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Abstract Introduction : Although therapeutic advances have improved results of cutaneous melanoma (CM), senti nel node-positive patients still have substantial risk to develop recurrent disease. We aim to investigate prog nostic indicators associated with disease recurrence in positive-sentinel lymph node biopsy (SLNB) patients in a Latin-American population. Methods : Retrospective analysis of CM patients and positive-SLNB (2010-2020). Patients were divided into two groups: Group A (completion lymph node dissection, CLND), Group B (active surveillance, AS). Association of demographics, tumor data and SLN features with recurrence-free (RFS), distant metastases-free (DMFS) and melanoma specific (MSS) survival was analyzed. Results : Of 205 patients, 45 had a positive SLNB; 27(60%) belonged to Group A and 18(40%) to Group B. With a median follow-up of 36 months, 16 patients (12 in Group A and 4 in Group B) developed recurrent dis ease and estimated 5-yr RFS at any site was 60% (CI95%, 0.39 - 0.77) (44.5% in CLND group vs. 22% in AS group; P = 0.20). Estimated 5-yr DMFS and MSS: 65% (CI 95%, 0.44 - 0.81) and 73% (CI 95%, 0.59 - 0.89) with no differ ences between groups (p = 0.41 and 0.37, respectively). Independent predictors of poorer MSS were extranodal extension (ENE) and MaxSize > 2 mm of melanoma deposit in SLN. Factors independently associated with DMFS: Breslow depth > 2 mm, ENE, number (≥ 2) of posi tive SN and CLND status. Conclusion : Primary tumor and SN features in mela noma provide important prognostic information that help optimize prognosis and clinical management. AS is now the preferred approach for most positive-SLNB CM patients.

Resumen Introducción : Si bien los avances terapéuticos han permitido mejorar los resultados del melanoma cutáneo (MC), los pacientes con ganglio centinela positivo (BGCP) aún tienen riesgo elevado de desarrollar recurrencia de la enfermedad. Nuestro objetivo fue investigar in dicadores pronósticos asociados a dicho evento en una población latinoamericana. Métodos : Análisis retrospectivo de pacientes con MC y BGCP entre 2010-2020. Los pacientes se dividieron en 2 grupos: Grupo A (linfadenectomía terapéutica) y Grupo B (Vigilancia activa, VA). Se analizaron datos demográficos, tumorales y características del GC junto con sobrevida-libre de recurrencia (SLR), libre de metástasis a distancia (SLMD) y específica de melanoma (SEM). Resultados : De 205 pacientes, 45 presentaron BGCP; 27 (60%) perteneció al Grupo A y 18 (40%) al Grupo B. Con una mediana de seguimiento de 36 meses, 16 pa cientes (12 en Grupo A y 4 en Grupo B) desarrollaron enfermedad recurrente con una SLR a 5 años de 60% (IC95%: 0.39-0.77) (44.5% en Grupo B vs. 22% en Grupo A; P = 0.20). Las SLMD y SEM estimadas a 5 años fueron de 65% (CI 95%, 0.44 - 0.81) y 73% (CI 95%, 0.59 - 0.89) sin diferencias entre ambos grupos (p = 0.41 y 0.37, respec tivamente). Los predictores independientes de peor SEM fueron: extensión extranodal (ENE) y MaxSize > 2mm de depósito tumoral en GC. Los factores asociados de forma independiente con SLMD fueron Breslow >2mm, ENE, número (≥ 2) de GC positivos y el status (positividad) de la linfadenectomía. Conclusión : Características del tumor primario y del GC brindan información importante que ayuda a optimi zar el pronóstico y manejo clínico de los pacientes con MC. La VA es actualmente el abordaje de elección para la mayoría de los pacientes con BGCP.

