Flexible and stretchable wearable biomedical devices provide a platform for continues long-term monitoring of biological signals during neutral body movements thus enabling early intervention and diagnostics of various diseases. This thesis evaluates novel flexible and stretchable bio interfacing medical devices based on microneedle patches and split ring resonator for healthcare diagnostics. Flexible and stretchable microneedle patches were realized by integrating a soft polymer substrate with sharp stainless steel microneedles. This was realized using a magnetic assembly technique. Investigations have shown that the flexible microneedle patch can provide conformal and reliable contact with wrinkles and deformations of the skin. In addition, transdermal monitoring of potassium ions using the proposed flexible microneedle patch have been demonstrated by coating the microneedles with a potassium sensing membrane. Ex-vivo test on the microneedle potassium sensor performed on chicken and porcine skin was able to detect change in potassium concentration in the skin. Furthermore, a novel flexible bio-interface spilt ring resonator (SRR) for the monitoring of intera cranial pressure (ICP) is demonstrated. The sensor was fabricated by depositing a 500 nm gold film on a thermoset thiolene epoxy polymer substrate. The flexible sensor was able to clearly detect the pressure variation that might be an indication of increased ICP in the skull. The proposed methodology of heterogeneous integration of hard materials on a soft and flexible substrate demonstrates a first proof of concept of flexible wearable bio-interfacing devices with vastly different material properties with the potential for continuous and real-time health monitoring. / <p>QC 20190306</p>

Irreversible electroporation is a minimally invasive technique for the non-thermal destruction of cells in a targeted volume of tissue, using brief electric pulses, (~100 µs long) delivered through electrodes placed into or around the targeted region. These electric pulses destabilize the integrity of the cell membrane, resulting in the creation of nanoscale defects that increase a cell’s permeability to exchange with its environment. When the energy of the pulses is high enough, the cell cannot recover from these effects and dies in a non-thermal manner that does not damage neighboring structures, including the extracellular matrix. IRE has been shown to spare the major vasculature, myelin sheaths, and other supporting tissues, permitting its use in proximity to these vital structures. This technique has been proposed to be harnessed as an advantageous non-thermal focal ablation technique for diseased tissues, including tumors. IRE electric pulses may be delivered through small (ø ≈ 1 mm) needle electrodes, making treatments minimally invasive and easy to apply. There is sub-millimeter demarcation between treated and unaffected cells, which may be correlated with the electric field to which the tissue is exposed, enabling numerical predictions to facilitate treatment planning. Immediate changes in the cellular and tissue structure allow real-time monitoring of affected volumes with imaging techniques such as computed tomography, magnetic resonance imaging, electrical impedance tomography, or ultrasound. The ability to kill tumor cells has been shown to be independent of a functioning immune system, though an immune response seems to be promoted by the ablation. Treatments are unaltered by blood flow and the electric pulses may be administered quickly (~ 5 min). Recently, safety and case studies using IRE for tumor therapy in animal and human patients have shown promising results. Apart from these new studies, previous work with IRE has involved studies in healthy tissues and small cutaneous experimental tumors. As a result, there remain significant differences that must be considered when translating this ablation technique towards a successful and reliable therapeutic option for patients. The dissertation work presented here is designed to develop irreversible electroporation into a robust, clinically viable treatment modality for targeted regions of diseased tissue, with an emphasis on tumors. This includes examining and creating proving the efficacy for IRE therapy when presented with the many complexities that present themselves in real-world clinical patient therapies, including heterogeneous environments, large and irregular tumor geometries, and dynamic tissue properties resulting from treatment. The impact of these factors were theoretically tested using preliminary in vitro work and numerical modeling to determine the feasibility of IRE therapy in heterogeneous systems. The feasibility of use was validated in vivo with the successful treatment of human mammary carcinomas orthotopically implanted in the mammary fat pad of mice using a simple, single needle electrode design easily translatable to clinical environments. Following preliminary theoretical and experimental work, this dissertation considers the most effective and accurate treatment planning strategies for developing optimal therapeutic outcomes. It also experimentally characterizes the dynamic changes in tissue properties that result from the effects of IRE therapy using ex vivo porcine renal cortical tissue and incorporates these into a revised treatment planning model. The ability to use the developments from this earlier work is empirically tested in the treatment of a large sarcoma in a canine patient that was surgically unresectable due to its proximity to critical arteries and the sciatic nerve. The tumor was a large and irregular shape, located in a heterogeneous environment. Treatment planning was performed and the therapy carried out, ultimately resulting in the patient being in complete remission for 14 months at the time of composing this work. The work presented in this dissertation finishes by examining potential supplements to enhance IRE therapy, including the presence of an inherent tumor-specific patient immune response and the addition of adjuvant therapeutic modalities. / Ph. D.

Background: Minimally invasive surgery (MIS) requires intense education and training with structured supervision and feedback. However, a standardized training structure is lacking in Germany. This nationwide survey aimed to assess the current state of minimally invasive surgery (MIS) training and factors impacting surgeons' satisfaction. - Methods: Between July and October 2021, an online survey was conducted among general, abdominal, and thoracic surgeons in Germany. The survey collected data on department size, individual operative experience, availability of MIS training equipment and curricula, and individual satisfaction with training. A linear regression analysis was conducted to investigate factors influencing the surgeons’ satisfaction with the MIS training. - Results: A total of 1008 surgeons participated in the survey, including residents (26.1%), fellows (14.6%), attendings (43.8%), and heads of departments (15.2%). Of the respondents, 57.4% reported having access to MIS training equipment, 29.8% and 26% had a curriculum for skills lab MIS training and intraoperative MIS training, respectively. In multivariate linear regression analysis, strongest predictors for surgeons’ satisfaction with skills lab MIS training and intraoperative training were the availability of respective training curricula (skills lab: β 12.572; p < 0.001 & intraoperative: β 16.541; p < 0.001), and equipment (β 5.246; p = 0.012 & β 4.295; p = 0.037), and experience as a first surgeon in laparoscopy (β 12.572; p < 0.001 & β 3.748; p = 0.007). Additionally, trainees and teachers differed in their satisfaction factors. - Conclusion: Germany lacks standardized training curricula and sufficient access to MIS training equipment. Trainees and teachers have distinct factors influencing their satisfaction with MIS training. Standardized curricula, equipment accessibility, and surgical experience are crucial for improving surgeons’ satisfaction with training.

