DIAGNOSIS, NATURAL HISTORY AND MANAGEMENT OF GASTRINOMAS

胃泌素瘤和其他恶性胰腺内分泌肿瘤（PET）的自然病史和治疗主要基于术前报告和小系列，因为它们的发病率相对较低。胃泌素瘤是最常见的症状，恶性PET和足够数量的患者（n=265）已进入我们的方案，以便进行系统评估。目前正在进行研究，评估这些肿瘤的自然史，包括表现和初步诊断，决定预后的因素的定义以及改进诊断这些肿瘤的方法。我们的患者在发病5年后才被诊断为ZES。对261例ZES患者的临床表现、误诊和相关病症的分析结果现已完成，并发表在《医学》杂志上。在此基础上，确定了一系列重要的临床参数，这些参数可以提示诊断并可能减少5年的诊断延迟。目前正在对酸分泌参数进行类似的分析，以确定有助于诊断ZES的标准。详细的研究也正在调查这些肿瘤的管理，包括评估定位肿瘤范围的新方法（内镜超声，生长抑素受体闪烁成像[SRS]），确定手术切除在有限转移性疾病和无肝转移患者中的作用；积极切除在选定患者中的作用，以及手术在MEN1或无MEN1患者中的作用。目前正在研究长期控制酸分泌可能产生的副作用，包括对维生素B-12和铁吸收的影响以及类胃癌的发展。最后，正在研究通过化疗、使用干扰素、放射和生长抑素类似物来治疗晚期疾病。去年，我们对手术治疗ZES患者的长期前瞻性研究的结果被报道（NEJM 341:635, 1999），涉及151个连续病例。本研究确立了手术治疗无MEN1患者的价值，并论证了手术治疗无MEN1患者的无效。

The natural history and management of gastrinomas and other malignant pancreatic endocrine tumors (PET's) is largely based on antedotal reports and small series because of their relatively low incidence. Gastrinomas are the most common symptomatic, malignant PET and sufficient numbers of these patients (n=265) 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. The diagnosis of ZES in our patients was found to be 5 years from onset. The results of an analysis in 261 patients of the clinical presentation of patients with ZES, misdiagnosis and associated conditions has now been completed and is in press in Medicine. Based on this analysis a series of important clinical parameters that should suggest the diagnosis and possibly reduce the 5-year delay in diagnosis were identified. A similar analysis is now being performed on the acid secretory parameters to identify criteria that will assist in the diagnosis of ZES. Detailed studies are also underway investigating the management of these tumors including assessment of newer methods to localize tumor extent (endoscopic ultrasound, somatostatin receptor scintigraphy [SRS]), definition of the role of surgical resection in both limited metastatic disease and patients with no hepatic metastases; the role of aggressive resection in selected patients, and the role of surgery in patients with MEN1 or without MEN1. The possible side-effects of longterm acid secretory control are being examined including effects on vitamin B-12 and iron absorption as well as the development of gastric carcinoids. Lastly, medical treatment of advanced disease by chemotherapy, use of interferon, radiation and somatostatin analogues is being examined. This last year the results of our long-term prospective study of surgery for cure in patients with ZES was reported (NEJM 341:635, 1999) involving 151 consecutive cases. This study established the value of surgery for cure in patients without MEN1, and demonstrates its ineffectiveness in patients without MEN-1.