Ganglio centinela positivo en melanoma: factores predictivos y resultados del vaciamiento ganglionar / Positive sentinel lymph node in melanoma: predictive factors and results of completion lymph node dissection

RESUMEN Antecedentes: la biopsia del ganglio centinela (GC) es la técnica aceptada para determinar el pronóstico en estadios iniciales de melanoma cutáneo. La ventaja del vaciamiento ganglionar (VG) cuando el GC resulta positivo ha sido recientemente cuestionada. Objetivo: describir los porcentajes y factores asociados a metástasis en el GC, y en los ganglios no centinela (GnC) en los VG de pacientes con GC positivo. Material y métodos: se llevó a cabo un estudio retrospectivo de los registros clínicos y patológicos de 139 pacientes operados por melanoma cutáneo entre enero de 2012 y diciembre de 2019. Resultados: a 96 (69%) pacientes se les realizó biopsia de GC. El promedio de edad fue 61,7 años ± 17,5 (19-93); 53 (55,2%) fueron hombres. La lesión primaria estuvo ubicada en: extremidades 47 (49%), tronco 39 (40,6%), cabeza y cuello 10 (10,4%). El promedio de espesor de Breslow fue 5,01 mm (1,05- 50 mm) y se encontró ulceración en 35 casos (36,4%). El GC fue identificado en todas las oportunidades y en 39 (40,6%) fue positivo. Hubo asociación con el espesor ≥ 3 mm (p = 0,000017) y con la ulceración (p = 0,0011). A los pacientes con GC positivo se les efectuó el VG del territorio afectado: 23 axilar, 10 inguinal y 6 cervical. Veintitrés (59%) presentaron metástasis en GnC. Se asoció con el espesor (p = 0,022) y la ulceración (p = 0,019). Conclusión: existió un alto porcentaje de GnC positivos en la población estudiada, vinculado al espesor y la ulceración. Estas características, así como la dificultad de un estricto seguimiento, inducen a no abandonar el VG en pacientes con GC positivo.

ABSTRACT Background: Sentinel lymph node (SLN) biopsy is the technique accepted to determine the prognosis of early cutaneous melanomas. The advantage of lymph node dissection (LND) when SLN biopsy is positive has recently been questioned. Objective: The aim of this study is to describe the percentages and factors associated with SLN and non-sentinel node (NSN) metastases in LNDs of SLN-positive patients. Material and methods: The clinical records and pathology reports of 139 patients undergoing surgery for cutaneous melanoma between January 2012 and December 2019 were retrospectively reviewed. Results: Ninety-six (69%) patients underwent SLN biopsy. Mean age was 61.7 ± 17.5 years (19-93) and 53 (55.2%) were men. The primary lesion was located in the extremities in 47 (49%) cases, in the trunk in 39 (40.6%), and in the head and neck in 10 (10.4%). Mean Breslow thickness was 5.01 mm (1.05-50 mm) and ulceration was found in 35 cases (36.4%). The SLN was identified in all the cases and was positive in 39 (40.6%). There was an association with thickness ≥ 3 mm (p = 0.000017) and ulceration (p = 0.0011). Those patients with positive SLN biopsy underwent LND of the territory involved: axillary in 23, inguinal in 10 and cervical in 6. Twenty-three (59%) presented NSLN metastases and were associated with thickness (p = 0.022) and ulceration (p = 0.019). Conclusion: There was a high percentage of positive NSLN in the population studied which was associated with thickness and ulceration. These characteristics and the difficulty to achieve strict follow-up are the reasons for completion LND in SLN-positive patients.

Research progress of sentinel lymph node biopsy technique in cervical cancer / 中华肿瘤杂志

Cervical cancer is the most common gynecological malignant carcinoma in Chinese women, which seriously threatens women's health. Lymph node metastasis is the most important factor affecting the prognosis and adjuvant treatment of patients with early cervical cancer. Conventional systematic lymphadenectomy has always been a reliable method to detect lymph node metastasis. However, this procedure may affect the quality of life of patients because of high risks of complications. Recently, sentinel lymph node biopsy (SLNB) has been researched aiming to assess the status of pelvic lymph node metastasis intraoperatively, avoid unnecessary lymphadenectomy and achieve the goal of individualized diagnosis and treatment. Exploring efficient tracing methods and pathological ultra-staging is the key to the clinical application of SLNB for cervical cancer, and understanding the latest relevant clinical research progress will help SLNB to be applied in the clinic as soon as possible to benefit patients with cervical cancer.

