Based on figure from American Association for Cancer Research (2010) & Global Cancer Statistics (2011), Liver cancer (HCC) is the sixth most frequently diagnosed cancer globally and third leading cause of cancer death (Jemal, A. et al., 2011; Jemal, A., Center, M. M., DeSantis, C. et al., 2010). In Hong Kong, Liver Cancer caused 1488 deaths in 2009 in total; it is 2nd and 4th leading killer of cancer death among Hong Kong male and female respectively (Hong Kong Cancer Registry, 2010). However, surgical resection for HCC remains as mainstream treatment modality and extensive studies on post-operative surgical outcomes for different HCC treatment modalities have been published. Nevertheless, the influence of kidney function on surgical outcomes on HCC patient stays novel and it emerges a need to explore on the relation. This study aims to compare the surgical outcomes of post hepatectomy HCC patients between reduced kidney function and normal kidney function in terms of (1) Length of hospital stay, (2) Survival rate, (3) Hospital Mortality and (4) Overall post operative complications. The kidney function can be reflected by the glomerular filtration rate (Thomas, R., Stanley, B. & Datta, S., 2007; Daugirdas, J. T., 2011). The direct measurement of GFR is a complicated and expensive procedure, which is not clinical possible to screen every patient. Thus this study adopted modified Cockcroft- Gault (CG) Formula, one type of creatinine based glomerular filtration rate estimation formulas with normalization to body surface area. Modified CG formula calculate the estimated glomerular filtration rate (eGFR) based on age, body weight, body height, gender and serum creatinine level (Himmelfarb, J. & Sayegh, M. H., 2010; Daugirdas, J. T., 2011; Joanna, Q. H. & Heather A. N., 2011). The eGFR of 452 HCC patients with major hepatectomy was evaluated and categorized into different kidney function groups according to the chronic kidney disease staging system suggested by K/DOQI, National Kidney Foundation. Hence, the surgical outcomes from different kidney function groups are analyzed and compared. Length of hospital stay was analyzed by Kruskal-Wallis Test. Hospital mortality and incidences of post-op complication are analyzed by Chi-square test. Lastly, the survival rate is analyzed by Kaplan-Meier Log rank test; the result is presented in form of survival curve, then 5-year survival rate of different group of samples are obtained and compared. Result of the study shows no evidence that patients with chronic kidney disease will have a longer hospital stay and more prone to surgical complications post operatively. However, it is indicated that the hospital mortality is associated with the severity of kidney function reduction and suggested that patients with chronic kidney disease are at higher risk of post-operative death than those with normal kidney. Patient with severe reduction of kidney function should be aware of high foreseeable chance of death after the surgery and special caution need to be taken. Surprisingly, the result revealed that the overall survival improves with the severity of kidney function reduction and the patients with worse kidney function are more likely to have a better survival. Nevertheless, the result on survival rate suspected to be biased by possible confounders and underlying co-morbidities of samples. In conclusion, eGFR formula is recommended in clinical estimation of kidney function for the patients. Also, it is suggested that HCC patients with reduced kidney function are more susceptible to hospital death after hepatectomy than normal individuals. Thus, cautious consideration and risk analysis before operation is particularly crucial for HCC patient with chronic kidney disease. / published_or_final_version / Medicine / Master / Master of Medical Sciences

published_or_final_version / abstract / Surgery / Master / Master of Surgery

published_or_final_version / Surgery / Master / Master of Surgery

High intensity focused ultrasound (HIFU) is an emerging non-invasive thermal ablative modality that can be utilised for the treatment of solid organ tumours, including liver cancer. Acoustic cavitation is a phenomenon that can occur during HIFU and its presence can enhance heating rates. One major limitation of thermal ablative techniques in general, such as radiofrequency and microwave ablation, is the heat sink effect imparted by large vasculature. Thermal advection from blood flow in vessels ≥ 3 - 4 mm in diameter has been shown to significantly reduce heating rates and peak temperatures in the target tissue, potentially leading to treatment failure. With regards to HIFU therapy, a clearer understanding is required of the effects of blood flow on heating, cavitation and thermal tissue necrosis, which is the treatment endpoint in clinical thermal ablation. Therefore, the overall aim of this thesis project was to elucidate the effects of blood flow on HIFU-induced heating, cavitation and histological assessment of thermal ablation. A unique isolated, perfused porcine liver model was used in order to provide a relevant test bed, with physiological and anatomical characteristics similar to the in vivo human liver. The normothermic liver perfusion device used in all studies presented in this work can keep an organ alive in a functional state ex vivo for in excess of 72 hours. A further advantage of the liver perfusion device was that it allowed blood flow to be stopped completely and resumed rapidly, allowing studies to be conducted under zero flow conditions. A therapeutic HIFU system was used in order to deliver HIFU therapy to regions of hepatic parenchyma adjacent (≤ 3 mm) to large (≥ 5 mm) blood vessels or away from vasculature (≥ 1 cm) at either 1.06 MHz or at 3.18 MHz. Cavitation events during HIFU therapy were spatio-temporally monitored using a previously developed passive acoustic mapping (PAM) technique. The cavitation threshold at each frequency was determined through assessment of acoustic emissions acquired through PAM during HIFU exposure at a range of acoustic pressures. Real time thermal data during HIFU therapy were obtained using an implantable 400 μm thermocouple, aligned with the HIFU focus, in order to assess the effect of large vessel blood flow on peak tissue temperatures. Thermal data were obtained at 1.06 MHz, in the presence of acoustic cavitation and at 3.18 MHz, in the absence of cavitation, both in the presence and complete absence of blood flow. Finally, histological assessment of cell viability and cell death was performed in order to determine whether any heat sink effect could be overcome, with the achievement of complete tissue necrosis in treatment regions directly adjacent to large vasculature. This work demonstrated for the first time that in perfused, functional liver tissue, the presence of large vasculature and physiological blood flow does not significantly affect ablative HIFU therapy, both in terms of peak focal tissue temperatures attained and histological evidence of complete tissue necrosis. Therefore, HIFU may be superior to other ablative modalities in treating tumours in tissue regions adjacent to major vascular structures, but further work needs to be performed to correlate the experimental findings with clinical outcomes.