Fernandez Cornelius J, Agarwal Mayuri, Pottakkat Biju, Haroon Nisha Nigil, George Annu Susan, Pappachan Joseph M
Department of Endocrinology and Metabolism, Pilgrim Hospital, United Lincolnshire Hospitals NHS Trust, Boston PE21 9QS, United Kingdom.
Department of Surgical Gastroenterology, Jawaharlal Institute of Post Graduate Medical Education and Research (JIPMER), Puducherry 605006, India.
World J Gastrointest Surg. 2021 Mar 27;13(3):231-255. doi: 10.4240/wjgs.v13.i3.231.
Our understanding about the epidemiological aspects, pathogenesis, molecular diagnosis, and targeted therapies of neuroendocrine neoplasms (NENs) have drastically advanced in the past decade. Gastroenteropancreatic (GEP) NENs originate from the enteroendocrine cells of the embryonic gut which share common endocrine and neural differentiation factors. Most NENs are well-differentiated, and slow growing. Specific neuroendocrine biomarkers that are used in the diagnosis of functional NENs include insulin, glucagon, vasoactive intestinal polypeptide, gastrin, somatostatin, adrenocorticotropin, growth hormone releasing hormone, parathyroid hormone-related peptide, serotonin, histamine, and 5-hydroxy indole acetic acid (5-HIAA). Biomarkers such as pancreatic polypeptide, human chorionic gonadotrophin subunits, neurotensin, ghrelin, and calcitonin are used in the diagnosis of non-functional NENs. 5-HIAA levels correlate with tumour burden, prognosis and development of carcinoid heart disease and mesenteric fibrosis, however several diseases, medications and edible products can falsely elevate the 5-HIAA levels. Organ-specific transcription factors are useful in the differential diagnosis of metastasis from an unknown primary of well-differentiated NENs. Emerging novel biomarkers include circulating tumour cells, circulating tumour DNA, circulating micro-RNAs, and neuroendocrine neoplasms test (NETest) (simultaneous measurement of 51 neuroendocrine-specific marker genes in the peripheral blood). NETest has high sensitivity (85%-98%) and specificity (93%-97%) for the detection of gastrointestinal NENs, and is useful for monitoring treatment response, recurrence, and prognosis. In terms of management, surgery, radiofrequency ablation, symptom control with medications, chemotherapy and molecular targeted therapies are all considered as options. Surgery is the mainstay of treatment, but depends on factors including age of the individual, location, stage, grade, functional status, and the heredity of the tumour (sporadic inherited). Medical management is helpful to alleviate the symptoms, manage inoperable lesions, suppress postoperative tumour growth, and manage recurrences. Several molecular-targeted therapies are considered second line to somatostatin analogues. This review is a clinical update on the pathophysiological aspects, diagnostic algorithm, and management of GEP NENs.
在过去十年中，我们对神经内分泌肿瘤（NENs）的流行病学、发病机制、分子诊断和靶向治疗的认识有了显著进展。胃肠胰（GEP）NENs起源于胚胎肠道的肠内分泌细胞，这些细胞共享共同的内分泌和神经分化因子。大多数NENs分化良好，生长缓慢。用于功能性NENs诊断的特定神经内分泌生物标志物包括胰岛素、胰高血糖素、血管活性肠肽、胃泌素、生长抑素、促肾上腺皮质激素、生长激素释放激素、甲状旁腺激素相关肽、5-羟色胺、组胺和5-羟吲哚乙酸（5-HIAA）。诸如胰多肽、人绒毛膜促性腺激素亚基、神经降压素、胃饥饿素和降钙素等生物标志物用于非功能性NENs的诊断。5-HIAA水平与肿瘤负荷、预后以及类癌性心脏病和肠系膜纤维化的发展相关，然而，几种疾病、药物和食用产品可错误地升高5-HIAA水平。器官特异性转录因子有助于鉴别分化良好的NENs未知原发灶的转移。新兴的新型生物标志物包括循环肿瘤细胞、循环肿瘤DNA、循环微小RNA和神经内分泌肿瘤检测（NETest）（同时测量外周血中的51种神经内分泌特异性标记基因）。NETest对胃肠道NENs的检测具有高灵敏度（85%-98%）和特异性（93%-97%），并有助于监测治疗反应、复发和预后。在治疗方面，手术、射频消融、药物症状控制、化疗和分子靶向治疗均被视为选择。手术是主要治疗手段，但取决于个体年龄、位置、分期、分级、功能状态和肿瘤的遗传情况（散发性或遗传性）。药物治疗有助于缓解症状、处理无法手术的病变、抑制术后肿瘤生长和处理复发。几种分子靶向治疗被认为是生长抑素类似物的二线治疗。本综述是关于GEP NENs病理生理学方面、诊断算法和治疗的临床最新进展。