Expert consensus on clinical application of sentinel lymph node biopsy for cervical cancer / 中华肿瘤杂志

Cervical cancer is a common gynecologic malignancy. Most patients with early-stage cervical cancer received unnecessary systemic pelvic lymphadenectomy, which increased the risk of surgical complications. At present, sentinel lymph node biopsy has been applied in the clinical practice of cervical cancer abroad, however it is still at the starting stage in China in need of application and promotion. The Obstetrics and Gynecology Committee of Chinese Research Hospital Association invited domestic experts in the field of gynecologic oncology to discuss the application value, patient evaluation, technical methods, operation steps, pathological examination and many other key points of sentinel lymph node biopsy based on the current research status, and reached the consensus of clinical application on sentinel lymph node biopsy in cervical cancer to guide the standardized application of the technique in China.

Resultados preliminares en la implementación de una técnica de detección de ganglio centinela en cáncer de cuello uterino y endometrio en un hospital público y centro formador en chile / Preliminary results in the implementation of a sentinel node detection technique in cervical and endometrial cancer in a public hospital and training center in Chile

Resumen Objetivo Evaluar el rendimiento diagnóstico de la técnica de azul patente (disponible en todo el territorio nacional) en el ganglio centinela para la estadificación del cáncer cérvico uterino y en-dometrial. Método Estudio prospectivo realizado entre enero de 2014 y diciembre de 2018. Se evaluó la técnica de azul patente para la detección de ganglio centinela en la estadificación del cáncer cérvico uterino y endometrial, antes de la linfadenectomía pélvica estándar. La inyección del azul patente se aplicó en el cuello uterino (1 cc 1 cm de profundidad y 1 cc superficial) a las 3 y 9 horas, 20 minutos antes del inicio de la cirugía (laparotomía o laparoscópica). La identifica-ción y extracción del ganglio centinela fue realizado por un ginecólogo oncólogo certificado y evaluado mediante histología tradicional con hematoxilina y eosina (H&E). Resultado Se realiza-ron un total de 80 cirugías. El ganglio centinela se identificó en 75 (94%) pacientes, 60 (75%) bilateralmente; Con una detección media de 1,9 nodos por paciente. El sitio de identificación más frecuente fue la fosa obturatriz (43,9%), seguida de los vasos ilíacos externos. Otro 2,6% de los nodos fueron encontrados en sitios poco comunes. Entre los ganglios linfáticos seleccio-nados, 10 casos fueron positivos para el cáncer. No hubo ganglio centinela falso negativo. La tasa de detección fue del 83%, con una especificidad del 95%. Conclusiones Los datos aquí expuestos nos permiten estandarizar e implementar el uso de gan-glio centinela con azul patente. El uso de GC adecua la cirugía a la necesidad de la paciente, con una clara disminución en la incidencia de complicaciones asociadas a la linfadenectomía. Este trabajo forma parte de un estudio inicial el cual se debe complementar con el uso de la tin-ción de verde de indocianina y el estudio anatomo patológico con ultraestadiaje para obtener una validación e implementación adecuada del GC en la etapificación en cáncer de cérvix y endo-metrio.

SUMMARY Objective To assess the diagnostic performance of patent blue dye technique (available in the whole country) in sentinel lymph node for cervical and endometrial cancer staging. Methods A prospective cohort study was conducted between January 2014 to December 2018. Patent blue dye technique was assessed for the detection of sentinel lymph node in cervical and endometrial cancer staging, before standard pelvic lymphadenectomy. Blue dye injection was applied in the cervix (1cc 1cm deep and 1cc superficial) at 3 and 9 hour, 20 minutes prior start-ing a surgery (laparotomy or laparoscopic). The sentinel lymph node was collected by a certified surgeon and assessed by traditional histologic hematoxylin and eosin stain. Results A total of 80 surgeries were performed. The sentinel lymph node was identified in 75 (94%) patients, 60 (75%) bilaterally; with an average detection of 1,9 nodes per patient. The most common site of identifi-cation was the obturator fossa, followed by the external iliac vessels (43,9%). 2,6% of the nodes were found in uncommon sites. 10 lymph nodes were cancer-positive. There were no false neg-ative sentinel node.Overall in our cohort the detection rate was 83% for specificity 95%. Conclusions Our data presented in this publication allow us to safely standardize and implement a sentinel lymph node technique with patent blue. This technique will allow us to adapt the sur-gery for the patient's needs, diminishing the incidence of complications associated with lym-phadenectomy. This is the first stage of our work which we must complement with indocyanine green and pathological study with ultrastaging to obtain an adequate validation and implementa-tion of sentinel node in cervical and endometrial cancer staging.