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Abstract Introduction : Immediate completion lymph node dissection (CLND) performed in patients with a positive sentinel lymph node biopsy (SLNB) cutaneous melanoma is not associated with improved melanoma specific survival versus active surveillance (AS) using nodal ul trasound. Clinical practice experience and outcomes of AS and adjuvant therapy is now starting to be published in literature. Methods : Retrospective analysis of patients with a positive-SLNB between June/2017-February/2022. Impact of management on any-site recurrence free survival (RFS), isolated nodal recurrence (INR), distant metasta sis-free survival (DMFS) and melanoma-specific survival (MSS) was evaluated. Results : From 126 SLNB, 31 (24.6%) were positive: 24 received AS and 7 CLND. Twenty-one (68%) received ad juvant therapy (AS, 67% and CLND, 71%). With a median follow-up of 18 months, 10 patients developed recur rent disease with an estimated 2-yr RFS of 73% (CI95%, 0.55-0.86) (30% in AS group vs. 43% in dissection group; P = 0.65). Four died of melanoma with an estimated 2-yr MSS of 82% (CI 95%, 0.63-0.92) and no differences between AS and CLND groups (P = 0.21). Estimated 2-yr DMFS of the whole cohort was 76% (CI 95%, 0.57-0.88) with no differences between groups (P = 0.33). Conclusion : Active surveillance strategy has been adopted for most positive-SLNB cutaneous melanoma patients. Adjuvant therapy without immediate CLND was delivered in nearly 70% of patients. Our results align with outcomes of randomized control trials and previous real-world data.

Resumen Introducción : La linfadenectomía inmediata (LI) re alizada en pacientes con biopsia de ganglio centinela (BGC) positivo por melanoma cutáneo no está asociada a mejoría en la supervivencia libre de enfermedad vs. vigilancia activa (VA). Resultados oncológicos y experi encia en la práctica clínica con dicha conducta asociados a tratamiento adyuvante comienzan a ser publicados en la literatura. Métodos : Análisis retrospectivo incluyendo paci entes con BGC-positiva por melanoma cutáneo entre junio/2017-febrero/2022. Se evaluó impacto del manejo en: supervivencia libre de recurrencia (SLR), recurren cia ganglionar aislada (RGA), supervivencia libre de metástasis a distancia (SLMD) y supervivencia libre de enfermedad (SLE). Resultados : De 126 pacientes, 31 (24.6%) fueron positi vos: en 24 se realizó VA y en 7 LI. Veintiún pacientes (68%) recibieron tratamiento adyuvante (VA, 67% y LI, 71%). Con una media de seguimiento de 18 meses, 10 pacientes presentaron recurrencia de la enfermedad con una SLR estimada a 2 años del 73% (CI95%, 0.55-0.86) (30% en VA vs. 43% en LI; P = 0.65). Cuatro murieron de melanoma con una SLE a 2 años del 82% (CI 95%, 0.63-0.92); sin diferencia entre ambos grupos (P = 0.21). La SLMD a 2 años de toda la cohorte fue de 76% (CI 95%, 0.57-0.88; P = 0.33). Conclusión : La vigilancia activa se ha adoptado como conducta para la mayoría de los pacientes con BGC-positivo. El tratamiento adyuvante sin linfadenectomía inmediata se realizó en cerca del 70% de nuestra serie. Los resultados de nuestra serie son similares a los re portados en la literatura.

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BACKGROUND: Lymph mapping with sentinel node biopsy is the standard procedure for lymph node staging in patients with cutaneous melanoma with a tumor thickness of 1 mm or greater. Patients who have metastases in sentinel node must undergo complementary lymphadenectomy; however, it has not been shown to improve survival. OBJECTIVE: To know the prevalence in our setting of metastases in the product of complementary lymphadenectomy in patients with metastatic sentinel node. METHOD: Evaluation of a descriptive, retrospective, observational and analytical cohort of patients with metastatic sentinel node submitted to lymphadenectomy. Multivariate analysis of tumor thickness, neural invasion, location, sentinel node number, serum DHL level, lymph nodes dissected and extracapsular spread. RESULTS: 67 patients, 35 women and 32 men with a mean of 66 years, 22% had metastases in lymph nodes from complementary lymphadenectomy, 19% of them with extracapsular spread; no relationship with the Breslow level. Extracapsular spread in the sentinel node, lymphadenectomy time, and perineural invasion in the primary tumor were prognostic factors for non-sentinel node metastasis. CONCLUSIONS: In this series, 22% of the patients with a sentinel node-positive have metastases in the non-sentinel nodes, 19% of them with extracapsular spread, which justifies complementary lymphadenectomy.

