Molecular characterization of metastatic penile squamous cell carcinoma in developing countries and its impact on clinical outcomes: LACOG 2018 translational study.

BACKGROUND: Penile squamous cell carcinoma (PSCC) is a rare malignancy. However, in developing countries the incidence rate is higher. The understanding of molecular alterations is essential for evaluating possible targets for more effective systemic therapies. METHODS: We retrospectively collected clinical data of metastatic PSCC (mPSCC) patients who had received at least one prior systemic treatment from 3 Brazilian hospitals. Tumor samples were evaluated using the next-generation sequencing (NGS) Foundation One DX and immunohistochemistry (IHC). The objective was to identify and describe somatic genomic alterations known to be functional or pathogenic and their association with survival outcomes. RESULTS: Twenty-three patients were identified, 22 and 18 patients had tumor samples analyzed by IHC and NGS, respectively. PD-L1 expression (CPS ≥ 1%) was positive in 14 patients (63.6%). Regarding the genomic alterations, 16 patients (88.9%) had some clinically relevant genomic alterations. TP53, TERT, CDKN2A, PIK3CA, NOTCH1, and CDKN2B loss were identified in 66.7%, 50%, 50%, 33.3%, 27.8%, and 22.2% of the patients, respectively. No MSI or TMB high (≥10 mutations/MB) cases were identified. NOTCH1 mutation was identified only in HPV-negative patients and it was associated with worse OS (yes: 5.5 vs no: 12.8 months, P = .049) and progression-free survival (yes: 5.5 vs no: 11.7 months, P = .032). CONCLUSION: This study demonstrated that molecular alterations in mPSCC from developing countries are similar to those from developed countries. Predictive biomarkers for immunotherapy response such as TMB high or MSI were not identified. Specific gene mutations may identify patients with worse prognoses and open new avenues for therapeutic development.

Time interval between diagnosis to treatment of breast cancer and the impact of health insurance coverage: a sub analysis of the AMAZONA III Study (GBECAM 0115).

PURPOSE: Breast cancer (BC) is the most common type of cancer among women in Brazil. Evidence shows that delayed treatment onset is associated with increased mortality. This study aimed to evaluate median days between diagnosis and treatment and factors associated with delayed start of treatment (> 60 days after diagnosis): stage, treatment received, subtype, epidemiological characteristics, and type of healthcare coverage. METHODS: This analysis included 1709 stage I-III BC patients from AMAZONA III, a prospective, observational study, diagnosed from January 2016 to March 2018 in 22 centers in Brazil. RESULTS: The median number of days from diagnosis to beginning of first oncologic treatment was 46 days (IQR 28-75) overall, 43 days (IQR 25-75) for stage I disease, 49 days (IQR 28-81) for stage II, and 44 days (IQR 30-68) for stage III, (p = 0.1180). According to first treatment received, diagnosis-to-treatment interval was 43 days (IQR 29-65) for neoadjuvant chemotherapy and 48 days (IQR 26-81) for surgery. Diagnosis-to-treatment interval was higher in women treated in the public system versus the private system (56 vs. 34 days, p < 0.0001). Patients in the public system had an increased odds of delayed treatment initiation (OR 4.74 95% CI 3.09-7.26, p < .0001). The longer interval from diagnosis to treatment in the public system was independent of clinical stage, type of treatment (systemic vs surgery first), subtype and region of the country. CONCLUSION: By characterizing the delays in care delivery, our study will aid stakeholders to better design interventions and allocate resource to improve timely treatment for breast cancer in Brazil. CLINICALTRIALS: gov Identifier: NCT02663973, registered on January, 26th, 2016.

Influence of physician's lifestyle on the prescription of healthy habits to breast cancer patients (LACOG 1218).

BACKGROUND: Healthy lifestyle is capable of positively modifying the survival of breast cancer (BC) patients. We aimed to evaluate how physician's lifestyle influences on the prescription of healthy habits to BC patients. METHODS: An online questionnaire to evaluate physician lifestyle and prescription of healthy habits to BC patients was developed and circulated by e-mail to physicians dedicated to treat BC patients. A multivariate Poisson regression analysis assessed which factors of physician lifestyle could influence on prescription of healthy habits. RESULTS: A total of 267 physicians answered the questionnaire from October to November 2018. In terms of physician lifestyle, 228 (85.4%) had healthy eating habits and 236 (88.4%) practiced physical activity. Overall, 84.3% of the physicians advised their BC patients on the importance of lifestyle modification. Physicians who did not exercise regularly have a higher probability of not advising for health lifestyle (RR 2.48; p = 0.0265) as opposite to physicians ≥ 50 years-old (RR 0.37; p = 0.0118). Obesity treatment and management was performed by 45.3% of physicians. Being a breast surgeon (RR 1.29; p = 0.0025) or radiation oncologists (RR 1.82; p = 0.0025) were associated with not performing obesity treatment and management. About 53.4% of physicians referred overweight or obese patients to a dietitian and/or endocrinologist. Male gender (RR 1.35; p = 0.0296), breast surgeons (RR 1.99; p = 0.0001), and clinical practice in public health system (RR 1.53; p = 0.0012) were associated with not referring as opposed to physicians ≥ 50 years-old (RR 0.46; p = 0.0005). CONCLUSION: Our survey showed some influence of physician's lifestyle on the prescription of healthy habits to BC patients. Physicians who practice physical activity regularly had a higher probability of advising lifestyle modification and about half of physicians did some type of overweight and obese management.

