published_or_final_version / Surgery / Master / Master of Surgery

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Thesis (M.S.)--University of Hong Kong, 1998. / "1998"--Cover. Includes bibliographical references (leaves i-xxiii).

Thesis (M.S.)--University of Hong Kong, 1998. / "1998"--Cover. Includes bibliographical references (leaves i-xxiii) Also available in print.

published_or_final_version / abstract / toc / Medicine / Master / Master of Philosophy

Thesis (Ph. D.)--University of Wisconsin--Madison, 1970. / Typescript. Vita. Description based on print version record. Includes bibliographical references.

Cryosurgery is the destruction of undesired biological tissues by freezing. Modern cryosurgery is frequently performed as a minimally-invasive procedure, where multiple hypodermic, needle-shaped cryoprobes are inserted into the target area to be treated. The aim of the cryosurgeon is to maximize cryoinjury within a target region, while minimizing damage to healthy surrounding tissues. There is an undisputed need for temperature-field reconstruction during minimally invasive cryosurgery to help the cryosurgeon achieve this aim. The work presented in this thesis is a part of ongoing project at the Biothermal Technology Laboratory (BTTL), to develop hardware and software tools to accomplish real-time temperature field reconstruction. The goal in this project is two-fold: (i) to develop the hardware necessary for miniature, wireless, implantable temperature sensors, and (ii) to develop mathematical techniques for temperature-field reconstruction in real time, which is the focus of the work presented in this thesis. To accomplish this goal, this study proposes a computational approach for real-time temperature-field reconstruction, combining data obtained from various sensing modalities such as medical imaging, cryoprobe-embedded sensors, and miniature, wireless, implantable sensors. In practice, the proposed approach aims at solving the inverse bioheat transfer problem during cryosurgery, where spatially distributed input data is used to reconstruct the temperature field. Three numerical methods have been developed and are evaluated in the scope of this thesis. The first is based on a quasi-steady approximation of the transient temperature field, which has been termed Temperature Field Reconstruction Method (TFRM). The second method is based on analogy between the fields of temperature and electrical potential, and is thus termed Potential Field Analogy Method (PFAM). The third method is essentially a hybrid of TFRM and PFAM, which has shown superior results. Each of these methods has been benchmarked against a full-scale finite elements analysis using the commercial code ANSYS. Benchmarking results display an average mismatch of less than 2 mm in 2D cases and less than 3 mm in 3D cases for the location of the clinically significance isotherms of -22°C and -45°C. In an advanced stage of numerical methods evaluation, they have been validated against experimental data, previously obtained at the BTTL. Those experiments were conducted on a gelatin solution, using proprietary liquid-nitrogen cryoprobes and a cryoheater to simulate urethral warming. The design of the experiment was aimed at creating a 2D heat-transfer problem. Validation results against experimental data suggest an average mismatch of less than 2 mm, for the hybrid of TFRM + PFAM method, which is of the order of uncertainty in estimating the freezing front location based on ultrasound imaging.

Com objetivo de avaliar a eficácia da criocirurgia no tratamento de neoplasias de pele e/ou partes moles de cães e gatos, foram utilizados 40 animais, 27 cães e 13 gatos de raças e idades variadas encaminhados ao Serviço de Cirurgia de Pequenos Animais do Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo. Foram tratadas 57 lesões utilizando-se o nitrogênio líquido por meio da técnica do spray, destas 17 (29,83%) foram caracterizadas como neoplasia epitelial benigna, 22 (38,60%) neoplasia epitelial maligna, 4 (7,01%) neoplasia mesenquimal benigna, 10 (17,54%) neoplasia mesenquimal maligna, 3 (5,27%) não neoplásicos e 1 (1,75%) não caracterizado. Houve remissão total de 49 (85,96%) lesões em 32 (80%) animais. Diante destes resultados pode-se concluir que a criocirurgia foi eficaz no tratamento de tumores de pele e/ou partes moles de cães e gatos. / With the aim to evaluate the effectiveness of cryosurgery in the treatment of skin and soft tissue neoplasias of the dogs and cats it was used 40 animals, 27 dogs and 13 cats of differents ages and breeds referred to the Surgery Service of Small Animals of the Veterinary Hospital of the University of São Paulo. Fifty seven lesions were treated with the spray technique using liquid nitrogen. 17 (29,83%) were benign epithelial lesions, 22 (38,60%) malignant epithelial lesions, 4 (7,01%) benign mesenchymal lesions, 10 (17,54%) malignant mesenchymal lesions, 3 (5,27%) not neoplasia, 1 (1,75%) not characterized. There was total remission of the 49 (85,96%) lesions in 32 (80%) animals. It was concluded that the cryosurgery was effective to treat skin and/or soft tissue tumor of the dogs and cats.

