Development of Microscopic Spectral Markers for Diagnosis of Pancreatic Lesions

描述（由申请人提供）：胰腺癌（PC）仍然是最致命的癌症之一，其5年生存率不到5%。内镜超声（EUS）引导下的细针穿刺（FNA）细胞学检查通常用于获得可疑胰腺实性和囊性病变的病理诊断，以指导患者的进一步处理（即术前手术计划或新辅助治疗）。然而，细胞学对胰腺实性病变的平均敏感性为80%，对囊性病变诊断恶性肿瘤的敏感性甚至低于30%，这往往阻碍了细胞学的发展。现有肿瘤标志物的疗效也不理想。本应用程序的主要目的是探索内源性显微光谱标记物作为潜在的生物标记物，以提高胰腺实性和囊性病变恶性肿瘤的诊断准确性。为了实现这一目标，我们将致力于开发一种新型光学仪器-多模式多维部分波光谱显微镜（MD-PWS），该仪器可提供多维弹性光散射信号的综合评估，该信号包含亚细胞或分子水平的全套3D波矢量。我们假设MD-PWS衍生的显微光谱标记将检测胰腺癌和胰腺囊肿患者细胞学上非恶性细胞的细微结构变化，这些细胞具有高恶性潜能，比传统细胞学或其他临床可用的生物标记更敏感。我们将探讨MD-PWS显微光谱标记在胰腺实性病变和囊性病变中提高恶性肿瘤细胞学诊断的可行性。MD-PWS衍生的显微光谱标记也将在亚细胞水平上提供对胰腺细胞结构特征的重要见解。该项目的结果将作为多中心合作的理由，以在临床环境中充分评估该技术。我们的长期目标是开发一种简单、经济、高灵敏度的显微镜系统，以提高胰腺癌的诊断准确性和风险分层策略的发展。最终，我们提出的技术还可以为各种癌症提供更好的诊断方案。

DESCRIPTION (provided by applicant): Pancreatic cancer (PC) remains one of the most deadly cancers, with a dismal 5-year survival rate of less than 5%. Endoscopic ultrasound (EUS) guided fine-needle aspiration (FNA) cytology is often performed to obtain a pathological diagnosis of suspicious pancreatic solid and cystic lesions to guide further management of patients (i.e., preoperative surgical planning or neoadjuvant treatment). However, cytology is often stymied by the average sensitivity of 80% for pancreatic solid lesions and even more dismal sensitivity of less than 30% for diagnosing malignancy in cystic lesions. The efficacy of existing tumor markers also remains sub-optimal. The major objective of this application is to explore endogenous microscopic spectral markers as potential biomarkers to improve the diagnostic accuracy of malignancy on pancreatic solid and cystic lesions. To achieve this goal, we will address the development of a novel optical instrument - multi-mode multi- dimensional partial-wave spectroscopic microscopy (MD-PWS) that provides a comprehensive assessment of multi-dimensional elastic light-scattering signals that contain a full set of 3D wave-vectors at sub-cellular or molecular level. We hypothesize that MD-PWS derived microscopic spectral markers will detect subtle structural alterations in cytologically non-malignant-appearing cells from patients with pancreatic cancer and pancreatic cyst that carries a high malignant potential, more sensitive than conventional cytology or other clinically available biomarkers. We will explore the feasibility of MD-PWS microscopic spectral markers to improve the cytological diagnosis of malignancy in pancreatic solid lesions as well as cystic lesions. MD-PWS derived microscopic spectral markers will also provide significant insights into the structural characteristics of pancreatic cells at sub-cellular level. The results from this project will serve as a justification for a multi-center collaboration to fully evaluate this technology in a clinical setting. Our long-term goal is to develop a simple, cost-effective and highly sensitive microscopy system to improve the diagnostic accuracy and development of risk stratification strategies for pancreatic cancer. Ultimately, our proposed technology could also lead to development of better diagnostic protocols for a wide variety of cancers. PUBLIC HEALTH RELEVANCE: This project is significant to the public health issue of diagnosis and early detection of pancreatic cancer. The accurate diagnosis of pancreatic solid and cystic lesions is clinically challenging. A highly sensitive microscopy system to improve the diagnostic accuracy for pancreatic malignancy and high-risk cystic lesions that have a high malignant potential could help the development of risk stratification and prevention strategies for pancreatic cancer.