A Dissertation submitted to the Faculty of Health Sciences of University of the Witwatersrand, Johannesburg, in fulfillment of the requirements for the degree of Master of Medicine in Surgery. Johannesburg, 2017 / Background: Hurthle cell neoplasms (HCN) are considered a variant of follicular thyroid neoplasms, and accounts for 3-10% of neoplasms of the thyroid gland. They include Hurthle cell adenomas (HCA) and carcinomas (HCC). Differentiating HCA from HCC preoperatively is currently not possible. We retrospectively searched for demographic and histopathological factors which can be used to predict the risk of malignancy in HCN. Aim: To determine the prevalence of HCC and its demographic factors and histopathological features that can be used to predict the risk of malignancy in HCN. Methods: Records of all patients who underwent thyroidectomy at Academic Hospitals associated with University of the Witwatersrand from January 2001 to October 2015 were reviewed. Patients’ demographic data and the final histology of HCN were further analyzed including pre-operative fine needle aspiration cytology (FNAC) results. Data collected included patients’ demographic, final histology, tumor size and preoperative FNAC result. Data was entered into Excel Spreadsheet and analyzed using STATICA 13.1 program. Results: At total of 2641 records of thyroidectomies were found of which 25.6% (676/2641) were for thyroid neoplasms. Only 15.8% (107/676) of the neoplasms were HCNs and 25.2% (27/107) of HCNs were HCCs. Hurthle cell carcinoma made up 5.6% (27/481) of thyroid carcinomas. 70.4% (19/27) of HCCs were incidentally found following thyroidectomy for multinodular goiter (MNG). The mean tumor size was significantly greater for carcinomas than for adenomas (4.9 cm vs. 3.5 cm; p = 0.016). The risk of malignancy increased from 11.1% when the size was less or equal to 1cm, through 33.3% for size of 1-4cm to 51.8% when the size was greater than 4cm in diameter. A total of 58 FNACs results of 107 HCNs were available for further analysis. Thirty one (53.4%: 31/58) of FNAC results were suspicious for HCN (Bethesda IV), seven (12.1%: 7/58) suspicious of papillary carcinoma (Bethesda V) and eight (13.8%: 8/58) were reported as benign (Bethesda II). Around 10.3% (6/58) were non-diagnostic (Bethesda I) whereas 8.6% (5/58) were reported as atypia of unknown significance (Bethesda III). Both HCA and HCC were more prevalent in females, 88.7% (71/80) and 77.8% (21/27); respectively. The mean age of the patients who had HCA and HCC in years was 52.3+/- 15.6 SD and 55.0 +/- 15.0 SD, respectively. Conclusion: Majority of HCCs are diagnosed following thyroidectomy for benign disease. Close to a quarter of HCNs are malignant and the risk of malignancy increases with size. Age and gender are not useful to predict malignancy in HCNs. We recommend total thyroidectomy for thyroid nodule greater than 4cm in diameter if FNAC result is suggestive of HCN as the risk of malignancy is above 50%. / MT2017

The problem with which this investigation is concerned is that of determining the nature of events leading to the change of normal cells into malignant cells. The design of the study is multi-phasic: (A) to establish the presence or absence of an oncongenic virion, (B) to demonstrate by use of the electron microscopy any ultracellular alteration in malignant or transformed tissues, (C) to investigate the nature of the transforming agent in the murine lymphosarcoma, and (D) to employ various methods to demonstrate cellular transformations in vivo and in vitro.

Tumour angiogenesis, the formation of new blood vessels within a tumour, is a hallmark of cancers, that allows them to grow beyond a critical size and to metastasize to other organs. As the key driver of tumour angiogenesis, αvβ3 integrin is both an established therapeutic target for anti-angiogenic drugs and a biomarker for imaging agents. Accurate detection of αvβ3 integrin in angiogenic tumours impacts patient prognosis and could report on therapy response. Over the last twenty years, novel αvβ3 integrin-targeted radiotracers have been developed for PET imaging of tumour angiogenesis. While most radiotracers have shown their utility as diagnostic tools, only a few focussed on evaluating response to treatment, partly due to complex biology of the integrin receptors. The aim of this project was the in-vitro biological testing of a novel αvβ3-targeted radiotracer, [3H]ZMPZAT71, and the corresponding unlabelled compound for targeted delivery of a cytotoxic drug, paclitaxel (PTX). Firstly, this piece of work involved validation of this radiotracer to assess expression of αvβ3 integrin. Secondly, [3H]ZMPZAT71 was investigated as a biomarker for assessing response to pharmacological inhibitors of cell signalling pathways. Thirdly, the targeting moiety (ZMPZAT71) conjugated with paclitaxel was studied for integrinmediated drug delivery. The results presented herein demonstrate that radiotracer binding to αvβ3 integrin is dependent not only on the expression levels, but also on the activation status of αvβ3 integrin. Furthermore, this piece of information was used to explain radiotracer binding in response to various pharmacological inhibitors of key cell signalling pathways. Additionally, the integrin-targeted chemotherapeutic exhibited selective cytotoxic effect, explained by enhanced apoptosis of cancer cells compared to PTX alone, together with anti-migratory and anti-invasive effects from the targeting moiety. This study provides valuable information about the molecular mechanisms regulated by αvβ3 integrin, supporting the development of integrin-targeted therapeutics and imaging.