<p>Uvod: Akutni apendicitis predstavlja jedno od najče&scaron;ćih abdominalnih hirur&scaron;kih oboljenja u dečjem uzrastu. Lečenje je operativno, primenom otvorene hirurgije ili primenom minimalno invazivne hirurgije tj. laparoskopske apendektomije. Iako je laparoskopska apendektomija, zbog svojih prednosti, stekla popularnost kod mnogih hirurga, jo&scaron; uvek nije &scaron;iroko primenjena metoda na na&scaron;im prostorima. Prednost izvođenja laparoskopske apendektomije u odnosu na otvorenu metodu u dečjem uzrastu je i dalje nedovoljno definisana i predmet je mnogih istraživanja. Cilj istraživanja je da se utvrdi da li je dužina hospitalizacije kod dece operisane laparoskopski zbog akutnog apendicitisa kraća u odnosu na otvorenu metodu, kao i da se utvrdi da li postoji razlika u pojavi postoperativnih komplikacija između ove dve hirur&scaron;ke metode. Pored toga, cilj istraživanja je i da se utvrdi uticaj obe metode lečenja na kvalitet života i brzinu uspostavljanja svakodnevnih aktivnosti. Metodologija: Na Klinici za dečju hirurgiju, Instituta za zdravstvenu za&scaron;titu dece i omladine Vojvodine, sprovedena je prospektivna, kontrolisana randomizirana studija, u trajanju od deset meseci, u koju su bili uključeni svi pacijenti sa akutnim apendicitisom, kod kojih je planirana apendektomija, a čiji roditelji su dali pismeni pristanak za uče&scaron;će u istraživanju. Svi ispitanici su podeljeni u dve osnovne grupe u odnosu na operativnu tehniku: otvorena i laparoskopska apendektomija. Potom su svi ispitanici podeljeni u tri podgrupe, u zavisnosti od stepena upaljenosti crvuljka (negativni, nekomplikovani i komplikovani apendicitis). Svaki ispitanik je imao svoj individualni protokol istraživanja gde su preoperativno zabeleženi: uzrast, pol, simptomi (vrsta i dužina), fizikalni pregled, laboratorijske analize (broj leukocita, hematokrit), ultrazvučni nalaz, procena op&scaron;teg stanja, udružena oboljenja, vreme od prijema do operacije, preoperativna antibiotska terapija. Intraoperativno je analizirano: vrsta hirurgije, nalaz na apendiksu, prisustvo peritonitisa, udružena patologija, dužina operacije i trajanje pneumoperitoneuma (kod laparoskopske apendektomije), patohistolo&scaron;ki nalaz apendiksa, bakteriolo&scaron;ki bris abdomena. Postoperativno su analizirani: antibiotska terapija (vrsta i dužina), započinjanje peroralnog unosa, utvrđivanje postoperativnog bola, febrilnost, uspostavljanje peristaltike creva, izgled rane, postoperativne komplikacije (infekcija rane, intraabdominalni apscesi, ileus) i dužina hospitalizacije. Posebno su analizirani kvalitet života pacijenata nakon operacije pomoću modifikovanog upitnika SF 10 za dečji uzrast, kao i uspostavljanje svakodnevnih aktivnosti pomoću Activity Assessment Scale (AAS), modifikovane za dečji uzrast, nakon svakog postoperativnog dana, prvih sedam dana, nakon mesec dana, tri i &scaron;est meseci od operacije. Svi pacijenti su operisani u uslovima op&scaron;te anestezije. Klasična, otvorena apendektomija je vr&scaron;ena kroz naizmenični rez u desnoj ilijačnoj jami. Po otvaranju peritoneuma, cekum je izvučen i načinjena je klasična apendektomija. Laparoskopska apendektomija je vr&scaron;ena kroz tri 5 mm porta. Pneumoperitoneum je kreiran otvorenom metodom po Hasson-u, kroz infraumbilikalnu inciziju, a preostala dva porta su postavljena desno i levo ilijačno. Mezenteriolum je zbrinut pomoću ultrazvučnih makaza. Postavljene su intrakorporalne ligature i apendiks je odstranjen kroz desni port. Rezultati: Tokom perioda od deset meseci operisano je ukupno 125 pacijenata uzrasta od 2 do 18 godina, zbog akutnog apendicitisa. Laparoskopskom tehnikom je operisano 60 pacijenata (48%), a otvorenom metodom 61 (48,8%). Kod 4 pacijenta je načinjena konverzija, tj. promena operativne tehnike iz laparoskopske u otvorenu metodu. Nije bilo statistički značajne razlike između terapijskih grupa u odnosu na stepen upaljenosti apendiksa, vrstu i dužinu trajanja simptoma, u dijagnostičkim procedurama, kao ni u vremenu proteklom od prijema u bolnicu do operacije. Srednje operativno vreme je iznosilo 65 minuta (25-185 min) za laparoskopsku grupu i 45,49 minuta (25-90 min) za otvorene apendektomije (razlika je statistički značajna, p&lt;0,001). Crevna peristaltika, kao i započinjanje peroralnog unosa, se statistički značajno ranije uspostavljaju u grupi laparoskopsko operisanih. U grupi laparoskopskih apendektomija, postoperativne komplikacije (infekcija rana i formiranje intraabdominalnih apscesa) su se javile kod 8,33% ispitanika (5/60), a u otvorenoj grupi kod 4.91%, (3/61), &scaron;to nije bilo statistički značajno (c2 = 0,152; df = 1; p = 0,696). Dužina hospitalizacije kod dece operisane laparoskopski je iznosila 5,95 } 1,21 dana, a otvoreno 6,43 } 1,09 dana, &scaron;to je statistički značajna razlika (t = -2,206; p = 0,029). Rezultati Man-Vitnijevog U testa su pokazali statistički značajno bolji ukupni skor svakodnevnih aktivnosti za grupu laparoskopskih apendektomija (Z = -7,608; p = 0,000). U svim ispitivanim indikatorima kvaliteta života, deca laparoskopske grupe su imala veći skor. Deca sa akutnim apendicitisom operisana laparoskopski značajno ranije postižu visok stepen kvaliteta života (t = 2,407; p = 0,018). Zaključak: Prednost minimalno invazivne hirurgije u terapiji akutnog apendicitisa u dečjem uzrastu ogleda se u bržem uspostavljanju ponovnog funkcionisanja gastrointestinalnog trakta, kraćoj hospitalizaciji, a samim tim i bržem sveukupnom oporavku, vraćanju svakodnevnim aktivnostima i dobrom kvalitetu života. Postoperativne komplikacije se podjednako javljaju, kako kod otvorene, tako i kod laparoskopske operativne tehnike.