Development of geriatric oncology in Latin America: A report from the Latin American Cooperative Oncology Group.

Population aging represents a critical issue for global cancer care, notably in low- and middle-income countries (LMIC). Latin America is a large region composed of 21 countries with notable diversity in both human development and access to quality healthcare. Thus, it is necessary to understand how care for older individuals is being delivered in such large and diverse regions of the world. This review describes the recent advances made in Mexico, Brazil, and Chile, focusing on the creation and implementation of educational, research, and clinical activities in geriatric oncology. These initiatives intend to change healthcare professionals' perceptions about the care for older adults and to improve the way older patients are being treated.

The impact of a breast cancer diagnosis on marital outcomes and factors associated with divorce and separation.

Objective: To analyze marital outcomes, divorce or separation, and its association with demographic, socioeconomic, and clinicopathological factors among breast cancer (BC) survivors after 2-years of diagnosis. Methods: We performed a retrospective analysis of marital status at baseline and at years 1 and 2 of follow-up of women aged ≥ 18 years diagnosed with invasive BC participating in the AMAZONA III (GBECAM0115) study. The BC diagnosis occurred between January 2016 and March 2018 at 23 institutions in Brazil. Results: Of the 2974 women enrolled in AMAZONA III, 599 were married or living under common law at baseline. Divorce or separation occurred in 35 (5.8%) patients at 2 years of follow-up. In the multivariate analysis, public health insurance coverage was associated with a higher risk of marital status change (8.25% vs. 2.79%, RR 3.09, 95% CI 1.39 - 7.03, p = 0.007). Women who underwent mastectomy, adenomastectomy or skin-sparing mastectomy were associated with a higher risk of divorce or separation (8.1% vs. 4.49%, RR 1.97, 95 CI 1.04 - 3.72, p = 0.0366) than those who underwent breast-conserving surgery. Conclusion: Women covered by the public health system and those who underwent mastectomy, adenomastectomy or skin-sparing mastectomy were associated with a higher risk of divorce or separation. This evidence further supports the idea that long-term marital stability is associated with a complex interplay between socioeconomic conditions and stressors, such as BC diagnosis and treatment. ClinicalTrials Registration: NCT02663973.

The impact of a breast cancer diagnosis on marital outcomes and factors associated with divorce and separation

Abstract Objective To analyze marital outcomes, divorce or separation, and its association with demographic, socioeconomic, and clinicopathological factors among breast cancer (BC) survivors after 2-years of diagnosis. Methods We performed a retrospective analysis of marital status at baseline and at years 1 and 2 of follow-up of women aged ≥ 18 years diagnosed with invasive BC participating in the AMAZONA III (GBECAM0115) study. The BC diagnosis occurred between January 2016 and March 2018 at 23 institutions in Brazil. Results Of the 2974 women enrolled in AMAZONA III, 599 were married or living under common law at baseline. Divorce or separation occurred in 35 (5.8%) patients at 2 years of follow-up. In the multivariate analysis, public health insurance coverage was associated with a higher risk of marital status change (8.25% vs. 2.79%, RR 3.09, 95% CI 1.39 - 7.03, p = 0.007). Women who underwent mastectomy, adenomastectomy or skin-sparing mastectomy were associated with a higher risk of divorce or separation (8.1% vs. 4.49%, RR 1.97, 95 CI 1.04 - 3.72, p = 0.0366) than those who underwent breast-conserving surgery. Conclusion Women covered by the public health system and those who underwent mastectomy, adenomastectomy or skin-sparing mastectomy were associated with a higher risk of divorce or separation. This evidence further supports the idea that long-term marital stability is associated with a complex interplay between socioeconomic conditions and stressors, such as BC diagnosis and treatment. ClinicalTrials Registration: NCT02663973.

Complications of central venous catheter insertion in a teaching hospital.

