This dissertation investigated the use of a variety of multivariate statistical procedures to answer questions regarding the value of a number of medical tests and procedures in the diagnosis of space-occupying liver disease. Also investigated were some aspects of test ordering behavior by physicians. A basic methodology was developed to deal with archival data. A number of methodological problems were addressed. Discriminant function analysis was used to determine which procedures and tests served to provide the best classification of disease entities. Although the results were not spectacular, some variables, including a physical examination variable and a number of laboratory procedures were identified as being important. A more detailed analysis of the role of the laboratory variables was afforded by the use of stepwise logistic regression. In these analyses pairs of disease classifications were compared. Two of the more specific laboratory tests, total bilirubin and alkaline phosphate, entered into the equations to provide a fit to the data. Logistic regression analyses employing patient variables mirrored the results obtained with the discriminant function analyses. Liver-spleen scan indicants were also employed as predictor variables in a series of logistic regression analyses. In general, for a range of comparisons, those indicants cited in the literature as being valuable in discriminating between disease entities entered into the equations. Log-Linear models were used to investigate test ordering behavior. In general, test ordering was independent of department. The sole exception being that of the Gynecology-oncology department which relies heavily on Ultrasound. Log-Linear analyses investigating the use of a number of procedures showed differential use of procedures consistent with what is usually suggested in the medical literature for the combination of different imaging and more specialized procedures. Finally, a set of analyses investigated the ordering of a number of procedures relative to specific disease classifications. This set of analyses suffers, as do a number of the other analyses, from insufficient numbers of cases. However, some indications of differential performance of tests for different disease classifications were evident. Suggestions for further study concentrated on the development of experimental procedures given the results of this study.

This thesis sought to investigate novel methods for protecting the liver from ischaemia reperfusion injury in the context of liver transplantation. Research in the heart, brain and kidneys has suggested that hypoxia inducible factor (HIF) may play a key role in the delayed phase of ischaemic preconditioning and can protect organs for up to 3 days. However, although there is good evidence for the potential of HIF to protect organs from ischaemia, the HIF pathway still presents some what of a paradox because it targets both pro-death (e.g. BNIP3,NIX) as well as pro-survival genes (e.g. HO-I, EPO). HIF is primarily controlled by 3 oxygen dependent prolyl hydroxylases (PHD 1 , PHD2, PHD3), and inhibition of these prolyl hydroxylases leads to HIF activation. It was hypothesised that differential inhibition of PHD 1,2 or 3 may result in selective gene regulation and may confer greater or less protection against ischaemia reperfusion injury. To investigate this hypothesis mouse embryonic fibroblasts (MEFs) were isolated from PHDl, 2, and 3 knock-out (KO) embryos and compared to MEFs derived from WT littermate controls. In these MEFs, cell growth and proliferation, as well as cell survival following exposure to anoxia and inducers of apoptosis was studied. The principal findings were that PHD2 is the dominant regulator of HIF in normoxia. PHD2 knock-out MEFs exhibited glycolytic metabolism and had a lower oxygen consumption compared to wild-type MEFs. Gene array studies confirmed the dominant role of PHD2 but also demonstrated that PHD 1 upregulates a number of HIF target genes, albeit to a lesser extent than PHD2. There were no differences, however, in susceptibility to hypoxic injury in the PHDl, 2, and 3 knock-out MEFs compared to wild-type controls. A further aim of the study was to investigate whether prolyl hydroxylase inhibition using dimethyloxalyglycerine (DMOG) may protect the liver in a rodent model of ischaemia reperfusion injury. DMOG effectively upregulated HIF and IllF target genes. Serum transaminases (AST and AL T) were significantly lower in the DMOG treated animals compared to the normal saline treated controls 24 hours following ischaemia. This protection was similar to the protection conferred by surgically induced ischaemic preconditioning. This thesis provides important insights into the individual function of the prolyl hydroxylases and provides preliminary evidence that prolyl hydroxylase inhibitors may be useful in the treatment of ischaemia reperfusion injury in liver transplantation.

