Infra-inguinal arterial bypass is becoming increasingly popular as a means of alleviating incapacitating symptoms of atherosclerosis and other progressive diseases affecting the arteries of the lower limb. The role of this procedure in limb salvage is controversial but an aggressive attitude is emerging from many centres. It is accepted that the majority of atherosclerotic patients have a short life expectancy but reconstructive vascular surgery has an important role to play in improving their quality of life. Progress in infra-inguinal bypass surgery has centred mainly on the development of synthetic grafts but the perfonnance of autologous saphenous vein has not been bettered in terms of longterm results and cost-effectivity. The initial experience of infra-inguinal bypass at Groote Schuur Hospital, Cape Town, is examined retrospectively with the objective of demonstrating the possible influence of patient factors and specific surgical practices on the outcome of results.

The work presented includes over thirty peer reviewed published manuscripts based on studies undertaken during my surgical career. As Principal Investigator, I led the study conception/design/data acquisition/analysis/interpretation and was involved with writing the final drafts of all manuscripts prior to their formal submission to high impact factor peer-reviewed specialist journals. The thesis is divided into subsections reflecting my development and different interests within surgery. The subsections start with my learning basic research principles, moving onto clinical problem solving in general surgical dilemmas, followed by a collection of papers in my subspecialty of vascular surgery. The work culminates with a group of papers focused on aneurysmal disease, specifically, abdominal aortic aneurysms (AAA), the clinical impact of which has had a bearing on the introduction of a National AAA Screening Program in Wales in 2013. I conclude these sections with a collection of papers that reflect my long term commitment to surgical training both at regional level (as Secretary and Deputy Chairman to the Higher Surgical Training Committee and Chairman of the Basic Surgical Training Committee) and national level including my involvement with the Four Royal Colleges of Surgeons for the Intercollegiate Examinations in General Surgery. This examination is undertaken at completion of junior surgical training and used to confirm a doctor's competence for safe independent practice as a consultant. In conclusion, over forty years of academic research during my career as a vascular surgeon has provided unique insight into the pathophysiology, treatment and ultimately prevention of artherosclerotic disease. These findings have improved health policies in Wales and significantly reduced patient morbidity and mortality.

published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Medical Sciences

Penetrating injuries of the intrathoracic great vessels are well recognized although uncommon. In the First World War no survivors with thoracic vascular injury were recorded among soldiers treated with penetrating injuries to the chest as recorded by Makins. The first record of successful repair of a penetrating thoracic aortic injury was in 1922 by Dshanelidze in Russia. Similar to Makins' experience, De Bakey and Simeone in the Second World War recorded no surviving patients with involvem_ent of the thoracic aorta and its branches among American soldiers. Furthermore, no injuries to the thoracic aorta and its branches were recorded in Korean war soldiers undergoing vascular surgery by both Jahnke and Hughes. Rich reported 3 survivors of aortic injuries in the Vietnam war among 1000 patients with vascular injuries. By 1969 only 43 successfully treated cases had been reported but increasing numbers of patients sustaining injuries to the great arteries at the level of the thoracic inlet have been reported subsequently in civilian practice. Experience has grown over the years but patient numbers remain small and individual surgeons may only manage 2 or 3 of these patients in his life time. The largest single reported series consists of 93 patients in Memphis over a 13 year period. All victims were rapidly transported to hospital and were resuscitated en route. As a consequence, a large number critically ill patients reached hospital who may have died in earlier years. However some of these patients inevitably died in hospital contributing to the high mortality of 16, 7% reported. Our experience is different in that most of our victims who reach hospital will survive as poor community triage facilities prevent more than 95% of penetrating thoracic vascular trauma victims reaching hospital alive, hence we have a selection of less severely injured patients who eventually reach our hospital alive producing our mortality rate of 5%. Another important difference is that most of our patients suffered stab wounds as compared to gunshot wounds noted in the Memphis. Buchan and Robbs in Durban reported on 52 patients who had penetrating cervicomediastinal vascular injury with a remarkably similar experience to our own in Cape Town with the exception of a larger number of aortic injuries (21 out of 52 patients) recorded and a higher mortality rate of 17% as a result of these aortic injuries.

