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

published_or_final_version / Community Medicine / Master / Master of Public Health

Background Colorectal cancer (CRC) is one of the most common cancers with high morbidity and mortality among both genders and yet it carries a better prognosis when detected early. Colorectal cancer screening using faecal occult blood test (FOBT) is proven to be cost-effective, however worldwide FOBT uptake rate is suboptimal which directly affects the cost-effectiveness of the screening program. Identifying those factors that influence the uptake of colorectal cancer screening using FOBT will allow implementation of relevant measures when planning a population based screening program. Methods A structured electronic search using PubMed and Medline was conducted in order to identify studies that included factors influencing the uptake of CRC screening by using FOBT. Qualities of included studies were assessed by quality assessment checklist STROBE. Results Factors that contributed to the low uptake rate of CRC screening by FOBT were identified and summarized. They were broadly divided into 3 groups. Demographic factors: age, gender, social economic status, insurance status and education, for ethnicity, employment status and obesity further studies in the future may be needed. Subject factors: subject’s attitudes and knowledge towards CRC screening, type of FOBT screening, health concerned behavior, frequency of clinical visit and physiciancomment. Provider factors: health care system factor and physicians’ factors. Conclusion Different factors, in particular those factors that were associated with low FOBT uptake rate in CRC screening, were reviewed and summarized in this paper. With the continuous effort from worldwide as well as local investigators, timely measures can be implemented to tackle this deathly disease and to ensure cost effectiveness of a screening program. / published_or_final_version / Public Health / Master / Master of Public Health

BACKGROUND: Colorectal cancer is usually asymptomatic until later stage and the 5-year survival for stage III or IV are 68% and 10 % because of delayed diagnosis. Worldwide, it is the 4th leading cause of death among cancers which accounted for 694,000 deaths in 2012. While healthy diet and lifestyle helps prevent colorectal cancer, increased surveillance through screening has been suggested to attribute to the decreasing trend of colorectal cancer incidence in the United States in the past decade. Identifying what type of colorectal cancer screening methods is more effective is of public health relevance to Hong Kong where colorectal cancer ranks the top leading cancer. OBJECTIVES: To conduct a systematically review on current literatures to examine whether endoscopy screening by flexible sigmoidoscopy or colonoscopy is more effective for reducing the mortality and incidence of colorectal cancer than no screening as many colorectal cancers arise from adenomatous polyps, which polypectomy is hypothesized to be protective. Meanwhile, different countries adopt different kinds of colorectal cancer screening modalities, but yet, there is no agreement for the types of screening. METHODS: Four databases, Medline (OVIDSP), Pubmed, CINAHL plus (EBSCOhost), Embase (OVIDSP) were used to search for published journals. Reference list of the identified articles were screened for more relevant studies. RESULTS: A total of 8 studies were included in this systematic review. There were only 2 randomized controlled trials (RCTs) on screening for colorectal cancer using flexible sigmoidoscopy in asymptomatic and average-risk people and no RCT was found for colonoscopy. Based on the studies reviewed, findings were inconsistent on whether endoscopy screening is more effective in reducing overall colorectal cancer incidence and mortality than no screening. Endoscopy screening, either sigmoidoscopy or colonoscopy was associated with lower incidence of distal colorectal cancer. CONCLUSION: Screening by flexible sigmoidoscopy or colonoscopy is not clearly associated with lower overall colorectal cancer risks based on current systematic review. Randomized controlled trials or retrospective cohorts are required to clarify the effectiveness of endoscopy screening before considering the implementation of population-wide colorectal cancer screening. / published_or_final_version / Public Health / Master / Master of Public Health

Colorectal cancer is a serious health problem that has concerned people for decades. In Hong Kong, it is the most common cancer and the second leading cause of death. Among colorectal cancer patients, around 40-50% of them will develop metastatic disease. Chemotherapy is playing an important role all the time in the treatment of advanced colorectal cancer. In the past decade, the application of targeted therapies in treatment has largely improved efficacy and prolonged survival. Bevacizumab and cetuximab are two commonly used targeted agents in daily clinical practice of Hong Kong. Since multiple clinical trials have studied bevacizumab and cetuximab in combination with other chemotherapies, limited data is available in Asian patients. Therefore, we conduct three 5-year retrospective analyses based on patients received treatment in Hong Kong Queen Mary Hospital, to investigate the clinical efficacy and toxicity of those two drugs. The first study examined the use of bevacizumab in treating KRAS mutated type patients. We found the efficacy and results were consistent with historical data. In the next analysis of cetuximab, comparable data were shown which suggested the consistency with previous studies. The last study is aim to compare bevacizumab and cetuximab in previously untreated wild-type KRAS patients. Identical response rates, progression-free survival and overall survival were finally reported. / published_or_final_version / Medicine / Master / Master of Philosophy

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Errata pasted onto t.p. verso. / Bibliography: leaves 129-148. / 148 leaves : [3] col. ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Investigates the relationship between folate states and colorectal cancer risk using the rat AOM intestinal cancer model. Results indicate that folate status can play an important role in modulating colorectal carcinogenesis. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 2000