ANTECEDENTES: El mapeo linfático con biopsia del ganglio centinela es el procedimiento estándar de estadificación ganglionar en pacientes con melanoma cutáneo con grosor tumoral de 1 mm o mayor. Los pacientes que tienen metástasis en él deben ser sometidos a linfadenectomía complementaria; sin embargo, esta no ha mostrado mejorar la superviviencia. OBJETIVO: Conocer la prevalencia en nuestro medio de metástasis en el producto de linfadenectomía complementaria en pacientes con ganglio centinela metastásico. MÉTODO: Evaluación de una cohorte descriptiva, retrospectiva, observacional y analítica de pacientes con ganglio centinela metastásico sometidos a linfadenectomía, con análisis multivariado de grosor tumoral, invasión neural, localización, número de ganglios centinela, concentración sérica de deshidrogenasa láctica, ganglios disecados en linfadenectomía y ruptura capsular. RESULTADOS: Hubo 67 pacientes (35 mujeres y 32 hombres), con una media de 66 años de edad, en el 22% hubo metástasis en ganglios de linfadenectomía complementaria y en el 19% ruptura capsular; sin relación con el nivel de Breslow. La ruptura capsular en el ganglio centinela, el tiempo de linfadenectomía y la invasión perineural fueron factores pronóstico de metástasis en ganglios no centinela. CONCLUSIONES: En esta serie, el 22% de los pacientes tuvieron metástasis en ganglios no centinela, el 19% de ellos con ruptura capsular, lo cual justifica la linfadenectomía complementaria.

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La biopsia selectiva del ganglio centinela (BSGC) se ha desarrollado de tal manera que reemplazó a la linfadenectomía electiva en el tratamiento del melanoma cutáneo (MC). Numerosos estudios demostraron que el estado del ganglio centinela es un factor pronóstico independiente en relación con la supervivencia global y la supervivencia libre de enfermedad de los pacientes con melanoma. El objetivo del presente trabajo fue realizar una revisión bibliográfica para comprender la utilidad y las indicaciones de la BSGC en pacientes con MC a partir de la evidencia actual publicada.

Sentinel lymph biopsy (SLNB) has been developed in such a way that is has replaced elective lymphadenectomy in the treatment of cutaneous melanoma (CM). Numerous studies have shwn that sentinel node status is an independent prognostic factor in relation to overall survival and disease-free survival of patients with CM. The purpose of this article is to carry out a literature review to understand the usefulness and indications of SLNB in patients with CM based on the current evidence.

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OBJETIVO: O objetivo desse estudo foi verificar o efeito do treinamento resistido na sobrevida de camundongos C57BL/6 com caquexia associada ao melanoma cutâneo. MATERIAL E MÉTODOS: A amostra foi constituída por 64 (camundongos C57BL/6 fêmeas, com idade entre 10 e 12 semanas, com cerca de 50 ± 5 gramas de peso corporal. Os camundongos foram distribuídos aleatoriamente em quatros grupos: i. camundongos controle, com indução de tumor, inativos fisicamente (Controle, n = 16); ii. camundongos submetidos ao treinamento resistido diário somente antes da indução tumoral (Treino 1, n = 16); iii. camundongos submetidos ao treinamento resistido diário antes e após da indução tumoral (Treino 2, n = 16); iv. camundongos submetidos ao treinamento resistido diário após a indução tumoral e apresentado quadro caquético (Treino 3, n = 16). No procedimento para treinamento resistido (TR) com choque, foi utilizada uma escada com 110 cm de altura, 18 cm de largura, 2 cm entre os degraus e 80 graus de inclinação. No procedimento para TR com choque, foi utilizada uma escada 110 cm de altura, 18 cm de largura, 2 cm entre os degraus e 80 graus de inclinação. O exercício resistido baseia-se na subida dos camundongos. Na plataforma de saída, aplicava-se um choque elétrico como estímulo para subir as escadas, nesta etapa era aplicada o choque nas quatro patas do animal com uma tensão elétrica de 20 volts a uma frequência de 45 Hertz durante seis séries de oito repetições, cada uma com noventa segundos de intervalo entre as séries. Os grupos de camundongos foram submetidos a acompanhamento por no máximo 15 dias após o diagnóstico da caquexia a fim de comparar a sobrevida geral relacionada ao câncer entre os grupos de estudo. As curvas de sobrevivência de KaplanMeier foram estimadas para cada evento e as curvas dos diferentes grupos foram comparadas usando o teste de Log-rank. O tempo de sobrevida proposta foi de 25 dias após inoculação. RESULTADOS: Os resultados apresentados nesse estudo mostraram que não houve diferença significativa (p <0,05) entre as propostas de treino. CONCLUSÃO: Não houve diferença na sobrevida de animais com caquexia associada ao modelo tumoral singênico de melanoma cutâneo com intervenção de exercício resistido ou sedentários.

