Development of Microscopic Spectral Markers for Diagnosis of Pancreatic Lesions

描述(申请人提供)：胰腺癌(PC)仍然是最致命的癌症之一，5年生存率不到5%。超声内窥镜(EUS)引导下细针吸取(FNA)细胞学检查常用于诊断可疑的胰腺实性和囊性病变，以指导患者的进一步治疗(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灵敏度为80%，对囊性病变的诊断灵敏度不到30%，这往往阻碍了细胞学的发展。现有的肿瘤标记物的疗效也不是很理想。这一应用的主要目的是探索内源性显微光谱标志物作为潜在的生物标志物，以提高对胰腺实性和囊性病变的恶性肿瘤诊断的准确性。为了实现这一目标，我们将致力于开发一种新型光学仪器-多模多维部分波光谱显微镜(MD-PWS)，它可以在亚细胞或分子水平上对包含完整3D波矢的多维弹性光散射信号进行全面评估。我们假设MD-PWS衍生的显微光谱标记物将检测来自胰腺癌和胰腺囊肿患者的细胞学非恶性外观细胞的细微结构变化，这些细胞具有较高的恶性潜能，比传统细胞学或其他临床可用的生物标记物更敏感。我们将探讨MD-PWS显微光谱标记物提高胰腺实性病变和囊性病变细胞学恶性诊断的可行性。MD-PWS衍生的显微光谱标记也将在亚细胞水平上为胰腺细胞的结构特征提供重要的见解。该项目的结果将作为多中心合作的理由，以在临床环境中全面评估这项技术。我们的长期目标是开发一种简单、经济有效和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制定。最终，我们提出的技术还可能导致开发出更好的诊断方案，适用于各种癌症。 公共卫生相关性：该项目对胰腺癌的诊断和早期发现的公共卫生问题具有重要意义。胰腺实性和囊性病变的准确诊断在临床上具有挑战性。一个高灵敏度的显微镜系统可以提高对胰腺恶性肿瘤和具有高恶性潜能的高危囊性病变的诊断准确率，有助于制定胰腺癌的风险分层和预防策略。

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.