</p> / <p>Introduction: Acute appendicitis is one of the most common abdominal surgical diseases in children. Operative treatment means open surgery or minimally invasive surgery (laparoscopic appendectomy). Although laparoscopic appendectomy, gained popularity among many surgeons, it is still not widely accepted in our region. The advantage of laparoscopic appendectomy compared to the open method in children is still not sufficiently defined and is the subject of further research. The aim of the research was to determine whether the length of hospital stay after laparoscopic surgery in children with acute appendicitis is shorter compared to the open method, as well as to determine whether there is a difference in the occurrence of postoperative complications after these two operative techniques. In addition, the aim of the research was to determine the effect of both methods of treatment on quality of life and everyday functioning. Methodology: This prospective, randomized controlled study was performed at the Clinic for Pediatric Surgery, Institute of Children and Youth Healthcare of Vojvodina, during a period of ten months. All patients with acute appendicitis, whose parents have given written consent, were included in research. All patients were divided into two basic groups, in relation to the surgical technique: open or laparoscopic appendectomy. Then, all of them were divided into three groups, depending on the degree of appendicitis (negative, uncomplicated and complicated appendicitis). Each participant had their own individual research protocol where we recorded preoperatively: age, sex, symptoms (type and length), physical examination, laboratory tests (white blood cell count, hematocrit), ultrasound finding, general state (ASA classification), associated diseases, time from admission to surgery, preoperative antibiotic therapy. During the operation we analyzed: type of surgery, degree of the appendicitis, the presence of peritonitis, associated pathology, length of surgery and duration of pneumoperitoneum (in laparoscopic appendectomy), hystopathologic findings of the appendix, a bacteriology. Postoperatively we analyzed: antibiotic therapy (type and length), oral intake, postoperative pain, fever, establishing peristalsis, the appearance of postoperative complications (wound infections, intra-abdominal abscesses, ileus) and length of hospitalization. Especially, we analyzed the quality of life of patients after surgery using the modified questionnaire SF 10 for children; and the establishment of daily activities using Activity Assessment Scale (AAS), modified for children; after each postoperative day, the first seven days, one month, three and six months after surgery. All patients were operated under general anesthesia. Open appendectomy was performed through incision in the right iliac fossa. Peritoneum was opened, the cecum was pulled out and classic appendectomy was made. Laparoscopic appendectomy is performed through three 5 mm ports. Pneumoperitoneum was created by the Hasson techique, through the infraumbilical incision, and the remaining two ports are set at right and left iliac region. Mezenteriolum was ligated by ultrasonic scissors. After putting intracorporal ligature, appendix was removed through the right port. Results: Over a period of ten months we operated 125 patients , aged 2 to 18 years, due to acute appendicitis. Laparoscopic technique was performed in 60 patients (48%), and the open method in 61 (48,8%). In 4 patients the conversion was made (operative technique changed from laparoscopic to open method). There were no statistically significant differences between the treatment groups with respect to the degree of appendix inflammation, the type and duration of symptoms, the diagnostic procedures, as well as the time from hospital admission to the surgery. Medium operative time was 65 minutes (25-185 min.) for laparoscopic group and 45,49 minutes (25-90 min.) for open appendectomy (the difference is statistically significant, p&lt;0,001). Intestinal peristalsis, as well as the initiation of oral intake was significantly sooner established in the laparoscopic group. Postoperative complications (wound infections and intra-abdominal abscess formation In laparoscopic appendectomy) occurred after laparoscopy in 8,33% of patients (5/60), and in the open group in 4,91% (3/61), which was not statistically significant (c2 = 0,152, df = 1; p = 0,696). Length of hospital stay in children operated by laparoscopy was 5,95 } 1,21 days and by open technique 6,43 } 1,09 days, which is significantly longer (t = -2,206; p = 0,029). Results of the Mann-Whitney U test showed significantly better overall record of daily activities for a group of laparoscopic appendectomy (Z = -7,608; p = 0,000). In all tested indicators of quality of life, children from laparoscopic group had a higher score. Children with acute appendicitis treated by laparoscopic surgery achieved a high level of quality of life, significantly earlier (t = 2,407; p = 0,018). Conclusion: The advantage of minimally invasive surgery in the treatment of acute appendicitis in children is reflected in the faster re-establishment of functioning of the gastrointestinal tract, shorter hospitalization and therefore, a faster overall recovery, resuming normal activities and a good quality of life. Postoperative complications occur equally in both, open as well as in laparoscopic operative techniques.</p>

Réalisé sous la co-direction des Drs Denis Bouchard et Michel Pellerin / La sternotomie médiane est l’approche classique pour la chirurgie de la valve mitrale. Elle permet une exposition optimale, mais est associée à un traumatisme chirurgical important, car elle requiert la séparation de l’os sternal. Le présent mémoire porte sur une solution alternative à la sternotomie dans le contexte de la chirurgie mitrale : la chirurgie minimalement invasive (CMI) par minithoracotomie antérolatérale. Trois études ont été réalisées dans le cadre de ce travail. Dans un premier temps, une étude de cohorte regroupant 200 patients consécutifs a permis d’évaluer le taux de succès des réparations mitrales réalisées par minithoracotomie et d’évaluer la durabilité de ces réparations à moyen terme. Par la suite, une étude comparative a été réalisée afin d’évaluer deux méthodes de clampage aortique pour la CMI, soit l’occlusion endovasculaire avec ballon et l’occlusion transthoracique. Enfin, une étude avec analyse par score de propension (propensity score) a permis de comparer la CMI à la sternotomie en ce qui a trait à une complication fréquente en chirurgie cardiaque, l’insuffisance rénale aiguë. La première étude a permis de conclure que la