Performance of Thyroid Fine-Needle Aspiration Biopsy in a Low- and Middle-Income Country.

INTRODUCTION: The 6 categories of the Bethesda System for Reporting Thyroid Cytology (TBSRTC) with associated risk of malignancy (ROM) provide evidence-based clinical management guidelines. This study aimed to determine the ROM and accuracy of FNAB in South Africa (SA). METHODS: Thyroid specimens from 3 pathology laboratories registered between January 2015 and December 2019 were considered for inclusion. ROM was obtained per TBSRTC category by cytohistological correlation and dividing the total number of specimens with malignant histology by the total number of cases operated. Accuracy was calculated based on the Bethesda category and eventual malignant histology. RESULTS: Seventeen thousand seven hundred and seventy-three histology and 4,791 cytology cases were identified. Of the 4,791 cytology cases, 931 (19%) underwent surgery. More than a third (333, 35.8%) of cases were confirmed as malignant following histological assessment, with the majority being benign (584, 62.7%). The ROM for the nondiagnostic and benign categories was 24.3% and 20.5%. The highest ROM was for category VI (91.5%), followed by categories V (69.5%), IV (51.9%), and III (38.8%). Thyroid FNAB had a sensitivity of 73%, specificity of 74%, and overall accuracy of 74%. CONCLUSION: Bethesda categories II and IV have a relatively higher ROM in SA compared to findings from other developed countries. The diagnostic accuracy of thyroid FNAB in SA and the high rate of nondiagnostic diagnoses (38%) require further investigation. A national thyroid registry could provide location-specific data to aid the implementation of appropriate local policies and national guidelines for practicing thyroid surgeons.

Pathology-supported genetic testing for the application of breast cancer pharmacodiagnostics: family counselling, lifestyle adjustments and change of medication.

BACKGROUND: Pathology-supported genetic testing (PSGT) enables transitioning of risk stratification from the study population to the individual. RESEARCH DESIGN AND METHODS: We provide an overview of the translational research performed in postmenopausal breast cancer patients at increased risk of osteoporosis due to aromatase inhibitor therapy, as the indication for referral. Both tumor histopathology and blood biochemistry levels were assessed to identify actionable disease pathways using whole exome sequencing (WES). RESULTS: The causes and consequences of inadequate vitamin D levels as a modifiable risk factor for bone loss were highlighted in 116 patients with hormone receptor-positive breast cancer. Comparison of lifestyle factors and WES data between cases with vitamin D levels at extreme upper and lower ranges identified obesity as a major discriminating factor, with the lowest levels recorded during winter. Functional polymorphisms in the vitamin D receptor gene contributed independently to therapy-related osteoporosis risk. In a patient with invasive lobular carcinoma, genetic counseling facilitated investigation of the potential modifying effect of a rare CDH1 variant co-occurring with BRCA1 c.66dup (p.Glu23ArgfsTer18). CONCLUSION: Validation of PSGT as a three-pronged pharmacodiagnostics tool for generation of adaptive reports and data reinterpretation during follow-up represents a new paradigm in personalized medicine, exposing significant limitations to overcome.

Online anatomy education during the Covid-19 pandemic: Opinions of medical, speech therapy, and BSc Anatomy students.

With the emergence of the Covid-19 pandemic in 2020, it was difficult to predict if the "cadaveric-based (golden) standard" of teaching anatomy would be possible in the unforeseeable future. This forced traditional anatomical teaching and learning practices to be transitioned to remote online platforms. This study explored the opinions of anatomy students (n = 51), on their online learning experience of anatomy during the Covid-19 pandemic. A mixed methods approach using a descriptive, exploratory study design was conducted, by use of an online survey. The survey consisted of a six-point Likert scale and was assembled into four sub-categories. Likert scale options ranged from; strongly disagree, to strongly agree, and not applicable. Results obtained seem to tally with expectations, indicating an adequate theoretical course component with room to improve practical online teaching. Most participants had a positive perception of the theoretical course content, duration, and platforms of communication. Virtual classes were simple to navigate with few technical difficulties experienced by the participants. Students also noted having access to sufficient study material, videos, and additional online material. Overall, more than half of all participants reported adapting well to the remote learning environment, however, the greatest challenge experienced highlighted a sense of deprivation from the lack of cadaver exposure and hands-on instruction. This research highlighted the effects of the pandemic on the modality of anatomy education and how it affected students. Although anatomy is multi-modal, it can be concluded that it is possible to achieve academic success by using online learning methods.

