A research report submitted to the Faculty of Medicine, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Science in Medicine in Nuclear Medicine. / Forty (40) female patients with breast masses underwent Technetium 99m Sestamibi scintigraphy in order to evaluate its usefulness in differentiating benign from malignant breast disease and to compare scintigraphy to mammography. Informed consent was obtained from each patient. Scintigraphy consisted of anterior chest and lateral and oblique breast planar images, obtained 5 minutes after intravenous injection of 20 rnecuries (740 MBq) Technetium 99m Sestamibi. Eleven (11) of the 40 patients also had Technetium 99m Methylene Diphosponate breast scintigraphy for comparison. Four nuclear medicine physicians of who three also graded the MDP images performed grading of the Sestamibi scintigraphic images. The grading method, although focussing on the absence (0) or presence (>0) of uptake of isotope, was also designed for comparison of the Sestamibi and MDP images. Statistical analysis showed good correlation between observer grading. Breast scintigraphy was compared to mammography in 27 ofthe 40 patients. Of the 26 malignant breast masses confirmed on histology, 19 were positively identified on Sestamibi scanning giving a sensitivity of 73%, 2 results were inconclusive (grading (0·1) and 5 had a grading 0, of the 8 patients with confirmed lymph node metastases, only 2 were positive on the Sestamibi scans, with 1 inconclusive result. Of the 19 benign breast masses, 9 were visible on Sestamibi scans with additional 3 inconclusive results (grading of 0-1). Statistical analysis showed no significant difference in the Sestamibi and MDP grading. In comparison to mammography, breast scintigraphy was less accurate in distinguishing benign from malignant breast masses. Mammography identified 85.7% of the malignant breast masses and 72.7% of the benign breast masses. Sestamibi scintigraphy identified 76.2% of the malignant breast masses and only 36.4% of the benign breast masses. / Andrew Chakane 2018

The management of breast cancer has changed over the last century, with surgeries becoming less invasive and adjuvant therapies becoming indispensible. Sentinel lymph node biopsies (SLNB) have replaced axillary nodal dissections as a method of staging an axilla in early breast cancer. However, 70% of SLNBs are negative. The aim of this study was to determine if wecould decrease the rate of negative sentinel lymph node biopsies? A retrospective review over a 10 month period was undertaken. Patients undergoing a SLNB and who had a documented negative axillary ultrasound report were included. One hundred and fifty onepatients were eligible for inclusion. Patients’ ultrasound reports and initial biopsy specimen characteristics (ER/PR/Her2-neu, LVI, Grade, Location) were compared to their axillary nodal findings on histology. An ultrasound was able to predict a pathologically negative axilla in 71.6% of patients. Exclusion of micrometastasis increased the negative predictive value to82.8%. If the ultrasound was negative in a histologically positive axilla, it was likely that only 3 or less nodes were involved. Nodal metastasis could not be predicted based on the tumour characteristics that were reported on the initial tumour biopsy specimens(ER/PR/Her2- neu, LVI, Grade, Location). LVI and DCIS on the initial biopsy specimens were poorly correlated with the final histology specimen findings.. The results show that an ultrasound cannot currently replace a SLNB as an accurate means of evaluating an axilla. A clear limitation is the inability to detect micrometastasis, however the role of micrometastasis in axillary staging is diminishing. Ultrasonographic evaluation of the axilla is currently reported in a non-standardised manner. Classification systems do exist, and if applied to current reporting will increase the negative predictive value of ultrasonography. In the future, the combination of improved reporting standards of axillary ultrasounds, as well as the surgical conservatism with regard to the management of micrometastasis and small volume metastasis in the axilla will hopefully reduce the rate of negative SLNB’s.

