Variables pronósticas de pacientes con melanomas gruesos. Análisis de 362 casos / Prognostic variables in patients with thick melanomas. Analysis of 362 cases

Resumen Antecedentes: Los estudios sobre factores pronóstico de melanoma están basados en poblaciones caucásicas, con predominio de melanomas delgados (Breslow < 3 mm). Los pacientes mexicanos muestran predominio de melanomas gruesos (Breslow ≥ 3 mm). Objetivo: Identificar factores asociados al pronóstico de pacientes con melanomas gruesos. Material y métodos: Se analizó la influencia pronóstica de factores clinicopatológicos en 362 melanomas gruesos. Resultados: La mediana de Breslow fue de 7 mm, 271 (74.9 %) pacientes tuvieron melanoma acral y 49 (13.5 %) melanoma nodular. El 56.6 % de los pacientes se encontró en etapa clínica [EC] III), 269 (74.3 %) tenía ulceración y 15 (4.1 %) márgenes positivos. Las variables asociadas con menor supervivencia global [SG] fueron la EC (p < 0.001), Breslow (p = 0.044), ulceración (p = 0.004), mitosis (p < 0.001) y margen < 2 cm (p < 0.001) . En el análisis multivariante los factores que influyen en SG fueron la EC, mitosis y el margen quirúrgico. Conclusiones: En pacientes con melanomas gruesos la SG es influida por un margen positive, mitosis y EC.

Abstract Background: Studies on prognostic factors in melanoma are based on Caucasian populations, with a predominance of thin melanomas (Breslow <3 mm). Mexican patients show a predominance of thick melanomas (Breslow ≥ 3 mm). Objective: To identify factors associated with the prognosis of patients with thick melanomas. Material and methods: The prognostic influence of clinicopathological factors was analyzed in 362 thick melanomas. Results: The Breslow median was 7 mm, 271 (74.9 %) patients had acral melanoma and 49 (13.5 %) nodular melanoma. The 56.6 % of patients were found in clinical stage [CS] III), 269 (74.3 %) had ulceration, and 15 (4.1 %) had positive margins. The variables associated with lower overall survival [OS] were CS (p < 0.001), Breslow (p = 0.044), ulceration (p = 0.004), mitosis (p < 0.001) and margin < 2 cm (p < 0.001). In the multivariate analysis, the factors influencing OS were CD, mitosis, and the surgical margin. Conclusions: In patients with thick melanomas, OS is influenced by a positive margin, mitosis and CS.

Worse survival of invasive melanoma patients in men and de novo lesions

Abstract Background: The incidence and mortality of melanoma is increasing in many countries, including Brazil. Survival studies are still scarce in our country, but much needed to know and address this problem better. Objective: To analyze the disease-specific survival of patients with invasive melanoma and to correlate it with clinical and histopathological variables. Methods: Retrospective cohort analysis of 565 cases of invasive melanoma in a tertiary hospital with the objective of testing variables that could be associated with a worse prognosis, such as gender, phototype, thickness, histological type and presence of pre-existing clinical lesion at the site of the tumor. Results: The worst survival rates were significantly associated with thicker tumors (p < 0.001), male sex (p = 0.014), high phototype (p = 0.047), nodular melanoma (p = 0.024) and "de novo" lesions (p = 0.005). When all variables were adjusted for melanoma thickness, male patients (p = 0.011) and "de novo" melanomas (p = 0.025) remained associated with worse survival. Study limitations: Retrospective study of a single tertiary hospital. Conclusions: Although the causes are still unknown, melanoma-specific survival was statistically worse for males and for "de novo" melanomas even after adjustment of tumor thickness.

Survival analysis of children and adolescents with melanoma / Análise de sobrevida no melanoma infantojuvenil

ABSTRACT Objectives: to analyze the survival in juvenile melanoma. Methods: retrospective study conducted by hospital record review and cancer records of patients aged 0 to 19 years, with histologically proven melanoma and treated between 1997 and 2017 at the Erasto Gaertner Hospital in Curitiba-PR. Results: the sample comprised 24 patients, female (62.5%), mean 14.14 ± 4.72 years old, with head and neck melanoma (37.5%), chest (25%) and extremities. (20.8%). Signs and symptoms at diagnosis were increased lesion size (25%), bleeding (20.8%) and pruritus (16.6%). There was a Breslow II and IV index and Clark IV level, with a statistical tendency between Breslow IV and death (p = 0.127), and significance between Clark V and death (p = 0.067). Nine (37.5%) patients had metastases, six (25%) with distant metastases died (p = 0.001), five were girls (20.8%). Surgery was the standard treatment and chemotherapy the most used adjuvant (37.5%). The average time between diagnosis and death was 1.3 ± 1.2 years and survival were 3.7 ± 3.2 years. Conclusion: there was a delay in diagnosis, high morbidity and mortality and average survival less than five years.

RESUMO Objetivos: analisar a sobrevida no Melanoma Infantojuvenil. Métodos: estudo retrospectivo realizado mediante revisão de prontuários e registros hospitalares de câncer, de pacientes na faixa etária de 0 a 19 anos, com melanoma comprovado histologicamente e atendidos entre 1997 e 2017 no Hospital Erasto Gaertner em Curitiba-PR. Resultados: amostra composta por 24 pacientes, sexo feminino (62,5%), média de 14,12 ± 4,72 anos de idade, com melanoma em cabeça e pescoço (37,5%), tórax (25%) e extremidades (20,8%). Os sinais e sintomas ao diagnóstico foram aumento do tamanho da lesão (25%), sangramento (20,8%) e prurido (16,6%). Ocorreu Índice de Breslow II e IV e Nível de Clark IV, com tendência estatística entre Breslow IV e óbito (p=0,127) e significância entre Clark V e óbito (p=0,067). Nove (37,5%) pacientes apresentaram metástases, seis (25%) com metástases à distância morreram (p=0,001), cinco eram meninas (20,8%). A cirurgia foi o tratamento padrão e a quimioterapia o adjuvante mais utilizado (37,5%). A média de tempo entre diagnóstico e óbito foi de 1,3 ± 1,2 anos e de sobrevida foi 3,7 ± 3,2 anos. Conclusão: houve atraso no diagnóstico, alta morbimortalidade e média de sobrevida menor do que cinco anos.

