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published_or_final_version / abstract / toc / Surgery / Master / Master of Surgery

The development and progression of carcinogenesis is a major area of interest to many scientists. Numerous factors, including both environmental and genetic have been implicated in the causation of cancer. It is clear that both these factors and others contribute to neoplastic development and progression. Microsatellites are short tandem repeat sequences which are located in the intron segments of the genome. These noncoding sequences range from 2 to 6 base pairs. An increase or decrease in the number of repeat sequences is referred to as microsatellite instability, also referred to as genetic instability. It is thought that microsatellite instability arises as a result of defects in DNA repair process. During DNA synthesis, the DNA repair genes ensure that the correct nucleotide is incorporated into the newly synthesised DNA strand, so when a mismatch base is incorporated, this is promptly removed and replaced with the correct base. However, if the repair system is defective this would give rise to numerous genetic aberrations along that region of the genome. Recently, microsatellite instability and allelic imbalance/loss of heterozygosity have been shown to play an important role in the development of many cancers, especially colorectal cancer (CRC) associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. This study was undertaken to investigate microsatellite instability and allelic imbalance in colorectal and oesophageal carcinomas in the KwaZulu Natal region of South Africa. The molecular analysis was correlated with clinicopathological data to establish a baseline level on which further studies could be performed. In addition, this study represents the first fluorescent based microsatellite analysis of these two common cancers in South Africa. Normal and tumour DNA was isolated from formalin fIxed paraffin embedded tissue. Fluorescent-based DNA technology using an automated DNA sequencer (Alf Express Automated DNA Sequencer) was employed. CY5 labelled primers for microsatellite markers (DCC, D18S34, D18S58, D3S659, D2S123 and D3S1255) were used. The data was captured and analysed using the Fragment Manager Software. The informativity of the microsatellite markers used in this study ranged from 50% to 71.8%. LOH/AI in the region of the DCC gene in the under 35 years of age CRC was 39.1%, while MSI in this region occurred in 31.25% of cases. The DNA repair gene status in these young patients was as follows: LOH/AI: 31.3% and MSI: 40.4%. In the over 50 years of age CRC, LOH/AI in the 18q region was 28% and MSI was 38%. The DNA repair genes (hMSH2 and hMLH1) in this cohort showed LOH/AI in 24% and MSI also in 24%. As regards oesophageal cancer, LOH/AI in the 18q region was 20.5% and MSI 7.7%. The repair genes showed LOH/AI in 17.9% and MSI in 10.25% of cases. When the molecular events were correlated with clinicopathological features, no statistically significant pattern emerged. However, it must be remembered that relatively small numbers of cases (39) were analysed.In conclusion: • No statistical correlation was found between clinicopathological characteristics and the molecular analysis in either CRC and oesophageal cancer. • LOH/AI and MSI was higher in the under 35 age group. • LOH/AI and MSI in 18q, 2p and 3p in sporadic CRC were similar to other fluorescent-based studies in patients over 50 years of age. • LOH/AI and MSI in 18q, 2p and 3p in oesophageal cancer was similar to studies from other geographical areas. • Finally, fluorescent-based microsatellite PCR and analysis was found to be an objective and efficient technique. / Thesis (Ph.D.)-University of Natal, 1998.

Physical activity (PA) is related to prevention and rehabilitation (rehab) of oncology patients, however little is known about PA habits of patients with cancer. Purpose. The purpose of this study was to assess and characterize PA habits, fatigue, and mood states of cancer survivors from before participation in an exercise rehab program to the final week of a 16 session exercise rehab program. Methods. Eleven subjects (9 women, 2 men, with an average age 60.9±1 0.1 years) wore an Actigraph GT1M accelerometer and New Lifestyle series pedometer a week before beginning an exercise rehab program (baseline), the first week (week 1) and the final week of exercise rehab (week 8). Intensity counts/minute and steps were measured by the GT1M and steps were calculated by the pedometer. Results. Ten subjects were classified under the sedentary step index, walking <5,500 steps/day and further grouped under the subcategory for chronic diseased individuals proposed by Tudor-Locke and Myers of 3,500-5,500 steps/day. One subject was recorded by the accelerometer to meet the Surgeon General, American College of Sports Medicine/Center for Disease Control and Prevention, the American Cancer Society, and 10,000 step/day PA guidelines throughout the study. The accelerometer underestimated rehab activity of 4 subjects who exercised on the Nu-step during rehab. PA habits of steps and intensity varied at baseline, week 1, and week 8 and on rehab and non-rehab days. There were no patterns seen determined by diagnosis, treatment, or staging of cancer. Five subjects increased their 6 minute walk distance, 6 subjects decreased in total mood disturbance, and 4 subjects lowered their perception of fatigue. Conclusion. The intervention, exercise, with 11 cancer survivors maintained PA habits, functional ability, fatigue, and mood states over time and on rehab and non-rehab days. / School of Physical Education, Sport, and Exercise Science