CMI peut être réalisée avec un taux de réparation quasi parfait, et ce malgré la courbe d’apprentissage associée à la technique minimalement invasive. Ces réparations semblent être durables, tel que démontré par une survie sans réopération de 98.3 ± 1.2% à 5 ans. La seconde étude a permis de démontrer que l’occlusion transthoracique est plus fiable que l’occlusion endoaortique et qu’elle est associée à des temps opératoires diminués et à une plus faible incidence de complications procédurales. Enfin, la troisième étude a démontré une association significative entre la CMI et une diminution du risque d’insuffisance rénale aiguë. En conclusion, la minithoracotomie antérolatérale est une excellente alternative à la sternotomie médiane. Tout en diminuant le traumatisme chirurgical, cette approche ne compromet pas la qualité de l’acte chirurgical et présente des bénéfices cliniques. / Median sternotomy is the classic approach for mitral valve surgery. This technique allows optimal exposure but is considered invasive as it requires section of the sternal bone. This thesis discusses an alternative sternotomy : minimally invasive mitral valve surgery (MIMVS) through a right anterolateral minithoracotomy. Three studies were conducted as part of this work. First, a cohort study involving 200 consecutive patients was used to evaluate the success rate of mitral valve repairs performed by minithoracotomy and assess the midterm durability of these repairs. Second, a comparative study was conducted to evaluate two methods of aortic clamping for MIMVS, namely the endovascular balloon occlusion technique and the transthoracic occlusion approach. Finally, a propensity score analysis study was performed to compare MIMVS and sternotomy with respect to a common complication following cardiac surgery : acute renal failure. The first study demonstrated that MIMVS can be performed with a near perfect repair rate, despite the learning curve associated with the minimally invasive technique. These repairs appear to be durable, as evidenced by a freedom from reoperation rate of 98.3 ± 1.2% at 5 years. The second study demonstrated that transthoracic clamping is more reliable than endoaortic occlusion and is associated with shorter operative times and a lower incidence of procedural complications. Finally, the third study found a significant association between MIMVS and a decreased risk of postoperative acute renal failure. In conclusion, the anterolateral minithoracotomy appraoch is an excellent alternative to median sternotomy. While decreasing surgical trauma, this approach does not compromise the quality of surgery and is associated with important clinical benefits.

近年来，血管类疾病已经成为人类健康的第一杀手。每年有成百上千万人死于血管疾病。血管介入术是一种非常有前景的血管类疾病的治疗手段。血管介入术是一种微创手术，它已经被广泛的用于治疗中风，血管狭窄，血管瘤等疾病。相对于传统的开放式手术，它具有风险低，恢复快，住院时间短等优点。该疗法通常在透视影像的引导下由导管和导线在血管内协同完成手术过程。因为介入术的复杂性和特殊性，作为介入手术医生的必要技能，掌握手术中手眼协同，各种手术器具的使用和复杂细致的手术流程无疑是一个巨大的挑战。因此，迫切地需要一种高效、安全的训练系统。相对于传统的训练方法，基于虚拟现实技术的训练系统是一种非常好的训练手段。 / 为了建立一套高仿真的介入手术训练模拟器，首先，我们要为病人的血管网重建三维模型。我们提出了一种自动的提取中心线的方法，用来从分割好的CTA/MRA体数据中获取病人血管网的中心线。基于改进的平行传递算法，沿着这些中心线，生成了一系列连续的标架。根据这些标架，我们构造了血管的横截面，并在此基础上生成了光滑连续的三维血管模型。 / 其次，作为血管介入术中最基础和最重要的手术器械，我们为导管和导线建立了物理模型。我们提出了一种基于最小势能原理的可变形的模型用于模拟导管和导线对于受力的反应。我们还提出了一个快速并且稳定的多网格算法来保证模拟的真实性和严格的实时交互要求。另外，我们做了几组实验。通过这些实验，验证了多网格算法在稳定性、实时性、模拟的真实性等方面满足了我们对于训练用模拟系统的要求。 / 再次，为了模拟血管栓塞术的手术过程，我们提出了一种模拟线圈填充血管瘤的过程的新方法。通过加总线圈弯曲变形的弹性势能、血管瘤变形的弹性势能以及外力做的功，我们建立了在血管栓塞术的环境下的总势能模型。为了求解这个模型，我们提出了一个基于有限元方法的求解器。从而模拟了线圈在介入医生的操作下慢慢的进入血管瘤，并缠绕起来的过程。 / 另外，我们提出了一个分层圆柱网格模型（LCGM）用于模拟在血管网中血流的运动。这一模型在几何上和拓扑结构上都非常适合我们的应用。我们将血液在血管中的流动近似为一维的层流，并用一组线性等式描述了血管网中流速与血压的关系。通过求解这一线性系统，得到了在分层圆柱网格模型下血流的速度场。依据这个血流的速度场，我们采用平流-扩散模型来模拟造影剂在血管中的传播的过程。 / Vascular diseases have been becoming the number one cause of death worldwide in recent years. Millions of people were killed by vascular diseases each year. An increasingly promising therapy for treating vascular diseases is Vascular Interventional Radiology (VIR). VIR is a minimally invasive surgery (MIS) procedure, which has been widely used to cure stroke, angiostenosis, aneurysm and etc. A low risk, an accelerated recovery and a shorter stay in hospital are important advantages over the traditional vascular surgery. This therapy is performed by a guidewire-catheter combination inside the blood vessels under the guidance of the fluoroscopic imaging. Because of the complexity and particularity of these procedures, it is a great challenge to master hand-eye coordination, instrument manipulation and procedure protocols for each radiologist mandatory. An efficient and safe training system is needed urgently. In contrast to these traditional training methods, virtual reality (VR) based simulation systems is a pretty good surrogate. / In order to build a high fidelity interventional simulator for physician training, firstly, we reconstructed the three dimensional (3D) model for the vascular network of the patients. An method of automatic skeleton extraction was proposed to acquire the centerline of the vascular network from the segmented volume data from CTA/MRA. A series of continuing frames were generated along with the centerline based on improved parallel transporting method. According to these frames we built the crossections of the vessels and further the 3D vascular model with the smooth meshes. / Secondly, as the most basic and important instruments in the VIR procedure, the catheter and guidewire were modeled and simulated physically. We developed a deformable model to simulate complicated behaviors of guidewires and catheters based on the principle of minimum total potential energy. A fast and stable multigrid solver was proposed to ensure both realistic simulation and real time interaction. A series of experiments were conducted to evaluate our multigrid solver in terms of stability, time performance, the capability of simulating catheter behaviors and the realism of catheter deformation. / Thirdly, to simulate the procedure of embolization, we proposed a novel method to simulate the motion of coil and their interactions with the aneurysm. We formulated the total potential energy in the embolization circumstance by summing up the elastic energy deriving from the