Acessibilidade do termo de consentimento na pesquisa clínica no Brasil / Accessibility of the consent form in Brazilian clinical research / Accesibilidad al formulario de consentimiento en la investigación clínica en Brasil

Resumo O termo de consentimento livre e esclarecido tem a função de informar o participante de pesquisas clínicas sobre a natureza da pesquisa e seus direitos, formalizando sua decisão de participar. Estudos indicam que esse documento é redigido de modo complexo, comprometendo a autonomia do participante. Para este trabalho, foram redigidos dois termos de consentimento da mesma pesquisa hipotética, com estilos de redação diferentes. Ambos os termos foram analisados pela ferramenta Coh-Metrix Port, que avalia métricas linguísticas e acessibilidade textual. A análise indicou que os textos são complexos e exigem alta escolaridade para serem entendidos. Esses achados reforçam a percepção de que, no Brasil, os termos de consentimento podem ter sua real função comprometida e apontam a importância de modificar sua forma de elaboração.

Abstract The informed consent form informs clinical research patients about the nature of the research and their rights, formalizing their decision to participate; however, studies show that this document is written in a complex manner, compromising patient autonomy. Two consent forms from the same hypothetical research were developed with different writing styles and analyzed by the Coh-Metrix Port tool, which evaluates linguistic metrics and textual accessibility. Results showed that both texts were complex and required high schooling level to be understood. These findings reinforce the perception that consent forms may have their real function compromised and point to the importance of changing its elaboration.

Resumen El formulario de consentimiento informado tiene la finalidad de mostrar la naturaleza de la investigación y sus derechos al participante de la investigación clínica para formalizar su decisión de participar en el estudio. Los estudios indican que la redacción de este documento es compleja, lo que compromete la autonomía del participante. Para este estudio se redactaron dos formularios de consentimiento de una misma investigación hipotética, con diferentes estilos de escritura. Para el análisis de ambos formularios se utilizó la herramienta Coh-Metrix Port, que evalúa las métricas lingüísticas y la accesibilidad textual. Los resultados apuntaron a que los textos son complejos, lo que requiere un alto nivel de educación para su comprensión. Estos hallazgos coinciden que, en Brasil, los formularios de consentimiento pueden tener su finalidad comprometida y señalan la necesidad de modificar su forma de elaboración.

Translation and cultural adaptation of the Functional Assessment of Chronic Illness Therapy - Cervical Dysplasia (FACIT-CD) to evaluate quality of life in women with cervical intraepithelial neoplasia / Tradução e adaptação cultural do Functional Assessment of Chronic Illness Therapy - Cervical Dysplasia (FACIT-CD) para avaliar qualidade de vida em mulheres com neoplasia intraepitelial cervical

ABSTRACT Objective To translate and perform the cultural adaptation of the tool Functional Assessment of Chronic Illness Therapy - Cervical Dysplasia (FACIT-CD) to the Portuguese language. Methods A descriptive cross-sectional study, with translation and cultural adaptation of the assessment tool performed according to international guidelines and the Functional Assessment of Chronic Illness Therapy (FACIT) protocol group. It involved eight experts, six from Brazil, one from Portugal and one from the United States. After translation and back-translation of the tool, the semantic analysis process was carried out. We randomly included 20 women aged between 18 and 70 years with altered cervical cytology exam, seen at the Department of Prevention and Gynecologic Oncology - Hospital de Câncer de Barretos. Results The sample consisted of women with low education level. In the first pre-test, ten women participated and half of them considered the questions CD1, CD2 and CD3 as difficult, because they did not understand the meaning of the term "pelvic area". The question CD5, "I worry about spreading the infection", was also considered difficult to understand by five women. After the reconsideration of the expert committee and FACIT group, the second pre-test was performed. At this stage, we concluded that the previously raised understanding problems had been solved. Conclusion The translated version of FACIT-CD in universal Portuguese language is equivalent to the original version in English and was easily understood by patients with cervical intraepithelial neoplasia.

RESUMO Objetivo Traduzir e adaptar o instrumento Functional Assessment of Chronic Illness Therapy - Cervical Dysplasia (FACIT-CD), para a língua portuguesa. Métodos Estudo descritivo, transversal, com metodologia de tradução e adaptação cultural de instrumento de avaliação, realizado por meio de diretrizes internacionais e seguindo o protocolo do grupo Functional Assessment of Chronic Illness Therapy (FACIT). Envolveu oito especialistas, sendo seis nativos do Brasil, um de Portugal e um dos Estados Unidos. Ao término do processo de tradução e retrotradução, deu-se início ao processo de análise semântica. Foram incluídas aleatoriamente 20 mulheres entre 18 e 70 anos com exame de citologia cervical alterado, atendidas no Departamento de Prevenção e Ginecologia Oncológica do Hospital de Câncer de Barretos. Resultados A amostra foi composta por mulheres com baixa escolaridade. No primeiro pré-teste participaram dez mulheres, sendo que a metade considerou as questões CD1, CD2 e CD3 difíceis por não compreenderem o significado do termo "região pélvica". A questão CD5, "Estou preocupada em disseminar a infecção", também foi considerada de difícil entendimento por cinco mulheres. Após as reconsiderações do comitê de especialistas e do grupo FACIT, foi realizado o segundo pré-teste. Nesta fase, pode-se concluir que os problemas de entendimento anteriores foram resolvidos. Conclusão A versão traduzida do FACIT-CD é equivalente à versão original em inglês e em língua portuguesa universal, sendo facilmente compreendida pelas pacientes com neoplasia intraepitelial cervical.

