Cancer advocacy in residency education: From principles to competencies.

INTRODUCTION: The global cancer burden is increasing. Current global evidence indicates there will be a 47% rise of cancer cases for the period 2020-2040. The cancer rate differential also is evident within countries and regions. Efforts have been used to reduce the health disparities; however, the inequity prevails. One potential way to help reduce the disparity is through advocacy by physicians. METHODS: Two recent systematic review articles on advocacy among physicians note that physicians are unlikely to be taught advocacy in medical education, and also note there are no advocacy competencies or skill sets that are either taught or valued in medical education. We explore literature and develop a model to understand the components of advocacy in medical education, specifically in resident training. We follow the model's main components by examining principles of advocacy, relevant domains of advocacy, and competencies and values for advocacy education. RESULTS: Four ethical principles of advocacy education are identified: beneficence, non-maleficence, autonomy, and justice. These principles must be applied in meaningful, culturally sensitive, respectful, and promotion of the well-being ways. Three domains are identified: the practice domain (provider-patient interaction), the community domain (provider-community collaboration), and the health policy domain (the larger social environment). Advocacy occurs differently within each domain. Finally, competencies in the form of knowledge, skills, and values are described. We present a table noting where each competency occurs (by domain) as well as the value of each knowledge and skill. POLICY SUMMARY: The significance of including advocacy instruction in medical education requires a change in the current medical education field. Besides valuing the concept of including advocacy, principles, domains, and competencies of inclusion are critical. In summary, we encourage the inclusion of advocacy education in resident medical programs so physicians become competent medical providers at diverse levels of society.

Pseudotrombocitopenia dependiente de EDTA en un niño de 5 años: Reporte de caso

Introducción: La pseudotrombocitopenia dependiente del ácido etilendiaminotetraacético (PTCP-EDTA) es un fenómeno de laboratorio con una prevalencia estimada del 0,1-2% entre los pacientes hospitalizados y entre el 15-17% en los pacientes ambulatorios evaluados por trombocitopenia aislada. Se produce por cambios conformacionales a nivel de las glicoproteínas de la superficie plaquetaria que inducen la agregación de plaquetas tras la exposición al EDTA. Esta agregación da lugar a una falsa disminución del conteo de unidades totales de plaquetas al utilizar analizadores automatizados.  Presentación del caso: Presentamos el caso de un paciente de 5 años que presentaba niveles bajos de plaquetas sin signos de hemorragia activa. El paciente fue ingresado en el hospital mientras se estudiaba la causa de su bajo conteo plaquetario. Para el diagnóstico de PTCP-EDTA, se realizó un frotis de sangre periférica y se compararon los niveles plaquetarios utilizando el tubo con anticoagulante de citrato. Conclusión: La PTCP-EDTA suele ser un diagnóstico que se pasa por alto y que puede dar lugar a procedimientos innecesarios y gastos adicionales para los pacientes que presentan este fenómeno in vitro. (provisto por Infomedic International)

Introduction: Ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia (PTCP-EDTA) is a laboratory phenomenon with an estimated prevalence of 0.1-2% among hospitalized patients and between 15-17% in outpatients evaluated for isolated thrombocytopenia. It is caused by conformational changes at the level of platelet surface glycoproteins that induce platelet aggregation following EDTA exposure. This aggregation results in a false decrease in total platelet unit count when using automated analyzers. Case presentation: We present the case of a 5-year-old patient who presented with low platelet levels without signs of active bleeding. The patient was admitted to the hospital while the cause of his low platelet count was being studied. For the diagnosis of PTCP-EDTA, a peripheral blood smear was performed and platelet levels were compared using the tube with citrate anticoagulant. Conclusion: PTCP-EDTA is often an overlooked diagnosis that may result in unnecessary procedures and additional expense for patients presenting with this phenomenon in vitro. (provided by Infomedic International)

Global Cancer Surgery: pragmatic solutions to improve cancer surgery outcomes worldwide.

The first Lancet Oncology Commission on Global Cancer Surgery was published in 2015 and serves as a landmark paper in the field of cancer surgery. The Commission highlighted the burden of cancer and the importance of cancer surgery, while documenting the many inadequacies in the ability to deliver safe, timely, and affordable cancer surgical care. This Commission builds on the first Commission by focusing on solutions and actions to improve access to cancer surgery globally, developed by drawing upon the expertise from cancer surgery leaders across the world. We present solution frameworks in nine domains that can improve access to cancer surgery. These nine domains were refined to identify solutions specific to the six WHO regions. On the basis of these solutions, we developed eight actions to propel essential improvements in the global capacity for cancer surgery. Our initiatives are broad in scope, pragmatic, affordable, and contextually applicable, and aimed at cancer surgeons as well as leaders, administrators, elected officials, and health policy advocates. We envision that the solutions and actions contained within the Commission will address inequities and promote safe, timely, and affordable cancer surgery for every patient, regardless of their socioeconomic status or geographic location.

