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.
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.
