Sutureless Laparoscopic Partial Nephrectomy Using Laser Tissue Welding: Preclinic

使用激光组织焊接进行无缝腹腔镜肾部分切除术：临床前

• 批准号: 8312097
• 负责人: GILAD E AMIEL
• 金额: $ 40.9万
• 依托单位: LASER TISSUE WELDING, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-10 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8312097
• 关键词: Abdomen; Abdominal Abscess; Ablation; Accounting; Address; Adverse event; Aftercare; Albumins; Animals; Anticoagulation; Area; Benign; Bile fluid; Biocompatible Materials; Biological Preservation; Blood; Blood Coagulation Disorders; Burn injury; Caliber; Cerebrospinal Fluid; Clinical; Clinical Research; Clinical Trials; Coagulation Process; Complex; Control Groups; Creatinine clearance measurement; Defect; Device Safety; Devices; Diagnosis; Domestic Pig; Drug resistance; Environment; Esophageal; Evaluation; Excision; Extravasation; Family suidae; Fiber Optics; Fistula; Frequencies; Goals; Government; Grant; Guidelines; Healed; Hematoma; Hemorrhage; Hemostatic Agents; Hemostatic function; Histologic; Hospital Costs; Hospitals; Human; Hypospadias; Image; In Vitro; Incidence; Institutional Review Boards; Kidney; Kidney Neoplasms; Lasers; Length; Length of Stay; Lesion; Life; Liquid substance; Liver; Liver neoplasms; Lymph; Malignant - descriptor; Marketing; Mediating; Medical; Medicine; Methods; Morbidity - disease rate; Necrosis; Neoplasms; Nephrectomy; Nephrons; Newly Diagnosed; Normal tissue morphology; Nuclear; Operative Surgical Procedures; Optics; Organ; Organ Donor; Outcome; Pancreas; Patients; Perforation; Persons; Phase; Postoperative Hemorrhage; Postoperative Period; Prevalence; Procedures; Pseudomonas aeruginosa; Randomized; Renal Cell Carcinoma; Renal Mass; Renal carcinoma; Renal function; Renal pelvis; Resected; Robotics; Safety; Scanning; Septicemia; Small Business Innovation Research Grant; Solid; Spinal Cord; Spinal nerve structure; Spleen; Staging; Sterility; Sterilization; Streptococcus pyogenes; Study Subject; Surface; Surgeon; Surgical sutures; Technology; Testing; Therapeutic Effect; Time; Tissues; Toxic effect; Toxicology; Transfusion; Trauma; United States; Urethra; Urethral Diverticulum; Urethral Stricture; Urine; Vascular blood supply; Visceral; Warm Ischemia; Welding; base; biomaterial compatibility; blood product; cancer transplantation; college; commercial application; gastrointestinal; healing; improved; in vivo; innovation; liver repair; liver transplantation; methicillin resistant Staphylococcus aureus; migration; minimally invasive; mortality; novel; pre-clinical; preclinical efficacy; preclinical safety; pressure; prevent; prospective; prototype; radiofrequency; reconstruction; renal artery; repaired; response; scaffold; seal; secondary infection; success; tissue repair; tissue support frame; tissue trauma; tissue welding; tumor; urinary

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. PUBLIC HEALTH RELEVANCE: The current proposal aims at Nephron Sparing surgery of small renal lesions. In 2008 there were approximately 46,410 newly diagnosed cases of kidney cancer in the United States, the majority of which represent renal cell carcinoma (RCC). The prevalence of cancer of the kidney and renal pelvis is 296,074, with 61.3% localized or 181493 patients. Although the overall incidence of RCC has been steadily increasing for the past two decades, in large part due to the increased application of abdominal imaging, there has been a concurrent downward stage migration, with small renal masses, defined as lesions with a maximum diameter of 4 cm or less, now accounting for the largest proportion of newly diagnosed renal tumors. Most of these lesions can be safely resected without the need to remove the whole kidney. However, this requires clamping of the renal artery for the length of the procedure and complex reconstructive suturing of the kidney resulting in loss of kidney function. With LTW technology we hope to eliminate the need for suturing the kidney, significantly reduce renal artery clamp time and improve hemostasis, which will improve renal preservation and function. Laser tissue welding (LTW) is an enhanced non-compressive and non-ablative surgical capability that can seal low pressure fluid leaks instantly and accurately, including blood, gastrointestinal fluids, urine, bile, lymph, and cerebrospinal fluid. LTW is specifically useful when dealing with solid visceral organs with a soft friable parenchyma, such as the liver and kidney. It enables the surgeon to undertake resections in non-anatomical planes join and seal the parenchyma with minimal thermal damage. Relevance Laser Tissue Welding is an enhanced surgical capability, a new paradigm that can address important unmet medical needs. Saves lives: Quickly repairs and controls of hemorrhage in patients who cannot clot. Blood conservation: Reduced transfusion requirements. Salvages organs and tissues: Joins and seals without burning. Enabling curative surgical resection: Does not ablate tumors or normal parenchyma. Provides intraoperative tissue diagnosis of tumor free margins. Shorting operating time: Quick and accurate. Faster Healing and Shorter hospital stay: Due to decreased tissue trauma. Can be used in a contaminated environment : Sterilizes contaminated wounds of drug- resistant super bugs like Methicillin-Resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes and Pseudomonas aeruginosa. Fibro-optic capable: Minimally invasive laparoscopic & robotic applications.