Melanoma mortality in Brazil: trends and projections (1998-2032) / Mortalidade por melanoma no Brasil: tendências e projeções (1998-2032)

Abstract Melanoma is the main serious skin cancer, due to its high lethality. This study aimed to make projections and analyze melanoma mortality trends in Brazil. Mortality Information System data were utilized for the period 1998-2012, which were projected until 2032, using the age-period-cohort model, with software R. The analysis of trends was made by Joinpoint regression, with 95% confidence interval, estimating the annual percentage change. It was revealed higher amounts of deaths in men for all regions. Brazilian trends presented reductions in men (APC = -0.4; CI95% = -0.6; -0.1; p < 0.01) and in women (APC = -0.8; CI95% = -0.9; -0.7; p < 0.01). The Midwest region presented increases for both sexes, while the Southeast region presented reducing trends for both sexes. In the North, there was stability for men and increases followed by stability in women, while the South presented reductions in men and stability in women; finally, the Northeast revealed one joinpoint per sex, with an increase followed by stability in men, and stability followed by reducing trends in women. The highest rates of the country were found in the South and Southeast regions, however, with reducing trends throughout time. Higher mortality trends in men were associated with later diagnoses in this group.

Resumo O melanoma é o mais grave câncer de pele, devido à alta letalidade. Este estudo objetiva projetar e analisar tendências da mortalidade por melanoma no Brasil. Os dados são do Sistema de Informação sobre Mortalidade, no período de 1998 a 2012, os quais foram projetados até 2032, usando o modelo idade-período-coorte, no software R . A análise de tendências foi feita pela Regressão loglineal ( Joinpoint regression ), com intervalo de confiança de 95%, para estimar a porcentagem anual de mudança. Revelou-se maior quantitativo de mortes em homens em todas as regiões. As tendências no Brasil apontaram para redução em homens (APC = -0,4; IC95% = -0,6; -0,1; p < 0,01) e em mulheres (APC = -0,8; IC95% = -0,9; -0,7; p < 0,01). A região Centro-oeste teve aumento para os dois sexos, em oposição ao Sudeste, com redução em ambos. No Norte, houve estabilidade em homens, e aumento seguido de estabilidade em mulheres, enquanto o Sul teve redução em homens e estabilidade em mulheres; e, por fim, o Nordeste teve um joinpoint em cada sexo, com aumento seguido de estabilidade em homens; e estabilidade seguida de redução em mulheres. As maiores taxas do país foram no Sul e Sudeste, todavia, com tendência a redução ao longo do tempo. A maior mortalidade em homens foi associada ao diagnóstico mais tardio.

Experiencia En El Manejo De Los Pacientes Con Melanoma En El Instituto Oncológico Nacional De Panamá En Los Años 2012 Al 2017 / Ex perienc e In The Management Of Patients With Melanoma In The National Oncology Ins titute Of Panama In The Years 2012 To 2017

Introducción: A nivel mundial hay un incremento de la incidencia de melanoma, Panamá no escapa a esta realidad. Para todas las etapas hay riesgo de recurrencia inclusive luego de una cirugía adecuada y elevadas probabilidades de fallecer a causa de metástasis. Este trabajo busca conocer la experiencia del ION en el tratamiento de estos pacientes, la cual no ha sido publicada a la fecha. Objetivos: Descri­ bir las características de los pacientes con melanoma y determinar la Supervivencia Global (OS) y la Su­ pervivencia Libre de Recurrencia (RFS). Metodología: Estudio retrospectivo de los pacientes con melanoma referidos al ION en los años 2012 a 2017 y el análisis de OS y RFS por el método de Kaplan­ Meier. Resultados: Un total de 247 pacientes de melanoma fueron atendidos en el ION en el periodo del estudio; 51.8% eran masculinos con mediana de edad de 65 años. El sitio más común fue acral (31%). En total 46% de nuestros pacientes están en etapas III­IV. Un 65% del total fueron operados, de éstos 80% con resección amplia, 27% con evaluaciones de ganglio centinela y 25% linfadenectomías. Encon­tramos 39% ulcerados y la histología más frecuente fue nodular con 31.6%. Hubo 31.4% de recurren­cias, de los cuales 63.8% era a distancia. La mOS: 55.8 meses en no metastásicos vs 13.1 meses en metastásicos (p<0.0001). La mRFS para los operados fue 53.6 meses y los factores pronósticos fueron ulceración (p=0.007) y realización de linfadenectomía (p=0.000). Conclusión: El diagnóstico de melano­ ma en la población panameña se hace en etapas avanzadas, lo que influye en su pronóstico. Su tasa de supervivencia está muy por debajo de otros países tanto desarrollados como en vías de desarrollo. Estos resultados deben tomarse con cuidado, ya que los factores clásicos descritos en múltiples estu­ dios, no parecen influenciar a nuestra población (edad, sexo, sitio anatómico, subtipo, mitosis). Siendo una enfermedad tan letal hace falta realizar estudios prospectivos a nivel nacional, así como fortalecer la red de prevención y atención primaria.

Introduction: Worldwide there is an increase in the incidence of melanoma, Panama does not escape this reality. For all stages there is a risk of recurrence even after adequate surgery and high chances of death due to metastasis. This work seeks to know the experience of ION in the treatment of these pa­ tients, which has not been published to date. Objectives: To describe the characteristics of patients with melanoma and determine the Global Survival (OS) and the Free Survival of Recurrence (RFS). Metho­ dology: Retrospective study of patients with melanoma referred to the ION in the years 2012 to 2017 and the analysis of OS and RFS by the Kaplan­Meier method. Results: A total of 247 melanoma patients we­ re treated at the ION during the study period; 51.8% were male with a median age of 65 years. The most common site was acral (31%). In total 46% of our patients are in stages III­IV. 65% of the total were ope­ rated, of these 80% with wide resection, 27% with sentinel lymph node evaluations and 25% lymphade­ nectomy. We found 39% ulcerated and the most frequent histology was nodular with 31.6%. There were 31.4% of recurrences, of which 63.8% were distant. The mOS: 55.8 months in non­metastatic vs 13.1 months in metastatic (p <0.0001). The mRFS for the operated patients was 53.6 months and the prog­ nostic factors were ulceration (p = 0.007) and lymphadenectomy (p = 0.000). Conclusion: The diagnosis of melanoma in the Panamanian population is made in advanced stages, which influences its prognosis. Its survival rate is well below other developed and developing countries. These results should be taken with care, since the classical factors described in multiple studies do not seem to influence our population (age, sex, anatomical site, subtype, mitosis). Being such a lethal disease, it is necessary to carry out prospective studies at the national level, as well as to strengthen the prevention and primary care network

