A Dissertation submitted to the Faculty of Health Sciences, School of Public Health, University of the Witwatersrand, to fulfil the requirement to acquire a degree of Master of Science in Medicine Johannesburg 30 September 2014 / Background In South Africa cervical cancer has an age standardised incidence rate of 23 per 100 000 in women below the age of 35 and 76 per 100 000 amongst women over 35. The National Department of Health (NDoH) introduced the national cervical cancer screening policy guidelines in 2000, with the aim to screen 70% of women aged between 30 and 59 over a 10-year period. Health managers at provincial and district level were expected to implement this policy at their respective levels. Research has shown that implementing national health policies is often challenging due to management weaknesses, including the lack of guidelines or tools on how managers should plan and allocate budget for services. Aim The aim of this study is to develop and test an approach to planning and budgeting that would assist health managers to follow a rational process to plan and estimate budget requirements for implementing the cervical cancer screening policy at subnational level. Method This study was conducted in three districts in South Africa. The study was conducted in four phases. A situational analysis of budgeting practices was conducted in the first phase, to describe existing planning and budget allocation practices for cervical cancer screening programmes in the study sites and identify any existing gaps. The process requirements for implementing a cervical cancer screening programme were then identified prospectively in the second phase. Informed by the situation analysis and the process requirements, a computer-based planning and budget estimation program was developed in the third phase and tested through interviews with key informants in the fourth phase of the study. Results The situational analysis revealed a lack of involvement of interviewed programme managers at all the levels, in planning and budgeting for implementing cervical cancer screening programmes. The participants’ descriptions of budget allocation processes indicated that there was no defined process for allocating budget to services and the allocations were not specifically informed by assessed programme needs in their respective areas of jurisdiction. Process requirements for cervical screening were identified and documented for the following aspects of a cervical screening programme: calculating target population to inform planning for service provision, staff and equipment audits, equipment and supplies, material required for systems functioning (e.g., tools, forms, guidelines), transport and communication systems, community information education and communication (IEC) strategies, staff training, laboratory services and services for the treatment of High grade Squamous Intraepithelial Lesions (HSIL). A computerbased planning and budget estimation program, which could enable managers to define and quantify resources needed to implement a cervical screening programme was developed, informed by the documented process requirements. The testing of the computerised planning and budget estimation program indicated that the program could improve planning and help managers to estimate budget requirements for implementing cervical screening. Respondents indicated that the program was relatively easy to use and also felt that it could potentially be useful for programme planning as follows: a) it could serve as a tool for programme needs assessment, b) it could facilitate rational budget estimations, c) managers could use it as a bottom-up tool to motivate for resources, and d) managers could use it to refute inadequate budget allocations where possible. Conclusion The findings of the situational analysis support existing literature in revealing very little if any change in relation to inherent challenges in implementing cervical cancer screening services in South Africa. The findings of this study are relevant for public health programme planning and budgeting beyond cervical screening. Since managers at sub-national level are delegated to implement policy, it is imperative that they are provided with tools that may guide them to plan and budget for services on the basis of needs in their areas of jurisdiction. This study provides one such tool.