OBJECTIVE: The objective of this study was to verify the effect of resistance training on the survival of C57BL / 6 mice with cachexia associated with cutaneous melanoma. MATERIAL AND METHODS: The sample consisted of 64 (female C57BL/6 mice, aged between 10 and 12 weeks, with approximately 50 ± 5 grams of body weight. The mice were randomly distributed into four groups: i. control mice, with tumor induction, physically inactive (Control, n = 16); ii. mice submitted to daily resistance training only before tumor induction (Training 1, n = 16); iii. Mice submitted to daily resistance training before and after tumor induction (Training 2, n = 16); iv. Mice submitted to daily resistance training after tumor induction and presented a cachectic condition (Training 3, n = 16). In the resistance training procedure (RT) with shock, a 110 cm high, 18 cm wide, 2 cm between the steps, and 80 degrees inclination ladder was used. In the procedure for shock resistance training (TR), a ladder 110 cm high, 18 cm wide, 2 cm between the rungs, and 80 degrees of inclination was used. The resisted exercise is based on the climbing of the mice. On the exit platform, an electric shock was applied as a stimulus to climb the stairs. In this step, the shock was applied to the four legs of the animal with an electric voltage of 20 volts at a frequency of 45 Hertz during six series of eight repetitions, each with ninety-seconds intervals between the series. The mice groups underwent follow-up for no more than 15 days after diagnosis of cachexia to compare overall cancer-related survival between the study groups. Kaplan-Meier survival curves were estimated for each event, and the curves of the different groups were compared using the Log-rank test. The proposed survival time was 25 days after inoculation. RESULTS: The results presented in this study showed no significant difference (p <0.05) between the training proposals. CONCLUSION: There was no difference in animals' survival with cachexia associated with the syngeneic melanoma skin tumor model with either resistance exercise or sedentary intervention.

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A male 15-year-old captive Siberian tiger (Panthera tigris altaica) developed pelvic limb hypermetry over the past 10 years. Recently, an ulcerated black nodule located caudally to the right ear was observed. The animal was submitted to surgery for removing the tumor, but died during anesthetic recovery. At necropsy, another infiltrative nodule was observed caudally to the right ear. Histologically, both nodules corresponded to melanocytic neoplasia, varying from heavily pigmented to amelanotic, with metastasis to mediastinal lymph nodes, spleen and lung. Lipofuscinosis and corpora amylacea were histologically observed in the central nervous system. Macroscopic and histologic findings confirmed the diagnosis of skin metastatic melanoma in a captive adult Siberian tiger.(AU)

Um tigre-siberiano (Panthera tigris altaica) de cativeiro, macho, de 15 anos de idade, apresentou hipermetria dos membros pélvicos nos últimos 10 anos, e recentemente, foi observado um nódulo preto e ulcerado caudalmente à orelha direita. O animal foi submetido à cirurgia para remoção do nódulo e morreu durante a recuperação anestésica. À necropsia, outro nódulo infiltrativo, foi detectado caudalmente a orelha direita. Histologicamente, ambos os nódulos correspondiam à neoplasia melanocítica, com células variando de fortemente pigmentadas a amelanóticas, com metástase para linfonodos mediastinais, baço e pulmão. Havia lipofucsinose e corpora amilácea no sistema nervoso central. Os achados macroscópicos e histológicos confirmam o diagnóstico de melanoma cutâneo metastático em um tigre-siberiano adulto de cativeiro.(AU)

