Sutureless Laparoscopic Partial Nephrectomy Using Laser Tissue Welding: Preclinic

描述(申请人提供)：在适当选择的肾癌患者中，保留功能的肾实质是重要的，保留肾单位的手术可以替代根治性肾切除术。在肿瘤控制方面，腹腔镜肾部分切除术(LPN)显示了良好的效果，但由于肾实质止血、肾盏重建、肾实质修补、出血和长时间热缺血等重大技术挑战，LPN仍未得到充分应用。激光组织焊接公司(LTW)使用一种非压缩、非消融技术来连接和密封组织，以控制血液、胃肠道液体、尿液、胆汁、淋巴和脑脊液的泄漏。这就是拯救生命的时候 用于固体内脏器官的表面，如肝、脾、胰腺和肾脏，涉及创伤、癌症和存在凝血疾病或抗凝的移植。临床前活体实验4，6项动物研究和第一阶段SBIR原型制造已经完成，这些材料的特性和有效性得到了验证。在第二阶段SBIR下，我们公司已经在FDA IDE批准下开始了肝脏切除的人体临床试验。快速通道阶段I：特定目标*(时间：6个月)1.使用激光组织焊接组合装置进行的腹腔镜肾部分切除术：12头猪8周的临床前安全性和有效性研究。本研究的目的是评价生物相容性和毒性。 目的：探讨激光组织焊接技术在家猪腹腔镜肾部分切除术后的应用。将12头猪随机分为两组，每组6头猪(对照组和试验组)。对照组和治疗组都将暂时阻断器官的血液供应10分钟，并将接受部分肾切除。研究组采用组织焊接法，对照组采用肾部分切除术，不作其他处理。所有动物将在8周时被终止。2.侦查器材豁免报送和审批。3.IRB批准快速通道第二阶段特定目标*(时间：24个月)使用激光组织焊接器的腹腔镜肾部分切除术：安全性和有效性临床试验。1.10例先导性人体可行性临床研究。2.Pivotal单中心前瞻性随机临床研究，随机分为试验组和对照组各20例。这些是正在接受机器人辅助的腹腔镜下切除T1a(4厘米)肾肿瘤的实际患者。所有受试者都将接受肾动脉闭塞和肿瘤切除。研究组进行组织焊接，对照组常规缝合创面。安全性将通过列出不良事件的频率来评估，例如术后30天因a)继发性感染、腹内脓肿形成和败血症，b)晚期出血或继发性出血或血肿；c)尿漏；d)肾功能受损或通过肌酐清除和MAG3核肾扫描显示的长期肾功能损害，以及e)死亡率。疗效将通过比较以下患者的客观反应率来确定：a)完全止血；b)实现止血所需的肾动脉夹时间；c)术中和术后失血；d)输血产品；e)手术时间；f)ICU住院时间；g)住院时间和f)住院总费用。技术创新：使用我们合适的生物材料的LTW是一种增强的手术能力，能够准确、即时地对组织进行止血封闭，而不会受到压缩、消融或热损伤，从而使外科干预成为可能。这些未得到满足的临床需求是：封闭涉及多发性创伤和肿瘤的实体内脏器官(肝、肾、胰腺和脾)；脊髓和神经重接；污染伤口的消毒；硬脑膜、食道和十二指肠穿孔的封闭；以及为组织植入提供支架。预期结果：提交一份单一的上市前批准(PMA)申请，每个解剖区域都有单独的IDE申请。潜在商业应用：LTW可用于密封和连接所有组织。应用包括肝创伤修复和原发和转移性肝肿瘤的术后切除；将供体器官池扩大一倍的分离式肝移植；良性和恶性病变的部分肾切除术；尿路修复：治疗尿道下裂、尿路狭窄、尿路憩室和 尿瘘和目前使用缝线的所有外科手术。

DESCRIPTION (provided by applicant): Preservation of functioning renal parenchyma is important and nephron-sparing surgery substitutes for radical nephrectomy in appropriately selected patients with renal cell carcinoma. Laparoscopic partial nephrectomy (LPN) has demonstrated excellent outcomes in terms of oncologic control, but is under-used due to major technical challenges of parenchymal hemostasis, pelvi-caliceal reconstruction, parenchymal renorrhaphy, bleeding and prolonged warm ischemia. Laser Tissue Welding, Inc. (LTW) uses a non-compressive, non-ablative technology to join and seal tissues for controlling the leakage of blood, gastrointestinal fluids, urine, bile, lymph, and cerebrospinal fluid. It is life saving when used on the surfaces of solid visceral organs, such as the liver spleen, pancreas and kidney, involved in trauma, cancer and transplantation in presence of coagulopathies or anticoagulation. Preclinical in vivo chronic4, 6 animal studies and with a phase I SBIR prototype manufacturing of characterized and validated biomaterials was completed. Under a phase II SBIR our company has commenced human clinical trials for the liver resections under a FDA IDE approval. Fast Track Phase I: Specific Aims* (Time: 6 months) 1. Laparoscopic partial nephrectomy using laser tissue welding combination device: Eight week preclinical safety and efficacy studies in 12 pigs. The purpose of this study is to evaluate biocompatibility and toxicity for performing the laser tissue welding procedure applied to the kidney of domestic pigs after laparoscopic partial nephrectomy. Twelve pigs will be randomly assigned to two groups of 6 pigs each (control and treatment). Both the control group and the treatment group will have temporary occlusion of the organ's blood supply for ten minutes and will undergo a partial nephrectomy. The study group will undergo tissue welding and the control group partial nephrectomy without additional treatment. All animals will be terminated at 8 weeks. 