数据库中识别出1990年至2016年间接受1型多发性内分泌腺瘤相关胰腺神经内分泌肿瘤切除术的患者：荷兰MEN研究组和国际MEN1胰岛素瘤研究组数据库。进行Cox回归以比较无功能胰腺神经内分泌肿瘤患者与胰岛素瘤患者的无肝转移生存期，并确定与无肝转移生存期相关的因素。
在153例1型多发性内分泌腺瘤患者中，61例接受了无功能胰腺神经内分泌肿瘤切除术，92例接受了胰岛素瘤切除术。在切除淋巴结的患者中，56%（18/32）的无功能胰腺神经内分泌肿瘤有淋巴结转移，而胰岛素瘤为10%（4/41）（P = .001）。无功能胰腺神经内分泌肿瘤的估计10年无肝转移生存率为63%（95%置信区间42%-76%），胰岛素瘤为87%（72%-91%）。在调整肿瘤大小、世界卫生组织肿瘤分级和年龄后，无功能胰腺神经内分泌肿瘤发生肝转移或死亡的风险增加（风险比3.04 [1.47-6.30]）。在胰腺神经内分泌肿瘤≥2 cm的患者中，无功能胰腺神经内分泌肿瘤（2.99 [1.22-7.33]）和世界卫生组织2级（2.95 [1.02-8.50]）与无肝转移生存期相关。
切除的1型多发性内分泌腺瘤相关无功能胰腺神经内分泌肿瘤患者的无肝转移生存期明显低于胰岛素瘤患者。术后咨询和随访方案应根据肿瘤类型而定，至少应考虑肿瘤大小和世界卫生组织分级。