Comparative histological study on wound healing on rat's skin treated with Mitomycin C or Clobetasol propionate

PURPOSE:To compare histologically the action of Mitomycin C and that of Clobetasol propionate for surgical wound healing in rats.METHODS:A circular skin fragment was surgically removed from 57 Wistar rats. Twenty-two animals were treated with Mitomycin C with topical medication in a single dose, 22 with Clobetasol propionate with a cream medication once a day for 15 days and 13 did not receive any medication. The animals were euthanized 30 and 60 days, and the scars subjected to histological examination.RESULTS: The histological analysis on the samples did not show statistically significant differences regarding the quantities of fibroblasts, fibrocytes and vascular proliferation in the three groups, in the evaluations after 30 and 60 days. In the treated groups with Mitomycin C and Clobetasol there was a decrease in collagen concentration over the 30-day period and an increase in collagen concentration over the 60-day period, in comparison with the control group.CONCLUSIONS: The actions of Mitomycin C and Clobetasol were equivalent and not interfere in fibroplasias and in angiogenesis. Both drugs initially cause a decrease in collagen over a 30-day period and an increase over a 60-day period, demonstrating a delay in the wound healing.

Evaluation of inter-rater reliability of subjective and objective criteria for diagnosis of lymphedema in upper and lower limbs / Avaliação da confiabilidade entre os critérios subjetivos e objetivos utilizados para o diagnóstico de linfedema nos membros superiores e inferiores

The diagnosis of lymphedema can be obtained objectively by measurement methods, and also by subjective methods, based on the patient's complaint. OBJECTIVE: To evaluate inter-rater reliability of objective and subjective criteria used for diagnosis of lymphedema and to propose a lymphedema cut-off for differences in volume between affected and control limbs. METHODS: We studied 84 patients who had undergone lymphadenectomy for treatment of cutaneous melanoma. Physical measures were obtained by manual perimetry (MP). The subjective criteria analyzed were clinical diagnosis of lymphedema in patients' medical records and self-report of feelings of heaviness and/or increase in volume in the affected limb. RESULTS: For upper limbs, the subjective criteria clinical observation (k 0.754, P<0.001) and heaviness and swelling (k 0.689, P<0.001) both exhibited strong agreement with MP results and there was moderate agreement between MP results and swelling (k 0.483 P<0.001), heaviness (k 0.576, P<0.001) and heaviness or swelling (k 0.412, P=0.001). For lower limbs there was moderate agreement between MP results and clinical observation (k 0.423, P=0.003) and regular agreement between MP and self-report of swelling (k 0.383, P=0.003). Cut-off values for diagnosing lymphedema were defined as a 9.7% difference between an affected upper limb and control upper limb and a 5.7% difference between lower limbs. CONCLUSION: Manual perimetry, medical criteria, and self-report of heaviness and/or swelling exhibited better agreement for upper limbs than for lower limbs for diagnosis of lymphedema...

O diagnóstico de linfedema pode ser obtido tanto de forma objetiva, por métodos de mensuração, quanto por métodos subjetivos, através da queixa do paciente. OBJETIVO: Examinar a confiabilidade entre critérios objetivos e subjetivos utilizados para o diagnóstico de linfedema e propor um ponto de corte para linfedema de membros superiores e inferiores. MÉTODOS: Foram estudados 84 pacientes submetidos à linfonodectomias para o tratamento do melanoma cutâneo. As mensurações dos membros foram feitas utilizando a perimetria manual. Os critérios subjetivos foram obtidos através do diagnóstico de linfedema nos prontuários dos pacientes (observação clínica) e de auto-relato de sensação de peso e/ou aumento de volume no membro afetado. RESULTADOS: Nos membros superiores, houve uma forte correlação entre a perimetria manual e cada um dos critérios subjetivos: observação clínica (k 0,754, P<0,001) e sensação de peso eaumento de volume (k 0,689, P<0,001); concordância moderada no aumento de volume (k 0,483, P<0,001), peso (k 0,576, P<0,001) e sensação de peso ou aumento de volume (k 0,412, P=0,001). Nos membros inferiores, houve concordância moderada entre a perimetria e observação clínica (k 0,423, P=0,003) e regular no aumento de volume (k 0,383, P=0,003). O ponto de corte para definir linfedema foi uma diferença de 9,7% entre o membro afetado e o controle, e 5,7% de diferença para membros inferiores. CONCLUSÃO: Perimetria, observação clínica e auto-relato de sensação de peso e/ou aumento de volume, apresentaram melhor concordância para membros superiores que para inferiores no diagnóstico de linfedema...

Eticidade do uso de placebo em pesquisa clínica: proposta de algoritmos decisórios / Ethics of the use of placebos in clinical research: a proposal for decision-making algorithms

O uso de placebo em pesquisa clínica tem sido motivo de debate nos últimos anos, sobretudo após a Associação Médica Mundial publicar, em 2002, nota de esclarecimento do parágrafo 29 da Declaração de Helsinki. O Brasil tem se destacado por sua posição firme e contrária ao uso flexível de placebo. Tanto o Conselho Federal de Medicina quanto o Conselho Nacional de Saúde editaram resoluções que normatizam seu uso no Brasil, de forma a não admiti-lo em caso da existência de um método terapêutico melhor. O presente artigo reforça essa posição e tem por objetivo descrever as diversas aplicações de placebo em pesquisa clínica, bem como trazer à luz a complexa decisão sobre a eticidade de seu uso. Além disso, os autores propõem uma reflexão acerca da utilização de placebo no âmbito da pesquisa, por meio de algoritmos decisórios baseados nas normativas éticas brasileiras...