Object Rupture of intracranial arteriovenous malformations is a leading cause of stroke in children and young adults. Treatment options include surgery and highly focused radiation (stereotactic radiosurgery). For large and deep seated lesions, the risks of surgery may be prohibitively high, while radiosurgery has a disappointingly low efficacy and long latency. Radiosurgery carries the most promise for significant advances, however the process by which radiosurgery achieves obliteration is incompletely understood. Inflammation and thrombosis are likely to be important in the radiation response and may be amenable to pharmacological manipulation to improve radiosurgical efficacy. Materials and methods Immunohistochemistry and electron microscopy were used to study normal cerebral vessels, cavernous malformations and AVMs, some of which had previously been irradiated. An attempt was made to culture AVM endothelial cells to study the immediate response of AVM endothelium to radiosurgery. The effects of radiosurgery in a rat model of AVM were studied using immunohistochemistry and the results used to determine the choice of a pharmacological strategy to enhance the thrombotic effects of radiosurgery. Results Vascular malformations have a different endothelial inflammatory phenotype than normal cerebral vessels. Radiosurgery may cause long term changes in inflammatory molecule expression and leads to endothelial loss with exposure of pro-thrombotic molecules. Ultrastructural effects of irradiation include widespread cell loss, smooth muscle cell (SMC) proliferation and thrombosis. Endothelial culture from AVMs proved difficult due to SMC predominance in initial cultures. Radiosurgery upregulated several endothelial inflammatory molecules in the animal model and may induce pro-thrombotic cell membrane alterations. The administration of lipopolysaccharide and soluble tissue factor to rats following radiosurgery led to selective thrombosis of irradiated vessels. Conclusions Inflammation and thrombosis are important in the radiosurgical response of AVMs. Lumen obliteration appears to be mediated by proliferation of cells within the vessel wall and thrombosis. Upregulation of inflammatory molecules and perhaps disruption of the normal phospholipid asymmetry of the endothelial and SMC membranes are some of the earliest responses to radiosurgery. The alterations induced by radiation may be harnessed to selectively initiate thrombus formation. Stimulation of thrombosis may improve the efficacy of radiosurgery, increasing treatable lesion size and reducing latency.

O domínio da técnica de microanastomose vascular é um pré-requisito essencial para a realização de procedimentos microcirúrgicos reconstrutivos, como reimplantes e transferência livre de tecidos. Até hoje, a técnica de sutura convencional é a mais aceita na prática clínica, por sua segurança e versatilidade. Apesar disso, ela apresenta alguns problemas por ser tecnicamente difícil, consumir tempo considerável e causar traumatismo adicional à parede do vaso. O objetivo deste estudo, foi testar um método alternativo de microanastomose arterial, reduzindo o número de pontos de sutura com aplicação do adesivo de fibrina. Sessenta ratos da raça Wistar foram submetidos a microanastomose vascular nas artérias femorais ou carótidas. Os animais foram divididos em quatro subgrupos de acordo com a artéria operada e a técnica de sutura empregada: FSC (femoral - sutura convencional), FAF (femoral - sutura mínima com adesivo de fibrina), CSC (carótida - sutura convencional) e CAF (carótida - sutura mínima com adesivo de fibrina). As duas técnicas de anastomose foram comparadas através de análise estatística dos parâmetros clínicos e histopatológicos. A média de pontos de sutura por anastomose nos subgrupos FSC e CSC foi de 7,7 e 9,5, respectivamente. No subgrupo FAF, as anastomoses foram realizadas com apenas quatro pontos de sutura e no subgrupo CAF, com apenas seis. O tempo de anastomose foi, em média: 15,81 minutos no subgrupo FSC, 13,62 minutos no subgrupo FAF, 18,87 minutos no subgrupo CSC e 17,33 minutos no subgrupo CAF. A aplicação do adesivo de fibrina reduziu, significativamente, o número de pontos e o tempo necessário para realização das anastomoses, nos subgrupos FAF e CAF. A intensidade do sangramento anastomótico também foi reduzida de maneira significativa nestes subgrupos. A freqüência da permeabilidade