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.

Ganglio centinela en cáncer de mama. Experiencia en nuestros primeros 100 casos / Sentinel Node in Breast Cancer. Our first 100 cases experience

Introducción Desde los trabajos presentados por Giuliano et al . en 1994 y sus posteriores validaciones, la biopsia del ganglio centinela se ha convertido en el standard de la evaluación axilar en estadios tempranos del cáncer de mama. Es de vital importancia respaldar esta técnica con altas tasas de identificación y de correlación anatomopatológica intraoperatoria/diferida. Objetivos 1) Determinar nuestra tasa de identificación usando solo azul patente. 2) Determinar la correlación entre el estudio intraoperatorio y diferido. 3) Determinar la tasa de recurrencia axilar. Material y método Se reclutaron 100 pacientes con cáncer de mama T1 T2 N0 o cdis extenso de alto grado diagnosticadas por punción con aguja fina (paf) o Core Biopsy. Se utilizó solo Azul Patente al 1%, inyección subareolar, masaje circular por 10 minutos, incisión axilar. Se reconoce como Ganglio Centinela al ganglio o a los ganglios teñidos de azul o con su linfático aferente con colorante. El estudio intraoperatorio se realizó por sección en fresco e impronta citológica. El diferido por coloración con Hematoxilina y Eosina. Las pacientes fueron seguidas por el cirujano actuante y/u oncología clínica. Resultados Se evaluaron 100 pacientes. Nuestra tasa de detección fue del 98%. Los falsos negativos intraoperatorios por impronta citológica fueron del 3%. Luego de un seguimiento promedio de 63,8 meses, no se detectaron recidivas axilares. El número total de Ganglios Centinela positivos fue del 26,5%. El promedio de Ganglios hallados fue de 1,2. Conclusiones La Biopsia de Ganglio Centinela usando Azul Patente como único método es una operación confiable, de bajo costo y al alcance de todo centro con interés de desarrollar dicha técnica.

Introduction Since Giuliano et al. publications in 1994 and forward validations, sentinel node biopsy (snp) has become the standard procedure for staging the axilla in early breast cancer. Therefore, it is of vital importance to back this technique up by a high rate of identification and high intraoperative/final pathology correlation. Objectives 1) To determine our identification rate by only using Patent Blue dye. 2) To determine the correlation between intraoperative and final pathology results. 3) To determine axillary recurrence. Materials and method A hundred patients have been recruited. Each was diagnosed with T1 T2 N0 Breast Cancer or extense high grade Ductal Carcinoma In situ (dcis) by fine needle aspiration (fna) and/or Core Biopsy. Patent Blue 1% was injected subareolary. In addition, circular massage was performed during 10 minutes and an axillary incision was made. The node or nodes dyed in blue or with coloured lymphatic afferent have been acknowledged as sentinel nodes. The node was analyzed intraoperatively by touch imprint citology. The final study was done with Hematoxilin Eosin coloration. Further follow up was in charge of the surgeon and/or clinical oncologist. Results A hundred patients were assesed. Our identification rate was 98%. The pathology intraoperative false negative rate was 3%. Afer an average of 63,8 months follow up, no axillary recurrence was detected. 26,5% of positive sentinel nodes was found. The average of sentinel nodes found was 1,2. Conclusions snb by using only patent blue dye is a low cost reliable technique, and available for every institution interested in its development.

A prospective randomized trial comparing patent blue and methylene blue for the detection of the sentinel lymph node in breast cancer patients / Estudo randomizado prospectivo comparando o azul patente ao azul de metileno para a detecção do linfonodo sentinela em pacientes com câncer de mama

Summary Introduction: Methylene blue is more widely available and less expensive than patent blue, with an apparently lower risk of anaphylaxis. Objective: The two dyes were compared regarding detection of the sentinel lymph node (SLN). Method: A prospective, randomized trial involved 142 patients with invasive breast carcinoma. Sixty-nine (49.3%) assigned to patent blue (group A) and 71 (50.70%) to methylene blue (group B). Thirty-five patients (25.0%) were clinical stage III or IV; 55 (38.7%) had axillary lymph nodes affected; and 69 (49.3%) underwent neoadjuvant chemotherapy. Two patients were excluded because the dye type was not recorded. Results: Patients and tumor characteristics were similar in both groups. SLNs were identified in 47 women (68.1%) in group A and 43 (60.6%) in group B (p=0.35). SLNs were affected in 22 cases (51.2%) in group A and 21 (48.8%) in group B (p=0.62). The SLN was the only node affected in 12 cases (54.5%) in group A and six (33.3%) in group B (p=0.18). The time and degree of difficulty involved in identifying the SLN were similar in both groups. There were no complications or allergies. Conclusion: Methylene blue performed as well as patent blue in identifying the SLN in breast cancer patients.