The use of placebos in clinical research has been a matter of considerable debate in recent years, notably when the World Medical Association published, in 2002, a note of clarification for paragraph 29 of the Helsinki Declaration. Brazil is known for its strong opposition to the flexible use of placebos. Both the Federal Council of Medicine and the National Health Council have published resolutions regulating the use of placebos in Brazil, preventing their use if there is a more effective therapeutic method already in place. The present study reinforces that position and aims to describe the various uses of placebos in clinical research, as well as examining the complex decisions relating to the ethics of their use. Additionally, the authors propose a reflection on the use of placebos through decision-making algorithms based on Brazilian ethical standards...

El uso del placebo en la investigación clínica ha sido un tema de debate en los últimos años, sobre todo después de que la Asociación Médica Mundial publicara, en 2002, una nota aclaratoria del párrafo 29 de la Declaración de Helsinki. Brasil se ha destacado por su firme posición en contra de la utilización flexible del placebo. Tanto el Consejo Federal de Medicina como el Consejo Nacional de Salud editaron resoluciones que regulan el uso del placebo en Brasil, no admitiéndose su uso cuando existe un mejor método terapéutico. El presente artículo refuerza esa posición y tiene como objetivo describir diferentes usos del placebo en la investigación clínica, así como contribuir en la discusión sobre la ética de su uso. Además, los autores proponen una reflexión sobre el uso del placebo en la investigación a través de algoritmos para la toma de decisiones, los cuales se basan en las normativas éticas de Brasil...

Presença de sintomas no momento do diagnóstico da recorrência do câncer do colo do útero está relacionada com pior prognóstico? / Recurrent cervical cancer: symptoms at diagnosis are related to a worse prognosis?

OBJETIVO: Aval iar as características clínicas e implicações prognósticas de pacientes portadores de recidiva de câncer do colo do útero. MÉTODOS: Por meio de revisão de prontuários foram avaliados todos os casos de câncer do colo do útero nos estádios IA a IVA que iniciaram acompanhamento em um hospital especializado da região Sudeste do Brasil de 2007 a 2009. Os episódios de recidiva foram categorizados conforme a localização da doença e foram coletadas informações sobre o tipo de tratamento e a sobrevida dessas pacientes. A casuística foi caracterizada por meio da estatística descritiva e as análises de associação foram realizadas pelo teste exato de Fisher. RESULTADOS: Dentre 469 prontuários selecionados foram identificados 50 casos de recidiva, sendo 31 sintomáticos no momento do diagnóstico da recorrência (62%) e 19 assintomáticos (38%). Dentre as mulheres com sintomas, oito solicitaram antecipação da consulta previamente agendada por apresentarem queixas clínicas. Pacientes com sintomas no momento do diagnóstico da recorrência apresentaram tendência a menores taxas de sobrevida global em dois anos em relação às pacientes assintomáticas (39,4 versus 67,6%) (p=0,081). Nenhuma portadora de recorrência a distância recebeu tratamento com intensão curativa, mas recebeu tratamento cirúrgico ou radioterápico visando remissão completa da doença. As mulheres que solicitaram antecipação da consulta por apresentarem sintomas tiveram significativa redução na taxa de sobrevida global em dois anos após a recorrência (0 versus 60,4%; p<0,001) em relação àquelas que compareceram à consulta na data agendada e nenhuma paciente desse grupo foi submetida a tratamento ...

PURPOSE: The aim of this study was to evaluate the clinical features and prognostic implications of patients with recurrent cervical cancer. METHODS: By reviewing the medical records we evaluated all patients with cervical cancer at stages IA to IVA who started treatment at a specialized hospital in the Southeast region of Brazil from 2007 to 2009. Recurrence episodes were categorized according to location of disease and information was collected regarding the type of treatment and survival of these patients. The sample was characterized by descriptive statistics and association analyses were performed using Fisher's exact test. RESULTS: Fifty cases of recurrence were identified among 469 selected records, with 31 patients being symptomatic at diagnosis of recurrence (62%); and 19 being asymptomatic (38%). Among women with symptoms, eight requested anticipation of the previously scheduled appointment because of the presence of clinical complaints. Patients with symptoms at the diagnosis of recurrence had lower rates of overall two-year survival (39.4 versus 67.6%) (p=0.081). None of the patients with recurrence at distance received curative intent treatment, but all received surgical treatment or radiotherapy aiming at full remission of the disease. Women who requested anticipation of the appointment because of the presence of symptoms had a significant reduction of overall two-year survival after recurrence (0 versus 60.4%; p<0.001) compared to those who attended the consultation on the scheduled date, and none of them received curative intent treatment. As expected, the patients who underwent palliative treatment with the main objective of improving quality of life and increasing survival but with no perspective of cure had a significant reduction in overall survival compared to those who were treated with curative intent (76.7 versus 35.4%; p<0.001). CONCLUSION: The benefit of detecting asymptomatic recurrence of cervical ...

