Diagnosis, Natural History And Management Of Gastrinomas

胃泌素瘤和其他恶性胰腺内分泌肿瘤(PET‘s)的自然病史、预后和治疗主要基于既往报道和小系列报道。无论患者是否患有MEN1，胃泌素瘤都是最常见的有症状的恶性PET，有足够数量的此类患者被纳入我们的方案，以便进行系统的评估。目前正在进行研究，评估这些肿瘤的自然历史，包括表现和初步诊断，决定预后的因素的定义，以及诊断这些肿瘤的改进方法，特别是在患有MEN1的患者中。我们的研究已经确定了25%的胃泌素瘤具有侵袭性生长的患者。评估血清胃泌素或嗜铬粒蛋白A的前瞻性研究表明，它们不能预测生长，需要进行系列成像研究。对有无侵袭性肿瘤患者胃泌素瘤的分子研究表明，HER2/neu基因发生改变，1Q杂合性丢失，EGF和HGF受体过度表达，它们的存在与侵袭性生长有关。年内完成的外科研究支持积极切除在晚期侵袭性疾病患者中的作用。外科研究也提供了强有力的支持，即胃泌素瘤可以发生在淋巴结，因此应该在手术中积极切除。长期控制胃酸分泌和长期高胃泌素血症可能产生的副作用正在研究中，包括对维生素B-12和铁吸收的影响，以及胃类癌的发展和识别这些的方法。最后，对ZES和MEN1患者的前瞻性研究表明，男性患者可能会患上胸腺类癌，这是一种极具侵袭性的肿瘤。它们的发病机制尚不清楚，因为它们缺乏11q13杂合性缺失，而11q13杂合性缺失通常存在于大多数MEN1患者的肿瘤中。

The natural history, prognosis and management of gastrinomas and other malignant pancreatic endocrine tumors (PET's) in patients without (sporadic disease) or with multiple endocrine neoplasia-type 1 (MEN1) is largely based on antedotal reports and small series. Gastrinomas are the most common symptomatic, malignant PET in patients with or without MEN1 and sufficient numbers of these patients have been entered into our protocols to allow systematic assessment. Studies are now underway, evaluating the natural history of these tumors including the presentation and initial diagnosis, definition of factors determining prognosis and improved methods to diagnose these tumors especially in patients with MEN1. Our studies have identified a cohort of 25% of patients in whom the gastrinomas have aggressive growth. Prospective studies assesssing serum gastrin or chromogranin A show they do not predict growth and serial imaging studies are needed. Molecular studies of gastrinomas of patients with or without aggressive tumors demonstrate alterations in the HER2/neu gene, loss of heterozgosity at 1q and overexpression of the EGF and HGF receptors occur in these tumors and their presence correlates with the aggressive growth. Surgical studies completed during the year support a role for aggressive resection in patients with advanced, aggressive disease. Surgical studies also provide strong support that gastrinomas can arise in lymph nodes and therefore they should be aggressively removed at surgery. The possible side-effects of longterm acid secretory control as well as long term hypergastrinemia are being examined including effects on vitamin B-12 and iron absorption as well as the development of gastric carcinoids and methods to identify these. Lastly, prospective studies on patients with ZES and MEN1 demonstrate male patients may develop thymic carcinoids which are extremely aggressive tumors. Their pathogenesis remains unknown because they lack 11q13 LOH which is usually found in most tumors which develop in patients with MEN1.