描述（由申请人提供）：在适当选择的肾细胞癌患者中，保留功能性肾实质的功能很重要，对自由基肾切除术的肾脏比较手术替代品。腹腔镜部分肾切除术（LPN）在肿瘤控制方面表现出了极好的结果，但由于实质止血，Pelvi - 卡尔维尔重建，实质性肾上腺法，骨质重质，出血和延长的温暖温暖的休眠色节，由于实质性止血的重大技术挑战而持续不足。激光组织焊接，Inc。（LTW）使用一种非压缩的非燃烧技术连接和密封组织，以控制血液，胃肠道液，尿液，胆汁，淋巴和脑脊液的泄漏。当 在凝血病或抗凝作用的情况下，用于固体内脏器官的表面，例如肝脏脾脏，胰腺和肾脏，涉及创伤，癌症和移植。临床前体内慢性4、6个动物研究以及I期SBIR原型制造的特征和验证生物材料的制造。在第二阶段SBIR下，我们的公司已根据FDA IDE批准开始了肝脏切除术的人类临床试验。快速轨道I：特定目标*（时间：6个月）1。使用激光组织焊接组合装置的腹腔镜部分肾切除术：八周的12头猪进行临床前的安全性和有效性研究。这项研究的目的是评估生物相容性和毒性 用于执行腹腔镜部分肾切除术后家用猪肾脏的激光组织焊接程序。十二头猪将随机分配给两组6个猪（对照和治疗）。对照组和治疗组都将暂时阻塞器官的血液供应十分钟，并进行部分肾切除术。研究组将进行组织焊接和对照组部分肾切除术，而无需其他治疗。所有动物将在8周时终止。 2。调查设备豁免提交和批准。 3。使用激光组织焊接装置的IRB批准快速II期特异性目标*（时间：24个月）腹腔镜部分肾切除术：安全性和有效性临床试验。 1。在10名患者中进行人类可行性临床研究。 2。关键一个中心前瞻性随机临床研究随机分配给20个测试受试者和20个对照。这些是对T1A（<4cm）肾肿瘤的机器人辅助腹腔镜切除的实际患者。所有受试者将受到肾动脉的阻塞和肿瘤切除。研究组将接受组织焊接和对照组的常规缝合缺陷。将通过制定不良事件的频率来评估安全性，例如由于a）继发性感染，腹腔内脓肿的形成和败血症，b）晚期出血或继发性出血或血肿； c）尿液泄漏； d）通过肌酐清除率和MAG3核肾脏扫描和E）死亡的肾功能和长期肾功能而对肾实质的损害。疗效将通过基于a）完全止血的患者数量来比较治疗和对照对客观反应率的对照来确定疗效； b）达到止血所需的肾动脉夹时间； c）术中和术后失血； D）输血； e）手术时间； f）ICU住宿； g）住院和f）总医院费用。技术创新：使用我们的礼节生物材料的LTW是一种增强的外科手术能力，可以准确，即时无需压缩，消融或热损伤就可以进行止血密封，从而使手术干预措施不可能进行。这些未满足的临床需求是密封涉及多发性的固体内脏器官（肝脏，肾脏，胰腺和脾脏）和肿瘤。脊髓和神经重新连接；污染的伤口灭菌，硬膜，食管和十二指肠穿孔的密封；并提供组织向内生长的支架。预期的结果：提交单个市场前市场批准（PMA）应用程序，并为每个解剖区域提供单独的IDE应用程序。潜在的商业应用：LTW可用于密封和连接所有组织。应用包括肝创伤修复和切除后原发性和转移性肝肿瘤；分裂肝移植量翻倍供体器官池；良性和恶性病变的部分肾切除术；尿道修复：用于尿道质量，尿道狭窄，尿道憩室和 尿道瘘管和目前使用缝合线的所有手术程序。 公共卫生相关性：当前的提案旨在针对小型肾脏病变的肾单位保留手术。 2008年，美国大约有4610例新诊断的肾癌病例，其中大多数代表肾细胞癌（RCC）。肾脏和肾脏骨盆癌的患病率为296,074，局部局部或181493例患者。尽管在过去的二十年中，RCC的总体发病率一直在稳步增加，在很大程度上是由于腹部成像的应用增加，但同时存在下降阶段迁移，肾脏肿块的较小肾脏（定义为最大直径为4 cm），现在最大的直径为4 cm，现在占新诊断已诊断出的肾脏肿瘤的最大比例。这些病变中的大多数可以安全切除，而无需去除整个肾脏。但是，这需要将肾动脉夹紧，以使肾脏的过程长度和复杂的重建性缝合，从而导致肾功能的损失。利用LTW技术，我们希望消除缝合肾脏的需求，大大减少肾动脉夹时间并改善止血，这将改善肾脏保存和功能。激光组织焊接（LTW）是一种增强的非压缩性和非燃烧性手术能力，可以立即，准确地密封低压流体，包括血液，胃肠道液，尿液，胆汁，淋巴和脑脊液液体。 LTW在处理具有柔软易碎实质（例如肝脏和肾脏）的固体内脏器官时特别有用。它使外科医生能够在非解剖平面上进行切除，并以最小的热损害密封实质。相关激光组织焊接是一种增强的外科手术能力，这是一种可以满足重要未满足医疗需求的新范式。挽救生命：快速维修和控制无法凝结的患者出血。节能：输血要求减少。打捞器官和组织：连接和密封而不会燃烧。 实现治疗性手术切除：不灌溉肿瘤或正常实质。提供术中组织诊断的无肿瘤边缘。短路运营时间：快速准确。更快的愈合和较短的医院住宿：由于组织创伤减少。可以在受污染的环境中使用：对耐药性超级虫的污染伤口，例如耐甲氧西林的金黄色葡萄球菌（MRSA），pyogenes链球菌和铜绿假单胞菌。 纤维电形：微创腹腔镜和机器人应用。