The purpose of this thesis is to explore the methodological and empirical issues relating to the economic evaluation of minimal access surgery (MAS). Given the likely increase in the utilisation of economic analysis in this area, it is crucial to explore whether the methods of economic evaluation have limitations in the face of the particular characteristics of MAS. The comparison of abdominal hysterectomy (AH) and transcervical endometrial resection (TCRE), for the treatment of menorrhagia, is used as a vehicle to develop methods in relation to MAS. Having reviewed the literature and issues relating to the economic analysis of this group of technologies, the empirical starting point of the thesis is the assessment of the limitations of economic evaluations alongside clinical trials, using a trial comparing AH and TCRE. Three major areas of weakness are identified, and alternative ways of addressing these weaknesses are explored in the remainder of the thesis. The first area of methodological development relates to the measure of benefit used in economic evaluation of MAS. In this clinical context, it is argued that the trade-offs that exist between MAS and conventional surgery, in terms of process characteristics and outcomes, should result in an important role for patients' preferences in the construction of a benefit measure. A cost-utility analysis using the standard quality-adjusted life year (GALY) is undertaken, using trial data augmented with valuation data from a further study. The lack of consistency between individual preferences and standard QALYs suggests a major weakness with this measure of benefit. The strengths and weaknesses of an alternative measure of benefit in cost-utility analysis - the ex ante healthy years equivalent (HYE) - are assessed based on a further valuation study. It is shown that it is feasible to elicit ex ante HYEs from patients and that this measure of benefit exhibits some consistency with other expressions of patients' preferences. However, the HYE is likely to impose a greater measurement burden than the standard QALY. The second area of methodological development in the thesis is the analysis of the generalisability of trial-based economic evaluation, given the limitations that often exist with the external validity of trials. A framework is developed within which trial and observational data can be synthesised. This facilitates the use of sensitivity analysis to explore the robustness of base-case (trial-generated) results to alternative sources of data, which may be more representative of routine practice. The third area of methodological development stems from the importance of patients' preferences in relation to MAS. This element relates to the use of methods to model and to evaluate management strategies which use patients' preferences to determine treatment allocation. It is concluded that preference-based decision making has the potential to be cost effective in relation to TCRE and AH, and MAS applications more generally. The thesis demonstrates the importance of continued development in the detailed methods of economic evaluation.

Liver resection, or hepatectomy, is a major abdominal surgery performed most often for the removal of malignant tumors of the liver, either primary or metastatic. It is often associated with significant blood loss and therefore, with blood transfusions. While transfusions are common, there is incomplete knowledge of their effects on clinical outcomes. Furthermore, both current practices and best practices in perioperative blood management, including blood product administration, are not well defined. This manuscript-based thesis will examine the clinical impact, current practices, and appropriate use of perioperative red blood cell transfusions for patients undergoing liver resection.

Background: Even with newer and repurposed anti-TB drugs almost a third of patients with XDR-TB have unfavourable outcomes. In patients with localised disease and adequate pulmonary reserve, surgery is an important adjunctive treatment. However, there are no outcome data from TB endemic countries, and the prognostic significance of pre-operative PET-CT findings remains unknown. Objectives: To report outcomes for resectional surgery in our setting, and to study whether PET activity outside of the resection influences treatment outcomes. Methods: A retrospective study of all XDR-TB patients undergoing surgery at Groote Schuur Hospital (GSH) between July 2010 and December 2016 was performed. PET-CT was performed in a subgroup. Patients were followed up to determine treatment outcomes at 24-months post- surgery. Treatment success and failure, including all-cause mortality, was determined. Results: In total, 35 patients underwent surgery. The mean age was 36, 49% were male and 26% were HIV-infected. Pneumonectomy was the most common procedure (57%). Three patients (9%) were lost to follow up by 24 months. Total all-cause mortality was 34%. Treatment success was achieved in 15/35 (43%). In patients who underwent pre-operative PET-CT, there were no overall radiological features or PET parameters that were found to be prognostic for treatment failure. Conclusion: Resectional surgery for DR-TB in combination with chemotherapy resulted in cure in less than half of patients. Our data do not support the use of PET-CT to preselect patients or prognosticate about their outcome. These data inform clinical practice and underscore the need to support antibiotic stewardship strategies in TB-endemic settings.