University of Macau / Institute of Chinese Medical Sciences

by Frankie Tat-kwong Lau. / Bibliography: leaves 63-70 / Thesis (M.Ph.)--Chinese University of Hong Kong, 1985

by Young Lee Kei, Ricky. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 205-207). / Abstract also in Chinese. / Acknowledgements --- p.i / Statement of Originality --- p.ii / Abstract --- p.iii / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- Anatomy of liver --- p.1 / Chapter 1.2 --- Anatomical Implications --- p.16 / Chapter Chapter 2 --- Background / Chapter 2.1 --- Common focal hepatic lesions --- p.21 / Chapter 2.2 --- Imaging techniques --- p.28 / Chapter 2.3 --- Characterization by sonography --- p.34 / Chapter 2.4 --- Color Power Angiography --- p.38 / Chapter Chapter 3 --- Hypothesis & Aims / Chapter 3.1 --- Hypothesis --- p.44 / Chapter 3.2 --- Aims & Objectives --- p.45 / Chapter Chapter 4 --- Material and Methods / Chapter 4.1 --- Materials --- p.47 / Chapter 4.2 --- Mode of confirmation --- p.52 / Chapter 4.3 --- Final number of subjects recruited --- p.54 / Chapter 4.4 --- Method for obtaining CD and CPA image --- p.58 / Chapter 4.5 --- Method for image analysis --- p.61 / Chapter 4.6 --- Statistical analysis --- p.68 / Chapter Chapter 5 --- Results / Chapter 5.1 --- Qualitative CD and CPA images assessment --- p.70 / Chapter 5.2 --- Interobserver qualitative analysis --- p.78 / Chapter 5.3 --- Spectral analysis --- p.84 / Chapter 5.4 --- Semi-quantitative signal parameters --- p.87 / Chapter 5.5 --- Dominance of quantified signals --- p.91 / Chapter 5.6 --- Distribution of signals in various lesions (graphical presentation) --- p.97 / Chapter 5.7 --- Penetrating vessel --- p.103 / Chapter 5.8 --- Relationship between size of lesion and quantified signal parameters --- p.104 / Chapter Chapter 6 --- Discussion / Chapter 6.1 --- Study Review --- p.109 / Chapter 6.2 --- Methods of quantitation --- p.110 / Chapter 6.3 --- Value of quantitation --- p.111 / Chapter 6.4 --- Instrumentation --- p.112 / Chapter 6.5 --- Subjects --- p.114 / Chapter 6.6 --- Image analysis --- p.115 / Chapter 6.7 --- Results --- p.117 / Chapter 6.8 --- Relationship between size and amount of signals --- p.131 / Chapter 6.9 --- Differentiation of focal hepatic lesions --- p.132 / Chapter 6.10 --- Origin of CPA signals in small hyperechoic lesions --- p.144 / Chapter 6.11 --- Limitations of CPA in focal hepatic lesion imaging --- p.146 / Chapter 6.12 --- Comparison with similar studies --- p.151 / Chapter 6.13 --- Validation of quantitation results --- p.158 / Chapter Chapter 7 --- Conclusions --- p.159 / References --- p.162 / Legends --- p.176 / Tables --- p.186 / Glossary of abbreviations --- p.193 / Selected publications relevant to thesis --- p.197 / Appendix --- p.198 / Bibliography --- p.205

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease associated with the worldwide spread of obesity. NASH predisposes development of fibrosis and hepatocellular carcinoma (HCC), but has no approved therapy due to incomplete understanding of the pathogenesis. Notch signaling normally specifies cell fate during development, but here we investigate how this pathway becomes dysregulated in NASH and contributes to fibrosis and cancer. In the first study, we show that hepatocyte Notch activity tracks with disease severity and treatment response in NASH patients, and is similarly increased in a mouse model of diet-induced NASH and liver fibrosis. Different genetic models demonstrate causatively that hepatocyte Notch induces liver fibrosis via secretion of the fibrogenic factor Osteopontin that activates hepatic stellate cells (HSCs), while pharmacologic inhibition of hepatocyte Notch could ameliorate NASH-associated fibrosis. In the second study, we research how hepatocyte Notch activation leads to HCC in mice on NASH diet. Transcriptomic analysis reveals nerve growth factor (NGF) as a Notch target gene in hepatocytes, and the abundance of hepatocyte NGF precursor protein (proNGF) is uniquely associated with HCC. We provide evidence that proNGF may facilitate HCC growth and expansion in a non-cell autonomous manner by inducing HSC deactivation and fibrosis remodeling. In summary, hepatocyte Notch maladaptively contributes to fibrogenesis and possibly HCC expansion by directly signaling to HSCs at different stages of NASH progression, and could be an accessible target for treatment of NASH-associated liver pathologies.

