Endoscopy

Endoscopy is a fast moving field, and new techniques are continuously emerging. In recent decades, endoscopy has evolved and branched out from a diagnostic modality to enhanced video and computer assisting imaging with impressive interventional capabilities. The modern endoscopy has seen advances not only in types of endoscopes available, but also in types of interventions amenable to the endoscopic approach. To date, there are a lot more developments that are being trialed. Modern endoscopic equipment provides physicians with the benefit of many technical advances. Endoscopy is an effective and safe procedure even in special populations including pediatric patients and renal transplant patients. It serves as the tool for diagnosis and therapeutic interventions of many organs including gastrointestinal tract, head and neck, urinary tract and others

Hepatic Surgery

Longmire, called it a "hostile" organ because it welcomes malignant cells and sepsis so warmly, bleeds so copiously, and is often the ?rst organ to be injured in blunt abdominal trauma. To balance these negative factors, the liver has two great attributes: its ability to regenerate after massive loss of substance, and its ability, in many cases, to forgive insult. This book covers a wide spectrum of topics including, history of liver surgery, surgical anatomy of the liver, techniques of liver resection, benign and malignant liver tumors, portal hypertension, and liver trauma. Some important topics were covered in more than one chapter like liver trauma, portal hypertension and pediatric liver tumors

METHODOLOGY FOR RESEARCH AND DEVELOPMENT OF NOVEL MEDICAL DEVICES FOR MINIMALLY INVASIVE INTERVENTIONS

The design of innovative medical device requires extensive and hard efforts to reach good results in terms of safety, efficacy and cost effectiveness. First of all the idea has to be set and a wide search of state of the art, both technological and academic, has to be developed. Then the materials, manufacturing processes and design constraints have to be understood. In this work three examples of innovative surgical devices for minimally invasive surgery and assistance have been presented. The Muneretto Beam catheter is a new device for atrial defibrillation. Starting from a catheter produced by Estech company for the treatment of atrial fibrillation by ablating cardiac tissue during surgery, a system for the magnetic guidance of the same has been implemented. Thanks to finite element analysis of various configurations of magnets and to several in vitro tests, a final configuration which allows a good balance between the sliding of the catheter on the tissues and the magnetic interaction and adhesion to tissues has been found. Further attention has been taken to the development of the cover and the right configuration and method of use of the device. The VideoDrain system is a new catheter for the monitoring of post-operative wound. After critical surgical procedures it is necessary to monitor the status of the surgical wound for avoiding second look surgical interventions. Therefore a new balloon catheter for allowing the vision of the abdominal cavity has been produced. Several in vitro and in vivo trials have been conducted and the device is at the pre-industrial stage. The FloSeal GI cath. is a new device for the gastrointestinal release of an haemostatic substance of the Baxter company: the Floseal thrombin matrix. It consists in a balloon catheter suited for the use in the lower and upper gastrointestinal tract in the occurrence of bleedings during endoscopic procedures. This device has been CE labelled and is now on the market. All the devices described in this work come from ideas of surgeons leader in innovation in the field of minimally invasive interventions. Their collaboration has been fundamental for the several phases of design and tests of the devices. This Ph.D. thesis is divided into five chapters. In the Introduction chapter the process of research and development of innovative MDs for minimally invasive surgery has been illustrated. The second chapter shows the efforts done to find a working configuration for the Muneretto Beam catheter and the subsequent first prototypes developed. The progress in the design of VideoDrain has been explained in the third chapter; the whole process goes from the idea to the animal test on prototypes and a preliminary risk analysis. The development of the Floseal GI Catheter is depicted in the fourth chapter; all the details of the materials used and tests done to ensure a CE mark have been reported. Finally, in the Conclusion chapter I have reported some lessons learned from the work in the field of MDs, as a student, researcher and engineer at close contact with the world of surgery and minimally invasive technologies. Some papers about a preliminary research activity in the field of minimally invasive surgery and robotic interventions have been also enclosed. These works have been very useful to start the understanding of the complex and amazing world of MIS

Noninvasive Thrombolysis Using Histotripsy Pulsed Ultrasound Cavitation Therapy.