O objetivo deste trabalho foi comparar o prognóstico de sobrevida da graduação histológica após efeito da quimioterapia (graus I versus II de Huvos), visando também identificar fatores prognósticos no que diz respeito à sobrevida livre de recidiva local (SLRL), sobrevida livre de metástase (SLM) e sobrevida global (SG), em pacientes portadores de osteossarcoma primário não metastático ao diagnóstico. Vinte e quatro entre 45 pacientes admitidos no Instituto de Ortopedia e Traumatologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo IOT/HC/FMUSP, entre 2000 e 2004, foram eleitos para o estudo, segundo os critérios de inclusão e exclusão utilizados. As probabilidades de sobrevida acumuladas foram feitas pela técnica de Kaplan-Meier e os índices I e II de HUVOS comparados pelos testes de Log Rank. A análise multivariada foi feita pela técnica de regressão logística com modelo de risco proporcional de COX e a validade estatística estabelecida para valores de p<0,05. Os graus I e II de Huvos, quando comparados, não foram considerados de valor prognóstico em nenhuma das sobrevidas estudadas (SLRL, SLM e SG). Os fatores adversos que influenciaram o risco de recidiva local e a sobrevida global, na análise univariada foram: subtipo histológico diferente do osteoblástico (p=0,017) e o tamanho tumoral maior que 15 cm (p=0,048). Em relação à SLM o subtipo não osteoblástico (p=0,007) teve um pior prognóstico. O subtipo histológico manteve sua significância na análise multivariada em todas as sobrevidas estudadas / The purpose of this study was to compare the prognostic of survivor of histologic graduation post chemotherapy (Huvos´s grade I versus II), aiming to identify prognostic factors concerning to local recurrence free survival (LRFS), metastases free survival (MFS) and overall survival (OS) in patients with nonmetastatic primary osteosarcoma. This study included 24 patients registred in the Instituto de Ortopedia e Traumatologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - Brazil, from 2000 to 2004. Survivor rates were calculed using Kaplan-Meier method. Huvos´s grade (I e II) were compared using the Log Rank test. Cox proportional hazards model was used for multifatorial analysis. Statistical significance was defined as a p value less than 0, 05. The Huvos´s grade I versus II was not significant factor for LRFS, MFS or OS. The adverse factors for LRFS and OS in univariate analysis were nonosteoblastic histologic subtypes (p=0,017) and large tumor (p=0,048). For MFS nonosteoblastic histologic subtypes (p=0,007) had worse prognostic. The histologic subtypes maintained their significance in multivariate testing on all studied survivor

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Stereotactic Body Radiation Therapy (SBRT) is a modern precision radiation therapy to deliver the dose in 1 to 5 fractions with high target dose conformity, and steep dose gradient towards healthy tissues. The dose delivered is influenced by the leaf width of the MLC, especially in case of SBRT. Treatment plans with high definition (HD) MLC having leaf-width 2.5 mm and normal MLC having leaf-width 5 mm, were compared to quantify dosimetric and radiobiological parameters. Dosimetric parameters conformity indices (CI), gradient indices (GI) and heterogeneity indices (HI) were compared. The radiobiological parameters were evaluated by normal tissue complication probability (NTCP) and tumor control probability (TCP) based on the equivalent uniform dose (EUD). The results show that there is dosimetric and radiobiological merit of the HD MLC over the normal MLC. However, the improvement is not consistent with all the plans and thus further research is required prior to conclusion. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection

The accuracy of dose calculation algorithms used for radiotherapy treatment planning play a significant role in the clinical outcome of various treatment regimens. Heterogeneities in human anatomy such as lung, air cavities, bone, soft tissue and fat present challenges to the dose calculation algorithms as they are prone to disrupt the charged-particle equilibrium. Monte Carlo (MC) based dose calculation algorithms are proven to be superior to all the current analytical algorithms owing to their ability to account for all the physical interactions that are involved in radiation transport. Numerous publications have examined the differences in physical doses calculated by analytical algorithms when compared to MC in dealing with heterogeneities. However, before this work the clinical significance of these differences in physical dose has never been investigated in detail. An EGSnrc, BEAMnrc and DOSXYZnrc based MC dose calculation engine was set up in a parallel computing environment to simulate three-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiation therapy (IMRT). A Varian 2100 C/D accelerator head was modeled and validated to match measurements of open and dynamic wedged fields in a homogeneous water phantom which was found to be in good agreement with measurements within 2%/2mm and 3%/3mm respectively. In addition, MC calculated doses in a heterogeneous lung phantom were compared to radiochromic film measurements. Overall, there was good agreement between the two, although large differences of upto 16% were found in some cases. This dose calculation system was used to perform MC simulations on computed tomography (CT) images. The clinical impact of the differences in absolute doses calculated by various photon dose calculation algorithms for two clinical tumour sites was investigated. The tumour control probability (TCP) and normal tissue complication probability (NTCP) were estimated using well established bio-mathematical radiobiological models. This work includes the analysis of 7 convolution (i.e. pencil-beam) and convolution-superposition (CS) based photon dose algorithms available in commercial treatment planning systems (TPSs) as well as MC, in treatment plans of non-small cell lung carcinoma (NSCLC) and nasopharyngeal carcinoma (NPC). In both NSCLC and NPC, the convolution algorithms overestimate the dose to the tumour and hence overestimate the TCP to up to 45%. Some of the CS algorithms were comparable to MC though others exhibit significant differences. In NSCLC, the absolute differences in the NTCP values with radiation pneumonitis and rib fracture as end points were not as large as the differences found in the TCPs. On the other hand, in NPC, the overestimation of probability of occurrence of xerostomia by some TPS algorithms may be preventing dose escalation. Parameters for the TCP model were derived by fitting the TCP predictions to published outcome for four widely varying dose-fractionation regimens for a patient cohort undergoing radical radiotherapy treatment for NSCLC. The derived parameter sets strongly depend on the accuracy of the dose calculation algorithm involved. Parameters derived based on dose-distribution data sets obtained using one particular dose calculation algorithm may not hold good when evaluating treatment plans calculated with a different algorithm. In this sub-study, the influence of dose calculation algorithms on TCP model parameters was evaluated. Significant differences were found in TCPs when calculated with inconsistent parameters. Hence, the choice of dose calculation algorithm is crucial and although some algorithms generally perform close to MC in handling inhomogeneities, it is necessary to understand how the underlying differences affect the predicted clinical outcome.