Thesis (M. Ph.)--Chinese University of Hong Kong. / Bibliography: l. 73-82.

Thesis (M.D.)—Boston University

The maxilla and mandible may be affected by a wide variety of lesions of developmental, neoplastic or inflammatory origin. These lesions have a vast array of clinical and radiographic presentations from which a dentist forms a clinical provisional diagnosis and treats the lesions accordingly. The aim of this study was to determine the range, demographic and clinical features of all histologically diagnosed radiolucent jaw lesions in a New Zealand population over a twenty-year period. Additionally, the provisional diagnosis was compared to the histopathological diagnosis in an effort to gain an insight into the difficulties practitioners face in clinically diagnosing radiolucent jaw lesions. Material and Methods: From the histopathology diagnostic service at the University of Otago School of Dentistry all specimens with a diagnosis of a radiolucent jaw lesion between 1986 and 2006 were retrieved and classified into six diagnostic categories. For each lesion the age, gender, site, clinical presentation, clinicians provisional diagnosis and the final histological diagnosis was gathered and analysed. Results: During the study period 4983 specimens were identified as radiolucent jaw lesions. The diagnostic category with the largest number of specimens was inflammatory lesions (72.8%), followed by developmental odontogenic cysts (21.8%). Malignant tumours accounted for less than 1% of all specimens. Concordance of provisional and histopathological diagnoses ranged from 81.0% for nasopalatine duct cyst to 0% for the majority of intra-osseous malignant tumours. Conclusions: The range and demographic features of radiolucent jaw lesions in this study are comparable to that of other populations with a European majority. No radiolucent jaw lesion can be reliably accurately diagnosed from clinical presentation and radiographic appearance alone.

The purpose of this study was to investigate a) PTTG expression in pituitary adenoma subtypes, b) the correlation between PTTG expression and clinico-pathological variables in patients with Cushing’s disease with ACTH secreting pituitary adenomas, and c) PTTG expression in brain tumour subtypes. PTTG expression was investigated in 89 pituitary and 88 brain tumours, and 54 ACTH adenomas of patients with Cushing’s disease. Our results show that PTTG is expressed in the cytoplasm of pituitary adenoma cells, and at higher levels in GH adenomas, with lower PTTG expression levels being exhibited by PRL adenomas. Significant differences were noted between PTTG expression in medically treated and non-treated GH adenomas. However, PTTG expression in ACTH adenomas did not correlate with clinico-pathological variables, making it an unsuitable prognostic indicator in such tumours. In brain neoplasms, PTTG was expressed at higher levels in malignant tumours, whereas in less aggressive tumours, PTTG expression was considerably lower.

The purpose of this study was to investigate a) PTTG expression in pituitary adenoma subtypes, b) the correlation between PTTG expression and clinico-pathological variables in patients with Cushing’s disease with ACTH secreting pituitary adenomas, and c) PTTG expression in brain tumour subtypes. PTTG expression was investigated in 89 pituitary and 88 brain tumours, and 54 ACTH adenomas of patients with Cushing’s disease. Our results show that PTTG is expressed in the cytoplasm of pituitary adenoma cells, and at higher levels in GH adenomas, with lower PTTG expression levels being exhibited by PRL adenomas. Significant differences were noted between PTTG expression in medically treated and non-treated GH adenomas. However, PTTG expression in ACTH adenomas did not correlate with clinico-pathological variables, making it an unsuitable prognostic indicator in such tumours. In brain neoplasms, PTTG was expressed at higher levels in malignant tumours, whereas in less aggressive tumours, PTTG expression was considerably lower.

Thesis (Ph. D.)--Oregon State University, 2001. / Typescript (photocopy). Includes bibliographical references. Also available on the World Wide Web.

Thesis (M. Med. Sc.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 49-58).