ThyroidPrint®: clinical utility for indeterminate thyroid cytology.

Molecular testing contributes to improving the diagnosis of indeterminate thyroid nodules (ITNs). ThyroidPrint® is a ten-gene classifier aimed to rule out malignancy in ITN. Post-validation studies are necessary to determine the real-world clinical benefit of ThyroidPrint® in patients with ITN. A single-center, prospective, noninterventional clinical utility study was performed, analyzing the impact of ThyroidPrint® in the physicians' clinical decisions for ITN. Demographics, nodule characteristics, benign call rates (BCRs), and surgical outcomes were measured. Histopathological data were collected from surgical biopsies of resected nodules. Of 1272 fine-needle aspirations, 109 (8.6%) were Bethesda III and 135 (10.6%) were Bethesda IV. Molecular testing was performed in 155 of 244 ITN (63.5%), of which 104 were classified as benign (BCR of 67.1%). After a median follow-up of 15 months, 103 of 104 (99.0%) patients with a benign ThyroidPrint® remained under surveillance and one patient underwent surgery which was a follicular adenoma. Surgery was performed in all 51 patients with a suspicious for malignancy as per ThyroidPrint® result and in 56 patients who did not undergo testing, with a rate of malignancy of 70.6% and 32.1%, respectively. A higher BCR was observed in follicular lesion of undetermined significance (87%) compared to atypia of undetermined significance (58%) (P < 0.05). False-positive cases included four benign follicular nodules and six follicular and four oncocytic adenomas. Our results show that, physicians chose active surveillance instead of diagnostic surgery in all patients with a benign ThyroidPrint® result, reducing the need for diagnostic surgery in 67% of patients with preoperative diagnosis of ITN.

Long-term Mammography Utilization after an Initial Randomized Intervention Period by all Underserved Chilean Women in the Clinics.

Chile has one of the highest rates of breast cancer in Latin America. Mammography rates among women, especially those of low socioeconomic status (SES), are thought to contribute to high breast cancer morbidity and mortality. A successful randomized controlled trial among women aged 50 to 70 in a low-SES primary care clinic in Chile led to a significant increase in mammography screening rates in a two-year intervention trial. This study assesses the sustainability of the intervention after ten years and identifies factors that might have been associated with a long-term effect using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. The mammography rates among women aged 50 to 70 in the low-SES intervention clinic were compared to two populations of women aged 50 to 70 from middle-SES clinics and to national data. Qualitative data were used to answer questions of adoption, implementation, and maintenance, while quantitative data assessed the reach and effectiveness. After ten years, low-SES women at the intervention clinic maintained significantly higher mammography screening rates vs. middle-SES women at the comparison clinics (36.2% vs. 30.1% and 19.4% p < 0.0001). Women of a low SES at the intervention clinic also had significantly higher screening rates compared to women of a low SES at a national level (44.2% vs. 34.2% p < 0.0001). RE-AIM factors contributed to understanding the long-term difference in rates. Mailed contact, outreach interventions, and the integration of health promoters as part of the Community Advisory Board were important factors associated with the effects observed. This study provides information on factors that could contribute to reducing the social gap on breast cancer screening.

The interdisciplinary and psychosocial gap in cancer survivorship: A longitudinal study in a Latin American Cancer Center.

BACKGROUND AND OBJECTIVES: There is lack of information on the quality of care provided to the rapidly increasing population of cancer survivors in Latin America. Our study attempts to address this gap and to identify areas needed to be improved. METHODS: A random sample of 210 breast and colorectal cancer survivors were selected from a hospital-based registry in Chile. Cancer registry information, electronic chart review, and personal interviews were used to assess medical and nonmedical care over a 5-year period. Survivorship care practices were compared to a standardized reference based on the US Institute of Medicine domains and the American Cancer Association guidelines. RESULTS: Over 80% of breast and colorectal cancer survivors received appropriate medical care, ongoing testing surveillance and risk factors assessment. Only a third of survivors were assessed for psychosocial disorders and 25% of them received interdisciplinary care. Overall, 66.1% of breast and 58.6% of colorectal cancer survivors reached the expected quality level of cancer survivorship care according to the reference standard (p < .001). CONCLUSION: Medical care practices reached a high standard in a leading cancer center in Latin America. However, a much stronger psychosocial assessment and interdisciplinary care is needed to improve survivorship cancer quality care.