O câncer de laringe é uma das neoplasias mais comuns das vias aéreas superiores. No Brasil a maioria dos casos são diagnosticados nos estádios clínicos III ou IV. Nos tumores T4a os resultados terapêuticos são discordantes na literatura. Alguns estudos referem melhores taxas de sobrevida global com o tratamento cirúrgico e outros demonstraram taxas de sobrevida global semelhantes entre pacientes submetidos a laringectomia total e os submetidos a quimioradioterapia. Concomitante ao surgimento destas novas modalidades terapêuticas, descritas nas últimas décadas, observou-se nos Estados Unidos queda nas taxas de sobrevida dos pacientes com tumores de laringe. O objetivo deste estudo foi avaliar fatores prognósticos em pacientes portadores de carcinoma epidermóide de laringe cT4aN0-3M0 tratados em quatro instituições - em três diferentes países - de acordo com variáveis demográficas, clínicas, terapêuticas e anatomopatológicas. Em relação as variáveis clínicas, foram observadas piores taxas de sobrevida global nos pacientes com mais de 65 anos, nos classificados como ASA III ou IV, nos casos com tumores com extensão para base de língua. Dentre os pacientes submetidos ao tratamento cirúrgico as piores taxas de sobrevida global foram observados nos casos com margens de ressecção comprometidas, nos com invasão vascular presente e os com estádio linfonodal pN2 ou pN3. As taxas de sobrevida global e câncer específica não diferiu entre os pacientes submetidos ao tratamento cirúrgico ou quimioradioterápico. Por outro lado as melhores taxas de sobrevida livre de recorrência local foi evidenciada nos pacientes submetidos ao tratamento cirúrgico. Na análise multivariada, foram fatores prognósticos independentes para o risco de óbito, a classificação pelo ASA (III ou IV) e o estadiamento linfonodal patológico (pN2 ou pN3) entre os pacientes submetidos à cirurgia, a faixa etária superior a 65 anos, a extensão do tumor para base de língua, para partes moles perilaríngeas e a presença de mais de uma estrutura invadida pelo tumor nos pacientes submetidos a quimioradioterapia. Em conclusão, diversas variáveis são potenciais fatores prognósticos relacionados a sobrevida global, no entando somente a classificação como ASA III ou IV e o estádio pN2 ou pN3 foram identificados como fatores prognósticos independente para o risco de óbito nos pacientes submetidos ao tratamento cirúrgico. Nos pacientes submetidos ao tratamento com quimioradioterapia a faixa etária superior a 65 anos, extensão para base de língua, para partes moles perilaríngeas e presença de duas ou mais estruturas invadidas foram os fatores prognósticos independentes para o risco de óbito / Laryngeal cancer is one of the most common neoplasms of the upper airways. In Brazil most cases are diagnosed at stages III or IV. In T4a tumors, there are discordant treatment results in the literature. Some studies refer to improved rates of overall survival with surgical treatment while other studies show similar rates of overall survival between patients submitted to total laryngectomy or chemoradiotherapy. Concomitant to the emergence of these new therapeutic modalities described in recent decades, a decline in survival rates of patients with laryngeal tumors has been registred in the United States. The aim of this study was to assess prognostic factors in patients with clinical stage cT4aN0-3M0 laryngeal epidermoid carcinomas treated in four institutions, in three different countries, according with demographic, clinical, therapeutic and pathologic variables. With regard to clinical variables, worse rates of