Educational programs covering the technical, treatment and emotional aspects of a cancer diagnosis have been shown to reduce anxiety levels, boost compliance with treatment regimens and improve survival rates. This study was designed to evaluate whether newly diagnosed cancer patients, after reviewing an educational intervention, felt they experienced decreased stress levels and more informed decision making ability. A descriptive, evaluative study was designed. Seventy-five newly diagnosed cancer patient's evaluation forms were examined. Responses were reviewed to see if these patients placed an important versus unimportant value on the individual components of an educational packet. Their responses were tallied and the results showed that an overwhelming majority of the patients felt that the packet components were important in helping them feel decreased stress levels and more informed in their decision making regarding their diagnosis of cancer. It was also determined that the majority of patients felt that the packet components were easy to understand. / Department of Physiology and Health Science

There is no abstract available for this dissertation. / Department of Educational Studies

Doctor of Health Science / It is well documented that for prostate cancer patients undergoing radiation therapy there is a correlation between target volume displacement and changes in bladder and rectal volumes. However, these studies have used a methodology that has captured only a subset of all treatment positions. This research used daily Computer Tomography (CT) imaging to comprehensively assess organ volumes, organ motion and their effect on dose, something that has never been performed previously, thus adding considerably to the understanding of the topic. Daily CT images were obtained using a Siemens Primus Linear Accelerator equipped with an in-room Somatom CT unit in the accelerator suite, marketed as ‘Primatom’, to accurately position the patient prior to treatment delivery. The internal structures of interest were contoured on the planning workstation by the investigator. The daily volume and location of the organs were derived from the computer to assess and analyse internal organ motion. The planned dose distribution was then imported onto the treatment CT datasets and used to compare the planned dose to i) the actual isocentre, where the isocentre was actually placed for that fraction, ii) the uncorrected isocentre, by un-doing any on-line corrections performed by the treatment staff prior to treatment delivery, and iii) the future isocentre, by placing the isocentre relative to internal organ motion on a daily basis. The results of this study did not confirm a statistically significant decrease in rectum volumes over time (hypothesis 1), however large fluctuations in bladder volume were confirmed (hypothesis 2). Internal organ motion for the rectum and bladder was demonstrated to be related to organ filling. Ideal planning volumes for these organs have been reported to minimise systematic and random uncertainty in the treatment volumes. An observed decrease in prostate volume over time, a systematic uncertainty in the location of the prostate at the time of the planning CT scan and a significant relationship between prostate centre of volume and rectum and bladder volumes has resulted in a recommendation that patients should be re-scanned during treatment to ensure appropriate clinical target volume coverage. A significant relationship between rectal and bladder volumes and the dose delivered to these organs was found (hypothesis 3). The dose delivered to the planning target volume was not related to the rectal or bladder volumes, although it was related to the motion of these organs. Despite these results only minimal effects on the dose delivered to any of the three isocentres occurred, indicating that the planned dose was accurately delivered using the methodology presented here (hypothesis 4). However the results do indicate that the patient preparation instructions need to be improved if margins are to be reduced in the future. It is unrealistic to assume that Image Guided Radiation Therapy will ever become routine practice due to infrastructure costs and time limitations. This research will inform radiation therapy centres of the variables associated with prostate cancer treatment on a daily basis, something that has never before been realistically achievable. As a result centres will be able to devise protocols to improve treatment outcomes.

Thesis (M.S.)--University of Toledo, 2008. / Typescript. "Submitted as partial fulfillments of the requirements for The Master of Science in Pharmaceutical Sciences in Pharmacology and Toxicology." "A thesis entitled"--at head of title. Bibliography: leaves 47-49.

Thesis (Ph.D.)--University of Alberta, 2009. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Faculty of Nursing. Title from pdf file main screen (viewed on October 31, 2009). Includes bibliographical references.

Thesis (M.S.)--University of Michigan, 1990.