bending of coils, the potential energy due to the deformation of the aneurysm and the work by the external forces. A novel FEM-based approach was proposed to simulate the deformation of coils. And the motion of coils and their responses to every input from the interventional radiologist can be calculated globally. / Fourthly, we proposed our Layered Cylindrical Gird Model (LCGM) for simulating blood flow in vascular network, which is pretty suitable for sampling the vascular network geometrically and topologically. The blood flow in vessels was regarded as 1D laminar flow and formulated into a set of linear equations based on the Poiseuille law to describe the relationship between the speed of flow and the pressure. Solving those equations, we got the velocity fields in the blood flow. In terms of the velocity fields, an advection-diffusion model was adopted to simulate the propagation of contrast agent with the blood flow. / Finally, all above techniques and procedures were implemented and integrated into a simulation system for training the medical students to acquire the endovascular skill, and an empirical study was also designed based on a typical selective catheteriza- tion procedure to assess the feasibility and effectiveness of the proposed system. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / 最后，我们将所有以上提到的技术和方法集成到模拟系统中用于训练医学院的学生，并使他们获得血管介入术的技能。并且，我们基于一个典型的导管插入术过程，使用经验分析的方法对模拟系统的可用性和效率进行了评估。 / Li, Shun. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 105-116). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in also Chinese. / Abstract --- p.i / Acknowledgement --- p.vi / Chapter 1 --- Introduction --- p.1 / Chapter 2 --- Vascular Modeling --- p.14 / Chapter 2.1 --- Introduction and Related Work --- p.14 / Chapter 2.2 --- Vascular Skeleton Graph Construction --- p.15 / Chapter 2.2.1 --- Chamfer distance transform and Dijkstra's shortest-path algorithm --- p.17 / Chapter 2.2.2 --- End vertices retrieval --- p.19 / Chapter 2.2.3 --- The algorithm of vascular skeleton extraction --- p.21 / Chapter 2.3 --- Vascular Modeling --- p.21 / Chapter 2.3.1 --- Tubular Model --- p.21 / Chapter 2.3.2 --- Bifurcation Model --- p.23 / Chapter 3 --- Catheter Simulation --- p.28 / Chapter 3.1 --- Introduction and Related Works --- p.28 / Chapter 3.2 --- Catheter Simulation --- p.31 / Chapter 3.2.1 --- Kirchhoff Theory of Elastic Rod --- p.32 / Chapter 3.2.2 --- Problem Formulation --- p.34 / Chapter 3.2.3 --- The Multigrid Iterative Solver --- p.38 / Chapter 3.3 --- Collision detection --- p.45 / Chapter 3.4 --- Validation of the Catheter Simulation Method --- p.47 / Chapter 3.4.1 --- Stability --- p.49 / Chapter 3.4.2 --- Time Performance --- p.50 / Chapter 3.4.3 --- Preservation of Curved Tip --- p.51 / Chapter 3.4.4 --- The realism of catheter deformation --- p.53 / Chapter 4 --- Coil Embolization Simulation --- p.59 / Chapter 4.1 --- Introduction and Related Work --- p.59 / Chapter 4.2 --- Methodology --- p.61 / Chapter 4.2.1 --- Total potential energy of a coil --- p.61 / Chapter 4.2.2 --- The FEM-based numeric solver for interactive coil simulation --- p.61 / Chapter 5 --- Angiography Simulation --- p.70 / Chapter 5.1 --- Introduction and related works --- p.70 / Chapter 5.2 --- The Equations of Fluid --- p.72 / Chapter 5.3 --- Layered Cylindrical Gird Model --- p.73 / Chapter 5.4 --- Numerical Method --- p.76 / Chapter 5.4.1 --- Evaluation of the velocity field of blood flow --- p.76 / Chapter 5.4.2 --- Evaluation of the density field --- p.78 / Chapter 5.5 --- Results --- p.81 / Chapter 6 --- System Implementation and Evaluation --- p.84 / Chapter 6.1 --- Introduction and Related Work --- p.84 / Chapter 6.2 --- System Construction --- p.85 / Chapter 6.3 --- Empirical Study of the Training System --- p.89 / Chapter 7 --- Conclusion and Discussion --- p.98 / Chapter 7.1 --- Geometric Modeling of Vasculature --- p.99 / Chapter 7.2 --- Catheterization Simulation --- p.99 / Chapter 7.3 --- Embolization Simulation --- p.100 / Chapter 7.4 --- Angiography Simulation --- p.101 / Chapter 7.5 --- System and Evaluation --- p.102 / Publication List --- p.103 / Bibliography --- p.105

A histerectomia é um dos procedimentos cirúrgicos mais frequentes em Ginecologia. As técnicas minimamente invasivas trazem benefícios às pacientes e possibilitam o retorno precoce às atividades diárias. O presente estudo envolveu 42 pacientes do Setor de Laparoscopia da Divisão de Clínica Ginecológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo com indicação de histerectomia. As pacientes foram randomizadas em dois grupos: HLM (21 pacientes submetidas à histerectomia total laparoscópica com 3 punções) e HLU (21 pacientes submetidas à histerectomia total laparoscópica com punção única umbilical). Foram analisados tempo cirúrgico, sangramento operatório (variação de hemoglobina pré e pós-operatória, e volume de sangue aspirado durante a cirurgia), resposta inflamatória aguda (dosagens seriadas de Proteína C Reativa, de citocinas: interleucina-6, interleucina-10, fator de necrose tumoral alfa, fator de crescimento endotelial vascular e de leucócitos), complicações operatórias imediatas e tardias, dor pós-operatória (escala visual analógica de dor) e grau de satisfação das pacientes (questionário validado de qualidade de vida SF36). O tempo cirúrgico foi significativamente maior no grupo das histerectomias por punção única umbilical comparado ao grupo de múltiplas punções (p= 0,001). O sangramento operatório foi semelhante entre os dois grupos. Não ocorreram complicações imediatas maiores, porém, em um caso de HLU, houve necessidade de realização de duas punções auxiliares para lise de extensas aderências pélvicas. Em relação à resposta inflamatória, os grupos se comportaram de forma semelhante nas dosagens de IL-6 (p = 0,833), IL-10 (p = 0,420), TNF alfa (p = 0,098), VEGF (p =0,092) e leucograma (p = 0,712). Embora o comportamento da proteína C-reativa tenha sido diferente entre os dois grupos, seus valores médios não apresentaram diferença estatisticamente significativa em nenhum momento avaliado (p = 0,666). A análise subjetiva da dor foi semelhante nos dois grupos estudados. Um ano após a