imediata e tardia foi de 100% em todos os subgrupos, exceto no subgrupo FAF, onde a permeabilidade tardia foi de 93,33%. Não foram observadas diferenças significativas entre as duas técnicas, em relação aos parâmetros histopatológicos avaliados (processo inflamatório, fibrose da camada média e hiperplasia subintimal). O autor concluiu que a técnica de sutura mínima com aplicação do adesivo de fibrina foi mais fácil e rápida que a técnica de sutura convencional, sem aumento da trombogenicidade das anastomoses, no modelo experimental utilizado. / Mastering of the microvascular anastomosis technique is an essencial requirement to perform reconstructive microsurgical procedures, such as replantation surgery and free tissue transfers. Until now, the conventional suture technique is the most widely accepted in the clinical setting, for its safety and versatility. However, this technique presents some problems for being technically difficult, time consuming and causes additional trauma to the vessel wall. The aim of this study was to test an alternative method of microvascular arterial anastomosis, by reducing the number of sutures with application of fibrin adhesive. Sixty Wistar rats underwent to microvascular anastomosis at the femoral or carotid arteries. The animals were divided into four subgroups, according to the operated artery and the employed suture technique: FCS (femoral - conventional suture), FFA (femoral - minimal suture with fibrin adhesive), CCS (carotid - conventional suture) and CFA (carotid - minimal suture with fibrin adhesive). Both anastomosis techniques were compared by means of statistical analisys of the clinical and histopathological parameters. The mean number of sutures required to complete the anastomosis was 7,7 in subgroup FCS and 9,5 in subgroup CCS. In subgroup FFA, the anastomosis was performed with only four sutures and in subgroup CFA, with only six. The mean anastomotic time was 15,81 minutes in subgroup FCS, 13,62 minutes in subgroup FFA, 18,87 minutes in subgroup CCS and 17,33 minutes in subgroup CCS. The application of fibrin adhesive, significantly reduced the number of sutures and the time taken to perform the anastomosis, in subgroups FFA and CFA. The amount of anastomotic bleeding was also significantly reduced in these subgroups. The immediate and late patency rates were 100% in all subgroups, except in subgroup FFA where it was 93,33%. No significant differences were observed among the two techniques, concerning the evaluated histopathological parameters (inflammatory process, medial fibrosis and subintimal hyperplasia). The author concluded that, the fibrin adhesive application with minimal suture technique was faster and easier than the conventional suture technique, without increasing the trombogenicity of the anastomosis, in this experimental model.

O domínio da técnica de microanastomose vascular é um pré-requisito essencial para a realização de procedimentos microcirúrgicos reconstrutivos, como reimplantes e transferência livre de tecidos. Até hoje, a técnica de sutura convencional é a mais aceita na prática clínica, por sua segurança e versatilidade. Apesar disso, ela apresenta alguns problemas por ser tecnicamente difícil, consumir tempo considerável e causar traumatismo adicional à parede do vaso. O objetivo deste estudo, foi testar um método alternativo de microanastomose arterial, reduzindo o número de pontos de sutura com aplicação do adesivo de fibrina. Sessenta ratos da raça Wistar foram submetidos a microanastomose vascular nas artérias femorais ou carótidas. Os animais foram divididos em quatro subgrupos de acordo com a artéria operada e a técnica de sutura empregada: FSC (femoral - sutura convencional), FAF (femoral - sutura mínima com adesivo de fibrina), CSC (carótida - sutura convencional) e CAF (carótida - sutura mínima com adesivo de fibrina). As duas técnicas de anastomose foram comparadas através de análise estatística dos parâmetros clínicos e histopatológicos. A média de pontos de sutura por anastomose nos subgrupos FSC e CSC foi de 7,7 e 9,5, respectivamente. No subgrupo FAF, as anastomoses foram realizadas com apenas quatro pontos de sutura e no subgrupo CAF, com apenas seis. O tempo de anastomose foi, em média: 15,81 minutos no subgrupo FSC, 13,62 minutos no subgrupo FAF, 18,87 minutos no subgrupo CSC e 17,33 minutos no subgrupo CAF. A aplicação do adesivo de fibrina