Student-Perceived Value on the Use of Clay Modelling in Undergraduate Clinical Anatomy.

Clay modelling is increasingly used as an anatomy teaching method to supplement practical dissection sessions. The use of clay modelling is an active, tactile learning tool utilized to improve student engagement and enhance students' understanding of anatomical relationships in human anatomy. Furthermore, not only does clay modelling engage more senses in the learning process, but it was also found that there are educational advantages to the group interactions that are associated with the construction process to further collaborative learning.The aim of the study was to explore the effect of building anatomical clay models on students' awareness and understanding of their own thought processes as well as to explore whether clay modelling promoted collaborative learning. This cross-sectional study entailed the use of clay modelling and reflective practice to promote metacognition in third-year BSc students (n = 10), at the University of Stellenbosch's (SU) Division of Clinical Anatomy. The third-year BSc students were asked to build anatomical clay models (in groups), complete a reflective assignment and an evaluation form as part of their assessment of the Applied Anatomy module. The reflective assignment was based on Gibb's reflective cycle. The inclusion of such an assignment would trigger students to reflect upon their learning experiences and thus promote their metacognition.Ten (10) BSc students volunteered to take part in the study. A mixed method approach was followed; the reflective assignments were qualitatively analyzed, while the evaluation forms were quantitatively (statistically) analyzed. Data obtained from the online evaluation forms indicated agreeable responses confirming that the clay modelling was a valuable learning tool. However, the participants preferred cadaveric dissection instead of clay modelling to learn anatomy. Furthermore, three themes became prominent from the thematic analysis of the reflective assignments, namely, (1) Advantages of clay modelling, (2) Challenges of clay modelling, and (3) Suggestions for future practice.The research suggests that the inclusion of hands-on clay modelling in the undergraduate clinical anatomy is a valuable learning tool. The participants perceived that it enhanced their anatomical knowledge and improved collaborative learning.

Clinicians' opinions on the clinical relevance of anatomy education at Stellenbosch University.

Anatomical science is a fundamental element of undergraduate medical education; thus, it is imperative that the course serves future medical professionals when entering clinical practice. However, anatomical education has faced challenges in recent years including decreased allocated time, increased class sizes and over-stretched staff. Technological advancements in anatomical education may provide relief to these issues. Therefore, exploring clinicians' perspective on the clinical relevance and efficacy of anatomical education, within an African context, can inform its future. This study used a qualitative research approach within an interpretive paradigm. Eight semi-structured one-on-one interviews were conducted with clinicians associated with Stellenbosch University and Tygerberg Hospital. Thematic analysis was employed to analyze the data, creating themes and codes. Trust worthiness of the data was ensured through peer debriefing and member checking. Results reveal that clinicians find clinically relevant anatomy valuable to students. However, some feel that this is not delivered effectively at present. Clinicians see potential for the incorporation of clinical technologies into anatomical pedagogy. Although clinicians are hopeful for new technological developments in anatomical education, concerns were reported about its autonomous nature. This study concludes that although clinically relevant anatomical education is beneficial to students, the time and the resources via which it is delivered should be considered. There is optimism for the future of anatomical education with the advancements of technologically based educational resources, however, new resources should be incorporated with planning and supervision.

Development of a Virtual Journal Club in Anatomy: a Responsive Pandemic Pedagogy.

