Diagnosis, Natural History And Management Of Gastrinomas

胃泌素瘤的诊断、自然史和治疗

• 批准号: 6535233
• 负责人: ROBERT JENSEN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6535233
• 关键词: Zollinger Ellison syndrome; autoradiography; clinical research; diagnosis design /evaluation; drug adverse effect; endocrine disorder; gastrins; gastrointestinal neoplasms; hormone receptor; human subject; human therapy evaluation; interferons; metastasis; neoplasm /cancer chemotherapy; neoplasm /cancer diagnosis; neoplasm /cancer radiation therapy; neoplasm /cancer surgery; octreotide; pancreatic islet neoplasm; patient care management; peptide hormone analog; prognosis; somatostatin; vitamin B12

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.

胃泌素瘤和其他恶性胰腺内分泌肿瘤(PET‘s)的自然病史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历史，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，特别是在患有MEN1的患者中。我们最近完成并发表了我们对261名散发性疾病患者的研究结果[医学79：379-411,2000；80：189-222,2001]。在分析57名MEN1和ZES患者的自然病史时，我们发现这些患者中近五分之一的人患有侵袭性疾病，导致存活率下降。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进行早期积极的治疗。目前还在进行详细的研究，调查这些肿瘤的治疗方法，包括评估新的肿瘤范围定位方法(内窥镜超声、生长抑素受体闪烁成像[SRS])、手术切除在局限性转移疾病和无肝转移患者中的作用、在选定患者中积极切除的作用以及手术在患有或不患有MEN1的患者中的作用。长期的酸分泌控制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。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进行晚期疾病的医疗治疗。去年，我们对奥曲肽(一种长效生长抑素类似物)用于进行性转移性胃泌素瘤患者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，大多数患者表现出生长稳定。与现有的奥曲肽化疗相比，奥曲肽副作用小，抗生长作用持久，表明奥曲肽现在应该是这些患者的首选治疗方法。