Metástasis pancreática como debut de carcinoma papilar de tiroides: caso clínico y revisión del perfil clínico patológico y molecular / Papillary thyroid carcinoma presenting with pancreatic metastases: report of one case

Pancreatic metastases of papillary thyroid carcinoma (PTC) are exceptional. We report a 80-year-old man consulting for obstructive jaundice and dysphonia. Abdominal ultrasonography showed biliary dilation and abdominal magnetic resonance imaging (MRI) showed a pancreatic head mass of 36 mm. A left vocal cord paralysis was confirmed and cervical computed tomography (CT) showed multiple thyroid nodules of up to 35 mm associated with bilateral cervical lymph nodes (LN). Positron emission tomography ( 18 F-FDG PET/CT) evidenced hyper-metabolic activity in bilateral cervical LN, lungs, pancreas and left intercostal soft tissue, as well as left gluteus. Thyroid biopsy reported a tall-cell variant of PTC, and endoscopic ultrasound guided fine needle aspiration (EUS-FNA) of pancreatic mass confirmed PTC metastasis. The molecular study was positive for BRAFV600E. Pancreatic metastasis from PTC can be accurately diagnosed with 18 F-FDG PET/CT and EUS-FNA, which is consistent with a predominant expression of BRAFV600E mutation and, thus, an aggressive presentation with poor short-term survival.

Mammography correlates to better survival rates in breast cancer patients: a 20-year experience in a University health institution.

Breast cancer (BC) is the most common malignancy in women. We retrieved medical records from >2,000 Chilean BC patients over the 1997-2018 period. The objective was to assess changes in clinical presentation or prognosis of our patients throughout these 20 years of practice. Although most variables did not display significant variations, we observed a progressive increase in stage IV BC over this period. Our data showed that tumour stage III/IV or HER2-enriched subtype tumours were associated with poorer prognosis. In contrast, we found that patients diagnosed by mammography had better overall survival. We speculate that better screenings and more sensitive imaging could explain the unexpected rise in stage IV cases. Our results support mammography screenings as an effective measure to reduce BC-related mortality.

A Thyroid Genetic Classifier Correctly Predicts Benign Nodules with Indeterminate Cytology: Two Independent, Multicenter, Prospective Validation Trials.

Background: Although most thyroid nodules with indeterminate cytology are benign, in most of the world, surgery remains as the most frequent diagnostic approach. We have previously reported a 10-gene thyroid genetic classifier, which accurately predicts benign thyroid nodules. The assay is a prototype diagnostic kit suitable for reference laboratory testing and could potentially avoid unnecessary diagnostic surgery in patients with indeterminate thyroid cytology. Methods: Classifier performance was tested in two independent, ethnically diverse, prospective multicenter trials (TGCT-1/Chile and TGCT-2/USA). A total of 4061 fine-needle aspirations were collected from 15 institutions, of which 897 (22%) were called indeterminate. The clinical site was blind to the classifier score and the clinical laboratory blind to the pathology report. A matched surgical pathology and valid classifier score was available for 270 samples. Results: Cohorts showed significant differences, including (i) clinical site patient source (academic, 43% and 97% for TGCT-1 and -2, respectively); (ii) ethnic diversity, with a greater proportion of the Hispanic population (40% vs. 3%) for TGCT-1 and a greater proportion of African American (11% vs. 0%) and Asian (10% vs. 1%) populations for TGCT-2; and (iii) tumor size (mean of 1.7 and 2.5 cm for TGCT-1 and -2, respectively). Overall, there were no differences in the histopathological profile between cohorts. Forty-one of 155 and 45 of 115 nodules were malignant (cancer prevalence of 26% and 39% for TGCT-1 and -2, respectively). The classifier predicted 37 of 41 and 41 of 45 malignant nodules, yielding a sensitivity of 90% [95% confidence interval; CI 77-97] and 91% [95% CI 79-98] for TGCT-1 and -2, respectively. One hundred one of 114 and 61 of 70 nodules were correctly predicted as benign, yielding a specificity of 89% [95% CI 82-94] and 87% [95% CI 77-94], respectively. The negative predictive values for TGCT-1 and TGCT-2 were 96% and 94%, respectively, whereas the positive predictive values were 74% and 82%, respectively. The overall accuracy for both cohorts was 89%. Conclusions: Clinical validation of the classifier demonstrates equivalent performance in two independent and ethnically diverse cohorts, accurately predicting benign thyroid nodules that can undergo surveillance as an alternative to diagnostic surgery.

