Neuroendocrinology. 2018;106(2):139-147. doi: 10.1159/000474941. Epub 2017 Apr 7.
Mesenteric fibrosis (MF) surrounding a lymph node metastasis is a known phenomenon in midgut neuroendocrine tumors (NETs) with characteristic radiological appearance. Its etiology is poorly understood as it affects some but not all midgut NET patients with lymphatic involvement. This study assessed a potential relationship of MF with carcinoid syndrome, urinary 5-hydroxyindoleacetic acid (5-HIAA), and carcinoid heart disease (CHD).
A cohort of 81 patients with pathologically proven NETs with the primary site in the midgut and mesenteric lymphatic metastases on imaging were retrospectively included. Imaging characteristics of lymphatic and hepatic metastases at diagnosis (size, number, burden, and morphologic features, including presence of MF), Ki67 grading, 5-HIAA, functionality, and development of CHD were analyzed.
Overall, 54% of patients had MF. The presence of MF was more frequently associated with mesenteric vessel encasement (100 vs. 46% without MF; p < 0.001), presence of hepatic metastases (91 vs. 62%; p = 0.002), larger hepatic tumor burden (15 vs. 5%; p = 0.001), and functionality (86 vs. 43%; p < 0.001). Multivariate analysis revealed 5-HIAA ≥395 µmol/day (p = 0.020), age (p = 0.013), and largest lymphatic metastasis ≥24 mm (p = 0.009) as independent predictors of MF, while functionality (p = 0.098) and CHD (p = 0.070) showed a tendency towards significance. MF was associated with decreased time to development of CHD in functional midgut NETs (p = 0.043).
We found a significant association of MF with metastatic patterns and with criteria of functionality. The association of MF with elevated 5-HIAA, and consecutively with carcinoid syndrome and potential development of CHD, suggests a linked pathophysiological mechanism, which might be similar to that of endocardial fibrosis.
肠系膜纤维化（MF）环绕淋巴结转移是一种已知的现象，发生于具有特征性影像学表现的中肠神经内分泌肿瘤（NETs）中。其病因尚不清楚，因为它会影响一些但不是所有有淋巴受累的中肠 NET 患者。本研究评估了 MF 与类癌综合征、尿 5-羟吲哚乙酸（5-HIAA）和类癌性心脏病（CHD）之间的潜在关系。
回顾性纳入了 81 例经病理证实的中肠部位原发 NET 患者，这些患者的影像学检查显示肠系膜淋巴结转移。分析了淋巴结和肝转移的诊断时的影像学特征（大小、数量、负荷和形态特征，包括 MF 的存在）、Ki67 分级、5-HIAA、功能性和 CHD 的发展。
总体而言，54%的患者存在 MF。MF 的存在与肠系膜血管包绕（100%与无 MF 的 46%相比；p<0.001）、肝转移（91%与 62%相比；p=0.002）、更大的肝肿瘤负荷（15%与 5%相比；p=0.001）和功能性（86%与 43%相比；p<0.001）更为相关。多变量分析显示，5-HIAA≥395µmol/天（p=0.020）、年龄（p=0.013）和最大淋巴结转移≥24mm（p=0.009）是 MF 的独立预测因素，而功能性（p=0.098）和 CHD（p=0.070）则有一定的相关性。在功能性中肠 NET 中，MF 与 CHD 的发病时间缩短有关（p=0.043）。
我们发现 MF 与转移模式和功能性标准有显著相关性。MF 与升高的 5-HIAA 的相关性，以及随之而来的类癌综合征和潜在的 CHD 发展，提示存在一种相关的病理生理机制，可能与心内膜纤维化类似。
