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在1型多发性内分泌腺瘤成年患者筛查中发现的无功能胰腺神经内分泌肿瘤,合适的管理措施是什么?

What is the appropriate management of nonfunctioning pancreatic neuroendocrine tumours disclosed on screening in adult patients with multiple endocrine neoplasia type 1?

作者信息

Challis Benjamin G, Casey Ruth T, Grossman Ashley, Newell-Price John, Newey Paul, Thakker Rajesh V

机构信息

Wolfson Diabetes and Endocrinology Clinic, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK.

Translational Science & Experimental Medicine, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.

出版信息

Clin Endocrinol (Oxf). 2019 Dec;91(6):708-715. doi: 10.1111/cen.14094. Epub 2019 Oct 1.

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is an inherited tumour syndrome characterised by a predisposition to the development of endocrine tumours of the parathyroid glands, pituitary and pancreas: 30%-80% of patients with MEN1 develop pancreatic neuroendocrine tumours (pNETs), with metastatic tumours and/or their sequelae contributing to increased morbidity and early mortality. The optimal management of nonfunctioning (NF) pNETs in MEN1 remains controversial. Whilst pancreatic resection is widely recommended for tumours >2 cm, for smaller tumours (≤2 cm) a well-established consensus guiding the indications for surgical intervention does not exist. Although total pancreatectomy may be curative for some patients, both short- and long-term complications make this an unsatisfactory option for many patients. For small (<2 cm) MEN1 NF-pNETs, some clinicians advocate surveillance based largely on retrospective data that suggest 50%-80% of these lesions are stable over time and infrequently exhibit accelerated growth rates. It is increasingly recognised, however, that NF-pNETs exhibit unpredictable malignant behaviour that is not determined by tumour size alone, thereby prompting other clinicians to advocate surgery for all MEN1 NF-pNETs, irrespective of size. Such uncertainty poses clinical management challenges with regards to the timing and extent of surgery, which is further hindered by the inability to stratify patients based on predicted tumour behaviour. It is therefore critical that future MEN1 research initiatives include: (a) the discovery of biomarkers that better predict tumour behaviour; (b) the evaluation of medical therapies that may delay, or even prevent, the need for pancreatic surgery; and, ultimately, (c) improvement in the quality of life for individuals with MEN1. Here, based on the published literature, we address the Clinical Question, 'What is the management of NF-pNETs disclosed on screening in adult patients with MEN1?'.

摘要

多发性内分泌腺瘤1型(MEN1)是一种遗传性肿瘤综合征,其特征是易发生甲状旁腺、垂体和胰腺的内分泌肿瘤:30%-80%的MEN1患者会发生胰腺神经内分泌肿瘤(pNETs),转移性肿瘤和/或其后遗症会导致发病率增加和早期死亡。MEN1中无功能(NF)pNETs的最佳管理仍存在争议。虽然对于直径>2 cm的肿瘤广泛推荐行胰腺切除术,但对于较小的肿瘤(≤2 cm),尚无指导手术干预指征的既定共识。尽管全胰切除术对某些患者可能具有治愈性,但短期和长期并发症使其对许多患者而言并非理想选择。对于小(<2 cm)的MEN1 NF-pNETs,一些临床医生主张主要基于回顾性数据进行监测,这些数据表明这些病变中有50%-80%随时间推移是稳定的,且很少表现出加速生长率。然而,人们越来越认识到,NF-pNETs表现出不可预测的恶性行为,这并非仅由肿瘤大小决定,因此促使其他临床医生主张对所有MEN1 NF-pNETs进行手术,无论其大小。这种不确定性在手术时机和范围方面带来了临床管理挑战,而无法根据预测的肿瘤行为对患者进行分层进一步阻碍了这一挑战的解决。因此,未来MEN1研究计划必须包括:(a)发现能更好预测肿瘤行为的生物标志物;(b)评估可能延迟甚至避免胰腺手术需求的药物治疗;最终,(c)改善MEN1患者的生活质量。在此,基于已发表的文献,我们探讨临床问题:“成年MEN1患者筛查中发现的NF-pNETs如何管理?”

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