Prolonged survival after surgical resection of cerebral metastasis from melanoma with multisystemic metastasis already present: a case report and literature review

ABSTRACT CONTEXT: Malignant melanoma is the third most common cause of cerebral metastases after breast and lung cancer. Despite advances in therapeutic options, the prognosis for patients with cerebral metastases from melanoma remains poor, with a median survival time of six months after diagnosis. CASE REPORT: A 65-year-old woman was diagnosed with a malignant melanoma on the third toe of her left foot.The tumorous spot was excised surgically. However, the melanoma reappeared after one year and skin biopsy confirmed recurrence of malignant melanoma. Investigations showed metastasis to the left pelvic region, left lobe of the liver and right lobe of the lung.The patient then received chemotherapy. Subsequently, the patient was brought to the emergency department with an altered level of consciousness (Glasgow coma scale: 9) and hemiplegia on the right side of her body. Computed tomography scans of the brain revealed hemorrhagic lesions in the parieto-occipital lobes of the brain. Urgent surgical evacuation was done to remove the lesion, following which the patient showed improvement in her score on the Glasgow coma scale and a concomitant decrease in weakness. She was discharged from hospital with full consciousness.The patient died of acute renal failure 14 months after the brain surgery and approximately 4 years after the initial presentation of the case. CONCLUSION: This case outcome is rare and shows the effectiveness of surgery to treat cerebral metastasis from malignant melanoma in a situation with multisystem metastasis already present.

Melanoma: clinical, evolutive and histopathological characteristics of a series of 136 cases

Abstract: BACKGROUND: The incidence of melanoma has been increasing in Brazil and all over the world. Despite improvements in diagnosis and treatment, mortality remains unchanged. OBJECTIVE: To associate clinical and histopathological aspects with the evolution of 136 cases of cutaneous melanoma. METHODS: Retrospective cohort study that analyzed all patients diagnosed with melanoma during the period from 2003 to 2011, with at least 4 years follow up. Archived slides were analyzed to study histopathological variables (Breslow, ulceration, mitoses and histological regression). Medical records were used to retrieve clinical variables (age, sex, localization, time of appearance, diameter) and progression (metastases or death). Association measures were assessed by statistical analysis. RESULTS: There was no statistically significant difference between groups according to age. Superficial spreading subtype showed lower Breslow (0.5mm) than acral lentiginous and nodular subtypes (2 and 4.6mm respectively), less ulceration and metastases (9.4% against 50 and 70.6%). Nodular subtype had higher mitoses' median (5.0/mm2) than superficial spreading and lentigo maligna (0.0/mm2, for both). Regression was more frequent in superficial spreading and lentigo maligna subtypes. There were only deaths by melanoma in the acral group, however, there were deaths for other reasons in groups superficial spreading one, acral lentiginous one and lentigo maligna two. STUDY LIMITATIONS: Use of medical records as a source of data to the study. CONCLUSIONS: Superficial spreading subtype presents better prognosis indicators. Histological subtype should be considered in follow-up and treatment protocols of patients with cutaneous melanoma.

Mortality due to cutaneous melanoma in south region of Brazil: a spatial approach

Abstract: Background: Cutaneous melanoma is a skin cancer with low incidence but high mortality rates. The South region of Brazil has the highest death rates by melanoma per 100,000 inhabitants of the country. Little is known about the spatial distribution of this malignancy in southern Brazil. Objectives: Identify the spatial patterns of deaths from cutaneous melanoma in South region of Brazil, using geoprocessing tools. Methods: This is an ecological and exploratory study of death information by cutaneous melanoma obtained from portal Datasus, for Brazil's southern region, from January 2008 to December 2012. Deaths were separated by gender and rates per 100,000 inhabitants were calculated and used to compile thematic maps, Moran maps and Kernel maps, using TerraView software. It was adopted an alpha = 5%. Results: There were data on 2378 deaths from cutaneous melanoma in the study period. High rates were identified in the northern and littoral regions of Rio Grande do Sul; the northeast of Santa Catarina; and west of Paraná - for the total population, with minor differences detected and indicated regarding gender. The global Moran index presented p-values of 0.03, 0.04 and 0.03, respectively, for male, female and overall deaths. All the micro-regions that showed high priority for intervention were detected in the Rio Grande do Sul. Conclusion: Spatial clusters of micro-regions with high death rates from cutaneous melanoma in South region of Brazil were identified, serving as an important tool for health managers.

La infección por Trypanosoma cruzi disminuye el desarrollo del melanoma maligno e incrementa la supervivencia en ratones C57BL/6 / Trypanosoma cruzi infection decreases malignant melanoma development and increases survival in C57BL/6 mice

Diversos agentes infecciosos interfieren en la progresión del cáncer. En esta investigación se estudió el efecto de la infección o inmunización con Trypanosoma cruzi (Tc) sobre el desarrollo del melanoma maligno. Se utilizaron 258 ratones machos C57BL/6 divididos en 5 grupos melanoma: melanoma control, melanoma Tc inmunizado, melanoma Tc agudo, melanoma Tc crónico y melanoma Tc infectado; 3 grupos controles: control sano, control Tc agudo, control Tc crónico. 100.000 células de melanoma B16-BL6 fueron inoculados vía intramuscular a los grupos melanoma; 3 ó 20 tripomastigotes/g de peso fueron inoculados vía intraperitoneal a los grupos Tc crónicos o Tc agudos previo a la inoculación del melanoma, respectivamente, el grupo melanoma Tc inmunizado fue inoculado con 30.000 epimastigotes fijados en formol y suspendidos en adyuvante completo de Freund, y el grupo melanoma Tc infectado fue inoculado con células de melanoma obtenidas de ratones melanoma Tc agudo. Se evaluó volumen tumoral, supervivencia, parasitemia e histopatología tumoral. Los grupos melanoma Tc: agudo, crónico y melanoma infectado, respectivamente, mostraron una disminución significativa del desarrollo tumoral y de la supervivencia al ser comparados con los grupos melanoma control e inmunizado. Los estudios histopatológicos mostraron áreas de necrosis asociadas con depósitos de melanina, degeneración citopática tumoral y amastigotes intracelulares contenidos en vacuolas parasitofóricas. En conclusión, Tc inhibe el desarrollo tumoral del melanoma maligno y aumenta la supervivencia de ratones C57BL/6, fenómeno que podría estar relacionado con la capacidad invasiva tumoral del parásito y a la respuesta inmune generada.