Avaliacao comparativa entre os metodos objetivo e subjetivo em laminas coradas pela imuno-histoquimica / Comparative assessment between objective and subjective methods in slides stained by immunohistochemistry

Métodos objetivos de avaliação são frequentemente cobrados em estudos científicos. Exames histológicos com coloração imuno-histoquímica podem ser avaliados por meio de fotometria. OBJETIVO: Comparar este método objetivo com a avaliação subjetiva realizada por três observadores independentes, utilizando lâminas de colesteatoma adquirido da orelha média. MÉTODO: Foram selecionadas um total de 54 imagens de colesteatomas imuno-histoquimicamente coradas pelos anticorpos anti-TNF-R2 (32 lâminas) e anti-TGF-α; (22 lâminas). O anticorpo secundário utilizado nos dois grupos foi o Max Polimer Detection System (Kit Novo Link, Novocastra®, UK). As amostras foram processadas por um scanner digital de lâminas (modelo ScanScope - Aperio). As áreas selecionadas foram submetidas à análise por fotometria. RESULTADOS: A avaliação objetiva por fotometria foi comparada com a avaliação subjetiva por três observadores e submetidas à análise estatística. A análise estatística revelou reprodutibilidade moderada (K valores entre 0,41 e 0,60) para os dois grupos. CONCLUSÃO: O presente estudo demonstrou que as características irregulares das lâminas de colesteatoma da orelha média coradas pela imuno-histoquímica impossibilita a sua adequada avaliação objetiva, enquanto a avaliação subjetiva por observadores experientes se mostrou mais confiável. .

Objective methods of assessment are often required in scientific studies. Histological tests with immunohistochemical staining can be assessed by photometry. OBJECTIVE: To compare this objective method with the subjective evaluation performed by three independent examiners, using slides of acquired middle ear cholesteatomas. METHOD: We selected a total of 54 cholesteatoma images, immunohistochemically stained by anti-TNF-R2 (32 slides) and anti-TGF-α, (22 slides). The secondary antibody used in the two groups was the Max Polymer Detection System (Novo Link Kit, Novocastra®, UK). The samples were processed by a digital slide scanner (ScanScope - Aperio). The selected sites were analyzed by photometry. RESULTS: The objective assessment by photometry was compared with the subjective evaluation by three examiners and subjected to statistical analysis. The Statistical analysis revealed moderate reproducibility (K values between 0.41 and 0.60) for both groups. CONCLUSION: Our study showed that the irregular characteristics of middle ear cholesteatoma slides stained by immunohistochemistry prevents its proper objective evaluation, while the subjective assessment by experienced examiners was more reliable. .

Método prático de obtenção de amostras de meato acústico externo e membrana timpânica para estudo histológico e imunohistoquímico / Method for removal of samples of ear canal and tympanic membrane for histologic and immunhistochemical study

Ossos temporais humanos constituem valiosas fontes de estudo das doenças relacionadas à orelha. Apesar dos vários métodos existentes para obtenção de amostras de ossos temporais de cadáveres, geralmente estes métodos não são descritos em detalhes nos artigos envolvendo pesquisa. OBJETIVOS: Descrever um método prático e rápido para obtenção de amostras de meato acústico externo e membrana timpânica, e verificar sua viabilidade para estudo histológico e imunohistoquímico. MATERIAL E MÉTODO: Para este estudo experimental, foram obtidas 31 amostras de meato acústico externo e membrana timpânica de cadáveres com a utilização de furadeira convencional e broca do tipo serra copo. O material foi dissecado para obtenção de amostras em bloco contendo o meato acústico externo e a membrana timpânica. Estas amostras foram analisadas por histologia e imunohistoquímica. RESULTADOS: Foi possível a remoção de amostras de pequeno volume e de boa qualidade, o que facilitou a obtenção de amostras contendo todo o meato acústico externo e membrana timpânica. Em todas as amostras, foi possível realização de estudo histológico e imunohistoquímico. CONCLUSÃO: O método aqui descrito foi facilmente exequível, reprodutível e produziu amostras de boa qualidade, seja para treinamento ou pesquisa experimental. Todas as amostras foram viáveis para a realização de estudo histológico e imunohistoquímico.

Temporal bones are valuable resources to study ear diseases. Although there are several methods for removing temporal bones from cadavers, such methods are not usually described in enough details in experimental research papers. OBJECTIVES: To describe a simple and rapid method for ear canal and tympanic membrane removal, and to evaluate its viability for histologic and immunohistochemical studies. MATERIALS AND METHODS: In this experimental study, we obtained 31 ear canal and tympanic membrane samples from cadavers, with a conventional power drill and plug cutter. The material was dissected and samples containing ear canals and tympanic membranes were obtained in blocks. The samples were analyzed by histology and immunohistochemistry. RESULTS: Removal of small and good quality samples containing entire ear canals and tympanic membranes. In all the samples, it was possible to perform both histological and immunohistochemical analyses. CONCLUSION: This method was easily achievable, reproducible and yielded good quality samples, both for training purposes and for experimental research. All the samples were viable for histological and immunohistochemical analyses.