cirurgia, verificamos a presença de hérnia umbilical em três pacientes submetidas à histerectomia por punção única umbilical, sem diferença significativa em relação à cirurgia com múltiplas punções (p = 0,09). Além disso, houve melhora da qualidade de vida em ambos os grupos, segundo avaliação feita antes e um ano após a cirurgia. Conclusões: A HLU apresentou tempo cirúrgico maior do que HLM; entretanto, não observamos diferença entre os grupos em relação ao sangramento operatório, à resposta inflamatória, à dor pós-operatória, às complicações e à qualidade de vida. As duas técnicas propostas para realização de histerectomia laparoscópica foram viáveis e seguras. Há limitações da técnica com punção umbilical única para pacientes com úteros volumosos ou com múltiplas aderências pélvicas / Hysterectomy is one of the most common surgical procedures in gynecology. Minimally invasive techniques bring benefits to patients and including early return to normal activities. This study included 42 women candidates to hysterectomy at the Gynecological Clinic Division of Clinics Hospital of São Paulo University Medical School. The patients were randomized in two groups: HLM (21 patients underwent to total laparoscopic hysterectomy with three abdominal incisions) and HLU (21 patients underwent to total laparoscopic hysterectomy with single umbilical incision). The surgical time, blood loss (pre and postoperative hemoglobin variation and total blood volume aspirated during the surgery), complications rate, acute inflammatory response (C-reactive protein, interleukin-6, interleukin-10, tumor necrosis factor alpha, vascular endothelium growth factor and leucogram), postoperative pain (Visual Analogical Pain Score) and patient satisfaction (Short Form 36 Health Survey) were analyzed. The operative time was significantly larger in the umbilical single incision hysterectomy group compared to the multiple incisions group (p = 0,001). Blood loss was similar in both groups. There were no major immediate complications; however, one hysterectomy started with single incision needed two additional trocars to remove extensive pelvic adhesions. In terms of inflammatory response, both groups were similar in terms of IL-6 (p = 0,833), IL- 10 (p = 0,420), TNF alfa (p = 0,098), VEGF (p =0,092) and leucogram (p = 0,712) measures. Although the C-reactive protein behavior was different between the groups, their average values showed no statistically significant difference in any evaluated moment (p = 0,666). Pain evaluation was similar in both groups. Twelve months after surgery we observed the presence of umbilical hernia in three patients submitted to single-port hysterectomy, with no significant difference compared to multiport hysterectomy (p = 0,098). There was improvement in quality of life, according assessment before and after surgery in both groups. Conclusions: Singleport laparoscopic hysterectomy did have significantly larger operative time than multiport laparoscopic hysterectomy; however, no difference was observed between the groups in terms of operative bleeding, inflammatory response, postoperative pain and quality of life. Both techniques for laparoscopic hysterectomy were feasible and safe. Single-port hysterectomy presented technical limitations in patients with large uterus or extensive pelvic adhesions

A artroscopia e a artrocentese são procedimentos considerados minimamente invasivos utilizados para o tratamento das disfunções temporomandibulares (DTM) e são métodos considerados intermediários entre a terapia conservadora e a cirurgia aberta da articulação temporomandibular (ATM). Apresentam como vantagem, em relação a cirurgia aberta, a pequena morbidade e o breve tempo de recuperação necessária aos pacientes. Desde o início do desenvolvimento da artroscopia esteve presente a preocupação com a possibilidade de danos a estruturas internas da ATM, com essa finalidade vários estudos em animais foram desenvolvidos evidenciando que realmente podem ocorrer lesões iatrogênicas as estruturas internas desencadeando processo degenerativo na articulação. A avaliação do mesmo potencial de lesão para artrocentese não existe, assim o objetivo deste trabalho foi avaliar o trauma operatório da artrocentese comparativamente a artroscopia aos tecidos da ATM em suínos. Realizou-se experimento em vinte ATM de dez cabeças de suínos sendo seis artroscopias; seis artrocenteses e oito ATM utilizadas como controle. Após a realização dos procedimentos as ATM foram cuidadosamente dissecadas, examinadas e fotografadas com registro de alterações traumáticas ao disco articular e as fibrocartilagens da fossa articular e da cabeça da mandíbula. As imagens das estruturas foram analisadas por outro examinador que não tinha conhecimento prévio de qual procedimento havia sido realizado em cada ATM classificando as lesões de acordo com o número e localidade em: ausente (sem alteração visível); leve (descolamento de fibrocartilagem da fossa ou cabeça da mandíbula isoladas e únicas), moderado (perfurações do disco e mais de um descolamento de fibrocartilagem da fossa ou cabeça da mandíbula) e severo (lacerações do disco e lesões múltiplas em mais de uma estrutura). Os dados também foram classificados em ausente e presente para uma comparação direta. Foi realizada análise estatística dos dados. No grupo controle ocorreram danos em duas das oito ATM durante a dissecção, que apresentaram características distintas das lesões constatadas após os procedimentos, nas outras seis nenhuma alteração traumática pode ser evidenciada. No grupo submetido a artrocentese os danos foram ausentes, leves e moderados em 16.7% respectivamente e severos em 50% da amostra. No grupo submetido a artroscopia ocorreram danos moderados em 66.7%, severos em 16.7%, ausentes em 16.7% e não ocorreram danos leves. Em ambos os grupos foram evidenciadas a presença de lesões em 83.3% das amostras. Apesar de não haver diferença estatisticamente significativa entre os danos verificados, em uma análise direta, a severidade das lesões constatadas após artrocentese foi maior. Conclui-se que a artrocentese e a artroscopia não são isentas de morbidade aos tecidos articulares e independentemente