Histotripsy is a noninvasive ultrasound therapy that utilizes short, high-amplitude, focused ultrasound pulses to mechanically reduce targeted tissue structures to liquid debris by acoustic cavitation. In this work, the physical mechanisms of histotripsy and its application as a method of thrombolysis were investigated. Cavitation activity which causes tissue breakdown during histotripsy was studied by high-speed photography. It was found that cavitation clouds form due to scattering of shock waves in a focused ultrasound pulse from individual inertial cavitation bubbles. The scattered shock is a large tensile wave which expands clusters of cavitation bubbles when the tensile pressure is greater than a measured threshold of approximately 30 MPa. The interaction of this cavitation with tissue and cells was explored with a phantom containing agarose and red blood cells to measure cavitation-based mechanical damage. The observations indicated that cell lysis may be achieved by bubble-induced tensile strain upon expansion, causing membrane rupture. Based on these studies, focused histotripsy therapy transducers were designed to controllably generate cavitation clouds in the vasculature for performing thrombolysis. Transducers were integrated with ultrasound imagers to provide feedback for targeting and monitoring progress of treatment. Rapid thrombolysis was observed when histotripsy was applied to clots in-vitro, and the resulting debris was mainly subcellular and unlikely to cause embolism. Additionally, it was observed that histotripsy can attract, trap, and destroy free clot fragments in a vessel phantom. Based on these observations, a noninvasive embolus trap (NET) was developed, acting as a filter to prevent embolism during the thrombolysis procedure. An in-vivo porcine model of deep-vein thrombosis was used to evaluate the safety and efficacy of the histotripsy thrombolysis technique. These experiments demonstrated the feasibility of the treatment and suggest histotripsy can achieve rapid clot breakdown in a controlled manner.Ph.D.Biomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/91496/1/adamdm_1.pd

Development of ultrasound-guided gene therapy to the sheep fetus.

Fetal gene therapy may treat genetic diseases before significant organ damage, target stem cell populations and avoid immune sensitisation. Candidate diseases include cystic fibrosis, haemophilia and lysosomal storage disorders. This thesis developed ultrasound-guided delivery of viral vectors to the sheep fetus for treatment of these diseases. For haemophilia B treatment we delivered adenovirus vectors containing the p-galactosidase reporter gene (adlacZ) or the human factor IX gene (adhFIX) by ultrasound guidance to the early gestation sheep fetus, when it is considered to be pre-immune. Intraperitoneal injection allowed the earliest time point for gene delivery, achieved the highest hFIX levels and the most localised p-galactosidase expression. Therapeutic hFIX levels were detected after intramuscular and intra-amniotic delivery suggesting that these are potentially alternative sites for therapeutic gene expression. For each route examined, no humoral immune response was observed to the transgene, although antibodies to the adenovirus vector were identified. We achieved intravascular delivery via umbilical vein injection therapeutic hFIX levels were detected. We developed ultrasound-guided transthoracic injection of the mid-gestation fetal trachea for cystic fibrosis treatment, p-galactosidase expression, measured by ELISA, was low after delivery of adlacZ vector alone, but increased 10 fold when the vector was complexed with DEAE dextran. Pretreatment of the fetal airways with sodium caprate increased expression by 90 fold the effect of the two agents was synergistic. Perflubron instillation following vector injection redistributed transgene expression from the large to the small airways. We developed ultrasound-guided fetal intragastric injection and achieved widespread transgene expression throughout the gastrointestinal epithelia after adlacZ vector delivery. For brain manifestation of lysosomal storage disorders we injected adlacZ vectors to the fetal ventricles under ultrasound guidance. Transduction of the choroid plexus was seen. Future application of integrating vectors such as lentivirus may allow for long term therapeutic correction and induce immune tolerance to the transgene