Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
1st Department of Propaupedic Internal Medicine, Endocrine Oncology Unit, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Endocrine. 2019 May;64(2):384-392. doi: 10.1007/s12020-018-1773-3. Epub 2018 Oct 2.
Our aim was to assess the prevalence of endocrine paraneoplastic syndromes (EPNS) in neuroendocrine neoplasms (NENs) and estimate its impact on patient outcomes.
This is a retrospective analysis of 834 patients with NENs (611 gastrointestinal, 166 thoracic, 57 of unknown and various other primary origin). We included 719 consecutive NEN patients treated at EKPA-Laiko Hospital, Athens, Greece and 115 patients with lung carcinoid (LC) treated at Uppsala University Hospital, Uppsala, Sweden. EPNS diagnosis was based on standard criteria.
Twenty-one patients with EPNS were detected: 16 with ectopic Cushing's syndrome (ECS), one with hypercalcaemia due to parathyroid hormone-related protein (PTHrP) secretion, three with hypercalcitonaemia and one patient with dual secretion of calcitonin and beta-human chorionic gonadotropin (β-HCG). All tumours were well-differentiated; 10 patients had Stage IV disease at diagnosis.
The prevalence of EPNS in the Greek cohort was 1.9%, whereas that of ECS among LC patients in both centres was 6.7%. Median overall survival (OS) for patients with EPNS was 160.7 months (95%CI, 86-235.4) and median event-free survival (EFS) was 25.9 months (95%CI, 0-57.2). Patients presenting with EPNS prior to NEN diagnosis had longer EFS compared to patients with synchronous or metachronous EPNS (log-rank P = 0.013). Patients with ECS of extra-thoracic origin demonstrated shorter OS and EFS compared to patients with ECS of lung or thymic origin (log-rank P = 0.001 and P < 0.001, respectively). LC patients with and without ECS were comparable in 5-year and 10-year OS rates (66.7% and 33.3% versus 89.8% and 60.2%, respectively; 95%CI [189.6-300.4 months], log-rank P = 0.94) and in median EFS, 67 versus 183 months, 95%CI [50.5-207.5], log-rank P = 0.12).
EPNS are relatively rare in patients with NENs and mainly concern well-differentiated tumours of the foregut. Among patients with EPNS, LC-related ECS may not adversely affect patient outcomes when diagnosed prior to NEN and effectively been treated.
我们旨在评估神经内分泌肿瘤（NEN）中内分泌副肿瘤综合征（EPNS）的患病率，并评估其对患者预后的影响。
这是对 834 例 NEN 患者（611 例胃肠道、166 例胸内、57 例来源不明和各种其他原发部位）的回顾性分析。我们纳入了在希腊雅典 EKPA-Laiko 医院治疗的 719 例连续 NEN 患者和在瑞典乌普萨拉大学医院治疗的 115 例肺类癌（LC）患者。EPNS 的诊断基于标准标准。
检测到 21 例 EPNS 患者：16 例为异位库欣综合征（ECS），1 例为甲状旁腺激素相关蛋白（PTHrP）分泌引起的高钙血症，3 例为高钙血症，1 例为降钙素和β-人绒毛膜促性腺激素（β-HCG）双重分泌。所有肿瘤均为高分化；10 例患者在诊断时为 IV 期疾病。
希腊队列中 EPNS 的患病率为 1.9%，而两个中心的 LC 患者中 ECS 的患病率为 6.7%。有 EPNS 的患者的总生存（OS）中位数为 160.7 个月（95%CI，86-235.4），无事件生存（EFS）中位数为 25.9 个月（95%CI，0-57.2）。与同时性或异时性 EPNS 患者相比，在 NEN 诊断前出现 EPNS 的患者 EFS 更长（对数秩 P=0.013）。起源于胸外的 ECS 患者的 OS 和 EFS 短于肺或胸腺起源的 ECS 患者（对数秩 P=0.001 和 P<0.001，分别）。有和没有 ECS 的 LC 患者在 5 年和 10 年 OS 率方面相似（分别为 66.7%和 33.3%与 89.8%和 60.2%；95%CI[189.6-300.4 个月]，对数秩 P=0.94），中位 EFS 分别为 67 个月和 183 个月，95%CI[50.5-207.5]，对数秩 P=0.12）。
EPNS 在 NEN 患者中相对少见，主要涉及前肠的高分化肿瘤。在有 EPNS 的患者中，当在 NEN 之前诊断出 LC 相关的 ECS 并有效治疗时，它可能不会对患者的预后产生不利影响。
