Diagnosis, Natural History And Management Of Gastrinomas

无（散发性疾病）或多发1型内分泌肿瘤（MEN1）患者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，决定预后的因素的定义以及改进诊断这些肿瘤的方法，特别是在MEN1患者中。我们最近完成并发表了261例散发疾病患者的研究结果[医学79:379- 411,2000；80:189 - 222, 2001]。在分析57例MEN1和ZES患者的自然病史时，我们发现近五分之一的患者具有侵袭性疾病，导致生存率降低。我们已经确定了这一群体的临床和实验室特征，可以用来识别他们并制定早期积极治疗。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，我们对进展性转移性胃泌素瘤患者使用奥曲肽（一种长效生长抑素类似物）的长期前瞻性研究的结果已经完成。这项研究表明奥曲肽对50%的患者的肿瘤生长有影响，大多数患者的肿瘤生长稳定。与现有的奥曲肽化疗相比，奥曲肽的副作用很小，抗生长效果持久，这表明奥曲肽现在应该是这些患者的首选治疗方法。

The natural history 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. We have recently completed and published our results in 261 patients with sporadic disease [Medicine 79:379-411, 2000; 80:189-222, 2001]. In analyzing the natural history of 57 patients with MEN1 and ZES, we have found almost one-fifth of these patients have an aggressive form of the disease leading to decreased survival. We have identified clinical and laboratory features of this group that can be used to identify them and institute early aggressive treatment. 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 the use of octreotide (a long-acting somatostatin analogue) in patients with progressive metastatic gastrinoma has been completed. This study shows octreotide has an effect on tumor growth in 50% of patients with the majority showing a growth stablization. In contrast to the established treatment of chemotherapy with octreotide there are with minimal side-effects and the anti-growth effect was long-lasting showing octreotide should now be the initial treatment of choice for these patients.