Some infectious pathogens have the capacity to affect cancer progression. In the present paper we studied the effect of infection or immunization with Trypanosoma cruzi (Tc) against malignant melanoma development. We worked on 258 C57BL/6 male mice divided in five melanoma groups: control melanoma, melanoma Tc acutely infected, melanoma Tc chronically infected, melanoma Tc immunized and infected melanoma; and three control groups: healthy, Tc acutely infected and Tc chronically infected. 100.000 B16-BL6 melanoma cells were inoculated in the thigh of melanoma groups; 3 or 20 trypomastigotes/g were inoculated intraperitoneally in chronic or acute Tc groups, before the melanoma injection, respectively; melanoma Tc immunized were subcutaneously inoculated with 30.000 formaldehide-fixed epimastigotes diluted in complete Freund´s adjuvant and the infected melanoma group was inoculated with melanoma cells obtained from melanoma Tc acutely infected mice. We evaluated survival, parasitemia, tumor volume and tumor histopathology. Results showed that in mice infected with Tc, the tumor development and survival were significantly lower as compared with control melanoma and melanoma Tc immunized. Histopathologically, the tumor displayed necrosis areas with melanin deposits, cytopathic degeneration and amastigotes in parasitophorous vacuoles. In conclusion, Tc inhibits the development of malignant melanoma, increasing C57BL/6 survival, a phenomena that could be related to the parasite tumoral invasive capacity, its ability to produce melanoma cell lysis and to induce a robust immune response.

Conjunctival melanoma: survival analysis in twenty-two Mexican patients / Melanoma conjuntival: análise de sobrevivência em vinte e dois pacientes mexicanos

Purpose: To describe the cases of conjunctival melanoma (CM) and report the disease-free interval (DFI) and overall survival (OS). Methods: The charts of 22 patients who were admitted to two hospitals between 1985 and 2006 were reviewed for pertinent data, including demographics, site of involvement in the conjunctiva and sub-sites, surgical treatment, and adjuvant treatment. Results: There were 10 (45.45%) males and 12 (54.55%) females. Mean age was 52.3 years. In this group, 15 patients (68.1%) involved the bulbar conjunctiva, and 7 (31.9%) involved the palpebral conjunctiva. Of the 22 patients, 72.72% had a history of conjunctival melanosis. The average tumor size was 20.4 mm. Eight (36.36%) patients underwent orbital exenteration, 2 (9.06%) had enucleation, 5 (22.72%) had wide excision of the lesion followed by radiotherapy, 2 (9.06%) had orbital exenteration with neck dissection, and the remaining 5 patients (22.72%) were considered adequately treated only with wide excision. Eight (36.36%) patients received adjuvant treatment. Disease-free survival at 5 years was 51% and the overall survival at 5 and 10 years was 50% and 37%, respectively. Conclusion: Conjunctival melanoma is a rare entity. Tumor behavior is aggressive, and the optimal treatment is surgery with adjuvant therapy. .

Objetivo: Descrever o intervalo livre de doença (DFI) e sobrevida global (OS) de pacientes com melanoma conjuntival (CM). Método: Prontuários de 22 pacientes que foram internados em dois hospitais entre 1985 e 2006 foram revisados para dados pertinentes, incluindo dados demográficos, local de envolvimento na conjuntiva e outros locais de acometimento, tratamento cirúrgico e tratamento adjuvante. Resultados: Dez (45,45%) homens e 12 (54,55%) mulheres foram selecionados. A média de idade foi de 52,3 anos. Em 15 pacientes (68,1%) CM envolveu a conjuntiva bulbar, e em 7 (31,9%) envolveu a conjuntiva palpebral. Dos 22 pacientes, 72,72% tinham história de melanose conjuntival. O tamanho médio do tumor foi de 20,4 mm. Oito (36,36%) pacientes foram submetidos à exenteração orbital, 2 (9,06% ) à enucleação, 5 (22,72%) à ampla excisão da lesão seguida de radioterapia, 2 (9,06%) à exenteração orbital com esvaziamento cervical e os restantes 5 pacientes (22,72%) foram considerados adequadamente tratados apenas com excisão ampla. Oito (36,36%) pacientes receberam tratamento adjuvante. Sobrevida livre de doença em 5 anos foi de 51% e sobrevida global em 5 e 10 anos foi de 50% e 37%, respectivamente. Conclusão: Melanoma conjuntival é uma entidade rara. Comportamento do tumor é agressivo, e o melhor tratamento é a cirurgia com terapia adjuvante. .