The COVID-19 pandemic forced changes to online teaching worldwide. The Clinical Anatomy journal club (JC) is key in the Bachelor of Science Honours (BScHons) programme and aims to improve scientific appraisal and communication abilities in anatomical research. An online JC through synchronous contact between members was deemed fitting as it could bridge the newly enforced geographical limitations due to the national lockdown in South Africa. Although common in clinical specialties, there are no published reports of anatomy themed online JCs. This project aimed to develop, implement, and appraise a synchronous virtual JC for Clinical Anatomy during the COVID-19 South African lockdown. A qualitative exploratory study design within an interpretive/constructivist paradigm was followed and aimed to explore students' perceptions of a virtual anatomy JC during the lockdown. The study was conducted at a South African institution, within the BScHons programme, and all enrolled students were invited to participate. Upon receipt of informed consent, an anonymous questionnaire was administered via Moodle for the BScHons students. The responses were analysed by thematic analysis, codes were developed, and themes were generated. Two main themes were generated from the results: the first related to the virtual format of the JC and the second focused on the content and topics covered during the JC sessions. The Clinical Anatomy staff and students adapted rapidly to the virtual JC and formed a community of practice. The benefits of teaching and learning within JC were maintained during the virtual format. It is envisioned that the JC will continue in a hybrid format (face-to-face and virtual) in future academic years. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01325-8.

Point-of-view technology to teach surgery.

BACKGROUND: Varied and limited opportunities to assist during operations, hamper surgical procedural training. Furthermore, the trainee's view of the procedure differs from that of the operating surgeon. New solutions could emerge when instruction under direct supervision can be combined with technological advances in surgical practice. This study assesses the feasibility of using the GoPro HERO™ to record operations for educational purposes, from the perspective of the surgical and technical team. METHOD: A "point-of-view" wearable GoPro camera was used to record standard operations at Tygerberg Academic Hospital, affiliated with Stellenbosch University, in Cape Town. Semi-structured interviews evaluated the practical acceptability of the GoPro in theatre by clinical personnel. The technical team reflected on picture quality, video editing and formatting. Techsmith Camtasia Studio 9® programme was employed for post- recording editing. RESULTS: Eight operations were performed by three surgeons. No interference with operative sterility, procedural length, nor functioning in the operating room was encountered by clinical personnel. Technically, the quality and picture field were adequate. All surgeons found the camera head band tight and the camera heavy. The limited battery life during recording was problematic throughout the study. CONCLUSION: Wearable cameras allow recordings of surgical procedures from the surgeon's view, for adjunctive educational purposes. This study confirms the feasibility and utility of GoPro to record real time operations without compromising patient care. The videos have cross-discipline potential for teaching within medicine. Creation of a video library as a resource to evaluate the educational value for trainees is envisioned.

CYP19A1 rs10046 Pharmacogenetics in Postmenopausal Breast Cancer Patients Treated with Aromatase Inhibitors: One-year Follow-up.

BACKGROUND: Significant individual variation in bone loss associated with aromatase inhibitors (AIs) emphasizes the importance of identifying postmenopausal breast cancer patients at high risk for this adverse effect. The study explores the clinical relevance of genetic variation in the Cytochrome P450 19A1 (CYP19A1) gene in a subset of South African patients during the first year of taking AIs for estrogen receptor (ER)-positive breast cancer. METHODS: The study population consisted of ER-positive breast cancer patients on AIs, followed in real-life clinical practice. Body mass index was measured and bone mineral density (BMD) was determined at baseline and at month 12. CYP19A1 genotyping was performed using real-time polymerase chain reaction analysis of rs10046, extended to Sanger sequencing and whole exome sequencing in 10 patients with more than 5% bone loss at month 12 at the lumbar spine. RESULTS: After 12 months of AI treatment, 72 patients had completed BMD and were successfully genotyped. Ten patients (14%) experienced more than 5% bone loss at the lumbar spine over the study period. Genotyping for CYP19A1 rs10046 revealed that patients with two copies of the A-allele were 10.79 times more likely to have an ordinal category change of having an increased percentage of bone loss or no increase at the lumbar spine, compared to patients with the GA or GG genotypes (CI of 1.771- 65.830, p=0.01). None of the 34 patients without lumbar spine bone loss at month 12 were homozygous for the functional CYP19A1 polymorphism. At the total hip region, patients with the AA genotype were 7. 37 times more likely to have an ordinal category change of having an increased percentage of bone loss or no increase (CI of 1.101- 49.336, p=0.04). CONCLUSION: Homozygosity for the CYP19A1 rs10046 A-allele may provide information, in addition to clinical and biochemical factors that may be considered in risk stratification to optimize bone health in postmenopausal breast cancer women on AIs. Further investigation is required to place the clinical effect observed for a single CYP19A1 gene variant in a genomic context.

