Diagnosis, Natural History And Management Of Gastrinomas

无（散发性疾病）或多发性1型内分泌肿瘤（MEN1）患者胃泌素瘤和其他胰腺恶性内分泌肿瘤（PET）的自然病史、预后和治疗主要基于术前报告和小系列研究。胃鞘瘤是有MEN1或没有MEN1的患者中最常见的症状性恶性PET，我们的研究方案中纳入了足够数量的此类患者，以便进行系统评估。目前研究正在进行中，评估这些肿瘤的自然史，包括表现和初步诊断，以及决定预后因素的定义，包括试图确定具有预后意义的肿瘤分子特征。我们的研究已经确定了一组患者，其中25%的患者胃泌素瘤具有侵袭性生长，25%的患者患有多发性内分泌肿瘤1型（MEN1）。今年，人们对后者的自然史进行了广泛的分析。对MEN1/ZES患者的前瞻性研究表明，他们经常发展为侵袭性胸腺类癌、脑膜瘤和皮肤病变（血管纤维瘤、胶原瘤），这对诊断该亚组很有用。这一年对伴有或不伴有侵袭性肿瘤的胃原质瘤患者的分子研究表明，1q和X染色体上的异质性缺失与侵袭性生长相关，这表明这些位置的未知肿瘤抑制基因对肿瘤生长很重要。本年度完成的外科研究支持在晚期侵袭性疾病患者中积极切除的作用。一项前瞻性研究也提供了强有力的证据，表明在手术探查时进行常规十二指肠切除术对于发现十二指肠胃原质瘤至关重要，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类胃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.