de serem procedimentos considerados minimamente invasivos não se pode desprezar o potencial de danos as superfícies articulares. / Arthroscopy and arthrocentesis are considered minimally invasive procedures for the treatment of temporomandibular disorders (TMD) and are situated between conservative therapies and open surgery of the temporomandibular joint (TMJ). When compared to open surgery they present the advantages of having a brief post operatory recovery time for the patient and little morbidity. Since the beginning of the development of arthroscopy the possibility of damage to the inner structures of the TMJ was a concern, as a result a series of studies in animals were made and it became clear that iatrogenic damage can really happen and trigger degenerative alterations in the joint. Considering that there are no studies that investigate the potential of causing structural damage to the TMJ during arthrocentesis the objective of this study was to evaluate the operative trauma of arthroscopy and arthrocentesis to the tissues of the TMJ using swine heads. Twenty TMJ of ten swine heads were used for six arthroscopies; six arthrocentesis and eight that were used as a control group. After the procedures the TMJ were carefully dissected, examined and photographed. Traumatic alterations to the articular disk and to the fossa and head of the mandible fibrocartilage were recorded. The images of the structures were analyzed by other examiner that did not had previous knowledge of witch procedure each TMJ was subjected to. The lesions that were identified were classified according to the location and number as: absent (no visible alteration); light (one isolated scuffing of the fibrocartilage of the fossa or the head of the mandible); moderate (disk perforation or multiple scuffing of the fibrocartilage of the fossa or head of the mandible) and severe (disk laceration or multiple lesions in more than one structure). The obtained data was also classified as absent or present for a direct comparison. Statistical analyses of the obtained data were made. In the control group damage to two of the eight TMJ was perceived during dissection, the characteristics of those lesions were clearly different from those observed after the procedures, in the other six none traumatic damage could be noticed. In the arthrocentesis group the damages were absent, light and moderate in 16.7% respectively and were severe in 50% of the sample. In the arthroscopy group damage was moderate in 66.7%, severe in 16.7%, absent in 16.7 and no light damage occurred. In both groups damage was present in 83.3% of the sample. Even though the difference between the groups was not statistically significant, making a direct analysis of the data, the severity of the lesions found in the arthrocentesis group was higher. It was concluded that arthrocentesis and arthroscopy are not absent of morbidity to the TMJ tissues and regarded of being minimally invasive procedures the potential of damage to the structures of the TMJ should not be minimized.

A histerectomia é um dos procedimentos cirúrgicos mais frequentes em Ginecologia. As técnicas minimamente invasivas trazem benefícios às pacientes e possibilitam o retorno precoce às atividades diárias. O presente estudo envolveu 42 pacientes do Setor de Laparoscopia da Divisão de Clínica Ginecológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo com indicação de histerectomia. As pacientes foram randomizadas em dois grupos: HLM (21 pacientes submetidas à histerectomia total laparoscópica com 3 punções) e HLU (21 pacientes submetidas à histerectomia total laparoscópica com punção única umbilical). Foram analisados tempo cirúrgico, sangramento operatório (variação de hemoglobina pré e pós-operatória, e volume de sangue aspirado durante a cirurgia), resposta inflamatória aguda (dosagens seriadas de Proteína C Reativa, de citocinas: interleucina-6, interleucina-10, fator de necrose tumoral alfa, fator de crescimento endotelial vascular e de leucócitos), complicações operatórias imediatas e tardias, dor pós-operatória (escala visual analógica de dor) e grau de satisfação das pacientes (questionário validado de qualidade de vida SF36). O tempo cirúrgico foi significativamente maior no grupo das histerectomias por punção única umbilical comparado ao grupo de múltiplas punções (p= 0,001). O sangramento operatório foi semelhante entre os dois grupos. Não ocorreram complicações imediatas maiores, porém, em um caso de HLU, houve necessidade de realização de duas punções auxiliares para lise de extensas aderências pélvicas. Em relação à resposta inflamatória, os grupos se comportaram de forma semelhante nas dosagens de IL-6 (p = 0,833), IL-10 (p = 0,420), TNF alfa (p = 0,098), VEGF (p =0,092) e leucograma (p = 0,712). Embora o comportamento da proteína C-reativa tenha sido diferente entre os dois grupos, seus valores médios não apresentaram diferença estatisticamente significativa em nenhum momento avaliado (p = 0,666). A análise subjetiva da dor foi semelhante nos dois grupos estudados. Um ano após a cirurgia, verificamos a presença de hérnia umbilical em três pacientes submetidas à histerectomia por punção única umbilical, sem diferença significativa em relação à cirurgia com múltiplas punções (p = 0,09). Além disso, houve melhora da qualidade de vida em ambos os grupos, segundo avaliação feita antes e um ano após a cirurgia. Conclusões: A HLU apresentou tempo cirúrgico maior do que HLM; entretanto, não observamos diferença entre os grupos em relação ao sangramento operatório, à resposta inflamatória, à dor pós-operatória, às complicações e à qualidade de vida. As duas técnicas propostas para realização de histerectomia laparoscópica foram viáveis e seguras. Há limitações da técnica com punção umbilical única para pacientes com úteros volumosos ou com múltiplas aderências pélvicas / Hysterectomy is one of the most common surgical procedures in gynecology. Minimally invasive techniques bring benefits to patients and including early return to normal activities. This study included 42 women candidates to hysterectomy at the Gynecological Clinic Division of Clinics Hospital of São Paulo