Anal melanoma: a rare, but catastrophic tumor / Melanoma anal: tumor raro, mas catastrófico

INTRODUCTION: Malignant melanoma of the anal canal is a rare and aggressive disease, which early diagnosis is difficult. Its presentation with no specific symptoms leads to a late diagnosis at an advanced stage. The prognosis of anorectal malignant melanoma is poor and frequently related to distant metastasis and absence of response of chemoradiotherapy. Surgery remains the mainstay of therapy; otherwise, the best approach is controversial. Considering no survival benefits for APR, wide local excision should be considered as the treatment of choice. METHODS: This report collects nine cases of anorectal melanoma treated at our division from 1977 to 2006, as well as a review of the literature. RESULTS: There were eight females and one male, of medium age 69 years (range: 41-85 years). Most frequent presentation was bleeding. Wide Local Excision (WLE) was performed in seven of them. Mean survival was 24 months, and six of them died on account of metastatic disease. CONCLUSION: Anorectal melanoma remains challenging. Efforts should be taken to early diagnosis, and wide local excision with negative margins is the preferred treatment. Abdominoperineal resection (APR) is a reasonable option for bulky tumors or when the sphincter is invaded. (AU)

INTRODUÇÃO: O melanoma maligno do canal anal é uma doença rara e agressiva, em que o diagnóstico precoce se torna difícil. Apresenta-se sem sintomas específicos, levando ao diagnóstico tardio e em fase avançada. O prognóstico é ruim e frequentemente relacionado a metástases a distância, bem como à ausência de resposta à rádio e à quimioterapia. A cirurgia permanece como terapia de escolha, no entanto a melhor abordagem ainda é controversa. Considerando não haver benefício na sobrevida da amputação abdômino-aerineal do aeto (AAPR), a excisão local ampla deve ser considerada o tratamento de escolha. MÉTODOS: São nove casos de melanoma anorretal tratados no serviço de coloproctologia do Hospital Naval Marcílio Dias (HNMD) de 1977 a 2006. RESULTADOS: Foram diagnosticados oito mulheres e um homem, com média de idade de 69 anos (41 - 85). A queixa mais frequente foi o sangramento anal. A excisão local ampla foi realizada em sete pacientes. A sobrevida média foi de 24 meses. CONCLUSÃO: O melanoma anorretal continua desafiante. Todos os esforços devem ser feitos para o diagnóstico precoce, tornando assim possível realizar a excisão local com margens negativas. A AAPR ainda é uma opção factível para tumores avançados ou quando o esfíncter anal está comprometido. (AU)

Avaliação dos efeitos da terapia fotodinâmica utilizando compostos fenotiazínicos sobre melanoma in vitro / Assessment of the effects of photodynamic therapy using phenothiazine compounds on in vitro melanoma

O câncer é considerado a segunda maior causa de morte em países ocidentais. Nos Estados Unidos da América (EUA) as mortes por câncer anualmente superam a soma das mortes provocadas em guerras como Vietnã, Coreia e as Grandes Guerras Mundiais. Apresentando-se como a mais agressiva das neoplasias dermatológicas, o melanoma cutâneo está associado à cerca de 75% das causas de morte por câncer de pele. Um dos tratamentos estudados para aplicação em pacientes com esta e outras patologias é a Terapia Fotodinâmica (TFD), que é baseada no uso de corantes de baixa toxicidade, que tem seletividade por alguns tecidos ou células e quando ativados por baixas doses de luz visível induzam alterações celulares como a produção ERO. Os fenotiazínicos são moléculas catiônicas com, absorção de luz na região entre 620-660nm, espectro que permite maior penetração nos tecidos, promovendo maior ação do composto em tecidos mais profundos. A irradiação foi feita com luz lazer com λ= 660nm, com potência de 100 mW, densidade de energia de 150 J/cm2 por 1 min. As quantificações de viabilidade celular foram feitas por método colorimétrico, e realizada a leitura em leitor de microplaca a 655 nm. A determinação das IC50 do Azul de Metileno e Azul de Toluidina O foi 2,5 μM e 8,4 μM, respectivamente. Utilizando a TFD observamos que os efeitos citotóxicos dos compostos fenotiazínicos apresentam significância estatística (p<0,05) tanto em AM quanto em ATO. Em microscopia óptica com coloração por May-Grunwald-Giemsa observamos que existe uma aparente diminuição do conteúdo citoplasmático e preservação nuclear nas células tratadas com TFD, além da diminuição da quantidade de células por campo. A avaliação ultraestrutural por Microscopia de varredura mostra células com visível extração citoplasmática após a TFD, apontando uma lesão membranar. Novas avaliações precisam ser feitas como estabelecer um melhor protocolo para aumentar os efeitos da TFD.

Cancer is considered the second leading cause of death in Western countries. In the United States of America (USA) cancer deaths annually exceed the total of deaths in wars like Vietnam, Korea and the Great World Wars. Presenting as the most aggressive of the skin neoplasms, cutaneous melanoma is associated with circa 75% of the deaths from skin cancer. One of the therapies used in patients with melanoma and other pathologies is Photodynamic Therapy (PDT), which is based upon the use of dyes of low toxicity, which has selectivity for certain tissues or cells and low doses when activated by visible light induce cellular changes such as ROS production. The phenothiazic dyes are cationic molecules, absorption of light in the region between 620-660 nm, allowing greater spectrum tissue penetration, promoting higher activity of the compound in deeper tissues. The irradiation was performed with laser light with λ = 660 nm with 100 mW, energy density of 150 J/cm2 for 1 min. Quantification of cell viability was performed by the colorimetric method, and performed a reading in a microplate reader at 655nm. Determination of IC50 of Methylene Blue and Toluidine Blue O was 2.5 μM and 8.4 μM respectively. Using the protocol of PDT observed that there is one of the cytotoxic effects of phenothiazine compounds with statistical significance (p <0.05) in both MB and in TBO. Through optical microscopy by staining with fast Panotic was observed that there is an apparent decrease in the cytoplasm in cells treated with MB and TBO as well as reduced number of cells per field. The Scanning Electron Microscopy, shows cells with cytoplasm extraction, after PDT, indicated possibility, membrane damage. New assessments need to be made to establish a better protocol to potentiate the effects of PDT.

