DIAGNOSIS, NATURAL HISTORY AND MANAGEMENT OF GASTRINOMAS

胃泌素瘤和其他恶性胰腺内分泌肿瘤（PET）的自然史和管理主要基于前期报告和小系列，因为它们的发病率相对较低。 胃癌是最常见的症状性恶性PET，我们的方案中已纳入足够数量的此类患者（n=265），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诊断这些肿瘤的改进方法。 我们的患者中ZES的诊断被发现是从发病起5年。 对261例ZES患者的临床表现、误诊和相关疾病的分析结果现已完成，并正在医学杂志上发表。基于该分析，确定了一系列重要的临床参数，这些参数应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ZES诊断的标准。 还正在进行详细的研究，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，生长抑素受体血管造影[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;选定患者中侵袭性切除的作用，以及手术在MEN 1或无MEN 1患者中的作用。 长期胃酸分泌控制的可能副作用正在研究中，包括对维生素B-12和铁吸收的影响以及胃类癌的发展。最后，正在研究通过化学疗法、使用干扰素、放射和生长抑素类似物治疗晚期疾病。 去年，我们报道了对ZES患者进行手术治疗的长期前瞻性研究结果（NEJM 341：635，1999），涉及151例连续病例。 这项研究确立了手术治疗无MEN-1患者的价值，并证明了其对无MEN-1患者的无效性。

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.