No description available.

by Wun Yuk Tsan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1996. / Includes bibliographical references (leaves 121-129). / ABSTRACT --- p.i / ACKNOWLEDGMENT --- p.iii / TABLE OF CONTENTS --- p.iv / TABLE OF FIGURES AND TABLES --- p.vi / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Ultrasonography in Clinical Medicine --- p.1 / Chapter 1.1.1 --- Ultrasonic features of the liver --- p.1 / Chapter 1.1.2 --- Image artifacts in liver ultrasonograms --- p.4 / Chapter 1.1.3 --- Characteristics of liver ultrasonic image --- p.6 / Chapter 1.2 --- Liver Carcinoma in Hong Kong --- p.9 / Chapter 1.2.1 --- Morphological features of liver carcinoma --- p.10 / Chapter 1.2.2 --- Ultrasonographic features of liver carcinoma --- p.11 / Chapter 1.3 --- Ultrasonography and Computer --- p.12 / Chapter 1.4 --- Objectives of Thesis --- p.14 / Chapter 1.4.1 --- Hypothesis of the thesis --- p.15 / Chapter 1.4.2 --- Methods of experiment --- p.15 / Chapter 1.5 --- Organization of this Thesis --- p.17 / Chapter CHAPTER 2: --- COMPUTERIZED MEDICAL IMAGING: A REVIEW --- p.19 / Chapter 2.1 --- Computer Vision and Medical Imaging --- p.19 / Chapter 2.1.1 --- Artificial intelligence --- p.21 / Chapter 2.1.2 --- Mathematics models --- p.23 / Chapter 2.2 --- Computer Vision and Ultrasonic Images of Liver --- p.25 / Chapter 2.2.1 --- Studies on radiofrequency (RF) --- p.25 / Chapter 2.2.2 --- Studies on amplitude derived data --- p.26 / Chapter 2.3 --- Implications of Previous Work --- p.28 / Chapter 2.4 --- Limitations of Previous Work --- p.30 / Chapter CHAPTER 3: --- STATISTICAL TEXTURE --- p.32 / Chapter 3.1 --- Statistical Textural Analysis --- p.32 / Chapter 3.2 --- Statistical Texture for Segmentation --- p.34 / Chapter 3.3 --- Statistical Features Studied in This Research --- p.35 / Chapter 3.3.1 --- First-order statistics --- p.35 / Chapter 3.3.2 --- Second-order statistics --- p.36 / Chapter 3.3.3 --- Higher-order statistics --- p.41 / Chapter 3.4 --- Novel Statistical Texture Features --- p.42 / Chapter 3.5 --- Stable Statistical Textures: A New Hypothesis --- p.43 / Chapter 3.6 --- Centroids of Statistical Texture Descriptors --- p.45 / Chapter CHAPTER 4: --- NORMAL LIVER IMAGES --- p.48 / Chapter 4.1 --- Further Description of Normal Liver USG --- p.48 / Chapter 4.1.1. --- Equalized images --- p.50 / Chapter 4.2 --- Stable Statistical Descriptors in Normal Liver Images --- p.50 / Chapter 4.3 --- Clustering Algorithm --- p.53 / Chapter 4.3.1. --- Accuracy of the algorithm --- p.58 / Chapter 4.3.2 --- The algorithm and ultrasound artifacts --- p.60 / Chapter 4.3.3 --- Fuzzy algorithm for clustering --- p.62 / Chapter 4.4 --- Evaluation of the Algorithm --- p.63 / Chapter CHAPTER 5: --- IMAGES OF LIVER CARCINOMA --- p.64 / Chapter 5.1 --- Characteristics of Liver Carcinoma --- p.64 / Chapter 5.2 --- Algorithm for Tumour Detection --- p.65 / Chapter 5.2.1 --- Which statistical descriptors to use? --- p.66 / Chapter 5.2.2 --- How to isolate the capsules subimages? --- p.68 / Chapter 5.2.3 --- How to estimate the position of the tumour cells in the descriptor curve? --- p.72 / Chapter 5.2.4 --- Refinements of the algorithm --- p.73 / Chapter 5.3 --- Results of the Algorithm --- p.75 / Chapter 5.4 --- Further Examples --- p.80 / Chapter 5.5 --- Evaluation of the Algorithm --- p.87 / Chapter 5.5.1 --- Time required by the algorithm --- p.87 / Chapter 5.5.2 --- Sensitivity --- p.88 / Chapter 5.5.3 --- False positives and negatives --- p.88 / Chapter CHAPTER 6: --- REVIEW AND PROSPECTS --- p.90 / Chapter 6.1 --- Conclusions --- p.91 / Chapter 6.1.1. --- The objectives --- p.91 / Chapter 6.1.2 --- Hypotheses --- p.91 / Chapter 6.1.3. --- Statistical features --- p.92 / Chapter 6.2 --- Evaluation --- p.93 / Chapter 6.2.1 --- Noises --- p.93 / Chapter 6.2.2 --- Statistical features --- p.94 / Chapter 6.2.3 --- Methodology --- p.96 / Chapter 6.3 --- Future Work and Research --- p.98 / Chapter 6.3.1 --- Implementation and further development of the system --- p.98 / Chapter 6.3.2 --- Future research of the system --- p.99 / Chapter 6.3.3 --- Fuzzy algorithm --- p.100 / Chapter 6.3.4 --- Further work on statistical texture features --- p.100 / Chapter 6.3.5 --- The commercial potential of the system --- p.100 / Chapter 6.4 --- Final Conclusion --- p.101 / APPENDICES --- p.102 / Appendix A: Program Listings --- p.102 / Listing 1: pcx.c --- p.103 / Listing 2: feature.c --- p.108 / "Listing 3: detect, c" --- p.108 / Listing 4: centroid. c --- p.117 / AppendexB: Further Readings --- p.120 / Chapter I. --- Textbooks on Computer Vision or Images --- p.120 / Chapter II. --- Reference Books on Processing Algorithms in C Language --- p.120 / REFERENCES --- p.121

