Natural History of Familial Carcinoid Tumor

类癌是一种罕见的肿瘤，不会或很少引起非特异性症状。因此，类癌患者通常出现在他们病程的晚期，此时由于转移疾病已经进展到无法治愈的状态。目前既没有实用的人群筛查试验，也没有有效的治疗方法，5年生存率低。由于散发性类癌的罕见，大规模的基因分析和开发敏感和特异的诊断试验一直没有成功。虽然不能归因于已知遗传综合征的家族性类癌家族非常罕见，但它们提供了一个独特的机会来促进对相关基因突变的识别。此外，罕见的家族性形式的突变基因也可能是更常见的零星发生类癌的原因。我们建议研究至少有两个已知的受影响成员患有类癌的家庭。我们的目标是诊断患有早期隐匿性疾病的患者，因此有可能治愈。因此，患有类癌肿瘤的终生风险高达50%的家庭成员在最初和随后两年的随访中将接受使用生化、内窥镜和成像手段的密集诊断评估。对受影响的家庭成员的早期表型分配以及从多个家系收集生殖系和肿瘤DNA也应有助于遗传分析导致疾病基因的识别。在疾病的不同阶段对受影响的家庭成员进行评估将有助于我们了解类癌肿瘤的自然历史以及各种诊断和监测试验的相对有效性。希望这些知识也适用于零星发生的类癌或其他家族性癌症综合征的患者。对于现有的或新诊断的原发或转移性类癌患者，没有计划的治疗方法。然而，这些患者可能会通过咨询肿瘤学和外科来评估潜在的治疗方法。

Carcinoid tumors are rare and cause either no or few nonspecific symptoms. Therefore, patients with carcinoid tumors most often present late in the course of their illness when there is already progression to an incurable state as a result of metastatic disease. At present there are neither practical population screening tests nor effective therapies and hence the 5 year survival rate is low. Due to the rareness of sporadic carcinoid tumors, large scale genetic analysis and development of sensitive and specific diagnostic tests have not been successful. While kindreds with familial carcinoid tumors that are not ascribable to known genetic syndromes are exceedingly rare, they provide a unique opportunity to facilitate the identification of the responsible gene mutation. In addition, the mutated gene in the rare familial form may also underlie the origin of the more common sporadic occurrence of carcinoid tumors. We propose to study families in which there are at least two known affected members with carcinoid tumors. We aim to diagnose patients with early and therefore potentially curable occult disease. Therefore, family members who have up to a 50% lifetime risk of harboring a carcinoid tumor will undergo an intensive diagnostic evaluation using biochemical, endoscopic and imaging modalities at initial and subsequent two year follow up encounters. Early phenotypic assignment of affected family members and collection of germline and tumoral DNA from multiple kindreds should also facilitate the genetic analysis leading to the identity of the disease gene. Evaluation of affected family members at varying stages of disease will contribute to our understanding of the natural history of carcinoid tumors and the relative utility of a variety of diagnostic and surveillance tests. Hopefully, such knowledge gained will also be applicable to patients with carcinoid tumors occurring sporadically or in the setting of other familial cancer syndromes. There is no planned treatment for patients with existing or newly diagnosed primary or metastatic carcinoid tumors. However, these patients may be evaluated by consultation with oncology and surgery for potential treatment.