reduziu, significativamente, o número de pontos e o tempo necessário para realização das anastomoses, nos subgrupos FAF e CAF. A intensidade do sangramento anastomótico também foi reduzida de maneira significativa nestes subgrupos. A freqüência da permeabilidade imediata e tardia foi de 100% em todos os subgrupos, exceto no subgrupo FAF, onde a permeabilidade tardia foi de 93,33%. Não foram observadas diferenças significativas entre as duas técnicas, em relação aos parâmetros histopatológicos avaliados (processo inflamatório, fibrose da camada média e hiperplasia subintimal). O autor concluiu que a técnica de sutura mínima com aplicação do adesivo de fibrina foi mais fácil e rápida que a técnica de sutura convencional, sem aumento da trombogenicidade das anastomoses, no modelo experimental utilizado. / Mastering of the microvascular anastomosis technique is an essencial requirement to perform reconstructive microsurgical procedures, such as replantation surgery and free tissue transfers. Until now, the conventional suture technique is the most widely accepted in the clinical setting, for its safety and versatility. However, this technique presents some problems for being technically difficult, time consuming and causes additional trauma to the vessel wall. The aim of this study was to test an alternative method of microvascular arterial anastomosis, by reducing the number of sutures with application of fibrin adhesive. Sixty Wistar rats underwent to microvascular anastomosis at the femoral or carotid arteries. The animals were divided into four subgroups, according to the operated artery and the employed suture technique: FCS (femoral - conventional suture), FFA (femoral - minimal suture with fibrin adhesive), CCS (carotid - conventional suture) and CFA (carotid - minimal suture with fibrin adhesive). Both anastomosis techniques were compared by means of statistical analisys of the clinical and histopathological parameters. The mean number of sutures required to complete the anastomosis was 7,7 in subgroup FCS and 9,5 in subgroup CCS. In subgroup FFA, the anastomosis was performed with only four sutures and in subgroup CFA, with only six. The mean anastomotic time was 15,81 minutes in subgroup FCS, 13,62 minutes in subgroup FFA, 18,87 minutes in subgroup CCS and 17,33 minutes in subgroup CCS. The application of fibrin adhesive, significantly reduced the number of sutures and the time taken to perform the anastomosis, in subgroups FFA and CFA. The amount of anastomotic bleeding was also significantly reduced in these subgroups. The immediate and late patency rates were 100% in all subgroups, except in subgroup FFA where it was 93,33%. No significant differences were observed among the two techniques, concerning the evaluated histopathological parameters (inflammatory process, medial fibrosis and subintimal hyperplasia). The author concluded that, the fibrin adhesive application with minimal suture technique was faster and easier than the conventional suture technique, without increasing the trombogenicity of the anastomosis, in this experimental model.

A utilização dos retalhos músculo-cutâneos na cirurgia plástica possibilitou grande avanço nas técnicas de reconstrução. Apesar de atualmente se apresentarem como técnica conhecida e reprodutível, existem ainda limitações quanto à morbidade na área doadora advinda da ressecção muscular. O desenvolvimento dos retalhos perfurantes e a aplicação clínica do retalho vascularizado na artéria perfurante muscular da artéria epigástrica inferior (DIEP) possibilitaram nova opção terapêutica em decorrência da completa preservação músculo-aponeurótica. Apesar dos benefícios funcionais em relação aos tradicionais retalhos músculo-cutâneos, o retalho DIEP exibe limitações como o tempo cirúrgico prolongado, a dificuldade técnica e o risco de lesão da artéria perfurante no trajeto intramuscular, todos decorrentes do calibre reduzido das artérias e da variabilidade anatômica. Embora a anatomia do músculo reto do abdome tenha sido exaustivamente estudada, escassas e imprecisas são as informações sobre a distribuição das artérias perfurantes, o trajeto intramuscular e as características do pedículo arterial. No presente estudo, a distribuição, o trajeto intramuscular e as dimensões do pedículo do retalho DIEP foram estudados em 15 cadáveres frescos não formolizados (30 retalhos) por técnica de coloração com tinta azul látex e posterior