University Medical School. The patients were randomized in two groups: HLM (21 patients underwent to total laparoscopic hysterectomy with three abdominal incisions) and HLU (21 patients underwent to total laparoscopic hysterectomy with single umbilical incision). The surgical time, blood loss (pre and postoperative hemoglobin variation and total blood volume aspirated during the surgery), complications rate, acute inflammatory response (C-reactive protein, interleukin-6, interleukin-10, tumor necrosis factor alpha, vascular endothelium growth factor and leucogram), postoperative pain (Visual Analogical Pain Score) and patient satisfaction (Short Form 36 Health Survey) were analyzed. The operative time was significantly larger in the umbilical single incision hysterectomy group compared to the multiple incisions group (p = 0,001). Blood loss was similar in both groups. There were no major immediate complications; however, one hysterectomy started with single incision needed two additional trocars to remove extensive pelvic adhesions. In terms of inflammatory response, both groups were similar in terms of IL-6 (p = 0,833), IL- 10 (p = 0,420), TNF alfa (p = 0,098), VEGF (p =0,092) and leucogram (p = 0,712) measures. Although the C-reactive protein behavior was different between the groups, their average values showed no statistically significant difference in any evaluated moment (p = 0,666). Pain evaluation was similar in both groups. Twelve months after surgery we observed the presence of umbilical hernia in three patients submitted to single-port hysterectomy, with no significant difference compared to multiport hysterectomy (p = 0,098). There was improvement in quality of life, according assessment before and after surgery in both groups. Conclusions: Singleport laparoscopic hysterectomy did have significantly larger operative time than multiport laparoscopic hysterectomy; however, no difference was observed between the groups in terms of operative bleeding, inflammatory response, postoperative pain and quality of life. Both techniques for laparoscopic hysterectomy were feasible and safe. Single-port hysterectomy presented technical limitations in patients with large uterus or extensive pelvic adhesions

Introdução: Descrita em 1983 e de sólida aplicação clínica, o impacto da microcirurgia endoscópica transanal (TEM) sobre a função anorretal permanece pouco conhecido. Os objetivos do presente estudo foram avaliar o impacto da TEM na função anorretal conforme avaliações clínicas (Wexner score) e funcional (manometria anorretal) antes e após a cirurgia. Método: Prospectivamente, 23 pacientes consecutivos com lesões retais foram operados com o uso do equipamento TEO® (Karl Storz, Tuttlingen, Alemanha). Para todos os pacientes, o valor do escore de Wexner foi obtido antes e após a cirurgia (7, 30 e 90 dias), e a eletromanometria anorretal foi realizada antes da cirurgia e também no pós-operatório (30 e 90 dias). Resultados: Quatorze pacientes eram homens. A idade média foi 53,7 (24-81) anos. A distância média da lesão à linha pectínea foi de 7 (2-15) cm. A histopatologia revelou adenoma em 14 (61%), tumor neuroendócrino em 5 (21,7%), carcinoma invasivo em 3 (13%) e pólipo hiperplásico em 1 (4,3%) caso. A duração média do seguimento pós-operatório foi de 5 (3-7) meses. O escore de Wexner foi significativamente menor aos 30 dias em comparação com 7 dias (Wilcoxon, p = 0,03). A capacidade retal foi significativamente menor aos 30 dias após a cirurgia e recuperada aos 90 dias após a cirurgia (ANOVA, p = 0,04). Conclusões: Após TEM, um impacto modesto na função anorretal pode ser observado. O comprometimento transitório resulta de perda de capacidade retal e não por comprometimento dos esfíncteres anais cessando completamente 90 dias após a cirurgia. Em última análise, não conseguimos detectar um impacto na qualidade de vida após TEM / Background: The impact of transanal endoscopic microsurgery (TEM) on anorectal function remains poorly available, particularly when considering that the technique involves undertaking full- or partial-thickness excision of the rectal wall. Moreover, in spite of wide adoption of TEM, its impact on quality of life remains unknown since most evidence derives from retrospective studies. Objective: The objectives of the present study were to evaluate the impact of TEM on sphincter function determined by clinical (Wexner score), functional (anorectal manometry), and quality of life (FIQL) evaluations conducted before and after surgery. Design: prospective, observational, single-center, 23 consecutive patients with rectal lesions underwent were operated on using the TEO® equipment (Karl Storz, Tuttlingen, Germany). Wexner and FIQL scores were obtained before and after surgery (7 days, 30 days and 90 days postoperatively). Anorectal manometry was obtained before surgery, and postoperatively after 30 and 90 days. Main Outcome Measures: Wexner and FIQL scores; anorectal manometry results. Results: Fourteen patients were men. Mean age was 53.7 (24-81) yrs. Mean distance from the lesion to the dentate line was 7 (2-15) cm. A full- thickness resection was undertaken in 18 (78.3%) cases. Histopathology revealed adenoma in 14 (61%), neuroendocrine tumor in 5 (21.7%), invasive carcinoma in 3 (13%), and hyperplastic polyp in 1 (4.3%) case. Postoperative rectal wound separation occurred in 2 patients and 1 patient developed atrial fibrillation. The mean duration of postoperative follow-up was 5 (3-7) months. Overall, Wexner score significantly declined between postoperative days 7 and 30 (Wilcoxon, p = 0.03). Rectal compliance exhibited significant decline 30 days after surgery and recovery at 90 days after surgery (ANOVA, p = 0.04). It was not possible to measure any difference in the FIQL results before and after surgery. Limitations: small sample size; limited follow-up. Conclusions: Following TEM, a modest impact on anorectal function could be confirmed. Interestingly, anorectal function impairment after surgery was not due to sphincter dysfunction, but resulted from loss of rectal compliance. Ultimately, we could not detect a significant impact on quality of life after TEM