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病史，包括肿瘤的表现和初步诊断，以及决定预后的因素的定义，包括试图确定具有预后意义的肿瘤的分子特征。我们的研究已经确定了25%的胃泌素瘤患者具有侵袭性生长，25%的患者患有多发性内分泌肿瘤1型(MEN1)。后者的自然历史在今年得到了广泛的分析。对MEN1/ZES患者的前瞻性研究表明，他们经常患上侵袭性胸腺类癌和脑膜瘤，还会出现皮肤病变(血管纤维瘤、胶原瘤)，这对诊断这一亚群是有用的。这一年对胃泌素瘤患者的分子研究表明，1Q和X染色体上的杂合性丢失与侵袭性生长相关，提示这些位置上未知的肿瘤抑制基因对肿瘤生长具有重要意义。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。一项前瞻性研究也提供了强有力的证据表明，在手术探查时常规十二指肠切开术对于发现十二指肠胃泌素瘤是必不可少的，并将提高这些患者的治愈率。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。

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 and definition of factors determining prognosis including attempting to identify molecular characteristics of the tumor that have prognostic significance. Our studies have identified a cohort of 25% of patients in whom the gastrinomas have aggressive growth and 25% who have multiple endocrine neoplasia type 1 (MEN1). The natural history of the latter group has been extensively analyzed this year. Prospective studies of MEN1/ZES patients show they frequently develop aggressive thymic carcinoids as well as meningiomas and also skin lesions (angiofibromas, collagenomas) that can be useful to diagnose this subgroup. Molecular studies of gastrinomas of patients with or without aggressive tumors during this year demonstrate loss of heterozgosity at 1q and on the X chromosome correlate with aggressive growth suggesting unknown tumor suppressor genes in these locations are important for tumor growth. Surgical studies completed during the year support a role for aggressive resection in patients with advanced, aggressive disease. A prospective study also provide strong evidence that routine duodenotomy at the time of surgical exploration is essential to find duodenal gastrinomas and will increase cure rate in these patients. 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.