dissecção. Constatou-se 6,3 artérias perfurantes por retalho, sendo que a maior parte das artérias de médio e grande calibre localizavam-se na região lateral do músculo reto do abdome. Na análise do trajeto intramuscular foram classificadas de artérias com trajeto retilíneo, aquelas localizadas exclusivamente no septo muscular e sua dissecção foi realizada sem secção das fibras musculares. No trajeto oblíquo, se evidenciou mais de um septo muscular e houve a necessidade de se realizar a secção muscular. As artérias perfurantes da região lateral apresentaram trajeto retilíneo em maior número quando comparadas às artérias da região medial do músculo reto do abdome. Na maioria das dissecções, a artéria epigástrica inferior mostrou dois ramos principais sendo o calibre do ramo lateral maior ao do ramo medial. A maioria das artérias perfurantes de médio e grande calibres apresentaram origem no ramo lateral dominante da artéria epigástrica inferior. As artérias perfurantes e o pedículo arterial do retalho revelaram comprimento médio de 5,3 e 15,7 cm respectivamente. O pedículo arterial com a artéria perfurante proveniente da região medial apresentou comprimento maior do que o pedículo que continha a artéria proveniente da região lateral. O presente estudo permitiu-nos concluir que a maior concentração de artérias perfurantes de maior calibre e a presença do trajeto retilíneo na região lateral do músculo reto do abdome, constituíram parâmetros anatômicos importantes no planejamento da técnica. As conclusões obtidas reforçam a relevância dos estudos anatômicos na programação da reconstrução com retalhos vascularizados por artérias perfurantes. / The introduction of musculocutaneous flaps in plastic surgery has resulted in a great step forward in reconstructive procedures. In spite of their well-known and reproducible technique, their use is limited by morbidity in the donor area resulting from muscle resection. The development of perforator flap and the clinical application of the deep inferior epigastric flap (DIEP) has provided a new therapeutic option resulting from complete muscle-aponeurotic preservation. Despite the functional benefits achieved in comparison to traditional musculocutaneous flaps, the DIEP flap has limitations. The latter include prolonged operative time, technical difficulty and the risk of injury to the perforating artery in the intramuscular pathway. These factors result from reduced diameter of the arteries and to anatomic variation. Although anatomy of the rectus abdominus muscle has already been studied, information regarding distribution of the perforator arteries, intramuscular pathway, and characteristics of the arterial pedicle is lacking and inaccurate. In this thesis, the distribution, intramuscular pathway and pedicle size of the DIEP flap were studied in 15 fresh cadavers. Thirty flaps were analyzed by staining with blue latex dye and subsequent dissection. An average of 6.3 perforator arteries per flap were observed, and the major concentration of medium and large diameter arteries in the lateral region of the rectus muscle. The intramuscular pathway analysis classified the arteries as rectilinear, those located solely in the muscle septum and their dissection was performed without muscle fibers section. In the oblique pathway, not a single septum was observed and muscle section was necessary. A larger number of the perforator arteries of the lateral region presented a rectilinear path compared to the arteries of the medial region. In the majority of dissections, the inferior epigastric artery exhibited two main branches with the lateral branch diameter greater than that of the medial branch. The majority of the perforator arteries of medium and large diameter originated in the dominant lateral branch of the IEA. The perforator arteries and the arterial pedicle of the flap displayed a mean length of 5.3 and 15.7cm respectively. The arterial pedicle presenting the perforator artery originating from the medial region was longer than the pedicle containing the artery originating from the lateral region. The major concentration of perforator arteries of larger diameter besides being rectilinear in the lateral region of the rectus muscle establishes important parameters for technical planning. The results obtained in this study emphasize the importance of the anatomic studies in planning reconstructions with perforator flaps.