Isolated limb perfusion with hyperthermia and chemotherapy: predictive factors for regional toxicity

OBJECTIVE: Isolated limb perfusion combined with melphalan is an accepted treatment for obtaining locoregional control in advanced melanoma of the extremities and other malignant neoplasias restricted to the limb. This study aims to examine the factors associated with toxicity caused by the regional method. We considered the technical aspects of severe complications associated with the procedure in an attempt to diminish the patient morbidity that occurs during the learning curve. METHODS: We conducted a retrospective analysis of the records of patients who underwent perfusion at the AC Camargo Hospital in São Paulo, Brazil between January 2000 and January 2009. The Wieberdink scale was applied to classify local toxicity and its relation to clinical and laboratory variables. RESULTS: Fifty-eight perfusions were performed in 55 patients. Most patients (86.2%) presented a toxicity level between I and III. Grade V toxicity was seen in five cases (8.6%), four of which occurred in the first 2 years. Creatine phosphokinase, an important predictive factor for toxicity, had an average value of 231.8 for toxicity grades I-III and 1286.2 for toxicity grades IV-V (p = 0.001). There was a relationship between the melphalan dose and toxicity, which was 77 mg (25 to 130 mg) for toxicity grades I-II and 93.5 mg (45 to 120 mg) for toxicity grades IV-V (p = 0.0204). CONCLUSION: It is possible to prevent the toxicity associated with melphalan by adjusting the dose according to the patient's body weight (especially for women and obese patients) and the creatine phosphokinase values in the postoperative period.

Analysis of physical therapy in patients who had radical lymphadenectomy for cutaneous melanoma

OBJECTIVE: Analyze if patients who had radical lymphadenectomies as a treatment for cutaneous melanoma underwent physiotherapy, observing whether or not lymphedema developed, in addition to observing what techniques were used and whether orientation as to the prevention of lymphedema was received. MATERIALS AND METHODS: We evaluated 84 patients submitted to axillary, inguinal and ilioinguinal lymphadenectomies as a treatment for cutaneous melanoma. The patients enrolled underwent an evaluation consisting of measurement of limb volume by manual perimetry and questions. RESULTS: The majority of patients with lymphedema (78.8 percent) underwent postoperative physical therapy. Somewhat troubling is the fact that only 12 individuals with lymphedema remain under treatment (36.4 percent), while the remaining 21 (63.6 percent) did not undergo physical therapy. The start of physical therapy after a 6-month postoperative period (p = 0.007) and after the onset of lymphedema (p = 0.005), performing manual lymph drainage (p = 0.008) and orientation on elastic sleeve or cuff (p < 0.001) showed statistically significant differences when compared to lymphedema and non-lymphedema patient groups. CONCLUSION: Most patients who had lymphedema underwent physiotherapy treatment. In place of a complete regimen of complex decongestive physical therapy, most patients inadequately substituted their physical therapy with isolated techniques. Most patients received orientation on how to prevent lymphedema.

Definition of gross tumor volume with FDG-18F PET-CT in patients with head and neck cancer: comparison of different delineation methods

Objective: Besides the high sensitivity and specificity of positron emission tomography (PET) for head and neck tumors, there is still a lack of consensus about how to use this method inradiotherapy planning. The aim of this study is to compare different gross tumor volume (GTV) obtained with PET images in comparison to the size of the target volume generated with CT scanalone, for treated and untreated head and neck lesions. Methods: Sixty lesions in fifty patients with head and neck squamous cell carcinoma were included in the study. Delineation of the GTV was achieved using computed tomography (CT) images alone (GTV-CT) and PET-CT images with the visual assessment method (GTVPET-CT) and standard uptake value (SUV) thresholds of 40, 50, 60 and 75 percent (GTV40%, GTV50%, GTV60%, GTV75%, respectively). Correlations were measured by the Spearman test and the Friedman test was used to verify differences between GTVs. Results: For all lesions (treated and untreated), only the GTVPET-CT showed a strong correlation with GTV-CT. For only the untreated lesions, GTVPET-CT and GTV75% showed a strong correlation with GTV-CT. The GTV50%, GTV60% and GTV75% showed statistically significant difference in relation to GTV-CT, while GTVPET-CT and GTV40% were similar to GTV-CT. Conclusion: The use of PET-CT changes the volume of the final target in head and neck tumors,depending on the methodology used to calculate the GTV. The results presented here showed that the GTV40% and the GTVPET-CT are those who are closer to the target volumes delineated by conventional CT

Tratamento cirúrgico do adenocarcinoma de reto por laparoscopia e por acesso convencional: estudo comparativo de tempo cirúrgico, complicações pós-operatórias, radicalidade oncológica e sobrevida / Treatment of rectal adenocarcinoma by laparoscopy and conventional route: a brazilian comparative study on operative time, postoperative complications, oncological radicality and survival

OBJETIVO: Comparar duas vias cirúrgicas (laparoscópica e convencional) para o tratamento de câncer de reto no que se refere às complicações pós-operatórias, radicalidade oncológica e sobrevida. MÉTODOS: Trata-se de estudo retrospectivo com 84 pacientes com câncer retal que foram admitidos no Hospital do Câncer de Barretos entre 2000 e 2003. Somente os indivíduos que se submeteram à operações eletivas (intenção curativa) foram incluídos. A via cirúrgica foi escolhida subjetivamente e não com base na localização do tumor. RESULTADOS: O acesso laparoscópico foi utilizado por 50 por cento dos pacientes. Não houve diferença (P> 0,05) entre os dois grupos em relação à: idade, sexo, topografia, estádio, tratamento neoadjuvante e adjuvante, número de linfonodos regionais dissecados, tamanho da peça cirúrgica, margens cirúrgicas, transfusões de sangue, taxas de complicações pós-operatórias, dias de hospitalização e a taxa de sobrevida global. O tempo cirúrgico foi maior no grupo laparoscópico (mediana: 210x127,5min, P<0,001). Houve diminuição do tempo cirúrgico com o aumento do número de laparoscopias realizadas pela equipe (rho: -0,387, P=0,020). CONCLUSÃO: As vias laparoscópica e convencional, para o tratamento de câncer de reto, foram equivalentes em relação às complicações pós-operatórias, radicalidade oncológica e sobrevida. Contudo, o tempo cirúrgico foi maior no grupo da laparoscopia.