Thesis (M.Sc.). / Title from title page of PDF (viewed 2008/01/30). Written for the Dept. of General Surgery. Includes bibliographical references.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Medicine in Diagnostic Radiology Johannesburg, 2013 / Palpable solid breast masses that are circumscribed and not calcified on mammogram or ultrasound are probably benign. There is controversy therefore, whether these deserve tissue diagnosis. More data is required to determine whether short term follow up can replace the need for biopsy. Benign appearing lesions greater than 3cm in diameter on ultrasound continue to undergo biopsy due to fear that a malignancy or phyllodes tumour might be missed. Published research reflects patients from Europe and North America, and no relevant data from Africa exists. AIM: This study aims to determine the histological spectrum of sonographically benign lesions greater than 3cm, which were biopsied, in our local population (majority of black patients) and to determine whether biopsy is indicated based on the local cancer risk. The study also aims to characterise the results by age and population group as well as correlate the histological result with the size of the lesion on ultrasound, the HIV status, family history and the seniority of the examining radiologists. MATERIALS AND METHODS: A retrospective descriptive study of biopsy results of sonographically benign breast masses was undertaken using biopsy procedural recording sheets. . The size of the lesions (continuous variables) mean with standard deviations was determined. The prevalence of lesions was expressed as a percentage. Other categorical variables were summarized as frequency and percentage. The vi histological spectrum of the lesions was determined. The HIV status and family history of the patients as well as the seniority of the reviewing radiologist was assessed. A Krusskal Wallis test and separate logistic regression analysis was used. RESULTS: A total of 68 patients (below 40 years of age) were included from a total of 13112 patients (of all ages) seen between 2007 and the end of 2010. 73 lesions were identified (65 benign and 8 malignant). The prevalence of benign lesions was 89.7%. .The prevalence of malignant lesions was 10.29%.There was little evidence to support lesion size for predicting histology (p value = 0.22) or benignity. There was little evidence that the family history and HIV status were significant. CONCLUSION: There was a high prevalence (10.29%) of malignancies in lesions classified by ultrasound as benign. The size of the lesion did not correlate with histological subtype or whether the lesion was benign or malignant. Training of sonographers, standardization of technique for established users and double reading, may produce a different result, as both junior and senior radiologists mistook malignant lesions for benign ones on ultrasound. Repeating this research using double reading after training may demonstrate whether there is a true higher prevalence of malignancy in ultrasonically benign breast lesions in our community. Until then, routine biopsy of these lesions is recommended.

Orientador: José Joaquim Titton Ranzani / Co-orientador: Adriana Camargo Ferrasi / Banca: Noeme Sousa Rocha / Banca: Rejane Maria Tommasini Grotto / Resumo: Introdução: A E-caderina é uma proteína transmembranosa, codificada pelo gene CDH1, que desempenha um papel importante na adesão intercelular de tecidos epiteliais. A perda da função ou expressão diminuída de E-caderina pode implicar em metástases e progressão do câncer. Nas neoplasias mamárias, metástases pulmonares ocorrem com maior frequência, porém as metástases oculares, especialmente na coroide, são relativamente comuns, mas pouco diagnosticadas clinicamente. Metodologia: Vinte e oito cadelas de diferentes raças, não-castradas, com idade superior a 5 anos, com diagnóstico de carcinoma mamário ao exame citopatológico, sem metástases pulmonares e/ou oculares, foram submetidas à mastectomia radical e ovariosalpingohisterectomia (OSH), sendo reavaliadas após três e seis meses de pós-operatório. O padrão de expressão relativa do gene CDH1 em tecidos tumorais e normais, foi avaliado pelo sistema TaqMan Universal PCR Master Mix; o padrão de metilação foi realizado utilizando-se a técnica de MSP-PCR; o sequenciamento do DNA, análise das mutações e polimorfismos foram realizados a partir do sangue periférico, utilizando-se a técnica de reação de terminação em cadeia pelo kit BigDye Terminator v.3 Cycle Sequencing. Análises imunohistoquímicas foram realizadas para avaliar a expressão da E-caderina. Resultados: Nenhuma das 28 cadelas estudadas apresentou metástase ocular ou pulmonar com três ou seis meses de pós-operatório. Em 57,1% dos casos uma menor expressão relativa do gene CDH1 foi identificada. Em 100% dos casos verificou-se o status metilado para o gene CDH1, reafirmando a hipótese de que células não-tumorais podem contribuir para estes resultados. Em 46,5% dos casos identificou-se expressão reduzida de E-caderina pela técnica de imunohistoquímica. Foram identificados 3 histotipos tumorais: carcinoma complexo, tubulopapilífero e carcinoma em tumor misto. Em 100% dos casos de carcinoma... / Abstract: Introduction: E-cadherin is a transmembrane protein, encoded by CDH1 gene, that has an important role in intercellular adhesion of epithelial tissues. Loss of function or decreased expression of E-cadherin may lead to cancer progression and metastasis. In mammary epithelial neoplasms, lung metastases occur more frequently, but the ocular metastasis, especially in the choroid, are relatively common but underdiagnosed clinically. Methods: Twenty-eight dogs of different breeds, non-castrated, older than five years, diagnosed with breast cancer by cytopathological examination, without pulmonary and/or ocular metastasis, have undergone to radical mastectomy and ovariosalpingohisterectomy (OSH), and re-evaluated after three and six months postoperatively. The pattern of relative expression of CDH1 gene in normal and tumor tissues was assessed by TaqMan Universal PCR Master Mix system; the pattern of methylation was performed using MSP-PCR; DNA sequencing analysis of mutations and polymorphisms were performed from peripheral blood using the termination chain reaction technique with BigDye Terminator v.3 Cycle Sequencing kit. Immunohistochemical analyzes were performed to evaluate the expression of E-cadherin. Results: None of the 28 dogs studied had ocular or pulmonary metastasis with 3 or 6 months postoperatively. In 57,1% of cases a decreased relative expression of CDH1 gene was identified. In 100% of cases there was methylated status for the CDH1 gene, confirming the hypothesis that non-tumor cells can contribute to these results. In 46,5% of the cases reduced E-cadherin expression by immunohistochemistry was identified. Three tumor histotypes were identified: complex carcinoma, tubulopapillary, and carcinoma in mixed tumor. In 100% of cases of tubulopapillary carcinoma was identified a reduced gene expression of CDH1 by both qPCR and by immunohistochemistry. The sequencing of the gene, 6 animals (21,4%) had silent mutations in exons 3, 7 ... / Mestre