A biópsia de linfonodo sentinela não deve ser recomendada para pacientes portadores de melanoma espesso / Sentinel node biopsy should not be recommended for patients with thick melanoma

OBJETIVO: verificar se há alguma relação entre o estado histopatológico do linfonodo sentinela, a recorrência e a mortalidade decorrente do melanoma espesso em pacientes submetidos à BLS ao longo de um seguimento significante. MÉTODOS: Oitenta e seis pacientes portadores de melanoma espesso submetidos à BLS foram selecionados de um banco de dados prospectivo. A linfocintilografia, o mapeamento linfático e a detecção gama intraoperatória foram realizados em todos pacientes. O linfonodo sentinela (LS) foi analisado por HE e por imunoistoquímica. Linfadenectomia total foi indicada para os pacientes com LS positivo. O estado histopatológico do LS foi relacionado à taxa de recorrência e de mortalidade por melanoma. RESULTADOS: Cento e sessenta e seis LS foram retirados dos 86 pacientes. As idades variaram de 18 a 73 anos. Havia 47 mulheres e 39 homens. Micrometástases foram encontradas em 44 pacientes. Quarenta e dois pacientes foram submetidos à linfadenectomia total. Sete pacientes tiveram outro linfonodo positivo. Entre os 44 pacientes com LS positivo houve 20 recorrências e 15 mortes. Houve 18 recidivas e 12 mortes no grupo de LS negativo. A espessura de Breslow não apresentou correlação com o estado histopatológico do LS. O estado histopatológico do LS não interferiu nas taxas de recorrência e de mortalidade (teste de Fisher, p=1.00). A mediana de seguimento foi 69 meses. CONCLUSÃO: Considerando a falta de evidência de benefício, a BLS não deve ser indicada para pacientes com melanoma espesso fora de estudos clínicos.

OBJECTIVE: To ascertain whether there is any relationship between the state of the sentinel lymph node histopathology, recurrence and mortality from thick melanoma in patients undergoing SLNB over a long follow-up. METHODS: Eighty-six patients with thick melanoma undergoing SLNB were selected from a prospective database. Lymphoscintigraphy, lymphatic mapping and intraoperative gamma probe detection were performed in all patients. The sentinel lymph node (SLN) was analyzed by HE and immunohistochemistry. Complete lymphadenectomy was indicated for patients with positive sentinel node. The histopathological SLN status was related to the rate of recurrence and mortality from melanoma. RESULTS: One hundred and sixty-six SLNs were taken from the 86 patients. Ages ranged from 18 to 73 years. There were 47 women and 39 men. Micrometastases were found in 44 patients. Forty-two patients underwent complete lymphadenectomy. Seven other patients had positive lymph node. Among the 44 patients with positive sentinel node, there were 20 recurrences and 15 deaths. There were 18 recurrences and 12 deaths in the group with negative SLN. The Breslow thickness was not correlated with the histopathological SLN status. The histopathological SLN status did not affect the rates of recurrence and mortality (Fisher test, p = 1.00). The median follow-up was 69 months. CONCLUSION: Considering the lack of evidence of benefit, SLNB should not be indicated for patients with thick melanoma outside of clinical studies.

Prognostic implications of cytopathologic classification of melanocytic uveal tumors evaluated by fine-needle aspiration biopsy / Implicação prognóstica da classificação citopatológica dos tumores melanocíticos da úvea avaliados pela biópsia aspirativa com agulha fina

PURPOSE: Determine whether cytopathologic classification of melanocytic uveal tumors evaluated by fine-needle aspiration biopsy (FNAB) is a significant prognostic factor for death from metastasis. METHODS: Retrospective analysis of cases of clinically diagnosed uveal melanoma evaluated by fine-needle aspiration biopsy from 1980 to 2006. Main outcome evaluated was death from metastasis. Associations between baseline clinical variables and cytopathologic classification were evaluated using cross-tabulation. Prognostic significance of cytopathologic classification was evaluated by Kaplan-Meier and Cox proportional hazards analysis. RESULTS: Of 302 studied biopsies, 260 (86.1%) yielded sufficient cells for cytopathologic classification. Eighty of the 260 patients who had a sufficient specimen have already died (P=0.021), 69 from metastatic uveal melanoma. Cell type assigned by cytopathology was strongly associated with metastasis/metastatic death in this series (P=0.0048). Multivariate analysis showed cytopathologic classification to be an independently significant prognostic factor for metastatic death (P=0.0006). None of the 42 patients whose tumor yielded insufficient aspirates (sampled in at least two sites) have developed metastasis or died of metastasis thus far. CONCLUSION: In this series, cytopathology of fine-needle aspiration biopsy samples obtained from uveal melanomas was strongly prognostic of death from metastasis. Insufficiently aspirates (2 or more sites sampled) proved to be prognostic of a favorable outcome (i.e., not developing metastasis).

OBJETIVO: Determinar se a classificação citopatológica de tumores melanocíticos da úvea avaliados pela biópsia aspirativa com agulha fina (BAAF) é um fator prognóstico significativo para óbito por metástases. Métodos: Análise retrospectiva de casos diagnosticados clinicamente como melanoma uveal e avaliados pela biópsia aspirativa com agulha fina entre 1980 e 2006. O evento principal analisado foi óbito por metástase. Associações entre variáveis clínicas à apresentação e classificação citopatológica foram avaliadas usando tabulação cruzada. Significância prognóstica da classificação citopatológica foi avaliada por análise de riscos proporcionais de Cox e Kaplan-Meier. RESULTADOS: Das 302 biópsias estudadas, 260 (86,1%) renderam um número suficiente de células para classificação citopatológica. Oitenta dos 260 pacientes que obtiveram um espécime suficiente (adequado) foram a óbito (P=0,021), 69 destes por melanoma uveal metastático. O tipo celular designado pela citopatologia apresentou forte associação com metástase/óbito por metástase nessa série (P=0,0048). Análise multivariada mostrou que a classificação citopatológica foi um fator prognóstico independente significativo para o óbito por metástase (P=0,0006). Nenhum dos 42 pacientes cujos tumores renderam um aspirado insuficiente (quando foram amostrados pelo menos 2 sítios) desenvolveu metástase e foi a óbito por metástase até o presente momento. CONCLUSÃO: Nessa série, a citopatologia dos espécimes obtidos pela biópsia aspirativa com agulha fina de melanomas uveais foi fortemente prognóstica para óbito por metástase. Os aspirados insuficientes (se duas ou mais áreas foram amostradas) provou ser um resultado prognóstico favorável (i.e., de não desenvolvimento de metástases).