Breast lesions with atypia in percutaneous biopsies, managed with surgery in the last 10 years.

INTRODUCTION: The optimal management of breast lesions with atypia (BLA), detected in percutaneous biopsies after screening mammograms, is a controversial issue. The aim of this paper is to compare histological diagnosis by percutaneous biopsy with the results of the surgical biopsy of these lesions and to analyse the changes to clinical approach this would imply. METHOD: A retrospective study was carried out on patients operated on between June 2007 and June 2017 with a diagnosis of BLA. One hundred and forty-seven patients were identified with a pre-operative diagnosis of flat epithelial atypia (FEA), atypical ductal hyperplasia (ADH), atypical lobular hyperplasia, lobular carcinoma in situ and other atypia. RESULTS: The average age at diagnosis of BLAs was 52 ± 9.4 years. Radiologically, the lesions presented as microcalcifications in 79%, nodules in 15.6% and other lesions 5.4%. 73.5% of these were biopsied by means of digital stereotaxis. All of the patients analysed underwent a partial mastectomy. Changes in a biologically high-risk lesion were observed in 26.5% of the surgical specimens, of which 75.5% corresponded with ADH and FEA. In the percutaneous biopsies consistent with ADH (40.1%), ductal carcinoma was discovered in 6.8% (5.1% in situ and 1.7% invasive), which implied specific, multi-disciplinary management. Of the FEAs, 84.8% required a second treatment (surgery and/or hormone therapy ± radiotherapy, depending on whether it concerned FEA 59.6%, ADH 21.2% or ductal carcinoma in situ 3.8%). CONCLUSION: These data show the clinical relevance in the diagnosis of ADH and FEA in percutaneous biopsies. For the diagnosis of FEA in particular, the associated risk of biologically high-risk lesions and ductal carcinoma is made evident.

The Combination of RET, BRAF and Demographic Data Identifies Subsets of Patients with Aggressive Papillary Thyroid Cancer.

The use of BRAFV600E and RET/PTC1 as biomarkers to guide the extent of surgery in patients with papillary thyroid cancer (PTC) remains controversial. We assessed the combined use of demographic data (sex and age) with mRNA expression levels and/or mutational status (BRAFV600E and RET/PTC1) to identify potential subsets of patients with aggressive histopathological features (lymph node metastases and extrathyroidal extension). In a cohort of 126 consecutive patients, BRAFV600E and RET/PTC1 mutations were found in 52 and 18%, respectively. By conditional bivariate analysis (CBVA), a 'high activity' profile of BRAF (BRAFV600E positive or high expression) and 'low activity' profile of RET (RET/PTC1 negative or low expression) was associated with extrathyroidal extension (ETE) (OR 4.48). Alternatively, a 'high activity' profile of RET (RET/PTC1 positive or high expression) and 'low activity' profile of BRAF (BRAFV600E negative or low expression) were associated with lymph node metastasis (LNM) (OR 12.80). Furthermore, in patients younger than 55 years, a low expression of BRAF was associated with LNM (OR 17.65) and the presence of BRAFV600E mutation was associated with ETE (OR 2.76). Our results suggest that the analysis of demographic and molecular variables by CBVA could contribute to identify subsets of patients with aggressive histopathologic features, providing a potential guide to personalised surgical management of PTC.

Papillary thyroid microcarcinoma: characteristics at presentation, and evaluation of clinical and histological features associated with a worse prognosis in a Latin American cohort.

