Resection Margins in Merkel Cell Carcinoma: Is a 1-cm Margin Wide Enough?

BACKGROUND: Guidelines regarding specific resection margins for primary Merkel cell carcinoma (MCC) are not well established. The current National Comprehensive Cancer Network (NCCN) guidelines recommend 1- to 2-cm resection margins. This study aimed to determine the impact of margin width on local recurrence (LR), disease-specific survival (DSS), overall survival (OS), and type of wound closure. METHODS: All patients who underwent resection of primary MCC at a single institution from 2000 to 2015 were reviewed. Patient demographics, clinicopathologic characteristics, treatments, and outcomes were reviewed. RESULTS: A total of 240 patients underwent resection of primary MCC with resection margin width identified in the operative report. The median age was 76 years, and 65.8% of the patients were men. Of the 240 patients, 85 (35.4%) had head and neck primaries, 140 (58.3%) had extremity primaries, and 15 (6.3%) had trunk primaries. In terms of margins, 69 patients (28.8%) had a margin of 1 cm, 36 patients (15%) had a margin of 1.1-1.9 cm, and 135 patients (56.2%) had a margin of 2 cm or more. The median follow-up period was 21 months. The LR rate was 2.9% for a margin of 1 cm, 2.8% for a margin of 1.1-1.9 cm, and 5.2% for a margin of 2 cm or more (p = 0.80). The 5-year OS was 63.6% for a margin of 1 cm, 59.7% for a margin of 1.1-1.9, and 70.7% for a margin of 2 cm or more (p = 0.66). The 5-year DSS was 80.3% for a margin of 1 cm, 66.2% for a margin of 1.1-1.9 cm, and 91.8% for a margin of 2 cm or more (p = 0.28). For wound closure, 43.5, 50, and 65.9% of the patients respectively required a flap or graft with a margin of 1, 1.1-1.9, and 2 cm or more (p = 0.006). CONCLUSIONS: A 1-cm resection margins did not increase the risk of LR. Margin width did not make a significant difference in DSS or OS. Larger resection margins increase the need for a graft or flap closure.

Neorickettsia helminthoeca associated lymphoid, enteric, and pulmonary lesions in dogs from Southern Brazil: An immunohistochemical study.

Neorickettsia helminthoeca (NH), the agent of salmon poisoning disease or canine neorickettiosis (CN), is a bacterial endosymbiont of the nematode Nanophyetus salmincola, and infections are spreading among specific fish-eating mammalians. This article describes the pathologic and immunohistochemical findings associated with spontaneous NH-induced infections in dogs from Southern Brazil. The principal pathologic findings were hypertrophy of Peyer patches and lymphadenopathy with lymphocytic proliferation, chronic interstitial pneumonia, and chronic enteritis associated with positive intralesional immunoreactivity to antigens of NH within macrophages and histiocytes. Positive immunoreactivity against canine parvovirus-2 (CPV-2) or/and canine distemper virus was not detected in the evaluated intestinal segments or in the samples from the cerebellum and lungs, respectively, from the dogs evaluated. These findings demonstrated that NH was involved in the enteric, pulmonary, and lymphoid lesions herein described, and provide additional information to confirm the occurrence of this bacterial endosymbiont within this geographical location. It is proposed that chronic pneumonia should be considered as a pathologic manifestation of NH-induced infections. Additionally, our results show that the occurrences of CN seem to be underdiagnosed in Southern Brazil due to the confusion with the incidence of CPV-2.

Effects of patulin and ascladiol on porcine intestinal mucosa: An ex vivo approach.