Relación entre ganglio centinela positivo y el espesor de Breslow en pacientes con melanoma cutáneo primario / Relationship between positive sentinel lymph node and Breslow's depth in patients with primary cutaneous melanoma

Introducción: es sabido que el pronóstico del melanoma cutáneo depende, entre otros factores, de la existencia de diseminación linfática a ganglios. La biopsia del ganglio centinela busca identificar metástasis ganglionares subclínicas. Objetivo: el presente estudio tuvo por objetivo analizar la asociación entre la presencia de ganglio centinela positivo, identificado mediante rastreo con radioisótopo 99mTc-coloide de Renio, y el espesor de Breslow hallado en la lesión primaria a nivel cutáneo. Metodología: se analizaron 52 pacientes. Se realizó la búsqueda del ganglio centinela por el método de rastreo con radioisótopo 99mTc-coloide de Renio y posterior biopsia del mismo, en pacientes tratados en el Instituto Nacional de Cancerología de México, entre enero de 2015 a agosto de 2016, con diagnóstico de melanoma cutáneo y espesor de Breslow mayor o igual a 1mm o con menor a 1mm y otros criterios de riesgo como la ulceración. Aquellos con biopsia positiva fueron sometidos a linfadenectomía. Además, se recogieron las siguientes variables: sexo, edad, localización, tipo de melanoma, espesor de Breslow y ulceración. Resultados: la edad media de la muestra fue 57 ± 15 años. El 63,5% de los pacientes fue del sexo masculino. El tipo histológico más frecuente fue el melanoma de extensión superficial (69,2%). Se detectó positividad del ganglio centinela en 46,2% y 28,8% presentó Breslow >4,0 mm. Se encontró relación entre la presencia de ganglio centinela positivo y espesor de Breslow (p=0,007). Conclusiones: a medida que aumenta el espesor de Breslow, lo hace también el encuentro de metástasis en ganglio centinela. Se recomienda realizar estudios de casos y controles para evaluar el factor predictivo que puede llegar a tener el encontrar ganglio centinela positivo.

Introduction: It is known that the prognosis of cutaneous melanoma depends, among other factors, on the existence of lymphatic spread to lymph nodes. Sentinel node biopsy seeks to identify subclinical lymph node metastases. Objective: The present study aimed to analyze the association between the presence of positive sentinel lymph node, identified by Rhenium 99mTc-colloid radioisotope tracing, and the Breslow´s depth found in the primary lesion at the cutaneous level. Methodology: 52 patients were analyzed. The sentinel lymph node was searched by the rhenium 99mTc-colloid radioisotope and subsequent biopsy of it in patients treated at the Instituto Nacional de Cancerología of Mexico, between January 2015 and August 2016, with a diagnosis of cutaneous melanoma and Breslow's depth greater-than or equal to 1mm or less-than 1mm and other risk criteria such as ulceration. Those patients with positive biopsy underwent lymphadenectomy. In addition, the following variables were collected: sex, age, location of the lesion, type of melanoma, Breslow's depth, and ulceration. Results: Mean age of the sample was 57±15 years. 63.5% of the patients were male. The most frequent histological type was superficial spreading melanoma (69.2%). 46.2% had positive sentinel lymph node. 28.8% presented Breslow >4.0 mm. A relationship was found between the presence of positive sentinel lymph node and Breslow's depth (p=0.007). Conclusions: As Breslow's depths increases, so does the metastasis encounter in sentinel lymphs nodes. It is recommended to carry out case-control studies to evaluate the predictive factor that may result in finding a positive sentinel lymph node.

Linfonodo centinela en cáncer de mama: correlación entre detección isotópica y quirúrgica / Pre and intraoperative scintigraphic detection of sentinel nodes in breast cancer

Background: Sentinel node detection localizes the first node that drains a malignant lesion aiming to detect tumor dissemination. Aim: To assess the yield of sentinel node detection in breast cancer, using pre or intraoperative scintigraphy. Material and Methods: Review of medical records of patients with breast cancer who had a scintigraphic detection of sentinel nodes. Lymph node scintigraphy and surgery were performed in the same day. Results: We studied 174 women aged 53 ± 13 years, operated with a diagnosis of breast cancer, including six highly suspicious lesions in the contralateral breast (totaling 180 studied breasts). Preoperative scintigraphy showed a sentinel node in 174 of 180 breasts (97%). Intraoperative gamma probe confirmed the presence of the sentinel node in the same 174 breasts and detected an additional one reaching a detection yield of 97%. Four patients in whom a sentinel node was not detected in the preoperative scintigraphy, had macrometastases. Frozen section biopsies were available in 177 of 180 breasts. Metastases were informed in 45 patients who underwent axillary lymph node dissection, plus one additional patient with a suspicious lesion. Conclusions: A high rate of sentinel node detection in the preoperative scintigraphy was observed. Most sentinel nodes not detected with nuclear medicine had macrometastases. In 71% of patients, the detection of sentinel node avoided axillary lymph node dissection.