OBJECTIVE: To compare two surgical routes (laparoscopic and conventional) for the treatment of rectal cancer with regard to postoperative complications, oncological radicality and survival. METHODS: This is a retrospective study of 84 patients with rectal cancer who were admitted to the Barretos Cancer Hospital between 2000 and 2003. Only individuals who underwent elective operations with curative intent were included. The surgical approach was subjectively chosen rather than by location of the tumor. RESULTS: The laparoscopic access was used by 50 percent of patients. There was no difference (P> 0.05) between the two groups regarding age, sex, topography, staging, neoadjuvant and adjuvant treatment, number of dissected lymph nodes, size of surgical specimen, surgical margins, blood transfusions, postoperative complication rates, hospital stay and overall survival. Surgical time was longer in the laparoscopic group (median: 210x127, 5 min, P <0.001). A reduction in surgical time was noted with the increasing number of laparoscopies performed by the team (rho: -0.387, P = 0.020). CONCLUSION: The laparoscopic and conventional routes, for the treatment of rectal cancer, were equivalent with respect to postoperative complications, oncological radicality and survival. However, the operative time was longer in the laparoscopic group.

TNF-R2 expression in acquired middle ear cholesteatoma / Expressão do TNF-R2 no colesteatoma adquirido da orelha média

Acquired middle ear cholesteatoma is a disease which promotes bone erosion resulting in potentially serious complications. The tumor necrosis factor alpha (TNF-α) is present in cholesteatoma and it is related to bone erosion, as shown by different authors. To understand the aggressiveness characteristics of cholesteatoma is necessary, however, to better address the presence and distribution of their receptors. OBJECTIVE: To evaluate the expression of type 2 TNF-α receptor (TNF-R2) in fragments of cholesteatoma and correlate it to the degree of inflammation present. MATERIAL AND METHODS: observational cross-sectional study, which analyzed 33 fragments of cholesteatomas through histological analysis and immunohistochemistry (using as primary antibody to TNF-R2 LabVision® brand). The evaluation was performed by means of a qualitative and semi-quantitative agreement with the observed intensity. For statistical analysis we used the Fisher exact test and Spearman´s correlation coefficient (considered statistically significant when p < 0. 05). RESULTS: The expression of TNF-R2 was present in all fragments, however a statistical analysis showed no correlation or association between inflammation and the expression of TNF-R2. CONCLUSIONS: TNF-R2 is present in cholesteatoma of the middle ear, however, its expression is not directly related to the degree of inflammation observed in patients with this disease.

O colesteatoma adquirido da orelha média promove erosão óssea, ocasionando complicações potencialmente graves. O fator de necrose tumoral alfa (TNF-α) está presente no colesteatoma adquirido da orelha média e relaciona-se com a erosão óssea, como demonstraram diferentes autores. Para que se compreenda as características de agressividade do colesteatoma, é necessário que se estude a presença e a distribuição seus receptores. OBJETIVO: Avaliar a expressão do receptor tipo dois do TNF-α (TNF-R2) em fragmentos de colesteatoma e relacioná-lo com o grau de inflamação. MATERIAL E MÉTODOS: Estudo observacional do tipo transversal. Foram analisados 33 fragmentos de colesteatomas, submetidos à análise histológica e imunoistoquímica (utilizando o TNF-R2 da marca Labvision®). A avaliação foi realizada de forma qualitativa e semiquantitativa, de acordo com a intensidade observada. Para a análise estatística, foram utilizados o teste exato de Fischer e o coeficiente de correlação de Spearman (estatisticamente significativo quando p < 0,05). RESULTADOS: A expressão do TNF-R2 estava presente em todos os fragmentos, entretanto a estatística não evidenciou correlação, nem associação entre o processo inflamatório e a expressão do TNF-R2. CONCLUSÕES: O TNF-R2 está presente no colesteatoma adquirido da orelha média. Entretanto, a sua expressão não está relacionada ao grau de inflamação.

Evaluation of prognostic factors in stage IIA breast tumors and their correlation with mortality risk

Breast tumors exhibit extensive molecular and clinical heterogeneity. One of the most utilized breast carcinoma classifications is based on its molecular aspects and subdivides breast cancer into five major groups based on the expression of certain genes. In this study, we evaluated which factors are important in determining a prognosis after 5 years of follow-up for patients with clinical stage IIA breast tumors. We took into consideration the different phenotypes (luminal A luminal B HER-2 overexpression, basal and triple-negative), various epithelial-mesenchymal (EMT) molecular markers and adhesion molecules (E-cadherin, P-cadherin, N-cadherin, vimentin, twist snail and slug) and NOS-2, in addition to clinical and demographic data, tumor characteristics and treatment types. METHODS: The study population consisted of 82 patients with breast cancer. We analyzed eight molecular markers by immunohistochemistry on tissue microarrays containing breast tumor specimens from patients with ten years of follow-up, and we classified each tumor according to its estrogen receptor, progesterone receptor and HER-2 expression. We then placed the tumor into one of the above categories. RESULTS: The presence of several clinical and demographic factors, various histopathologies, treatment forms and several immunohistochemical markers were not associated with a worse prognosis for group IIA patients. The factors that were associated with a mortality risk were the triple-negative (odds ratio (OR) = 11.8, 95 percent confident interval (CI) = 2.0-70.3, P = 0.007) and basal (OR =18.4, 95 percent CI = 1.8-184.7, P= 0.013) phenotypic patterns. CONCLUSIONS: The EMT markers and NOS-2 were not mortality risk factors. Basal and triple-negative phenotypic patterns were related to a higher mortality risk in patients with stage IIA tumors.