Baseline bone health status in multi-ethnic South African postmenopausal breast cancer patients at initiation of aromatase inhibitor therapy: A descriptive study.

INTRODUCTION: Osteoporosis (OP) risk factor assessment and bone mineral density (BMD) testing are frequently omitted at baseline in aromatase inhibitor (AI) studies, which may lead to misinterpretation of AI associated bone loss. The present study describes bone health of South African postmenopausal women of predominantly Mixed Ancestry, prior to AI treatment. METHODS: This descriptive baseline study, nested in a prospective AI cohort study, included postmenopausal women with endocrine sensitive breast cancer, aged 50 to 80 years. A baseline questionnaire documented demographic-, medical-, lifestyle- and fracture history. Body weight was assessed clinically, and body composition and BMD measured via dual energy absorptiometry (DXA). Data was analysed in STATA 14 using descriptive and inferential statistics. RESULTS: 101 participants were recruited, with a mean age of 61±7 years. Nearly a third (n = 32) of women at baseline fulfilled global criteria for bone protection (BMD T-score ≥-2SD (n = 18); BMD T-score -1.5SD to < -2SD with risk factors (n = 14). Lower body weight, body mass index (BMI), fat mass index and lean mass index were significantly associated with the participants with a BMD measurement in keeping with a diagnosis of OP (p <0.001). Low vitamin D was present in 93% of the cohort tested (n = 95), whilst deficient vitamin D status (<20ng/ml) was documented in 52 women (55%). CONCLUSIONS: In this study, a third of postmenopausal women considered for AI therapy fulfilled international criteria for bone protective pharmacological intervention. This emphasizes the need for clinical risk and BMD assessment in postmenopausal breast cancer patients at baseline. Body composition and bone health associations highlight bone fragility associated with lower body weight.

Genomic medicine and risk prediction across the disease spectrum.