INTRODUCTION: Central venous catheters are fundamental to daily clinical practice. This procedure is mainly performed by residents, often without supervision or structured training. OBJECTIVE: To describe the characteristics of central venous catheterization and the complication rate related to it. METHOD: Retrospective cohort study. Adult patients undergoing central venous catheter insertion out of the intensive care unit (ICU) of a teaching hospital were selected from March 2014 to February 2015. Data were collected from medical charts using an electronic form. Clinical and laboratory characteristics from patients, procedure characteristics, and mechanical and infectious complications rates were assessed. Patients with and without complications were compared. RESULTS: Three hundred and eleven (311) central venous catheterizations were evaluated. The main reasons to perform the procedure were lack of peripheral access, chemotherapy and sepsis. There were 20 mechanical complications (6% of procedures). Arterial puncture was the most common. Procedures performed in the second semester were associated with lower risk of complications (odds ratio 0.35 [95CI 0.12-0.98; p=0.037]). Thirty-five (35) catheter-related infection cases (11.1%) were reported. They were related to younger patients and procedures performed by residents with more than one year of training. Procedures performed after the first trimester had a lower chance of infection. CONCLUSION: These results show that the rate of mechanical complications of central venous puncture in our hospital is similar to the literature, but more attention should be given to infection prevention measures.

The diagnosis of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy is a prevalent genetic disease characterized by left ventricular hypertrophy, presenting dynamic obstruction of outflow tract with subaortic gradient happening at rest in 30% of the cases. It is attributed to the intricate interaction between the anterior mitral leaflet, the interventricular septum and altered flow vectors generated in left ventricle along with changes in outflow tract geometry. Mitral regurgitation in varying degrees is found with or without association with structural deformities of the valve apparatus. The exercise echocardiogram evidences latent obstruction easily induced by exercise in 60 to 75% of non-obstructive forms. The determination of the gradient under this condition must be considered in routine investigation of patients with mild or no obstruction at rest. The evaluation of hypertrophic cardiomyopathy incorporates methods based on the ultrasound image, which, along with MRI, allow recognizing ventricular obstruction generating mechanisms, thus facilitating the diagnosis and management of obstructive and latent obstructive forms.

Complications of central venous catheter insertion in a teaching hospital / Complicações de punções venosas centrais em um hospital de ensino

Summary Introduction: Central venous catheters are fundamental to daily clinical practice. This procedure is mainly performed by residents, often without supervision or structured training. Objective: To describe the characteristics of central venous catheterization and the complication rate related to it. Method: Retrospective cohort study. Adult patients undergoing central venous catheter insertion out of the intensive care unit (ICU) of a teaching hospital were selected from March 2014 to February 2015. Data were collected from medical charts using an electronic form. Clinical and laboratory characteristics from patients, procedure characteristics, and mechanical and infectious complications rates were assessed. Patients with and without complications were compared. Results: Three hundred and eleven (311) central venous catheterizations were evaluated. The main reasons to perform the procedure were lack of peripheral access, chemotherapy and sepsis. There were 20 mechanical complications (6% of procedures). Arterial puncture was the most common. Procedures performed in the second semester were associated with lower risk of complications (odds ratio 0.35 [95CI 0.12-0.98; p=0.037]). Thirty-five (35) catheter-related infection cases (11.1%) were reported. They were related to younger patients and procedures performed by residents with more than one year of training. Procedures performed after the first trimester had a lower chance of infection. Conclusion: These results show that the rate of mechanical complications of central venous puncture in our hospital is similar to the literature, but more attention should be given to infection prevention measures.

Resumo Introdução: Cateteres venosos centrais são fundamentais na prática clínica diária. Em hospitais de ensino, esse procedimento é realizado por médicos residentes, frequentemente sem supervisão ou treinamento estruturado. Objetivo: Descrever as características das punções venosas centrais e a taxa de complicações relacionadas. Método: Estudo de coorte retrospectiva. Foram selecionados pacientes adultos submetidos a punção venosa central fora de unidade de terapia intensiva (UTI) de um hospital de ensino no ano letivo de 2014 (março de 2014 a fevereiro de 2015). Os dados foram coletados por meio de revisão de prontuários com o uso de formulário eletrônico. Foram avaliadas características clínicas e laboratoriais dos pacientes, características do procedimento, taxa de complicações mecânicas e infecciosas relacionadas. Foram comparados os pacientes com complicações em relação àqueles sem complicações. Resultados: Foram avaliadas 311 punções venosas centrais. Os principais motivos para realização do procedimento foram falta de rede periférica, quimioterapia e sepse. Ocorreram 20 complicações mecânicas (6% dos procedimentos); punção arterial foi a mais comum. Procedimentos realizados no segundo semestre do ano letivo foram associados a menor risco de complicações (razão de chances de 0,35 [IC95 0,12-0,98; p=0,037]). Foram descritos 35 casos de infecção relacionada ao cateter (11,1%). Casos de infecção foram associados a pacientes mais jovens e procedimentos realizados por residentes com mais de um ano de treinamento. Procedimentos realizados após o primeiro trimestre tiveram menor chance de infecção. Conclusão: Esses resultados mostram que a taxa de complicações mecânicas de punção venosa central em nosso hospital é semelhante à da literatura; porém, maior atenção deve ser dada para medidas de prevenção de infecção.