Risk factors for development of upper limb lymphedema in patients submitted to surgery for breast cancer

OBJECTIVE: Lymphedema (LE) is an important sequel of lymph node dissection for breast cancer. However, the etiology of LE has never been fully clarified, despite its negative impact on quality of life. The aim of this study was to identify risk factors for upper limb LE in patients submitted to surgery for breast cancer. METHODS: This was a case-control study of 325 women with breast cancer submitted to axillary lymphadenectomy at the Ceará Cancer Institute between January 2000 and December 2007. The study population consisted of 101 LE patients and 224 controls. LE was defined as a > 10% difference in volume between the upper limbs on plethysmography. The dependent variables included, age, body mass index, type of surgery, postoperative complications and type of adjuvant treatment. RESULTS: The study identified three risk factors for LE: tumor stage II or higher (OR: 4.33; CI: 95%), surgical wound infection (OR: 1.0; CI: 95%) and irradiation of the supraclavicular fossa (OR: 2.90; CI: 95%). The prevalence of LE increased with the number of risk factors presented by each patient. The probability of developing LE was 6.95% for subjects with none of the risk factors identified in the study, 26.1% for one factor, 56% for two factors and 100% for all three factors. CONCLUSION: The main risk factors for LE identified in the present study were tumor stage II or higher, surgical wound infection and irradiation of the supraclavicular fossa. Based on these findings, an LE predictive score was devised for the study population.

NDRG1 protein overexpression in malignant thyroid neoplasms

OBJECTIVES: The aim of this study was to examine the expression of the N-myc downstream-regulated gene 1 protein in benign and malignant lesions of the thyroid gland by immunohistochemistry. INTRODUCTION: N-myc downstream-regulated gene 1 encodes a protein whose expression is induced by various stimuli, including cell differentiation, exposure to heavy metals, hypoxia, and DNA damage. Increased N-myc downstream-regulated gene 1 expression has been detected in various types of tumors, but the role of N-myc downstream-regulated gene 1 expression in thyroid lesions remains to be determined. METHODS: A tissue microarray paraffin block containing 265 tissue fragments corresponding to normal thyroid, nodular goiter, follicular adenoma, papillary thyroid carcinoma (classical pattern and follicular variant), follicular carcinoma, and metastases of papillary and follicular thyroid carcinomas were analyzed by immunohistochemistry using a polyclonal anti- N-myc downstream-regulated gene 1 antibody. RESULTS: The immunohistochemical expression of N-myc downstream-regulated gene 1 was higher in carcinomas compared to normal thyroid glands and nodular goiters, with higher expression in classical papillary thyroid carcinomas and metastases of thyroid carcinomas (P < 0.001). A combined analysis showed higher immunohistochemical expression of NDRG1 in malignant lesions (classical pattern and follicular variant of papillary thyroid carcinomas, follicular carcinomas, and metastases of thyroid carcinomas) compared to benign thyroid lesions (goiter and follicular adenomas) (P = 0.043). In thyroid carcinomas, N-myc downstream-regulated gene 1 expression was significantly correlated with a more advanced TNM stage (P = 0.007) and age, metastasis, tumor extent, and size (AMES) high-risk group (P = 0.012). CONCLUSIONS: Thyroid carcinomas showed increased immunohistochemical N-myc downstream-regulated gene 1 expression compared to normal and benign thyroid lesions and is correlated with more advanced tumor stages.

Inmunohistochemical evaluation of estrogen receptors alpha and beta in normal inferior turbinate mucosa / Evaluación inmunohistoquímica de los receptores de estrógenos alfa y beta en la mucosa normal de concha nasal inferior

It has been postulated that the nasal mucosa, like other human tissues, is affected by a complex interactive network of neuropeptides, cytokines, allergic and inflammatory mediators and hormones such as estrogen, in which associations between symptoms (e.g. nasal stuffiness and coryza) and hormonal variations deriving from pregnancy, use of hormonal contraceptives and menstrual cycle phases are observed. The objective is evaluating the presence of specific estrogen receptors (types alpha and beta) in inferior turbinate mucosa in healthy subjects without nasal symptoms. Samples of nasal inferior turbinate were removed from patients undergoing aesthetic nasal surgery, and analyzed using hematoxylin-eosin staining, followed by immunohistochemical preparations on paraffin-embedded sections from the material sample, to detect estrogen receptors alpha and beta. Positive immunohistochemical reactions for both beta and alpha receptors were found in various regions of the inferior nasal turbinate. In conclusion both alpha and beta receptors were found, though the expression of beta was greater and more intense in the anterior portion of the inferior turbinate. No difference was found between male and female patients regarding the intensity of expression of receptors in the inferior turbinate.