2. Investigational device exemption submission and approval. 3. IRB approval Fast Track Phase II Specific Aims* (Time: 24 months) Laparoscopic partial nephrectomy using laser tissue welding device: Safety and Efficacy Clinical Trial. 1. Pilot human feasibility clinical study in 10 patient. 2. Pivotal one center prospective randomized clinical study randomized to 20 test subjects and 20 controls. These are actual patients undergoing robotically assisted laparoscopic resection of T1A (<4cm) renal tumors. All subjects will undergo occlusion of the renal artery and resection of the tumor. The study group will undergo tissue welding and the control group conventional suturing of the defect. Safety will be assessed by tabulating the frequency of adverse events, such as 30 day postoperative morbidity due to a) secondary infection, intra-abdominal abscess formation and septicemia, b) late bleeding or secondary hemorrhage or hematoma; c) urine leak; d) damage to the kidney parenchyma evident by compromised renal function or long term renal function via creatinine clearance and MAG3 nuclear renal scan and e) mortality. Efficacy will be determined by comparing treatment and controls with respect to the objective response rate based on the number of patients who achieve a) complete hemostasis; b) Renal artery clamp time required to achieve hemostasis; c) intraoperative and postoperative blood loss; d) blood product transfusions; e) operative time; f) ICU stay; g) hospital stay and f) total hospital costs. Technology innovation: LTW using our propriety biomaterials is an enhanced surgical ability that enables hemostatic sealing of tissues accurately and instantly without compression, ablation or thermal damage, thus enabling surgical interventions not deemed possible before. These unmet clinical needs are sealing of solid visceral organs (liver, kidney, pancreas and spleen) involved in polytrauma, and neoplasms; spinal cord and nerve reattachment; sterilization of contaminated wounds, sealing of dural, esophageal and duodenal perforations; and providing a scaffold for tissue ingrowth. Anticipated Outcomes: Submission of a single pre-market market approval (PMA) application with separate IDE applications for each anatomical region. Potential commercial applications: LTW may be used to sealing and joining all tissues. Applications include liver trauma repair and after resection for primary and metastatic liver tumors; split liver transplants doubling donor organ pool; partial nephrectomy for benign and malignant lesions; urethral repair: for hypospadias, urethral stricture, urethral diverticulum, and urethral fistulae and all surgical procedures that currently use sutures.