Background: It is well recognized that not all patients with stage C colorectal cancer (CRC) derive a survival benefit from adjuvant chemotherapy. It would therefore be advantageous to identify factors that define a target group for treatment. It has been suggested that those most likely to benefit are women with proximal tumours. Recent work has suggested microsatellite instability (MSI) may be a useful marker however the limited studies performed are conflicting. Aim: To determine if gender, site, tumour histology or microsatellite (MSI) status predict survival benefit from 5FU-based adjuvant chemotherapy in stage C CRC. Method: Data was collated on stage C colorectal cancer cases that underwent curative resection over a 20-year period (inclusive of years prior to standard chemotherapy). Pathology was re-evaluated, DNA extracted from the formalin fixed paraffin specimen and MSI status established. Primary endpoint was cancer-related death. Kaplan-Meier curves were constructed for univariate analysis and differences analysed by log rank test. Multivariate analysis was performed using Cox proportional hazard model adjusting for age, gender, site, distinct pathological variables and MSI. A compounding effect between these factors and chemotherapy benefit was measured by interaction testing Results: 811 unselected cases were included in the study. Thirty-seven percent received chemotherapy. Chemotherapy significant improved cancer-specific survival (HR of dying 0.66 (95% CI 0.52-0.83 p=0.0003). Female gender offered a survival advantage overall (HR 0.81 95% CI 0.68-0.97; p=0.02) however site did not influence outcome (HR 1.03). On interaction testing, gender, site and tumour histology did not significantly influence the survival effect of chemotherapy. 802 cases were included in the MSI analysis of which 77 exhibited MSI. MSI status did not influence prognosis (HR of cancer death 1.45, 95% CI 0.90-2.21; p= 0.13). However, in the non-chemotherapy cohort, MSI conferred a significantly less favourable outcome (HR 1.89, 95%CI 1.13-3.16; p= 0.02). Chemotherapy produced a survival benefit in both the MSI (HR 0.08 95% CI 0.02-0.27; p=<0.0001) and the microsatellite stable (MSS) cohort (HR 0.62, 95% CI 0.47-0.81; p=0.001). On interaction testing, neither compounded the benefit of chemotherapy, however of all the tested parameters, MSI came closest to significance (p=0.08). Conclusion: These results suggest that 5FU-based adjuvant chemotherapy for stage C colorectal cannot be targeted using gender, tumour site, histological characteristics or MSI. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1522132 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2010

Thesis (Ph. D.)--University of Toronto, 2007. / Source: Dissertation Abstracts International, Volume: 68-05, Section: B, page: 2991.

Colorectal cancer (CRC) is one of the most common forms of neoplasia in Western populations but is uncommon in sub-Saharan Africa. In developing countries such as South Africa, differences in lifestyles and environment exist between the various population groups. These differences and the diverse patterns of cancer that exist, provide an ideal opportunity to study the pathogenesis of colorectal cancer. In South Africa, the incidence of CRC in black patients is approximately ten fold lower than that of white South African patients. The majority of black South African CRC patients presents with tumours without macroscopic polyps. Recently five genes involved in DNA mismatch repair (MMR) have been implicated in hereditary nonpolyposis colorectal cancer (HNPCC). In this retrospective study, paraffin-embedded normal and tumour tissues from 109 black, and 110 Caucasian CRC patients were studied. To screen for the possible involvement of DNA mismatch repair genes, the presence of microsatellite instability (MSI) was investigated. In total 40 patients presented with MSI-H tumours, 27/109 (24,8%) tumours from black patients and 13/110 (11,8%) tumours from Caucasian patients. The proportion of MSI-H tumours from black patients attending Chris Hani Baragwanath Hospital (CHB) (12,2%; 5/41) and that of Caucasian patients is in accordance to published results on sporadic tumours. However the finding that 32,4% of black patients attending Kalafong and Pretoria Academic Hospitals, have tumours with MSI-H is much higher than is commonly reported in Western populations and is significantly higher than that of the Caucasian patients (p = 0.002; χ2-test). It has been observed that patients who present at CHB live mainly in urban Johannesburg/Soweto, in comparison to those seen at KPH who are mostly from peri-urban and rural areas. Failure of PCR amplification, owing to the absence of high quality tissue, allowed 32 of the 40 MSI-H tumours to be fully screened for mutations in hMLH1 and hMSH2 using exon-by-exon PCR single strand conformation polymorphism (SSCP) analysis. Sixteen pathogenic mutations were found in 14 tumours, 10/22 (45%) from black patients and 4/10 (40%) from caucasian patients. Five tumours presented with two mutations each, one is a compound heterozygote and the other four tumours are double heterozygotes. Ten of the sixteen mutations identified, are novel. Five (5/32; 16%) of the pathogenic mutations are germline in origin, four (4/22; 18%) of which were detected in tumours from black patients. Thus HNPCC was diagnosed in ~0,93% (1/107) of Caucasian and 3,85% (4/104) of black patients via germline mutations. The frequency of recognised DNA repair gene mutations in black patients with HNPCC is four times higher than that in Caucasian patients with HNPCC. This is consistent with the notion that penetrance of HNPCC cancer is independent of environmental factors which is true as the frequency of HNPCC in a low incidence population (black South Africans) is much higher than that of a high incidence population (Caucasian South Africans). A missense mutation in hMSH2 (codon 127) was identified in three black patients. It is listed in the ICG-HNPCC database as a pathogenic mutation (in a Nigerian family). However, further investigation demonstrated that this is a polymorphic change exclusive to black Africans. Somatic mutations were detected in 6 (27%) tumours from black and 3 (30%) tumours from Caucasian patients. In conclusion, the observed microsatellite instability and mutations in hMLH1 and hMSH2 thus clearly implicate the involvement of DNA mismatch repair genes in the pathogenesis of colorectal cancers of black and Caucasian South African patients. This study represents the first investigation of DNA mismatch repair genes in tumours from both population groups. It is also the first report of black South Africans with HNPCC. / Dissertation (MSc (Human Genetics))--University of Pretoria, 2005. / Genetics / unrestricted