Objective We aimed to describe the presentation of papillary microcarcinoma (PTMC) and identify the clinical and histological features associated with persistence/recurrence in a Latin American cohort. Subjects and methods Retrospective study of PTMC patients who underwent total thyroidectomy, with or without radioactive iodine (RAI), and who were followed for at least 2 years. Risk of recurrence was estimated with ATA 2009 and 2015 classifications, and risk of mortality with 7th and 8th AJCC/TNM systems. Clinical data obtained during follow-up were used to detect structural and biochemical persistence/recurrence. Results We included 209 patients, predominantly female (90%), 44.5 ± 12.6 years old, 183 (88%) received RAI (90.4 ± 44.2 mCi), followed-up for a median of 4.4 years (range 2.0-7.8). The 7th and 8th AJCC/TNM system classified 89% and 95.2% of the patients as stage I, respectively. ATA 2009 and ATA 2015 classified 70.8% and 78.5% of the patients as low risk, respectively. Fifteen (7%) patients had persistence/recurrence during follow-up. In multivariate analysis, only lymph node metastasis was associated with persistence/recurrence (coefficient beta 4.0, p = 0.016; 95% CI 1.3-12.9). There were no PTMC related deaths. Conclusions Our series found no mortality and low rate of persistence/recurrence associated with PTMC. Lymph node metastasis was the only feature associated with recurrence in multivariate analysis. The updated ATA 2015 and 8th AJCC/TNM systems classified more PTMCs than previous classifications as low risk of recurrence and mortality, respectively.

Differential expression profile of CXCR3 splicing variants is associated with thyroid neoplasia. Potential role in papillary thyroid carcinoma oncogenesis?

Papillary thyroid cancer (PTC) is the most prevalent endocrine neoplasia. The increased incidence of PTC in patients with thyroiditis and the frequent immune infiltrate found in PTC suggest that inflammation might be a risk factor for PTC development. The CXCR3-ligand system is involved in thyroid inflammation and CXCR3 has been found upregulated in many tumors, suggesting its pro-tumorigenic role under the inflammatory microenvironment. CXCR3 ligands (CXCL4, CXCL9, CXCL10 and CXCL11) trigger antagonistic responses partly due to the presence of two splice variants, CXCR3A and CXCR3B. Whereas CXCR3A promotes cell proliferation, CXCR3B induces apoptosis. However, the relation between CXCR3 variant expression with chronic inflammation and PTC development remains unknown. Here, we characterized the expression pattern of CXCR3 variants and their ligands in benign tumors and PTC. We found that CXCR3A and CXCL10 mRNA levels were increased in non-metastatic PTC when compared to non-neoplastic tissue. This increment was also observed in a PTC epithelial cell line (TPC-1). Although elevated protein levels of both isoforms were detected in benign and malignant tumors, the CXCR3A expression remained greater than CXCR3B and promoted proliferation in Nthy-ori-3-1 cells. In non-metastatic PTC, inflammation was conditioning for the CXCR3 ligands increased availability. Consistently, CXCL10 was strongly induced by interferon gamma in normal and tumor thyrocytes. Our results suggest that persistent inflammation upregulates CXCL10 expression favoring tumor development via enhanced CXCR3A-CXCL10 signaling. These findings may help to further understand the contribution of inflammation as a risk factor in PTC development and set the basis for potential therapeutic studies.

Papillary thyroid microcarcinoma: characteristics at presentation, and evaluation of clinical and histological features associated with a worse prognosis in a Latin American cohort

ABSTRACT Objective We aimed to describe the presentation of papillary microcarcinoma (PTMC) and identify the clinical and histological features associated with persistence/recurrence in a Latin American cohort. Subjects and methods Retrospective study of PTMC patients who underwent total thyroidectomy, with or without radioactive iodine (RAI), and who were followed for at least 2 years. Risk of recurrence was estimated with ATA 2009 and 2015 classifications, and risk of mortality with 7th and 8th AJCC/TNM systems. Clinical data obtained during follow-up were used to detect structural and biochemical persistence/recurrence. Results We included 209 patients, predominantly female (90%), 44.5 ± 12.6 years old, 183 (88%) received RAI (90.4 ± 44.2 mCi), followed-up for a median of 4.4 years (range 2.0-7.8). The 7th and 8th AJCC/TNM system classified 89% and 95.2% of the patients as stage I, respectively. ATA 2009 and ATA 2015 classified 70.8% and 78.5% of the patients as low risk, respectively. Fifteen (7%) patients had persistence/recurrence during follow-up. In multivariate analysis, only lymph node metastasis was associated with persistence/recurrence (coefficient beta 4.0, p = 0.016; 95% CI 1.3-12.9). There were no PTMC related deaths. Conclusions Our series found no mortality and low rate of persistence/recurrence associated with PTMC. Lymph node metastasis was the only feature associated with recurrence in multivariate analysis. The updated ATA 2015 and 8th AJCC/TNM systems classified more PTMCs than previous classifications as low risk of recurrence and mortality, respectively.