Patulin (PAT) is a secondary metabolite mainly produced by Aspergillus and Penicillium that is frequently found contaminating apples and rotten fruits. Patulin can be transformed in potencially less toxic compounds such as ascladiol (ASC). Toxic effects of patulin were described in rats and in in vitro models, however concerning ascladiol, data are restricted to metabolic pathways. The aim of the present study was to evaluate the effects of different concentrations of PAT (10 µM, 30 µM, 100 µM) and ASC (30 µM, 100 µM) on intestinal tissue using the jejunal explant model. Explants from pigs were exposed for 4 h to PAT and ASC and after this period were processed for histological, morphometrical and immunohistochemical analysis. Mild histological changes were observed in jejunal explants exposed to PAT and ASC, however no significant difference in the lesional score or villi height was observed between the PAT/ASC-groups and the control. Also, explants exposed to 100 µM of PAT showed a significant decrease in goblet cells density and a significant increase in cell apoptosis. These results indicate that high levels of patulin can induce mild toxic effects on intestinal mucosa whereas ascladiol apparently is non-toxic to intestinal tissue.

Preparação para a aposentadoria e ócio: possíveis contribuições da abordagem Gestáltica / Preparation for retirement and leisure: possible contributions of Gestalt approach / Preparación para la jubilación y ocio: posibles contribuciones del enfoque Gestáltico

Na estruturação da vida humana é comum privilegiar os esforços de preparação à atividade laboral em detrimento à vivência do tempo livre, de modo que a aposentadoria se apresenta como uma mudança significativa que exige a ressignificação dos vínculos socioafetivos e ocupacionais desenvolvidos ao longo do ciclo de vida. Este estudo trata-se de um ensaio teórico que visa refletir acerca da aposentadoria e da vivência do ócio a partir das possíveis contribuições da abordagem gestáltica, baseando-se nos conceitos de pessoa, de awareness e de aqui-e-agora, além de elementos do trabalho grupal em Gestalt-terapia, os quais podem corroborar de forma relevante para o processo de preparação à aposentadoria, possibilitando aos sujeitos o contato mais efetivo e responsável com suas escolhas, formas de ser e estar no mundo.

In the structuring of human life, it is common to privilege efforts to prepare for working activities than to experience free time living, so that retirement presents itself as a significant change that requires the re-signification of the socio-affective and occupational bonds developed throughout the life cycle. This study is a theoretical essay that aims to reflect on retirement and leisure experience from the possible contributions of the Gestalt approach, based on the concepts of person, awareness and here-and-now, as well as elements of Gestalt therapy group work, which can contribute in a relevant way to the process of preparation for retirement, enabling the subjects the most effective and responsible contact with their choices and ways of being in the world.

En la estructuración de la vida humana es común ponderar los esfuerzos de la preparación para la actividad laboral en detrimento de la vivencia del ocio, de modo que la jubilación se presenta como un cambio significativo que exige la resignificación de los vínculos socio-afectivos y ocupacionales desarrollados a lo largo del ciclo de vida. Este estudio constituye un ensayo teórico que pretende reflexionar acerca de la jubilación y la vivencia del ocio a partir de las posibles contribuciones del enfoque gestáltico, basándose en los conceptos de persona, de conciencia y de aquí y ahora, además de elementos del trabajo grupal en Gestalt-terapia, los cuales pueden aportar de forma relevante al proceso de preparación para la jubilación, posibilitándole a los sujetos un contacto más efectivo y responsable con sus elecciones y formas de ser y estar en el mundo.

[Associated factors with discontinuation use of combined oral contraceptives]. / Fatores associados à descontinuação do uso de anticoncepcionais orais combinados.

PURPOSE: Due to the scarce information available in Brazil in relation to the number of women who initiated the use of combined oral contraceptives and prematurely discontinued, the objective was to assess the reasons for discontinuation of the use of several combined oral contraceptives among Brazilian women living in urban areas. METHODS: A cross-sectional study with 400 gynecologists registered withy the Brazilian Federation of Obstetricians and Gynecologists. Each physician interviewed 10 non-pregnant, not breastfeeding, not amenorrheic women aged 18 to 39 years who consulted requesting combined oral contraceptive (COC) with a questionnaire at the beginning of use and at six months later. The questionnaire included sociodemographic data, type of COC chosen or prescribed and reasons for discontinuation when it occurred during follow-up. The strategy of selection allowed the inclusion of women from different socioeconomic strata, however, only those attended at private or insurance offices. The sample size was estimated at 1,427 women. RESULTS: A total of 3,465 interviews were conducted at the first visit and 1,699 six months later. The women were 20 to 29 years old, 57.3% were single and an equal proportion of 45.0% attended high school or college. Most (60.7%) were nulligravidas and among those who had used some contraceptive before, 71.8% had used a COC. Among the more prescribed or chosen COC the most prevalent were monophasic with ethynil estradiol (20 µg) and regarding progestin the most prevalent was with gestodene (36.5%) followed by a COC with drosperinone (22.0%). At six months 63.5% still used COC. Among those who discontinued the main reasons were wishing to become pregnant (36.5%) and side effects (57.3%) and the most prevalent were headache (37.6%), weight gain (16.6%) and irregular bleeding (23.6%). CONCLUSIONS: The continuation rate of COC was low at six months and this study could contribute to a better counseling on the part of physicians of patients who initiate COC about side-events that are rare, minimal and temporary and about the benefits of COC use.