Diversas são as formas de tratamento do câncer de próstata, com resultados oncológicos e complicações variadas . A crioablação foi proposta nos anos 60 e com a evolução dos métodos de imagem a técnica ressurgiu; 44 pacientes, divididos em 3 grupos (portadores de tumor de alto risco, tumores de baixo risco e falha de tratamento após radioterapia) foram submetidos a crioterapia por via percutânea transperineal. Sobrevida livre de doença foi de 87% no grupo baixo risco, 34% no grupo alto risco e 58% no grupo de resgate após falha de radioterapia. A complicação mais freqüente foi disfunção erétil (94,5%); obstrução infravesical ocorreu em 9 pacientes (20,4%); 6 pacientes (13,6%) apresentaram algum grau de incontinência urinária. Não houve nenhum caso de fístula uretroretal ou mortalidade relacionada ao procedimento / There are several treatments for prostate cancer with an assorted oncologic results and complications. Cryoablation was proposed in the 60 and the improvement of radiological techniques allowed the perineal percutaneous treatment; 44 patients divided into three groups (high risk tumors, low risk tumors and patients with recurrent prostate cancer following radiotherapy) were submitted to perineal percutaneous prostate cryoablation. Biochemical-free survival was 87% in low risk group, 34% in the high-risk group and 58% in salvage cryoablation. Erectile dysfunction was the most frequent complication (94,5%); Infravesical obstruction occurred in 20,4% of the patients and six (13,6%) developed urinary incontinence. There were no urethrorectal fistulae or mortality related to the procedure

Intracellular ice formation (IIF), a major cause of cryoinjury in biological cells, is significantly more pronounced during freezing of tissue than during freezing of suspended cells. While extensive studies of IIF have been conducted for single cells in suspension, few have investigated IIF in tissue. Due to the increased complexity that arises from both cell-substrate and cell-cell interactions in tissue, knowledge of cryobiology of isolated cells cannot simply be extrapolated to tissue. Different theories have been hypothesized for the mechanisms of IIF in tissue, but none have been conclusively proven. Towards the goal of developing mathematical models to accurately predict the probability of IIF in tissues of one or more cell types, we have developed a novel high-speed video cryomicroscopy system capable of image acquisition at sampling rates up to 32,000 Hz. Specifically, the effects of cell adhesion to the substrate and cell-cell interactions were investigated with experimental (micropatterned endothelial cell constructs) and mathematical models (Monte Carlo simulations). We have reported the first direct observations of the IIF process recorded at unprecedented sub-millisecond and sub-micron resolution. For the majority of our experiments, IIF nucleation was determined to occur preferentially at the cell perimeter. This observation was not consistent with the commonly accepted hypotheses of ice nucleation in suspended cells and suggests that an alternative mechanism of IIF initiation is dominant in adherent cells. In addition, the kinetics of ice nucleation were shown to be influenced by time in culture, attached cell perimeter, fibronectin coating density, and degree of cell-cell contact. Moreover, an additional phenomenon, paracellular ice penetration was identified, and the frequency of formation was correlated with focal adhesion formation. The data and mathematical models presented in this thesis bring closer the goal of elucidating the primary mechanisms contributing to IIF in tissue; providing important contributions to both the fields of cryopreservation (minimizing IIF) and cryosurgery (maximizing IIF).