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A male 15-year-old captive Siberian tiger (Panthera tigris altaica) developed pelvic limb hypermetry over the past 10 years. Recently, an ulcerated black nodule located caudally to the right ear was observed. The animal was submitted to surgery for removing the tumor, but died during anesthetic recovery. At necropsy, another infiltrative nodule was observed caudally to the right ear. Histologically, both nodules corresponded to melanocytic neoplasia, varying from heavily pigmented to amelanotic, with metastasis to mediastinal lymph nodes, spleen and lung. Lipofuscinosis and corpora amylacea were histologically observed in the central nervous system. Macroscopic and histologic findings confirmed the diagnosis of skin metastatic melanoma in a captive adult Siberian tiger.(AU)

Um tigre-siberiano (Panthera tigris altaica) de cativeiro, macho, de 15 anos de idade, apresentou hipermetria dos membros pélvicos nos últimos 10 anos, e recentemente, foi observado um nódulo preto e ulcerado caudalmente à orelha direita. O animal foi submetido à cirurgia para remoção do nódulo e morreu durante a recuperação anestésica. À necropsia, outro nódulo infiltrativo, foi detectado caudalmente a orelha direita. Histologicamente, ambos os nódulos correspondiam à neoplasia melanocítica, com células variando de fortemente pigmentadas a amelanóticas, com metástase para linfonodos mediastinais, baço e pulmão. Havia lipofucsinose e corpora amilácea no sistema nervoso central. Os achados macroscópicos e histológicos confirmam o diagnóstico de melanoma cutâneo metastático em um tigre-siberiano adulto de cativeiro.(AU)

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Antecedentes: los melanomas en cabeza y cuello (MCC) han sido asociados con factores pronósticos diferentes de aquellos en otras localizaciones. Objetivo: comparar características demográficas, clínicas y resultados del tratamiento quirúrgico de pacientes con MCC y pacientes con melanomas en tronco y extremidades (MTE). Material y métodos: se llevó a cabo una revisión retrospectiva de las historias clínicas de pacientes operados por melanoma entre enero de 2012 y diciembre de 2017. Quince pacientes (22,3%) tuvieron MCC y 52 (77,7%) MTE. Resultados: ambos grupos tuvieron edad similar (63,8 ± 21,1 versus 58,5 ± 16), pero los MCC mostraron una tendencia con predominio masculino (80% versus 61,3%). Los MCC tuvieron menor espesor tumoral que los MTE (2,07 versus 5,5 mm) y mayor porcentaje de melanoma in situ, 5 (33,3%) versus 8 (15,3%), pero requirieron vaciamientos ganglionares más a menudo (33% versus 25%) así como reconstrucción del defecto primario con colgajos locales y miocutáneos. Durante el seguimiento, en el grupo de MCC, dos pacientes desarrollaron recidivas locales que fueron extirpadas, y otros tres desarrollaron metástasis a distancia en pulmón, intestino delgado y abdomen y fallecieron por la enfermedad; en el grupo de MTE un paciente tuvo recidiva local y cinco fallecieron de metástasis sistémicas. El tamaño de la muestra no permitió aplicar pruebas de significación entre las diferencias encontradas. Conclusión: los MCC se presentan en un amplio rango de edad y estadios, y tuvieron algunas diferencias clínicas con el MTE. Los defectos producidos por la extirpación de la lesión primaria requieren procedimientos reconstructivos más complejos la mayoría de las veces y se aconseja un abordaje multidisciplinario.