Genomic medicine is based on the knowledge that virtually every medical condition, disease susceptibility or response to treatment is caused, regulated or influenced by genes. Genetic testing may therefore add value across the disease spectrum, ranging from single-gene disorders with a Mendelian inheritance pattern to complex multi-factorial diseases. The critical factors for genomic risk prediction are to determine: (1) where the genomic footprint of a particular susceptibility or dysfunction resides within this continuum, and (2) to what extent the genetic determinants are modified by environmental exposures. Regarding the small subset of highly penetrant monogenic disorders, a positive family history and early disease onset are mostly sufficient to determine the appropriateness of genetic testing in the index case and to inform pre-symptomatic diagnosis in at-risk family members. In more prevalent polygenic non-communicable diseases (NCDs), the use of appropriate eligibility criteria is required to ensure a balance between benefit and risk. An additional screening step may therefore be necessary to identify individuals most likely to benefit from genetic testing. This need provided the stimulus for the development of a pathology-supported genetic testing (PSGT) service as a new model for the translational implementation of genomic medicine in clinical practice. PSGT is linked to the establishment of a research database proven to be an invaluable resource for the validation of novel and previously described gene-disease associations replicated in the South African population for a broad range of NCDs associated with increased cardio-metabolic risk. The clinical importance of inquiry concerning family history in determining eligibility for personalized genotyping was supported beyond its current limited role in diagnosing or screening for monogenic subtypes of NCDs. With the recent introduction of advanced microarray-based breast cancer subtyping, genetic testing has extended beyond the genome of the host to also include tumor gene expression profiling for chemotherapy selection. The decreasing cost of next generation sequencing over recent years, together with improvement of both laboratory and computational protocols, enables the mapping of rare genetic disorders and discovery of shared genetic risk factors as novel therapeutic targets across diagnostic boundaries. This article reviews the challenges, successes, increasing inter-disciplinary integration and evolving strategies for extending PSGT towards exome and whole genome sequencing (WGS) within a dynamic framework. Specific points of overlap are highlighted between the application of PSGT and exome or WGS, as the next logical step in genetically uncharacterized patients for whom a particular disease pattern and/or therapeutic failure are not adequately accounted for during the PSGT pre-screen. Discrepancies between different next generation sequencing platforms and low concordance among variant-calling pipelines caution against offering exome or WGS as a stand-alone diagnostic approach. The public reference human genome sequence (hg19) contains minor alleles at more than 1 million loci and variant calling using an advanced major allele reference genome sequence is crucial to ensure data integrity. Understanding that genomic risk prediction is not deterministic but rather probabilistic provides the opportunity for disease prevention and targeted treatment in a way that is unique to each individual patient.

Implementation of a breast cancer genetic service in South Africa - lessons learned.

BACKGROUND: Genetic testing for BRCA mutations has been available in the Western Cape of South Africa since 2005, but practical implementation of genetic counselling and testing has been challenging. OBJECTIVE: To describe an approach to breast cancer genetic counselling and testing developed in a resource-constrained environment at Tygerberg Hospital in Cape Town, Western Cape. METHODS: Genetic counselling is offered in a stepwise manner to our diverse patient population, with a focus on affected probands, and subsequent cascade testing. A record review of BRCA testing between 2005 and 2011 was performed. RESULTS; During this period 302 probands received genetic testing, with increasing numbers tested over time. Of 1 520 women treated for breast cancer since 2008, 226 (14.9%) accepted BRCA testing, and 39 tested positive (17.3% of those tested, and 2.6% of all women). Common founder mutations were detected in 11.9% of women (36/302), and comprised 73% (36/49) of mutations detected. Cascade testing increased after 2010: 16 female and 4 male family members of 19 probands accepted testing, with 6 positives being detected. CONCLUSION: A protocol-driven approach focusing on probands, with initial pre-test counselling by primary care staff has proven effective in establishing the service. Involvement of a clinical geneticist/genetic counsellor has permitted more detailed post-test counselling and increased use of cascade testing.

Time for a re-evaluation of mammography in the young? Results of an audit of mammography in women younger than 40 in a resource restricted environment.

Mammography in younger women is considered to be of limited value. In a resource restricted environment without access to magnetic resonance imaging (MRI) and with a high incidence of breast cancer in the young, mammography remains an important diagnostic tool. Recent technical advances and better regulation of mammography make a reassessment of its value in these conditions necessary. Data of all the mammograms performed at a tertiary hospital and private breast clinic between January 2003 and July 2009 in women less than 40 years of age were collected. Indications were the presence of a mass, follow-up after primary cancer therapy, and screening for patients perceived at high risk due to a family history or the presence of atypical hyperplasia. Data acquired were as follows: Demographics, prior breast surgery, indication for mammography, outcome of mammography, diagnostic procedures, and their results. Of 2,167 mammograms, 393 were performed for a palpable mass, diagnostic mammography. In these, the overall cancer detection rate was 40%. If the mammography was reported as breast imaging reporting and data system (BIRADS(®)) 5 versus BIRADS(®) 3 and 4 versus BIRADS(®) 1 and 2, a final diagnosis of malignancy was established in 96, 48, and 5%, respectively. Of 367 mammograms done for the follow-up after primary treatment of breast cancer, seven cancers were diagnosed for a detection rate of 1.9%. Of 1,312 mammograms performed for screening, the recall rate was 4%; the biopsy rate 2%, and the cancer diagnosis rate 3/1,000 examinations. In contrast to past series, this series has shown that recent advances in mammography have made it a useful tool in the management of breast problems in young women, notably in a resource-restricted environment. Women for screening should be selected carefully.

