Diagnosis, Natural History, Management and molecular ins

无多发性内分泌瘤1型（MEN 1）或多发性内分泌瘤1型（MEN 1）患者的胃泌素瘤和其他恶性胰腺内分泌肿瘤（PET）的自然史、预后、管理和分子基础主要基于产前报告和小系列研究。胃癌是有或无MEN患者中最常见的症状性恶性PET 1，我们的方案中已纳入足够数量的此类患者，以进行系统评估。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以及决定预后的因素的定义，包括试图确定具有预后意义的肿瘤的分子特征。我们的研究已经确定了一个队列，其中25%的胃泌素瘤具有侵袭性生长，25%的患者患有多发性内分泌瘤1型（MEN 1）。我们今年的长期研究表明，ZES/MEN 1患者发生脑膜瘤是一种内源性MEN 1肿瘤，严重食管疾病的发生率增加，包括癌前病变、异型增生。识别具有不同预后的患者使我们能够对肿瘤进行分子研究，试图识别可能导致侵袭性生长的遗传异常。今年在胃泌素瘤中发现了胰岛素样生长因子1（IGF-1）及其受体的表达增加，它们的存在与低治愈率，肿瘤生长增加和转移的发展相关。在以前的研究中，我们发现MEN 1基因，HER 2/neu基因，p16基因和其他生长因子的异常，但没有一个像IGF-1/IGF-1 R改变与侵袭性肿瘤生长一样强烈相关。这些分子预后标志物的可用性可能被证明在临床上有用，以确定谁需要更积极的抗肿瘤治疗的患者。我们的长期手术研究今年首次证明，常规手术探查可提高患者生存率，因此应在所有患者中进行。

The natural history, prognosis,management and molecular basis 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 and definition of factors determining prognosis including attempting to identify molecular characteristics of the tumor that have prognostic significance. Our studies have identified a cohort of 25% of patients in whom the gastrinomas have aggressive growth and 25% who have multiple endocrine neoplasia type 1 (MEN1). Our longterm studies this year demonstrate patients with ZES/MEN1 develope meningiomas as an intrinsic MEN1 tumor and have an increased occurrence of severe esophageal disease including the premalignant condition, dysplasia. The identification of patients with different prognoses allows us to do molecular studies of the tumor to attempt to identify genetic abnormalities that might contribute to aggressive growth. An increased expression of the insulin-like growth factor 1 (IGF-1) and its receptor was found in gastrinomas this year and their presence correlated with a low curability, increased tumor growth nd the development of metastases. In previous studies we identified abnormalities in the MEN1 gene, HER2/neu gene, p16 gene and other growth factors but none correlated as strongly as IGF-1/IGF-1R alterations with aggressive tumor growth. The availability of these molecular prognostic markers may prove clinically useful to identify patients who need more aggressvie anti-tumor treatment. Our longterm surgical studies demonstrated for the first time this year that routine surgical exploration for cure increases patient survival and therefore should be done in all patients.