Biophotonics to Couple Pancreatic with Upper GI Screening via Ultrathin Endoscopy

生物光子学通过超薄内窥镜将胰腺与上消化道筛查结合起来

• 批准号: 9195083
• 负责人: Vadim Backman
• 金额: $ 63.4万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9195083
• 关键词: Age; American; Area; Biomedical Engineering; Biophotonics; Caliber; Cancer Death Rates; Cancer Detection; Cancer Etiology; Case-Control Studies; Cessation of life; Clinical; Colon; Colonoscopy; Colorectal Cancer; Coupled; Coupling; Cyst; Cystic Lesion; Cystic Neoplasm; Data; Detection; Development; Diagnosis; Diagnostic; Diffusion; Disease; Duodenum; Dysplasia; Early Diagnosis; Endoscopes; Endoscopy; Epigenetic Process; Esophageal; Event; Excision; Failure; Family; Fiber; Fiber Optics; Flexible fiberoptic sigmoidoscopy; Gastric Polyp; Gastric mucosa; Gastroenterologist; Gastrointestinal tract structure; Gender; Genetic; Glass; Goals; Histologic; Imagery; Incidence; Lung; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of esophagus; Malignant neoplasm of gastrointestinal tract; Malignant neoplasm of pancreas; Modality; Mucous Membrane; Nature; Optical Biopsy; Optics; Pancreas; Pancreaticoduodenectomy; Patient Recruitments; Patient risk; Patients; Penetration; Performance; Physiological; Population; Prevalence; Procedures; Radiation; Recording of previous events; Reporting; Research; Risk; Risk stratification; Screening for cancer; Sedation procedure; Spectrum Analysis; Stomach; Symptoms; Techniques; Testing; Thinness; Training; Ultrasonography; Validation; Work; adenoma; advanced disease; cancer biomarkers; cancer risk; carcinogenesis; chronic pancreatitis; clinically significant; cohort; cost; cost effective; design; diabetic; gastrointestinal; high risk; malignant stomach neoplasm; miniaturize; minimally invasive; multidisciplinary; nanoarchitecture; new technology; novel; operation; pancreatic neoplasm; prevent; prognostic; public health relevance; screening; technology development; upper GI series

DESCRIPTION (provided by applicant): Upper gastrointestinal malignancies (esophageal, gastric and pancreatic) are one of the leading causes of cancer deaths among Americans largely due to its insidious nature leading to diagnosis at late stages. The clinical implementatio of ultrathin upper endoscopes has the potential for providing a major modality for cancer screening in that it is much more comfortable than conventional larger caliber endoscopes thus allowing patients to forego sedation with the consequent change in complications, cost and convenience. However, the promise has heretofore not been realized largely because of the failure of upper endoscopy to detect pancreatic cancer (PC), whose incidence dwarfs esophageal and gastric cancers. Our multi-disciplinary group of biomedical engineers, cancer biomarkers experts, gastroenterologists has focused on using a novel technology, low coherence enhanced backscattering (LEBS) to detect the ultra-structural and microvascular consequences of the genetic/epigenetic/physiological alterations in field carcinogenesis. While our prior work has largely focused on the colon (where the "condemned mucosa" is the clinical imperative behind assessment for synchronous/metachronous adenomas), our data have shown that the analysis of histologically and endoscopically normal duodenal peri-ampullary mucosa could predict PC (consistent with other reports on genetic/epigenetic events). Our preliminary data with a LEBS fiber-optic probe requiring a large working channel shows strong diagnostic performance. For this strategy to be clinically viable, however, the probe has to be miniaturized so that it can be delivered through ultrathin endoscopes. Therefore, we propose to develop a novel miniature sub-diffusion radiative transport fiber-array probe to be compatible with the 2 mm accessory channel of an ultrathin endoscope. We will assess clinical value in two scenarios: PC screening and cystic neoplasm management. With screening we will perform a case-control study with an independent validation set to test the potential of detecting the ultrastructural and microvascular markers of field carcinogenesis in the duodenal peri-ampullary mucosa via the probe for PC screening. For cystic neoplasm management, we will assess the value of duodenal interrogation for cyst diagnosis and prognostication of cysts with intermediate malignancy risk (IPMNs), both clinically vexing issues. By bridging ultrathin endoscopy with optical detection of PC field carcinogenesis in the duodenal periampullary mucosa, we propose to overcome what is arguably the major barrier thus far preventing upper GI cancer screening in population. The test could be performed comfortably in the office setting while minimizing cost, patient inconvenience and complications. This may also have applications for surveillance of patients at higher risk including those with IPMNs. Finally, this may herald another avenue in biophotonics research focusing on risk stratification as opposed to optical biopsy or dysplasia detection.

描述（由申请人提供）：上消化道恶性肿瘤（食管癌、胃癌和胰腺癌）是美国人癌症死亡的主要原因之一，很大程度上是因为其隐匿性导致晚期诊断。超薄上内窥镜的临床应用有可能为癌症筛查提供一种主要方式，因为它比传统的大口径内窥镜舒适得多，从而允许患者放弃镇静，从而改变并发症、成本和便利性。然而，迄今为止这一承诺尚未实现，很大程度上是因为上消化道内窥镜检查未能检测到胰腺癌（PC），而胰腺癌的发病率使食管癌和胃癌相形见绌。我们的多学科小组由生物医学工程师、癌症生物标志物专家、胃肠病学家组成，专注于使用新技术、低相干增强反向散射 (LEBS) 来检测现场致癌过程中遗传/表观遗传/生理变化的超微结构和微血管后果。虽然我们之前的工作主要集中在结肠（其中“废弃粘膜”是评估同步/异时性腺瘤的临床必要条件），但我们的数据表明，对组织学和内镜下正常的十二指肠壶腹周围粘膜进行分析可以预测 PC （与其他关于遗传/表观遗传事件的报告一致）。我们使用需要大工作通道的 LEBS 光纤探头的初步数据显示出强大的诊断性能。然而，为了使这种策略在临床上可行，探针必须小型化，以便可以通过超薄内窥镜传送。因此，我们建议开发一种新型微型亚扩散辐射传输光纤阵列探头，以兼容超薄内窥镜的2 mm辅助通道。我们将评估两种情况的临床价值：PC 筛查和囊性肿瘤管理。通过筛查，我们将使用独立的验证集进行病例对照研究，以测试通过 PC 筛查探针检测十二指肠壶腹周围粘膜中现场致癌的超微结构和微血管标志物的潜力。对于囊性肿瘤的治疗，我们将评估十二指肠询问对囊肿诊断和中等恶性风险囊肿（IPMN）预后的价值，这两个问题都是临床上棘手的问题。通过将超薄内窥镜与十二指肠壶腹周围粘膜中 PC 场癌变的光学检测结合起来，我们建议克服迄今为止阻碍人群上消化道癌症筛查的主要障碍。该测试可以在办公室环境中舒适地进行，同时最大限度地减少成本、患者的不便和并发症。这也可能适用于监测高风险患者，包括患有 IPMN 的患者。最后，这可能预示着生物光子学研究的另一条途径，重点是风险分层，而不是光学活检或发育不良检测。