Avaliação da atividade antineoplásica do extrato etanólico da própolis g6 baiana / Evaluation of the antineoplastic activity of the ethanol extract of propolis g6 Bahia

O câncer é uma doença caracterizada pelo processo proliferativo descontrolado de células transformadas. Devido à possibilidade de metástase, o melanoma cutâneo é considerado um dos cânceres mais agressivos. Produtos naturais derivados de plantas e outros organismos têm sido utilizados como fonte para o desenvolvimento de quimioterápicos empregados no tratamento de diversos tipos de câncer, inclusive do melanoma. A própolis é um produto natural produzido por abelhas a partir de exudatos de brotos e botões florais, e apresenta uma composição química complexa que influência sua atividade biológica. O presente trabalho propõe a investigação da atividade antineoplásica do extrato etanólico da própolis G6 baiana (EEPG6)...

Cancer is a disease process characterized by uncontrolled proliferation of transformed cells. Due to the possibility of metastasis, cutaneous melanoma is considered one of the most aggressive cancers. Natural products derived from plants and other organisms have been used as a source for the development of chemotherapeutic agents used in the treatment of various cancers, including melanoma. Propolis is a natural product produced by bees from exudates shoots and buds, and has a complex chemical composition that influence their biological activity. This study aims to investigate the anticancer activity of ethanol extract of G6 propolis from Bahia (EEPG6)...

Melanoma maligno conjuntival / Malignant melanoma of the conjunctiva

INTRODUÇÃO: Os tumores melanocíticos conjuntivais compreendem lesões que podem variar desde lesões benignas como os nevos conjuntivais, lesões pré-cancerosas como melanose adquirida primária com atipia até o melanoma maligno conjuntival. O reconhecimento das características clinicas destas lesões e seu diagnóstico preciso permitem o tratamento adequado, contribuindo para a redução da morbidade e mortalidade associados ao melanoma de conjuntiva. OBJETIVO: Revisão das características clinicas, diagnóstico e modalidades de tratamento clínico e cirúrgico das lesões precursoras (Nevos e melanose adquirida primária) e do maligno conjuntival. MÉTODOS: Revisão de literatura através de pesquisa no banco de dados MEDLINE, PUBMED, LILACS e SciELO no período de 1980 a 2011. As palavras-chave utilizadas, individualmente ou em conjunto, foram: "conjunctival melanoma", "primary acquired melanosis", "nevi", "treatment", "chemotherapy", "recurrence", "metastasis" e "mortality". RESULTADO: Características clínicas que permitem o diagnóstico do melanoma conjuntival e sua diferenciação de outras lesões pigmentadas conjuntivais foram consideradas. O estadiamento clínico e patológico, assim como modalidades de tratamento para o melanoma maligno foram revisadas. CONCLUSÕES: Pacientes portadores de lesões pigmentadas conjuntivais devem ser avaliados por um oftalmologista especialista. A história oftalmológica, a história familiar de melanoma, e características clínicas da lesão necessitam de cuidadosa avaliação, incluindo-se a determinação do risco de malignidade. A documentação fotográfica deve ser realizada. O tratamento clínico e planejamento cirúrgico devem ser baseados na suspeita clinica. A análise histopatológica por patologista experiente é fundamental para orientação do tratamento e para identificação de fatores prognósticos, principalmente em casos de doença maligna.

INTRODUCTION: Melanocytic tumors comprise a wide range of lesions. These lesions can be nevi, primary acquired melanosis with or without atypia or malignant as conjunctival melanoma. Early recognition of the clinical features allows precise diagnosis and adequate intervention, reducing the rates of metastatic disease and mortality associated with conjunctival melanoma. PURPOSE: To review clinical features, diagnosis, clinical and surgical treatment modalities of the different precursor pigmented lesions (Nevi and primary acquired melanosis) and malignant melanoma. METHODS: Literature review was performed accessing the database of MEDLINE, PUBMED, LILACS e SciELO between 1980 and 2011. The keywords used, individually or combined, were: conjunctival melanoma, primary acquired melanosis, nevi, treatment, chemotherapy, recurrence, metastasis e mortality. RESULTS: Relevant clinical information for the diagnosis of malignant melanoma and differentiation from other pigmented conjunctival lesions were accessed. Clinical and pathological features and different modalities of treatment for malignant melanoma have been reviewed. CONCLUSIONS: Patients presenting with a pigmented conjunctival lesion should be evaluated by an experienced ophthalmologist. Ocular history, family history of melanoma, and clinical features of the lesion need careful assessment and malignancy risk evaluation. Digital photo documentation should be performed. Clinical or surgical planning should be done based on the clinical suspicion. Careful histopathology analysis is required for treatment orientation and prognostic factors identification, mainly in cases of malignancy.

Melanoma cutáneo: mortalidad y características de los tumores incidentes en los dos extremos de la vida en la Argentina / Cutaneous melanoma in argentina: mortality and primary tumor

Objetivos. Conocer y comparar en la Argentina, en los jóvenes y adultos, la mortalidad por melanoma cutáneo (MC) y las características de casos incidentes para aportar información útil en el diseño y evaluación de acciones de prevención. Diseño. descriptivo y retrospectivo. Métodos. Se consideraron para el estudio: los jóvenes < 30 años (J) y adultos > 74 años (AM). Los datos de las defunciones para el cálculo de tasas de mortalidad en los períodos 1981-89, 90-98 y 99-07 fueron proporcionados por la Dirección de Estadísticas e Información de Salud del Ministerio de Salud. La información sobre los casos incidentes se obtuvieron del Registro Argentino de Melanoma Cutáneo (RAMC) para el período enero 2002- diciembre 2009. De ellos se estudió la localización, el espesor de Breslow y el tipo histológico.Resultados. En los sucesivos períodos las muertes por MC en J de ambos sexos fue 97, 93 y 123, y en AM 416, 654 y 1.307, respectivamente. En los AM las tasas de mortalidad aumentaron en el tiempo, y fueron siempre menores para las mujeres que para losvarones (varones: 6,3 muertes por MC promedio por cada 100.000 individuos por año en 81-89 a 13,4/100.000 99-07; mujeres: 4,4/100.000 81-89 a 7,5/100.000 en 99-07). El RAMC registró 4.100 casos, 258 fueron en J y 665 en AM. Fueron mujeres el 63% en J y el 47% en AM (p< 0,05). En las mujeres, el 56% de los MC en J y el 36% en AM tuvieron Breslow ≤ 1,00 mm (p< 0,004). En las mujeres predominaron las lesiones en piernas (el 43,4% en J y el 42,2% en AM), mientras que en los hombres fueron el 19,8% y el 12,4% respectivamente (p< 0,005). Conclusión. En las mujeres jóvenes, el menor espesor de Breslow al momento del diagnóstico y las menores tasas de mortalidad por MC con menor incremento temporal de las mismas podrían ser reflejo de una mayor influencia de las acciones de prevención y una mayor atención del propio cuerpo y de la salud por parte del género femenino. Cabe esperar que la continuidad de las actividades del ...

