Diagnostic Strategy and Risk Assessment of Cysts

在美国，超过2%的成年人患有胰腺囊肿症，随着腹部影像检查的增加，这些囊肿症的诊断率可能会增加。由于这些囊肿既可以是自限性病变，也可以是致命性侵袭性腺癌的真正先兆，因此它们构成了一个困难的临床管理问题。胰腺囊性肿瘤主要有三种类型：浆液性囊腺瘤(SCAs)、导管内乳头状粘液性肿瘤(IPMN)和粘液性囊性肿瘤(MCNs)。SCA被认为是完全良性的，而IPMN和MCNs通常与侵袭性成分有关。这项建议的最终目标是开发临床上有用的生物标记物，可以区分这些囊肿类型并改变临床决策。由于该孢子以前在基因组分析、生物标记物开发和胰腺囊肿分析领域取得的成功，这一目标现在是可行的。为了实现这一目标，我们建议对所有三种主要类型的胰腺囊性肿瘤的肿瘤细胞进行详细的分子分析(目标1)。这些分子发现将被用于开发囊液生物标记物(目标2)。囊液被选为目标临床样本是因为有希望的初步结果，也因为囊液在临床的关键决策点是常规可用的。在AIM#2中开发的最好的生物标记物将以回顾(AIM#3)和前瞻性(AIM#4)的方式与临床结果和结果相关。上述研究将确定胰腺囊肿发生机制的分子变化，并将有助于开发临床上有用的囊液生物标记物。

More than 2% of the adult population of the US harbors a pancreatic cyst and the increasing use of abdominal imaging is likely to increase the diagnosis of these lesions as incidental findings. Because these cysts can either be self-limiting lesions or represent true precursors to deadly invasive adenocarcinomas, they pose a difficult clinical management problem. There are three main forms of pancreatic cystic neoplasms, serous cystic adenomas (SCAs), intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs). SCAs are thought to be totally benign whereas IPMNs and MCNs are often associated with an invasive component. The ultimate goal of this proposal is to develop clinically useful biomarkers that can distinguish these cyst types and alter clinical decision-making. This goal is practical now due to previous successes of this SPORE in the areas of genomic analysis, biomarker development and pancreatic cyst analysis. To achieve this goal, we propose a detailed molecular-analysis of neoplastic cells from all three main types of pancreatic cyst neoplasms (Aim #1). These molecular findings will be used to develop cyst fluid biomarkers (Aim #2). Cyst fluid was chosen as the target clinical sample because of promising preliminary results and because cyst fluid is routinely available in the clinic at critical decision points. The best biomarkers developed in Aim #2 will be correlated with clinical findings and outcomes in both a retrospective (Aim #3) and prospective (Aim #4) manner. The above studies will identify molecular changes that underlie the pathogenesis of pancreatic cyst development and should allow the development of clinically useful cyst fluid biomarkers.