overall survival were observed in patients older than 65 years, classified as ASA III or IV, and tumors with tongue base extension. Among the patients who underwent surgical treatment, the worse rates of overall survival were in the cases of involved surgical margins, with vascular invasion present, and in cases with pathological metastatic lymph nodes pN2 or pN3 staging. The rates of overall survival and cancer specific survival did not differ among patients who underwent surgical treatment or chemoradiotherapy. Conversely, improved local recurrence-free survival rates were registred in patients who underwent surgical treatment. In multivariate analysis, the independent prognostic factors for the risk of death, were ASA III or IV classification, and pathological lymph nodes pN2 or pN3 staging among the patients who underwent surgery; age above 65 years, tumors with tongue base extension, extension into the perilaryngeal soft tissues and the presence of more than one structure invaded by tumor in patients who underwent chemoradiotherapy. In conclusion, several variables are potential prognostic factors related too verall survival, however only ASA III or IV and stage pN2 or pN3 were in dependent prognostic factors for the risk of death in patients undergoing surgical treatment. In patients undergoing chemoradiotherapy: age above 65 years, tumors extension to the base of tongue, perilaryngeal soft tissue invasion and presence of two or more structure sinvaded were independent prognostic factors for the risk of death

by Koo Sze Tak. / Thesis (M.Ph.)--Chinese University of Hong Kong, 1988. / Bibliography: leaves 148-165.

Leung Chun-on, Paul. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 149-167). / Content Page / Acknowledgments --- p.7 / Chapter / Chapter Chapter1 --- Introduction --- p.8 / Chapter Chapter2 --- Literature Review --- p.13 / Chapter 2.1 --- Anatomy of the cervix --- p.13 / Chapter 2.2 --- Classification --- p.14 / Chapter 2.2.1 --- Cervical intraepithelial neoplasia (CIN) --- p.14 / Chapter 2.2.2 --- Cervical cancer --- p.17 / Chapter 2.2.3 --- Incidence and screening --- p.21 / Chapter 2.2.4 --- Etiology / Chapter 2.2.4.1 --- Sexual and reproductive factors --- p.23 / Chapter 2.2.4.2 --- Smoking as a risk factor --- p.23 / Chapter 2.2.4.3 --- Male partner contribution --- p.24 / Chapter 2.2.4.4 --- Human papillomaviruses and cervical cancer --- p.24 / Chapter 2.2.4.5 --- Oral contraceptive pills --- p.27 / Chapter 2.2.4.6 --- Oncogenes and tumour suppresser genes --- p.28 / Chapter 2.2.4.7 --- Oncogenes and cervical cancer --- p.35 / Chapter 2.3 --- Immunohistochemical technique in cancer study / Chapter 2.3.1 --- Principle of immunostaining --- p.39 / Chapter 2.3.2 --- Fixation --- p.40 / Chapter 2.3.3 --- Section preparation --- p.41 / Chapter 2.3.4 --- The choice of antibodies --- p.41 / Chapter 2.3.5 --- Enzyme labels --- p.42 / Chapter 2.3.6 --- Blocking endogenous enzymes --- p.43 / Chapter 2.3.7 --- Blocking background staining --- p.43 / Chapter 2.3.8 --- Dilution preparation --- p.44 / Chapter 2.3.9 --- The Avidin-Biotin technique --- p.44 / Chapter 2.3.10 --- Control --- p.47 / Chapter 2.3.11 --- Antigen retrieval --- p.47 / Chapter 2.3.12 --- Cell counting and scoring --- p.49 / Chapter 2.4 --- The application of Polymerase Chain Reaction Single-Strand Conformation Polymorphism(PCR-SSCP) in cancer study --- p.52 / Chapter Chapter3 --- Materials and Methods --- p.56 / Chapter 3.1 --- Materials --- p.56 / Chapter 3.2 --- Methods --- p.61 / Chapter 3.2.1 --- Specimens collection --- p.61 / Chapter 3.2.2 --- Antibodies