Objectives. To compare mortality rates and main features of cutaneous malignant melanoma(CMM) between two age groups in Argentina (young and elderly patients), in order to increaseknowledge as well as improve planning and preventive actions for this disease.Study design. descriptive and retrospective.Methods. Group J was defined as patients younger than 30 years of age and Group AM patientsover 74 years old. Death reports for periods 1981-89 / 90-98 / 99-07 were provided by theDepartment of Statistics of the Health Ministry and incident cases between 2002 and December2009 by the Argentine Registry of Cutaneous Malignant Melanoma (RAMC). Tumor location,Breslow thickness index and histopathology characteristics were analyzed for all cases.Results. For successive periods, the total number of CMM-associated deaths for both gendersin Group J was 97, 93 and 123 respectively; while these figures were for Group AM 416, 654 and1,307 respectively. On older patients an increase in mortality rates was observed over elapsedtime, being always lower for women than for men (mortality rates for men were 6.3 /100,000population per year during the period of 1981-1989 and 13.4/100,000 between the years1999-2007. Mortality rates for women were: 4.4/100,000 during 1981-1989 and 7.5/100,000and in 1999-2007). RAMC registered 4,100 new cases, of which 258 belonged to Group J and665 to Group AM. Women comprised 63% on group J and 47% on group AM (p<0, 05). Womencomprised 56% of CMM in Group J and 36% on Group AM, having a Breslow tumor thickness≤ 1.00mm (p<0,004). Primary tumors located on lower limbs were more frequently observedamong women (43.4% and 42.2% for Group J and AM respectively), whereas on men this was19.8% and 12.4%, respectively (p<0,005)...

Melenoma - Resenha / Melanoma - Review

Background: Ipilimumab monotherapy (at a dose of 3 mg per kilogram of body weight), as compared with glycoprotein 100, improved overall survival in a phase 3 study involving patients with previously treated metastatic melanoma. We conducted a phase 3 study of ipilimumab (10 mg per kilogram) plus dacarbazine in patients with previously untreated metastatic melanoma. Methods: We randomly assigned 502 patients with previously untreated metastatic melanoma, in a 1:1 ratio, to ipilimumab (10 mg per kilogram) plus dacarbazine (850 mg per square meter of body-surface area) or dacarbazine (850 mg per square meter) plus placebo, given at weeks 1, 4, 7, and 10, followed by dacarbazine alone every 3 weeks through week 22. Patients with stable disease or an objective response and no dose-limiting toxic effects received ipilimumab or placebo every 12 weeks thereafter as maintenance therapy. The primary end point was overall survival. Results: Overall survival was significantly longer in the group receiving ipilimumab plus dacarbazine than in the group receiving dacarbazine plus placebo (11.2 months vs. 9.1 months, with higher survival rates in the ipilimumab-dacarbazine group at 1 year (47.3% vs. 36.3%), 2 years (28.5% vs. 17.9%), and 3 years (20.8% vs. 12.2%) (hazard ratio for death, 0.72; P<0.001). Grade 3 or 4 adverse events occurred in 56.3% of patients treated with ipilimumab plus dacarbazine, as compared with 27.5% treated with dacarbazine and placebo (P<0.001). No drug-related deaths or gastrointestinal perforations occurred in the ipilimumab-dacarbazine group. Conclusions: Ipilimumab (at a dose of 10 mg per kilogram) in combination with dacarbazine, as compared with dacarbazine plus placebo, improved overall survival in patients with previously untreated metastatic melanoma...

O tratamento do melanoma em estágios avançados ainda é um desafio, com taxas de sobrevida em dois anos entre 10% e 20% relatadas na literatura. Em 2010 foi demonstrado em estudo fase III ganho de sobrevida global e taxas de resposta significativas associadas ao ipilimumabe (IgG1 que inibe CTLA-4) em segunda linha de tratamento para melanoma metastático.Estudos prévios de fase II com ipilimumabe demonstraram relação entre dose-resposta e que sua associação na dose de 3 mg/kg com dacarbazina (250 mg/d por 5 dias) demonstrou respostas objetivas. Neste contexto, foi desenvolvido o presente estudo prospectivo, multicêntrico, randomizado 1:1 (ipilimumabe 10 mg/kg + dacarbazina 850 mg/m2 ou dacarbazina 850 mg/m2 + placebo - semanas 1, 4, 7, 10), seguido de dacabarzina droga isolada até a 22ª semana (indução). Os pacientes com respostas objetivas ou doença estável a partir da 24ª semana receberam terapia de manutenção com ipilimumabe ou placebo a cada 12 semanas, até progressão, toxicidade ou final do estudo.Dentre os pontos de destaque estão a associação com a dacarbazina que, apesar de não demonstrar ganhos de sobrevida como droga isolada, é rotineiramente utilizada na prática clínica e também na divisão do tratamento em fase de indução e manutenção.Os grupos foram bastante homogêneos e o objetivo principal foi avaliar a sobrevida global que demonstrou ser significativamente superior para o grupo com ipilimumabe associado (11,2 x 9,1 meses), com taxas de sobrevida em 1 e 2 anos também estatisticamente superiores. Dentre os efeitos colaterais se destacam que a não ocorrência de perfurações intestinais ou morte relacionada ao tratamento, apesar de serem mais frequentes os eventos adversos no grupo com ipilimumabe associado, com destaque para as alterações de função hepática. No estudo se conclui que a associação ipilimumabe+dacarbazina trouxe ganho de sobrevida para pacientes com melanoma metastático em primeira linha de tratamento...