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 5 uppsatser.

Thesis (Ph.D.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on March 11, 2009) Includes bibliographical references.

Made available in DSpace on 2016-05-17T16:51:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-06-03. Added 1 bitstream(s) on 2016-05-17T16:54:43Z : No. of bitstreams: 1 000858239.pdf: 1069135 bytes, checksum: cd8c808bc197da8ee3c265e8f3ff186a (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Introdução: A E-caderina é uma proteína transmembranosa, codificada pelo gene CDH1, que desempenha um papel importante na adesão intercelular de tecidos epiteliais. A perda da função ou expressão diminuída de E-caderina pode implicar em metástases e progressão do câncer. Nas neoplasias mamárias, metástases pulmonares ocorrem com maior frequência, porém as metástases oculares, especialmente na coroide, são relativamente comuns, mas pouco diagnosticadas clinicamente. Metodologia: Vinte e oito cadelas de diferentes raças, não-castradas, com idade superior a 5 anos, com diagnóstico de carcinoma mamário ao exame citopatológico, sem metástases pulmonares e/ou oculares, foram submetidas à mastectomia radical e ovariosalpingohisterectomia (OSH), sendo reavaliadas após três e seis meses de pós-operatório. O padrão de expressão relativa do gene CDH1 em tecidos tumorais e normais, foi avaliado pelo sistema TaqMan Universal PCR Master Mix; o padrão de metilação foi realizado utilizando-se a técnica de MSP-PCR; o sequenciamento do DNA, análise das mutações e polimorfismos foram realizados a partir do sangue periférico, utilizando-se a técnica de reação de terminação em cadeia pelo kit BigDye Terminator v.3 Cycle Sequencing. Análises imunohistoquímicas foram realizadas para avaliar a expressão da E-caderina. Resultados: Nenhuma das 28 cadelas estudadas apresentou metástase ocular ou pulmonar com três ou seis meses de pós-operatório. Em 57,1% dos casos uma menor expressão relativa do gene CDH1 foi identificada. Em 100% dos casos verificou-se o status metilado para o gene CDH1, reafirmando a hipótese de que células não-tumorais podem contribuir para estes resultados. Em 46,5% dos casos identificou-se expressão reduzida de E-caderina pela técnica de imunohistoquímica. Foram identificados 3 histotipos tumorais: carcinoma complexo, tubulopapilífero e carcinoma em tumor misto. Em 100% dos casos de carcinoma... / Introduction: E-cadherin is a transmembrane protein, encoded by CDH1 gene, that has an important role in intercellular adhesion of epithelial tissues. Loss of function or decreased expression of E-cadherin may lead to cancer progression and metastasis. In mammary epithelial neoplasms, lung metastases occur more frequently, but the ocular metastasis, especially in the choroid, are relatively common but underdiagnosed clinically. Methods: Twenty-eight dogs of different breeds, non-castrated, older than five years, diagnosed with breast cancer by cytopathological examination, without pulmonary and/or ocular metastasis, have undergone to radical mastectomy and ovariosalpingohisterectomy (OSH), and re-evaluated after three and six months postoperatively. The pattern of relative expression of CDH1 gene in normal and tumor tissues was assessed by TaqMan Universal PCR Master Mix system; the pattern of methylation was performed using MSP-PCR; DNA sequencing analysis of mutations and polymorphisms were performed from peripheral blood using the termination chain reaction technique with BigDye Terminator v.3 Cycle Sequencing kit. Immunohistochemical analyzes were performed to evaluate the expression of E-cadherin. Results: None of the 28 dogs studied had ocular or pulmonary metastasis with 3 or 6 months postoperatively. In 57,1% of cases a decreased relative expression of CDH1 gene was identified. In 100% of cases there was methylated status for the CDH1 gene, confirming the hypothesis that non-tumor cells can contribute to these results. In 46,5% of the cases reduced E-cadherin expression by immunohistochemistry was identified. Three tumor histotypes were identified: complex carcinoma, tubulopapillary, and carcinoma in mixed tumor. In 100% of cases of tubulopapillary carcinoma was identified a reduced gene expression of CDH1 by both qPCR and by immunohistochemistry. The sequencing of the gene, 6 animals (21,4%) had silent mutations in exons 3, 7 ...

