Diagnosis, Natural History, Management and molecular ins

无（散发性疾病）或多发1型内分泌肿瘤（MEN1）患者胃泌腺瘤和其他胰腺恶性内分泌肿瘤（PET）的自然病史、预后、处理和分子基础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，以及决定预后因素的定义，包括试图确定具有预后意义的肿瘤分子特征。我们的研究已经确定了一组患者，其中25%的患者胃泌素瘤具有侵袭性生长，25%的患者患有多发性内分泌肿瘤1型（MEN1）。我们今年的长期研究表明，患有ZES/MEN1的患者发展为脑膜瘤作为一种内在的MEN1肿瘤，并增加了严重食道疾病的发生率，包括癌前状态，不典型增生。对不同预后患者的识别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。胰岛素样生长因子1 （IGF-1）及其受体的表达增加今年在胃鞘瘤中被发现，它们的存在与低治愈率、肿瘤生长增加和转移的发展相关。在之前的研究中，我们发现了MEN1基因、HER2/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-1R改变与侵袭性肿瘤生长的相关性那么强。这些分子预后标记物的可用性可能在临床上证明对确定需要更积极的抗肿瘤治疗的患者有用。我们的长期外科研究在今年首次证明了常规手术治疗可以提高患者的生存率，因此应该在所有患者中进行。

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.