Background: Head and neck melanomas (HNMs) have been associated with prognostic factors different from those on other locations. Objective: The goal of the present study was to compare the demographic and clinical characteristics and the outcomes of surgical treatment between patients with HNM and those with trunk and extremity melanoma (TEM). Material and methods: The clinical records of patients undergoing surgery for melanoma between October 2014 and April 2018 were retrospectively reviewed. Fifteen patients (22.3%) had HNM and 52 (77.7) presented TEM. Results: There were no differences in age between both groups (63.8 ± 21.1 versus 58.5 ± 16), but there was a trend toward higher percentage of men in the HNM group (80% versus 61.3%). Patients with HNM had lower tumor thickness than those with TEM (2.07 versus 5.5 mm), higher incidence of melanoma in situ [5 (33.3%) versus 8 (15.3%)]; lymph node resection was more common (33% versus 25%) as well as reconstruction of the primary defect with local and musculocutaneous flaps. During follow-up, two patients in the HNM group developed local recurrences that were excised and three presented distant metastases in the lung, small bowel and abdomen and finally died due to the disease. In the TEM group, one patient had local recurrence and five died due to systemic metastases. The sample size was not sufficient to assess statistically significant differences. Conclusion: Head and neck melanomas occur in a wide age range and stages and has some clinical differences with TEM. The defects produced after the excision of the primary lesion often require more complex procedures and should be managed with a multidisciplinary approach.

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El melanoma cutáneo es una enfermedad grave y potencialmente mortal que afecta a la población de todo el orbe y que se encuentra condicionada por muchos factores de riesgo relacionados con algunos estilos de vida, que pueden ser modificables. El hallazgo oportuno y precoz de esta entidad clínica eleva la sobrevida de las personas afectadas y favorece el resultado terapéutico; sin embargo, en ocasiones no se diagnostica a tiempo. Actualmente ya se presenta en individuos más jóvenes de 25-29 años de edad y con gran probabilidad de generar metástasis, lo cual constituye una preocupación en el ámbito de la salud. Al respecto, se decidió efectuar esta revisión bibliográfica, con el fin de actualizar algunos elementos sobre el tema y darlos a conocer a la comunidad médica nacional y extranjera.

The cutaneous melanoma is a severe and potentially mortal disease that affects the population of the whole world and that is conditioned by many risk factors related to some lifestyles that can be modified. The opportune and early finding of this clinical entity elevates the survival of affected people and it favors the therapeutic result; however, it is not diagnosed on time occasionally. At present it is already presented in younger individuals with 25-29 years old and with great probability of generating metastasis, which constitutes a concern in the health field. In this respect, it was decided to make this literature review, with the purpose of to update some elements on the topic and to make them known in the national and foreign medical community.

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Most patients with cutaneous melanoma present with clinical stage 1 at diagnosis, i.e., with no evidence of lymph node or systemic metastases. However, since this is a type of neoplasm with high affinity to lymphatic tissue, between 30 and 60% of patients are estimated to have occult metastases on the lymph nodes of the area that drains the primary tumor site at the moment of diagnosis. This possibility depends on several histologic factors, especially thickness of the neoplasm. Historically, in order to reduce the rate of regional recurrence, lymphadenectomy was an essential part of cutaneous melanoma treatment, which has associated morbidity. In the decade of 1990, Morton et al. reported that lymph is initially received by a single lymph node in the lymphatic basin and that its histological status predicts the status of the others and that, therefore, in patients with sentinel lymph node free of metastases lymphadenectomy is not necessary, which reduces morbidity. In the present manuscript, indications, contraindications and requirements for sentinel lymph node identification are described, as well as its current value in cutaneous melanoma diagnostic and therapeutic process.

La mayoría de los pacientes con melanoma cutáneo se presenta en etapa clínica 1, es decir, sin evidencia de metástasis ganglionares ni sistémicas, sin embargo, al ser una neoplasia con alta linfofilia, se estima que al momento del diagnóstico entre 30 y 60 % de los pacientes tiene metástasis ocultas en los ganglios linfáticos de la zona que drena el sitio del tumor primario. Esta posibilidad depende de varios factores histológicos, principalmente el grosor de la neoplasia. Históricamente y con objeto de lograr disminuir la tasa de recurrencias regionales, la linfadenectomía, con la morbilidad asociada, era parte esencial del tratamiento. En la década de 1990, Morton et al. reportaron que un solo ganglio de la zona linfoportadora recibe la linfa inicialmente y que su estado histológico predice el estado de los demás, de tal manera que la linfadenectomía no es necesaria en pacientes con ganglio centinela sin metástasis, lo que disminuye la morbilidad. En el presente manuscrito se describen las indicaciones, contraindicaciones y requisitos para efectuar la identificación del ganglio centinela, así como su valor actual en el proceso diagnóstico terapéutico del melanoma cutáneo.

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