Orientador: Lenice do Rosário de Souza / Banca: Gilberto Uemura / Banca: Alcioni Artioli Machado / Resumo: Apesar do controle da replicação viral, o uso crônico dos antirretrovirais leva a diversas alterações no portador de HIV, dentre elas, lipodistrofia e envelhecimento precoce. Os objetivos foram avaliar a densidade mamográfica de mulheres acima de 35 anos que vivem com HIV/aids, relacionando a densidade mamária à idade, tempo de exposição à terapia antirretroviral (cART), contagem de linfócitos T CD4+, carga viral do HIV e presença de lipodistrofia com incidência de lipossubstituição mamária (LM). Métodos: Coorte observacional de mulheres, dividida em dois grupos, G1 com 59 infectadas e G2 com 73 não infectadas pelo HIV, com idades de 35 a 72 anos. Foram estudados idades à entrevista, à menarca, à última gestação e à menopausa; uso de hormônios, dor mamária, histórias prévias de cirurgias de mama e familiar de câncer de mama ou de ovário. Resultados: Houve diferenças de LM entre os grupos, quando analisadas por faixas etárias, de 35 a 40 anos (p=0,002) e de 41 a 45 anos (p=0,041) com maior proporção em G1 e em G2, nas faixas de 51 a 55 anos (p=0,046) e 56 a 60 anos (p=0,005). A chance de lipodistrofia foi 9,3 vezes maior após 10 anos de uso de cART, ocorrendo em 29 (49,2%) mulheres de G1. Conclusões: mulheres portadoras de HIV/aids apresentam LM em idades mais precoces quando comparadas a mulheres não infectadas pelo vírus, não se encontrando relação com número de gestações, lipodistrofia, ter aids ou infecção assintomática e contagem de linfócitos T CD4+ / Abstract: Background: Despite viral replication control, the chronic use of antiretroviral drugs leads to several changes in HIV carriers, among which are lipodystrophy and premature aging. The objectives were to evaluate mammographic density in women older than 35 years living with HIV/AIDS and relate breast density to age, time of exposure to antiretroviral therapy (cART), CD4 + T lymphocyte count, HIV viral load and the presence of lipodystrophy with incidence of breast fatty replacement (BFR). Methods: Observational cohort of women divided into two groups: G1, comprising 59 HIV-infected individuals and G2, consisting of 73 uninfected women, all aged 35 to 72 years. The following variables were studied: age at the moment of the interview, at menarche, at the last pregnancy and at menopause; use of hormones; breast pain; previous history of breast surgery and family history of breast or ovarian cancer. Results: BFR differences were observed between the groups when they were analyzed by age ranges, from 35 to 40 years (p=0.002) and from 41 to 45 years (p=0.041), with a higher proportion in G1 and in G2 at the age ranges of 51 to 55 years (p=0.046) and 56 to 60 years (p=0.005). The chance of lipodystrophy was 9.3- fold greater after 10 years of cART use, and it occurred in 29 (49.2%) women in G1. Conclusions: women with HIV/AIDS showed BFR at earlier ages when compared to uninfected women, and no relation to the number of pregnancies, lipodystrophy, having AIDS or asymptomatic infection or CD4 + T lymphocyte count was found / Mestre