Surgeon-read screening mammography: an analysis of 11,948 examinations.

INTRODUCTION: Mammography was pioneered by surgeons but is now the domain of radiologists. With ever-increasing cost pressures it must be examined whether interpretation of mammography by clinicians and radiation technologists is comparable to that of breast radiologists. We present the largest series of surgeon-read screening mammography to date. METHODS: All mammography performed between 2003 and 2009 at a comprehensive breast centre was recorded prospectively. First assessment was by a radiation technologist and consensus established after second reading by a breast surgeon, who took responsibility for the reading. Data recorded were: age, hormonal replacement therapy, prior breast surgery, indications for mammography and outcomes. Outcomes were classified based using the Breast Imaging Reporting and Data System (BIRADS). Indeterminate lesions were imaged further or underwent tissue acquisition. All BIRADS 5 lesions underwent tissue acquisition. RESULTS: Of 11,948 mammograms, 538 were reported as indeterminate/compatible with malignancy; 240 biopsies were performed, and 87 cancers diagnosed. In 40-49-year-old women (4,956 mammograms), the recall rate was 4.2%, the biopsy rate was 1.6%, the malignancy rate of biopsy was 23.7% and the cancer diagnosis rate was 3.6/1,000 examinations; for 50-69-year-old women these figures were 6,546, 4.7, 2.2, 44.1% and 10.0/1,000, respectively, and in women older than 70 years, they were 446, 5.6, 3.4, 33.3% and 11.2/1,000, respectively. Of all cancers, 32.2% were non-invasive; of invasive cancers, 49.1% were 10 mm or less in diameter and 75% were node negative. CONCLUSIONS: These results are similar to those in high-quality organized screening programs. The role of breast surgeons in mammography interpretation should be expanded.

Surgical mammography reporting in a limited resource environment.

BACKGROUND: Lack of resources and dedicated breast radiology has forced professionals other than radiologists to read mammography. We report a series of surgeon-read mammography in a developing country. METHODS: Data were collected prospectively form January 2003 to June 2008 for all mammography performed at a tertiary hospital. The data acquired were demographics, previous treatment for breast pathology, and indication for and outcome of mammography, including diagnostic procedures and their results. The results were benchmarked against standard performance indicators. RESULTS: Of 8,743 mammograms performed, 1,468 were for palpable lumps; the cancer diagnosis rate was 640 per 1,000 investigations (for 885 of these reported as compatible with malignancy, the cancer diagnosis rate was 95%; for 183 reported as indeterminate 60%, for 400 reported as benign/no abnormality 4%). Of 4,998 cancer follow-up mammograms, the cancer diagnosis rate was 15 per 1,000. For 76 of these reported as compatible with malignancy, the cancer diagnosis rate was 67%, for 161 reported as indeterminate, the biopsy rate was 36%, and cancer diagnosis rates of biopsy was 41%. Of 75 cancers diagnosed, 26 were locally recurrent after breast conservation and 49 new contralateral primaries, 84% of these were stage 0-I. Of 2,001 mammograms performed for screening, the biopsy rate was 4.5% and the cancer diagnosis rate of biopsy was 27%; the overall cancer diagnosis rate was 11 per 1,000 examinations; 96% of these were stage 0-1. CONCLUSIONS: Dedicated breast surgeons are equally proficient at mammography interpretation as radiologists. In resource-restricted environments, nonavailability of dedicated breast radiologists should not preclude development of breast units.