Se ha postulado que la mucosa nasal, al igual que otros tejidos humanos, se ve afectada por una compleja red interactiva de neuropéptidos, citoquinas, mediadores alérgicos e inflamatorios, y hormonas como el estrógeno, en el que las asociaciones entre los síntomas (por ejemplo, congestión nasal y catarro) y hormonales las variaciones derivadas del embarazo, se observó el uso de anticonceptivos hormonales y las fases del ciclo menstrual. El objetivo es evaluar la presencia de receptores de estrógenos específicos (tipos de alfa y beta) en la mucosa de la concha nasal inferior en sujetos sanos sin síntomas nasales. Las muestras de la concha nasal inferior fueron retirados de los pacientes sometidos a cirugía nasal estética y analizados mediante hematoxilina-eosina, seguidos de cortes de preparados de inmunohistoquímica incluídos en parafina de la muestra de material, para detectar los receptores de estrógenos alfa y beta. Las reacciones de inmunohistoquímica fueron positiva para ambos receptores alfa y beta, éstas se encuentran en diversas regiones del cornete nasal inferior. En conclusión, tanto los receptores alfa y beta se encuentran, aunque la expresión de la beta fue mayor y más intensa en la porción anterior de la concha nasal inferior. No se encontraron diferencias entre pacientes hombres y mujeres en relación con la intensidad de la expresión de los receptores en el concha nasal inferior.

Type I and type II endometrial adenocarcinomas: comparative study of ultrasonographic parameters

Objectives: The aim of this study was to compare ultrasonographic aspects of type I and II endometrial adenocarcinomas, seeking to identify differences that could predict the likely histological pattern before curettage. Materials and Methods: This was a retrospective study with 117 women with type I endometrial adenocarcinomas and 17 women with type II, admitted to the Barretos Cancer Hospital,, Barretos, Brazil between February 2007 and December 2009. Patient medical records were reviewed according to standardized form, collecting clinical and histopathologic information in addition to information related to ultrasonographic aspects. Results: The most commonly described ultrasonographic aspect was homogenous myometrium (65.8%), heterogeneous endometrial aspect (66.6%), regular endometrial basal layer (66.6%) and the endometrial cavity not filled by material (51.1%). Myometrial echogenicity proved the only variable in that there was no statistically significant difference, with heterogeneous aspect more frequently found in type II carcinoma (80.0% vs. 27.8%; p=0.039). Conclusions: This study noted few differences between the two groups in reference to ultrasonographic aspects. The only variable that demonstrated statistical significance was myometrial echogenicity. Other studies are necessary for the validation of results presented here

Goniometric analysis of affected joints in axillary, inguinal or ilioinguinal lymphadenectomies for the treatment of cutaneous melanoma

Objectives: The objective of this study is to compare the joint range of motion (ROM) reduction between the submitted limb to lymphadenectomy and contralateral and to evaluate if ROM restriction is also connected with lymphedema. Materials and Methods: Evaluated were 84 patients submitted to axillary lymphadenectomy (n=40), inguinal (21) or ilioinguinal (23) for the treatment of cutaneous melanoma, operated between 1990 and 2008. Individuals excluded were those with amputation of a limb or bilateral dissection that would make perimetry and goniometry comparison impossible. The invited patients were submitted to goniometric evaluation of the shoulder or hip and measurement of the upper or lower limbs through manual perimetry. Results: The difference of 4.2 degrees between the averages of ROM flexion (p=0.005) of the shoulder of the affected side in relation to the control, and 5.2 degrees in abduction (p=0.002) were sufficient to be statistically significant, with the exception of 3 degrees of external rotation (p=0.135). The differences between the means of hip ROM were also significant, varying 8.5 degrees in flexion (p <0.001) and 2.2 degrees in abduction (p=0.011). The ROM of the shoulder or hip of the affected side did not present differences between the 33 patients with lymphedema in relation to the 51 patients without lymphedema: shoulder with flexion (p=0.148), abduction (p=0.577) and external rotation (p=0.866); hip with flexion (p = 0.665) and abduction (p=0.795). Conclusion: In spite of individuals with lymphadenectomy show restriction of joint ROM in flexion and abduction of the shoulder and hip in the late postoperative period, there was no association between joint ROM, of the shoulder on both the hip and the presence of lymphedema.

Lymphatic drainage of the breast: from theory to surgical practice / Drenaje linfático de la mama: desde la teoría a la práctica quirúrgica

Until recently, complete removal of axillary lymph nodes was performed as part of the treatment of breast cancer. Sentinel lymph node biopsy (SLNB) in selected cases has reduced the number of cases of wide axillary dissection and the related morbidity. Knowledge of breast lymphatic drainage is essential for understanding the principles behind SLNB and also for performing safe and correct axillary lymphonodectomy. This paper describes in detail the anatomical issues relating to breast lymphatic drainage and the correlated axillary and extra-axillary lymph nodes. In addition, it shows the application of this theoretical knowledge to surgical practice, especially with regard to SLNB and lymphonodectomy. The surgical nomenclature is compared with the current International Anatomical Terminology.

Hasta hace poco, la eliminación completa de los linfondos axilares se realizaba como parte del tratamiento del cáncer de mama. En casos seleccionados la biopsia del linfonofo centinela ha reducido el número de casos de disección axilar y la morbilidad. El conocimiento del drenaje linfático de la mama es esencial para comprender los principios detrás del SNLB y también para la realización segura y correcta de la linfonodectomía axilar. Este trabajo describe en detalles los aspectos anatómicos en relación a la lactancia y correlaciona el drenaje linfático axilar y linfonofos extra-axilares. Además, se muestra la aplicación de estos conocimientos teóricos en la práctica quirúrgica, sobre todo con respecto al linfonofo centinela y la linfonodectomía. La nomenclatura quirúrgica es comparada con la actual Terminología Anatómica Internacional.