Resumo Introdução: O azul de metileno é mais facilmente encontrado para comercialização e a um preço menor que o azul patente. Parece ainda haver menor risco de anafilaxia. Objetivo: Comparar a taxa de detecção do linfonodo sentinela com o azul patente e com o azul de metileno. Método: Foram incluídas, de forma randomizada e prospectiva, 142 pacientes com diagnóstico de carcinoma mamário invasor, que consentiram em participar livremente do estudo. Foram injetados 2 mL de azul patente (grupo A) em 69 (49,3%) mulheres e de azul de metileno (grupo B) em 71 (50,70%), em localização periareolar ou peritumoral, seguido de 5 minutos de massagem. Trinta e cinco (25,0%) apresentavam estadiamento clínico 3 ou 4, e 55 (38,7%) apresentavam a axila clinicamente comprometida. Sessenta e nove (49,3%) fizeram quimioterapia neoadjuvante. Duas pacientes não tinham anotação do corante utilizado e foram excluídas. Resultados: Os dois grupos apresentaram características das pacientes e dos tumores semelhantes. Foram detectados linfonodos sentinela em 47 (68,1%) mulheres no grupo A e em 43 (60,6%) no grupo B (p=0,35). Havia linfonodos sentinela comprometidos em 22 (51,2%) casos no grupo A e em 21 (48,8%) casos no grupo B (p=0,62). O linfonodo sentinela foi o único gânglio comprometido em 12 (54,5%) casos no grupo A e em seis (33,3%) casos no grupo B (p=0,18). O tempo e o grau de dificuldade para identificação do linfonodo sentinela foram semelhantes nos dois grupos. Não houve relato de complicações ou de alergia em nenhum dos grupos. Conclusão: A utilização do azul de metileno para a identificação do linfonodo sentinela em pacientes com câncer de mama apresenta resultados semelhantes aos do azul patente.

Evaluation of physiological parameters of dogs submitted to uterine lymphatic mapping using patent blue V dye for anaphylaxis detection / Avaliação de parâmetros fisiológicos de cães submetidos ao mapeamento linfático uterino usando o corante azul patente V para a detecção de anafilaxia

Lymphatic mapping has been performed in humans and dogs. Although several cases of anaphylaxis have been reported in humans, there are no such reports in dogs. The objective of this study was to identify the occurrence of adverse reactions to patent blue V dye in bitches undergoing uterine lymphatic mapping procedures using cardiovascular and hematological evaluations. The experiment was performed in 14 mongrel bitches without any reproductive disease, randomly assigned into two equal groups (PBV- uterine lynphatic mapping and OHE; Control - OHE only). The animals were submitted to pre- and postoperative hematological and serum biochemistry exams (7 days). The anesthetic protocol was: sedation (morphine and acepromazine), induction (propofol), maintenance (isoflurane), transoperative analgesia (fentanyl). Systolic blood pressure was monitored throughout the procedure and arterial blood gas analysis was performed immediate pre and postoperatively. For lymphatic mapping was injected patent blue V in the uterine wall, 10 minutes before OEH. Comparisons between the pre- and postoperative parameters within the same animal were performed using the Wilcoxon-Mann-Whitney test. To compare the values between control and PBV group was obtaining the difference between the pre and post of each group, subjected to the Mann-Whitney test (significance of 5%). Differences were observed (P<0.05) between the pre- and postoperative evaluations in the PBV (total protein and the albumin serum), in both groups (arterial partial pressure of oxygen) and in the Control (arterial oxygen saturation). There were no signs of adverse reactions to the patent blue V dye in the healthy bitches submitted to lymphatic uterine mapping.(AU)

O mapeamento linfático tem sido realizado em humanos e cães. Embora inúmeros casos de anafilaxia já tenham sido relatados em humanos, não existem tais relatos em cães. O objetivo deste estudo foi identificar a ocorrência de reações adversas ao corante azul patente V em cadelas submetidas ao mapeamento linfático uterino, usando avaliações cardiovasculares e hematológicas. O experimento foi realizado em 14 cadelas mestiças, divididas igualmente em dois grupos (PBV- mapeamento linfático uterino e OEH; Controle - apenas OEH). Os animais foram submetidos a exames hematológicos e bioquímicos séricos no pré e pós-operatório (7 dias). O protocolo anestésico foi: sedação (morfina e acepromazina), indução (propofol), manutenção (isoflurano), analgesia trans-operatória (fentanil). A pressão arterial sistólica foi monitorada durante todo o procedimento e hemogasometria arterial no pré e pós-operatório imediato. Para o mapeamento linfático foi injetado azul patente V na parede uterina, 10 minutos antes de realizar a OEH. Comparações entre os valores do pré e pós-operatório do mesmo animal foram realizados pelo teste Wilcoxon-Mann-Whitney. Para a comparação dos valores entre Controle e PBV foi realizado a obtenção da diferença entre os valores pré e pós de cada grupo, submetidas ao teste de Mann-Whitney (significância de 5%). Diferenças foram observadas (p<0,05) entre as avaliações pré e pós-operatórias no PBV (proteína total e albumina), ambos os grupos (pressão parcial de oxigênio arterial) e no Controle (saturação de oxigênio arterial). Não houve sinais de reação adversa ao corante azul patente V em cadelas saudáveis submetidas ao mapeamento linfático uterino.(AU)