A utilização dos retalhos músculo-cutâneos na cirurgia plástica possibilitou grande avanço nas técnicas de reconstrução. Apesar de atualmente se apresentarem como técnica conhecida e reprodutível, existem ainda limitações quanto à morbidade na área doadora advinda da ressecção muscular. O desenvolvimento dos retalhos perfurantes e a aplicação clínica do retalho vascularizado na artéria perfurante muscular da artéria epigástrica inferior (DIEP) possibilitaram nova opção terapêutica em decorrência da completa preservação músculo-aponeurótica. Apesar dos benefícios funcionais em relação aos tradicionais retalhos músculo-cutâneos, o retalho DIEP exibe limitações como o tempo cirúrgico prolongado, a dificuldade técnica e o risco de lesão da artéria perfurante no trajeto intramuscular, todos decorrentes do calibre reduzido das artérias e da variabilidade anatômica. Embora a anatomia do músculo reto do abdome tenha sido exaustivamente estudada, escassas e imprecisas são as informações sobre a distribuição das artérias perfurantes, o trajeto intramuscular e as características do pedículo arterial. No presente estudo, a distribuição, o trajeto intramuscular e as dimensões do pedículo do retalho DIEP foram estudados em 15 cadáveres frescos não formolizados (30 retalhos) por técnica de coloração com tinta azul látex e posterior dissecção. Constatou-se 6,3 artérias perfurantes por retalho, sendo que a maior parte das artérias de médio e grande calibre localizavam-se na região lateral do músculo reto do abdome. Na análise do trajeto intramuscular foram classificadas de artérias com trajeto retilíneo, aquelas localizadas exclusivamente no septo muscular e sua dissecção foi realizada sem secção das fibras musculares. No trajeto oblíquo, se evidenciou mais de um septo muscular e houve a necessidade de se realizar a secção muscular. As artérias perfurantes da região lateral apresentaram trajeto retilíneo em maior número quando comparadas às artérias da região medial do músculo reto do abdome. Na maioria das dissecções, a artéria epigástrica inferior mostrou dois ramos principais sendo o calibre do ramo lateral maior ao do ramo medial. A maioria das artérias perfurantes de médio e grande calibres apresentaram origem no ramo lateral dominante da artéria epigástrica inferior. As artérias perfurantes e o pedículo arterial do retalho revelaram comprimento médio de 5,3 e 15,7 cm respectivamente. O pedículo arterial com a artéria perfurante proveniente da região medial apresentou comprimento maior do que o pedículo que continha a artéria proveniente da região lateral. O presente estudo permitiu-nos concluir que a maior concentração de artérias perfurantes de maior calibre e a presença do trajeto retilíneo na região lateral do músculo reto do abdome, constituíram parâmetros anatômicos importantes no planejamento da técnica. As conclusões obtidas reforçam a relevância dos estudos anatômicos na programação da reconstrução com retalhos vascularizados por artérias perfurantes. / The introduction of musculocutaneous flaps in plastic surgery has resulted in a great step forward in reconstructive procedures. In spite of their well-known and reproducible technique, their use is limited by morbidity in the donor area resulting from muscle resection. The development of perforator flap and the clinical application of the deep inferior epigastric flap (DIEP) has provided a new therapeutic option resulting from complete muscle-aponeurotic preservation. Despite the functional benefits achieved in comparison to traditional musculocutaneous flaps, the DIEP flap has limitations. The latter include prolonged operative time, technical difficulty and the risk of injury to the perforating artery in the intramuscular pathway. These factors result from reduced diameter of the arteries and to anatomic variation. Although anatomy of the rectus abdominus muscle has already been studied, information regarding distribution of the perforator arteries, intramuscular pathway, and characteristics of the arterial pedicle is lacking and inaccurate. In this thesis, the distribution, intramuscular pathway and pedicle size of the DIEP flap were studied in 15 fresh cadavers. Thirty flaps were analyzed by staining with blue latex dye and subsequent dissection. An average of 6.3 perforator arteries per flap were observed, and the major concentration of medium and large diameter arteries in the lateral region of the rectus muscle. The intramuscular pathway analysis classified the arteries as rectilinear, those located solely in the muscle septum and their dissection was performed without muscle fibers section. In the oblique pathway, not a single septum was observed and muscle section was necessary. A larger number of the perforator arteries of the lateral region presented a rectilinear path compared to the arteries of the medial region. In the majority of dissections, the inferior epigastric artery exhibited two main branches with the lateral branch diameter greater than that of the medial branch. The majority of the perforator arteries of medium and large diameter originated in the dominant lateral branch of the IEA. The perforator arteries and the arterial pedicle of the flap displayed a mean length of 5.3 and 15.7cm respectively. The arterial pedicle presenting the perforator artery originating from the medial region was longer than the pedicle containing the artery originating from the lateral region. The major concentration of perforator arteries of larger diameter besides being rectilinear in the lateral region of the rectus muscle establishes important parameters for technical planning. The results obtained in this study emphasize the importance of the anatomic studies in planning reconstructions with perforator flaps.