Linfadenectomia seletiva guiada (linfonodo sentinela) em oncologia / Guided selective lymphadenectomy (sentinel lymph node) in oncology

O linfonodo sentinela é o primeiro linfonodo a receber a drenagem linfática do tumor primário, sendo assim considerado o primeiro a receber células metastáticas. Ocasionalmente existe mais de um linfonodo sentinela. Se ele se mostra invadido, indica que outros linfonodos da cadeia também podem estar. Se não, é improvável que os outros linfonodos o estejam. Ou seja, o linfonodo sentinela é impalpável e a sua pesquisa busca a evitar o esvaziamento linfático desnecessário. Assim, a ênfase é colocada sobre o estadiamento de linfonodos regionais. Como os doentes que têm doença metastática limitada aos sítios regionais têm uma maior chance de cura, um benefício potencial do estadiamento dos gânglios regionais é selecionar pacientes para a ressecção cirúrgica curativa. O melanoma cutâneo, à semelhança de muitos cânceres, pode metastatizam por vias linfática ou hematogênica. Normalmente, a disseminação linfática apresenta-se antes da disseminação hematogênica, e o achado de metástase linfática é associado com um risco maior de doença sistêmica. Pacientes com linfonodos palpáveis ou com biópsia positiva para linfonodo sentinela devem ser submetidos à dissecção formal de todos os linfonodos da respectiva cadeia de drenagem. A presença de metástases linfáticas pode significar doença sistêmica, o que confere ao paciente um prognóstico sobrevida de 40% em 5 anos. A linfocintilografia para identificação de linfonodo sentinela metastático é indicada em casos de lesões melanomatosas acima de um milímetro e com sinais de gravidade (ulceração, crescimento vertical e extensa área de regressão espontânea - cerca de dois terços da lesão). Para melanomas de espessura menores, não há estudos sobre os critérios adequados para a sua realização. É realizada a linfocintilografia pré-operatória para determinar o primeiro linfonodo de drenagem da cadeia linfonodal acometida pelo tumor. Realiza-se com o uso de corante azul patente e o gama probe intra-operatório. É realizada então a biópsia do LS (determinado pela linfocintilografia) e procedido ao exame patológico. Caso haja LS positivo, a linfadenectomia deve ser realizada. Quando há ausência de metástase para linfonodo, o paciente é acompanhado clinicamente e com exames periódicos, e, ficando o linfonodo acometido pelo melanoma, indica-se a linfadenectomia seletiva. Apenas a retirada dos linfonodos regionais metastáticos não aumenta comprovadamente a sobrevida dos doentes, mas diminui a recorrência local e auxilia na identificação dos pacientes que podem ser beneficiados pela terapia adjuvante - tratamento complementar para o tumor primário. O câncer de mama tem seu prognóstico e tratamento definidos pela localização, idade de apresentação e estadiamento, e critérios de risco que levam em consideração critérios histopatológicos, biológicos e, mais recentemente, moleculares e genéticos. As cirurgias parciais recebem nomes variáveis, dependendo do volume mamário retirado: quadrantectomia, segmentectomia, centralectomia, tumorectomia, excisão ampla, adenomastectomia etc. e são associadas ou não esvaziamentos axilares do primeiro nível (amostragem, ou linfonodo sentinela) até radicais incluindo os três níveis da cadeia linfática axilar. As cirurgias parciais em casos de tumores invasivos de uma forma geral são acompanhada pela técnica de linfonodo sentinela, pela qual os linfonodos do Nivel I de drenagem são identificados através do corante azul patente ou de radiotraçador. Os membros da CONITEC presentes na 10 ª reunião ordinária do plenário do dia 08/11/2012 recomendaram a incorporação da linfadenectomia seletiva guiada (linfonodo sentinela) em oncologia no SUS. A Portaria N.º 28, de 12 de junho de 2013 - Toma a Decisão de incorporar o procedimento linfadenectomia seletiva guiada (linfonodo sentinela) em oncologia no Sistema Único de Saúde - SUS.