preparation --- p.63 / Chapter 3.2.3 --- Immunohistochemical staining and antigen retrieval procedures --- p.63 / Chapter 3.2.4 --- Cell counting and scoring --- p.68 / Chapter 3.2.5 --- PCR-SSCP analysis for myc gene mutation --- p.70 / Chapter 3.2.5.1 --- DNA extraction --- p.70 / Chapter 3.2.5.2 --- PCR --- p.72 / Chapter 3.2.5.3 --- Preparing the single strand DNA --- p.73 / Chapter 3.2.5.4 --- Electrophoresis --- p.73 / Chapter 3.2.5.5 --- Gel drying and scanning --- p.77 / Chapter 3.2.6 --- Statistical analysis --- p.77 / Chapter Chapter 4 --- Result --- p.78 / Chapter Chapter 5 --- Discussion --- p.126 / Chapter Chapter 6 --- Conclusions --- p.144 / Reference --- p.148

by Lai Duen Mun. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 82-91). / Abstract --- p.ii / Acknowledgements --- p.iii / Table of Contents --- p.vi / List of Tables --- p.v / List of Appendices --- p.vii / Introduction --- p.1 / Method --- p.28 / Results --- p.41 / Discussion --- p.63 / Limitation and Recommendation --- p.78 / Reference --- p.82 / Appendices --- p.92

by Wang Wei. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1991. / Includes bibliographical references (leaves 154-168). / ACKNOWLEDGMENTS --- p.v / SUMMARY --- p.vi / PUBLICATIONS --- p.viii / STATEMENT OF ORIGINALITY --- p.ix / LIST OF ABBREVIATIONS --- p.x / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter CHAPTER 2 --- LITERATURE REVIEW --- p.5 / Chapter 2.1 --- Chromosome --- p.6 / Chapter 2.2 --- Chromosome and Human Disease --- p.9 / Chapter 2.3 --- Chromosome and Tumour --- p.12 / Chapter 2.4 --- Chromosome in Gynaecologic Tumours --- p.17 / Chapter 2.4.1 --- Cervical tumour --- p.17 / Chapter 2.4.2 --- Uterine corpus tumour --- p.20 / Chapter 2.4.3 --- Ovarian tumour --- p.23 / Chapter 2.5 --- Methodology in cytogenetics --- p.26 / Chapter 2.5.1 --- Materials --- p.27 / Chapter 2.5.2 --- Methods of chromosome preparation --- p.28 / Chapter 2.5.3 --- Karyotype analysis --- p.34 / Chapter 2.6 --- Problems of cytogenetic analysis in solid tumour --- p.42 / Chapter CHAPTER 3 --- MATERIALS AND METHODS --- p.47 / Chapter 3.1 --- Chemicals and Solutions --- p.48 / Chapter 3.2 --- Chromosome preparation from solid gynaecologic tumours --- p.50 / Chapter 3.2.1 --- Solid tumour specimens --- p.50 / Chapter 3.2.2 --- Chromosome preparation --- p.54 / Chapter 3.3 --- Chromosome preparation from an established ovarian carcinoma cell line --- p.61 / Chapter 3.3.1 --- Origin of OCC1 cell line --- p.61 / Chapter 3.3.2 --- Characteristics of OCC1 cell line --- p.61 / Chapter 3.3.3 --- Maintaining of OCC1 cell line --- p.62 / Chapter 3.3.4 --- Chromosome preparation --- p.62 / Chapter 3.4 --- Karyotype analysis --- p.65 / Chapter CHAPTER 4 --- RESULTS --- p.66 / Chapter 4.1 --- Cytogenetic features of gynaecologic solid tumour --- p.67 / Chapter 4.1.1 --- Cervical cancer --- p.67 / Chapter 4.1.2 --- Uterine corpus cancer --- p.94 / Chapter 4.1.3 --- Ovarian cancer --- p.104 / Chapter 4.2 --- Cytogenetic features of OCC1 ovarian carcinoma cell line --- p.114 / Chapter CHAPTER 5 --- DISCUSSION --- p.123 / Chapter 5.1 --- Methodology of chromosome preparation in solid tumour --- p.124 / Chapter 5.2 --- Chromosome changes in gynaecologic solid tumour --- p.126 / Chapter 5.2.1 --- Cervical cancer --- p.126 / Chapter 5.2.2 --- Uterine corpus cancer --- p.132 / Chapter 5.2.3 --- Ovarian cancer --- p.138 / Chapter 5.2.4 --- In summary --- p.141 / Chapter 5.3 --- Chromosome changes in an OCC1 ovarian carcinoma cell line --- p.143 / Chapter CHAPTER 6 --- CONCLUSION --- p.148 / REFERENCES --- p.154