Fatores associados à descontinuação do uso de anticoncepcionais orais combinados / Associated factors with discontinuation use of combined oral contraceptives

OBJETIVO: Avaliar as razões para descontinuar diversos anticoncepcionais orais combinados entre mulheres brasileiras iniciantes do método, residentes em áreas urbanas. MÉTODOS: Estudo de corte transversal com 400 ginecologistas do Brasil, registrados na Federação Brasileira de Ginecologia e Obstetrícia. Cada médico entrevistou 10 mulheres não grávidas, não lactantes, não em amenorreia, com idades entre 18 e 39 anos que consultavam solicitando anticoncepcional oral combinado (ACO), com um questionário no início de uso e aos 6 meses posteriores. O questionário incluiu dados sociodemográficos, tipo de ACO escolhido ou prescrito e razões para descontinuação, caso ocorresse durante o seguimento. A estratégia de seleção permitiu a inclusão de mulheres de diferentes estratos socioeconômicos, mas somente atendidas em consultórios privados ou de convênios. O tamanho da amostra foi estimado em 1.427 mulheres. RESULTADOS: Foram obtidas 3.465 entrevistas na primeira visita e 1.699 aos 6 meses posteriores. As mulheres tinham predominantemente entre 20 e 29 anos, 57,3 por cento eram solteiras e em proporção quase igual de 45 por cento tinham ensino médio ou superior. A maioria (60,7 por cento) era nuligestas e dentre as que tinham usado algum método contraceptivo anteriormente, 71,8 por cento tinham utilizado ACO. Entre os ACO mais prescritos ou escolhidos, o mais prevalente foram os monofásicos com etinilestradiol (20 µg) e no tocante ao progestágeno, o mais prevalente foi com gestodeno (36,5 por cento), seguido por ACO com drosperinona (22,0 por cento). Aos 6 meses, 63,5 por cento continuavam em uso do ACO. Dentre as que descontinuaram o uso, as principais razões dadas foram: desejo de engravidar (36,5 por cento) e efeitos colaterais (57,3 por cento) como cefaléia (37,6 por cento), aumento de peso (16,6 por cento) e sangramento irregular (23,6 por cento). ..

PURPOSE: Due to the scarce information available in Brazil in relation to the number of women who initiated the use of combined oral contraceptives and prematurely discontinued, the objective was to assess the reasons for discontinuation of the use of several combined oral contraceptives among Brazilian women living in urban areas. METHODS: A cross-sectional study with 400 gynecologists registered withy the Brazilian Federation of Obstetricians and Gynecologists. Each physician interviewed 10 non-pregnant, not breastfeeding, not amenorrheic women aged 18 to 39 years who consulted requesting combined oral contraceptive (COC) with a questionnaire at the beginning of use and at six months later. The questionnaire included sociodemographic data, type of COC chosen or prescribed and reasons for discontinuation when it occurred during follow-up. The strategy of selection allowed the inclusion of women from different socioeconomic strata, however, only those attended at private or insurance offices. The sample size was estimated at 1,427 women. RESULTS: A total of 3,465 interviews were conducted at the first visit and 1,699 six months later. The women were 20 to 29 years old, 57.3 percent were single and an equal proportion of 45.0 percent attended high school or college. Most (60.7 percent) were nulligravidas and among those who had used some contraceptive before, 71.8 percent had used a COC. Among the more prescribed or chosen COC the most prevalent were monophasic with ethynil estradiol (20 µg) and regarding progestin the most prevalent was with gestodene (36.5 percent) followed by a COC with drosperinone (22.0 percent). At six months 63.5 percent still used COC. Among those who discontinued the main reasons were wishing to become pregnant (36.5 percent) and side effects (57.3 percent) and the most prevalent were headache (37.6 percent), weight gain (16.6 percent) and irregular bleeding (23.6 percent)...