O diagnóstico da obstrução da via de saída do ventrículo esquerdo na cardiomiopatia hipertrófica / The diagnosis of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy

A cardiomiopatia hipertrófica é uma doença genética prevalente caracterizada por hipertrofia ventricular esquerda, em que obstrução dinâmica da via de saída com geração de gradiente subaórtico incide em repouso em 30% dos casos. A obstrução é atribuida complexa interação entre o folheto anterior mitral, o septo interventricular e vetores anômalos de fluxo gerados no ventrículo esquerdo aliada a modificações na geometria da via de saída. Regurgitação mitral em grau variável é detectada associada ou não a deformidades estruturais do aparelho valvar. O ecocardiograma de esforço demonstra obstrução latente facilmente induzida por exercício em 60 a 75% das formas não obstrutivas. A determinação do gradiente nessas condições impõe-se na investigação de rotina dos pacientes com obstrução leve ou ausente em repouso. A avaliação da cardiomiopatia hipertrófica incorpora métodos de imagem baseados no ultrassom, os quais, adicionados ressonância magnética, possibilitam o reconhecimento de mecanismos geradores de obstrução ventricular, de modo a favorecer o diagnóstico e o manejo das formas obstrutivas e obstrutivas latentes.

Hypertrophic cardiomyopathy is a prevalent genetic disease characterized by left ventricular hypertrophy, presenting dynamic obstruction of outflow tract with subaortic gradient happening at rest in 30% of the cases. It is attributed to the intricate interaction between the anterior mitral leaflet, the interventricular septum and altered flow vectors generated in left ventricle along with changes in outflow tract geometry. Mitral regurgitation in varying degrees is found with or without association with structural deformities of the valve apparatus. The exercise echocardiogram evidences latent obstruction easily induced by exercise in 60 to 75% of non-obstructive forms. The determination of the gradient under this condition must be considered in routine investigation of patients with mild or no obstruction at rest. The evaluation of hypertrophic cardiomyopathy incorporates methods based on the ultrasound image, which, along with MRI, allow recognizing ventricular obstruction generating mechanisms, thus facilitating the diagnosis and management of obstructive and latent obstructive forms.

Avaliação qualitativa do efeito do ensino de pedagogia médica sobre a atividade docente em alunos do curso de Pós-Graduação em Medicina / Qualitative assessment of the effect of a medical pedagogy course on the teaching activity of graduate medical students

A situação atual do ensino médico, principalmente referente à formação de seus professores vem sendo questionada e sofrendo adaptações nos currículos de pós-graduação visando ao aprimoramento dos métodos de ensino dos docentes. O programa de pósgraduação em Medicina da UFCSPA, buscando adequar-se aos padrões ideais de formação pedagógica docente, inseriu no seu programa a disciplina de Pedagogia Médica. O objetivo deste estudo foi avaliar a qualidade de ensino dos alunos do programa de Pósgraduação que cursam a disciplina de Pedagogia Médica. Foram avaliados 2 grupos: o primeiro, constituído por 120 alunos que realizaram a prática didática simultaneamente às aulas teóricas de Pedagogia e o segundo grupo, também com 120 alunos, porém que realizaram a prática didática após a conclusão da disciplina. Em conclusão, os alunos do grupo 2 apresentaram uma melhor qualidade no processo de ensino-aprendizagem pelo uso de maior variedade dos métodos de ensino, recursos audiovisuais e formas de avaliação (AU)

Introduction: The current situation of medical education in our community, particularly concerning the preparation of university professors, has been questioned and eventually submitted to changes in the postgraduate curricula in order to improve the teaching methods of medical professors. Seeking to catch-up with the optimal standards for the pedagogical formation of professors, the postgraduate program of medicine has included the discipline of Medical Pedagogy in its curriculum. Methods: Two groups were evaluated. Group 1, composed of 120 students, performed the didactical practice concurrently with the theoretical classes of Pedagogy, and Group 2, composed of 120 students as well but who attended the didactical classes after having completed the discipline. Results and Conclusion: Students in Group 2 presented a higher quality in the teaching/ learning process because of their wider use of teaching methods, audiovisual resources, and evaluation forms (AU)