Surgical resection is the best option for both liver and kidney cancers, which providing the long term survival. However intraoperative blood loss can be a significant challenge, and is clearly associated with morbidity and mortality. Radiofrequency ablation (RFA) precoagulation has been introduced into liver and kidney surgery. Promising results have already achieved in reduction of intraoperative blood loss. In this thesis, a detailed explanation on precoagulation by RFA has been given. Our group developed a novel bipolar multi-array RFA device ??? InLine (ILRFA). In this thesis, we have investigated the performance in a variety of fields. In the study of ILRFA-assisted laparoscopic liver resection, ILRFA was easily employed through a hand port and achieved significant decrease of blood loss compared to control group (p < 0.05). In the liver trauma study, ILRFA produced a 63.88% reduction of blood loss in peripheral injury and 53.57% in central injury respectively. In postoperative evaluation of ILRFA-assisted liver resection, animals underwent an uneventful recovery, no complications occurred. Histological examination revealed a typical post RFA evolution. In ILRFA-assisted partial nephrectomy, the mean intraoperative blood loss 35 ?? 7 ml in the ILRFA and 152 ?? 94 ml in the control, a 77.0% reduction (P = 0.024). The mean blood loss per centimetre resection area was 2.09 ?? 1.41 ml/cm2 in the ILRFA compared with 12.79 ?? 1.68 ml/cm2 in controls, the reduction was 79.0% (P = 0.019). In ILRFAassisted laparoscopic partial nephrectomy, the mean intraoperative blood loss was 32 ?? 15 ml in the ILRFA and 187 ?? 69 ml in the control group, a 77.0% reduction (P = 0.043). The mean blood loss per centimetre resection area was 2.27 ?? 0.95 ml/cm2 in the ILRFA compared with 26.46 ?? 8.81 ml/cm2 in controls, the reduction was 79.0% (P = 0.047). In the renal trauma experiment, ILRFA also achieved promising results in haemostasis. We believe that ILRFA is a useful device which may help in the treatment of patients with liver and kidney illness.

Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 133-146).