Purpose: In oncological orthopedics, navigation systems are limited to use in specialized centers, because specific, expensive, software is necessary. To resolve this problem, we present a technique using general spine navigation software to resect tumors located in different segments. Materials and Methods: This technique requires a primary surgery during which screws are inserted in the segment where the bone tumor is; next, a CT scan of the entire segment is used as a guide in a second surgery where a resection is performed under navigation control. We applied this technique in four selected cases. To evaluate the procedure, we considered resolution obtained, quality of the margin and its control. Results: In all cases, 1 mm resolution was obtained; navigation allowed perfect control of the osteotomies, reaching the minimum wide margin when desired. No complications were reported and all patients were free of disease at follow-up (average 25.5 months). Conclusions: This technique allows any bone segment to be recognized by the navigation system thanks to the introduction of screws as landmarks. The minimum number of screws required is four, but the higher the number of screws, the greater the accuracy and resolution. In our experience, five landmarks, placed distant from one another, is a good compromise. Possible disadvantages include the necessity to perform two surgeries and the need of a major surgical exposure; nevertheless, in our opinion, the advantages of better margin control justify the application of this technique in centers where an intraoperative CT scanner, synchronized with a navigation system or a dedicated software for bone tumor removal were not available.

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El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Revisión por pares

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24477号 / 医博第4919号 / 新制||医||1062(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 中本 裕士, 教授 波多野 悦朗, 教授 万代 昌紀 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

A 54-year-old female presented with shortness of breath and cyanosis. Work up with chest X-ray and subsequent echocardiogram revealed an intracardiac bi-atrial mass leading to emergent cardiothoracic resection. Pathology was consistent with a primary cardiac high-grade osteosarcoma. Post-resection staging positron emission tomography-computed tomography (PET-CT) showed hypermetabolic mixed lytic and sclerotic lesion of T10 concerning for metastasis. She received five cycles of adriamycin and ifosfamide chemotherapy before discontinuation due to systolic dysfunction. Nine months later, she developed a high tumor burden with progressive disease and was treated with second-line gemcitabine/docetaxel with disappointing results. She is currently on treatment with cyclophosphamide and topotecan as third-line treatment with an excellent clinico-radiographic response. Osteosarcomas are aggressive with a high incidence of recurrence and metastasis. Fewer than 50 cases of primary cardiac osteosarcomas have been reported in the literature. Even though complete resection can be achieved in some cases, long-term results are usually poor. No standard therapy has been established.

Positional and area accuracies were calculated for digitized data taken from 1:20,000 scale aerial photographs and United States Geological Survey (USGS) 1:24,000 scale topographic maps. Positional accuracy was determined as the Euclidian distance between the digitized coordinate and the reference ground coordinate collected with global positioning systems (GPS). Area accuracy was the acreage difference between the digitized area and GPS calculated area. Three methods were employed to collect the digitized data: manual digitizing from topographic maps and aerial photographs followed by an affine transformation, and manual digitizing from aerial photographs while applying a single-photo space resection. Two study sites, one in low terrain relief and one in high terrain relief, were used to examine the effects of terrain on positional accuracies. The single-photo space resection technique provided the most accurate positional data on both study sites. The single-photo space resection produced mean positional accuracies of 5.0 to 6.0 meters. In comparison, the uncorrected digitized photo data produced mean positional accuracies of 7.0 to 26.0 meters. The effects of terrain displacement were evident in these data sets, as the mean positional accuracy at the low-relief study site was 18.96 meters less than the corresponding accuracy at the high-relief study site. The uncorrected digitized photo data set from the high-relief study site provided the highest mean positional accuracy, 25.86 meters. The topographic map digitized data from both study sites provided mean positional accuracies below 12.0 meters, but failed to meet National Map Accuracy Standards (NMAS) for 1:20,000 scale or smaller maps. The average area accuracy from both study sites proved to be not significantly different, regardless of the digitizing technique or terrain conditions. The average area accuracy between the two study sites differed by at most 0.05 hectares. Average percent area errors ranged from 9.96% to 11.74% on the low-relief study site and from 11.84% to 12.65% on the high-relief study site. / Master of Science