Full PROJ 1: Preclinical Evaluation, Clinical Trial Preparation and a Prospectiv

摘要： 仅在美国，每年就有超过30万例胃肠道切除和吻合术。5-15%的患者术后发生吻合部位裂开或渗漏，并与显著的术后发病率和死亡率相关。之前的临床前研究已经表明吻合处充分的组织氧合对于预防术后渗漏和并发症的重要性。外科医生传统上仅通过简单的目视检查来评估组织活力和血液供应。术中评估吻合组织活力的方法将有助于采取纠正措施并改善手术结局。我们假设通过无线脉搏血氧仪（WiPOX）设备实时监测组织氧合提供了可靠、客观的组织灌注测量，并且可以比目视检查更早地检测组织缺血，从而允许采取纠正措施以降低术后发病率和死亡率。我们的工程（CCNY）和外科（MSKCC）团队合作开发并验证了一种创新的WiPOX设备-这种手持式设备和微型探头为手术外科医生提供了实时、准确和方便的组织氧合监测。这将不仅使外科医生能够真实的实时监测血管损害，以便纠正任何导管扭曲，而且还将使外科医生能够自信地选择用于吻合的最大氧合部位。本提案将包括三个临床应用（目的）中的关键器械开发和确认步骤：1）使用已经在初步临床试验中验证的WiPOX模型，我们将对经历食管胃切除术的患者进行前瞻性临床试验，测试WiPOX是否可以（a）预测由组织氧合（Ti O2）损害引起的吻合口泄漏，以及（B）优化吻合口周围的Ti O2，从而减少术后吻合口漏。2)开发和测试一种新的WiPOX模型，用于检测接受微血管游离组织移植进行乳房重建的患者的早期皮瓣缺血，并进行初步临床试验。3)开发一种基于嵌入网格的多传感器阵列的新平台，以包裹肝脏或心脏，并在大型动物中测试该设备，以检测肝脏切除术和心脏搭桥手术期间的实时术中血流受损。

Abstract: More than 300,000 gastrointestinal resection and anastomosis per year are performed in the U.S. alone. Dehiscence or leakage from anastomotic sites following surgery occurs in 5-15% of patients and is associated with significant post-operative morbidity and mortality. Prior preclinical investigations have shown the importance of adequate tissue oxygenation at the anastomosis in preventing post-operative leakage and complications. Surgeons traditionally assess tissue viability and blood supply by simple visual inspection only. A method to assess anastomotic tissue viability intraoperatively would help perform corrective measures and improve surgical outcomes. We hypothesize that real-time monitoring of tissue oxygenation by wireless pulse oximetry (WiPOX) device provides a reliable, objective measure of tissue perfusion, and can detect tissue ischemia earlier than visual inspection, thereby allowing corrective actions to reduce post-operative morbidity and mortality. Our engineering (CCNY) and surgical (MSKCC) teams collaborated to develop and validate an innovative WiPOX device - this hand-held device and miniature probe provides operating surgeons with real-time, accurate, and convenient monitoring ofthe tissue oxygenation. This will not only enable the surgeon to monitor vascular compromise in real time in order to rectify any conduit twisting, but will also allow the surgeon to confidently select the site of maximal oxygenation for the anastomosis. This proposal will Include pivotal device development and validation steps in three clinical applications (Aims): 1) Using a WiPOX model already validated in pilot clinical trials, we will conduct a prospective clinical trial of patients undergoing esophagogastrectomy, testing whether WiPOX can (a) predict anastomotic leaks resulting from tissue oxygenation (Ti02) compromise, and (b) optimize peri-anastomotic Ti02, thereby decrease post-operative anastomotic leakage. 2) To develop and test a new WiPOX model to detect early flap ischemia in patients undergoing microvascular free tissue transfer for breast reconstruction and conduct a pilot clinical trial. 3) Develop a new platform based on a multi-sensor array embedded in mesh to envelope a liver or heart and test the device in large animals for detecting real-time intraoperative blood flow compromise during liver resections and heart bypass surgery.