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Nasopharyngeal carcinoma (NPC) is an aggressive head and neck cancer ranked as the 5th most common in Hong Kong. We aimed to study the role of dynamic contrast-enhanced MRI (DCE-MRI) and dynamic 2-deoxy-2-[fluorine-18]fluoro -D-glucose positron emission tomography (FDG-PET) for characterizing NPC tumors in newly-diagnosed patients, and to quantitatively evaluate the intratumoral heterogeneity of NPC. In Chapter 2 we employed semi-quantitative analysis of DCE-MRI to study the dynamic enhancement pattern by analyzing the time-intensity curves in 25 NPC patients. Our findings suggested that high blood flow caused a high initial intensity enhancement rate (ER), and that neovasculature due to tumor angiogenesis in tumors of larger volume or higher T-stage caused more accumulation of contrast agent which can be detected by DCE-MRI. PET and semi-quantitative DCE-MRI parameters were not correlated and may reflect different physiological/molecular processes in the microenvironment of NPC tumor. However the major limitation of semi-quantitative analysis was that the physiological correlates of these parameters were unclear. In Chapter 3 we applied quantitative analysis of DCE-MRI to study the permeability and perfusion characteristics in the same cohort as in Chapter 2. Our findings implied that the permeability may be high compared to blood flow in NPC tumor. We also observed significant correlations between iAUC (the initial area under the time-intensity curve) by semi-quantitative analysis and ve (the volume fraction of extravascular extracellular space) by quantitative analysis, and between the two rate constants (kep’s) from these two methods, which showed that semi-quantitative analysis was a feasible alternative in reflecting the physiological characteristics of NPC. However, we did not observe any significant correlation between PET and DCE-MRI quantitative parameters, also suggesting that PET and DCE-MRI reflected different physiological information in NPC. In Chapter 4 we applied dynamic PET scan to study the glucose metabolism in 18 NPC tumors (16 included in DCE-MRI cohort). Our findings showed that the overall FDG uptake was mainly composed of the FDG in tissue compartment (Ki), which was governed by the phosphorylation (k3) but not the transport of FDG (K1). This finding may further indicate a potential role of the phosphorylation rate k3 in NPC. Dynamic PET parameters did not correlate with DCE-MRI, indicating that the two modalities reflect different molecular information in NPC. In Chapter 5, intratumoral heterogeneity in NPC tumors of 40 patients was studied using 18F-FDG PET scan. Our findings showed that as tumors grew to a larger volume and higher T-stage, they showed more heterogeneous glucose metabolism. It was found that more heterogeneous tumor was associated with worse disease-free survival, indicating that tumor metabolic heterogeneity may play an important role for NPC patient prognosis. To summarize, these results showed that DCE-MRI and dynamic PET improved our understanding about the physiological/molecular process of NPC, and, these two modalities reflected different physiological information in the microenvironment of NPC tumors. This indicated that the relationship between supply of nutrients such as glucose and blood flow/permeability is complex and not directly related. Moreover, intratumoral heterogeneity by PET scan was also of importance in prognostication. / published_or_final_version / Diagnostic Radiology / Doctoral / Doctor of Philosophy

Thesis (M. Soc. Sc.)--University of Hong Kong, 1997. / Includes bibliographical references (leaf 138-147).

Thesis (Ph. D.)--University of Hong Kong, 1995. / Includes bibliographical references.

Thesis (M. Phil.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 101-124) Also available in print.

Thesis (M.Soc.Sc.)--University of Hong Kong, 1997. / Includes bibliographical references (leaf 138-147) Also available in print.

published_or_final_version / abstract / Medicine / Master / Doctor of Medicine

Nasopharyngeal carcinoma (NPC) is the 7th commonest cancer in Hong Kong. Improvements in radiotherapy had increased the cure. Unfortunately, up to 10% of the patient still suffered from local recurrence. Because of the deep location, nasopharyngectomy was considered a difficult operation. Developments in surgical approaches had now established nasopharyngectomy as a standard salvage for locally recurrent NPC. With improvements of endonasal endoscopic instruments and endoscopic techniques, endoscopic nasopharyngectomy as a minimally invasive surgery for salvaging small locally recurrent NPC have been reported in several cohorts with encouraging results. Robotic nasopharyngectomy remained difficult due to tight operation space and instrument considerations. The da Vinci surgical robot was marketed in 1999 as a tool to assist surgeons in performing complex surgical manipulations in tight spaces. It was later adapted to be used in the upper aerodigestive tract for endoscopic resection of small cancers transorally. As the da Vinci surgical robot was not designed for head and neck operations, adaptations are required when we tried to apply it to resect tumours in the nasopharynx. The present study aimed to develop the use of the da Vinci surgical robot to perform minimally invasive operations on the nasopharynx in a cadaveric model. Ten procedures on 3 cadavers were performed with the surgical robot. Due to instrument clutter, a transoral approach was preferred over transnasal approach. In transoral approach, the soft palate obstructs the access to the nasopharynx. We devised three approaches, namely palatal suspension approach, midline palatal split approach and lateral palatal flap approach. We also assess the advantages and limitations of the three approaches. From 2010-2014, 18 robotic nasopharyngectomies were performed. Median operation time was 232 minutes (range 125-574). Estimated median blood loss was 100ml (range 100-1800). Negative margins were achieved in 14 patients. The two-year actuarial local control was 83% and estimated mean survival was 42.7 months (95% confidence interval 35.0-50.3 months). A positive or close margin was significant associated with poor local control but not overall survival. Results were comparable to open or endoscopic nasopharyngectomy. There was no 30 days post-operative mortality but one patient suffered from hypoxic brain damage after developing angioedema in the recovery room. Two patients developed permanent palatal fistulas and one patient had severe trismus after operation. Symptomatic osteoradionecrosis occurred in three patients. When comparing the quality of life assessment with patients after open maxillary swing nasopharyngectomy operation, robotic nasopharyngectomy patients have a higher score in social functioning scale and lower symptoms scores on pain, mouth opening and social eating. The global health score and other functioning scores were statistically not different. Robotic nasopharyngectomy is a feasible minimally invasive operation for resecting selected cases of locally recurrent NPC. The operation is associated with minor long-term complications and better quality of life. Early oncological results in are also encouraging. With rapid development of medical robotic technologies, further research in the field should be continued. / published_or_final_version / Surgery / Master / Master of Surgery

published_or_final_version / Clinical Oncology / Doctoral / Doctor of Philosophy

published_or_final_version / Clinical Oncology / Doctoral / Doctor of Philosophy