Reflexão histórico-epistemológica sobre os fundamentos epidemiológicos da Clínica Médica contemporânea / Historical and epidemiological reflections about the epidemiologic foundations of contemporary Clinical Medicine

A medicina clínica apresentou a partir dos anos 1960 uma certa inflexão em seus mecanismos internos de produzir conhecimento, assim como em sua forma de aplicar esses conhecimentos na prática. A principal diferença em relação ao passado foi que, a partir dessa época, os problemas de natureza clínica, como diagnóstico diferencial, terapêutica e estimativa de prognóstico, passaram a ser processados predominantemente por instrumentos de análise padronizados e, principalmente, submetidos ao escrutínio de uma razão empírico-matemática. A entidade paciente deixou de ser um ente emissor de sintomas e sinais que são processados por um médico, para ser uma nova entidade em que esses signos, previamente estabelecidos e validados pelos estudos clínicos e pela razão matemática, são encaixados pelos médicos nas manifestações dos pacientes. Na mesma época em que esse processo ocorreu o mundo ocidental vivia um período de crise que se caracterizava por um baixo crescimento econômico e por um questionamento por parte da sociedade dos princípios normativos, tanto éticos quanto morais, que regiam sua forma de viver. Nos Estados Unidos, a partir de 1962 passou a ser uma exigência legal que toda droga nova, antes de ser comercializada, deveria provar, através de testes científicos, que ela tinha eficácia terapêutica, que de fato funcionava na patologia que se propunha tratar. A metodologia para promover esse tipo de demonstração foi construída a partir dessa exigência. As regras de prova científica de eficácia foram construídas a partir dessa demanda legal, e são chamadas genericamente de Epidemiologia Clínica. Vários agentes participaram ativamente do processo de definição das regras do método científico que foram então, a partir dessa data, implementadas e sedimentadas. Destacam-se nesse debate, a comunidade acadêmica, a sociedade civil, os economistas, os advogados e juizes, os agentes do governo, e, finalmente, a indústria farmacêutica...

Since 1960 Clinical Medicine suffered a kind of inflection in its internal mechanisms of producing theoretical knowledge, as well as in the way that this knowledge is applied in practical life. The most important difference in relation to the past was that problems of clinical nature like, differential diagnosis, therapeutical decisions, and prognosis estimation, started to be predominantly processed by standardized analytical instruments, and most important, they were always previously submitted to an empirical-mathematical reasoning. Individual patients were no longer a being that reported signs and symptoms that were processed by a physician, they started to be a new entity in which these signs, previously established and validated by clinical studies have to be necessarily engrafted by the physicians in patients manifestations. At the same time that this process occurred, western world was living an important critical period, characterized by a very slow economic growth, and by a reevaluation of its ethical and moral values. After 1962, in the United States, it became obligatory to prove, through empirical scientific evidence that a new drug was effective, before marketing and sales authorization was issued to a company who wanted to launch the drug. The scientific method designed to prove efficacy of a drug was actually developed after this legal demand. This method is called generically Clinical Epidemiology. Several actors participated in the discussion of the rules of this method. Medical Schools, government representatives, pharmaceutical industry can be cited; the latter played a very special role, since it acted as a secretary of the whole process. The reason behind this was that, at those times, the two major pillars of the pharmaceutical business, innovation capacity and patent law, were being severely criticized, and proposals for changing the way this things were being conducted in American society were about to become a reality...