Allergic reaction to patent blue dye in breast surgery - case report / Reação alérgica ao corante azul patente em cirurgia de mama - relato de caso

Abstract We present a case of allergic reaction to patent blue in a patient who underwent excision of sentinel lymph node associated with segmental breast resection. About 20 min after the dye injection, the patient developed hypotension (BP = 70 × 30 mmHg) associated with increased heart frequency. The patient was treated successfully with decreased inspired fraction of inhaled anesthetic and fluid replacement. At the end of the procedure, she presented with bluish urticarial-like plaques on the head, neck, upper limbs, and trunk; hydrocortisone was then used. The patient recovered uneventfully and was discharged from the PACU 2 h after the end of surgery without skin changes, and was discharged from hospital on the morning after surgery. The incidence of allergic reactions with the use of patent blue is far superior to the hypersensitivity reactions seen with anesthetic and adjuvant drugs. Therefore, the anesthesiologist must be aware of cardiovascular instability associated with skin changes during the use of patent blue, for early diagnosis and appropriate treatment of this hypersensitivity reaction to this dye.

Resumo Os autores apresentam um caso de reação alérgica ao azul patente em uma paciente submetida à exérese de linfonodo em sentinela associada a uma ressecção segmentar de mama. Paciente apresentou aproximadamente pós 20 minutos da injeção do corante hipotensão (PA = 70 × 30 mmHg) associada a aumento da frequência cardíaca. Foi tratada satisfatoriamente com diminuição da fração inspirada do anestésico inalatório e reposição volêmica. No fim do procedimento apresentava placas urticariformes azuladas em cabeça, pescoço, membros superiores e tronco e foi usada hidrocortisona. Evoluiu, sem intercorrências, na sala de recuperação pós-anestésica e teve alta duas horas após o término do procedimento cirúrgico sem a presença das alterações cutâneas. Alta hospitalar na manhã seguinte à cirurgia. A incidência de reações alérgicas com o emprego do azul patente é muito superior às reações de hipersensibilidade observadas com drogas anestésicas e adjuvantes. Portanto, o anestesiologista deve ficar atento à instabilidade cardiovascular associada a alterações cutâneas quando do uso do azul patente para o diagnóstico precoce e tratamento adequado dessa reação de hipersensibilidade com o emprego do corante.

Use of Fluorescence Imaging in Combination with Patent Blue Dye versus Patent Blue Dye Alone in Sentinel Lymph Node Biopsy in Breast Cancer / 한국유방암학회지

PURPOSE: Near-infrared fluorescence imaging with indocyanine green (ICG) has the potential to improve sentinel lymph node (SLN) mapping in breast cancer. In this clinical trial, we compared the potential value of ICG combined with blue dye with that of blue dye alone for detecting SLNs. METHODS: Patients undergoing SLN biopsy (SLNB) between November 2010 and November 2013 were included. Up to December 2011, SLNs were detected by using patent blue (PB) alone, and since January 2012, by using PB in combination with ICG. The patients were divided into the following two groups: group A (ICG-PB; n=96) and group B (PB; n=73), and SLN detection parameters were compared between the groups. All patients underwent level I and II axillary dissections after SLNB. RESULTS: In group A, the SLN detection rate was 96.9% (93/96), the accuracy of detection was 98.9% (92/93), and the false-negative rate (FNR) was 3.4% (1/29). In group B, the SLN detection rate was 84.9% (62/73), the accuracy of detection was 96.8% (60/62), and the FNR was 11.1% (2/18). The ICG-PB group showed significantly superior results compared to the PB group for SLN detection (p=0.005) and a greatly improved FNR. CONCLUSION: The combined fluorescence and blue dye-based tracer technique was superior to the use of blue dye alone for identifying SLNs, and for predicting axillary lymph node status in patients with breast cancer; in addition, the combined technique had reduced false-negative results.

Avaliação do linfonodo sentinela no tratamento do melanoma cutâneo: sistematização de técnica com linfocintigrafia e azul patente / Sentinel lymph node evaluation in the treatment of cutaneous melanoma: systematization of a technique using lymphoscintigraphy and patent blue

Melanoma incidence has been increasing worldwide. For localized melanoma, the status of the sentinel lymph node is the most important prognostic factor. This study aimed to evaluate the systematization of a technique to identify the sentinel lymph node anatomically by using lymphoscintigraphy and patent blue. Method: A total of 12 cases were studied between March 2009 and March 2012. The treatment protocol followed criteria established by the Brazilian Group of Melanoma. Patients were evaluated for age, sex, thickness of the primary lesion, localization of drainage site ofthe sentinellymph node,and presence ofmetastases. Results: The majority of patients were male and the mean age was 49.7 years. The types of thickness most frequently found were Breslow thickness 0- 1 mm and Clark levei lI. Ali of the dissected lymph nodes were stained with patent blue. Histological and immunohistochemical analysis of the lymph nodes were negative for metastases. Conclusions: The combined use of lymphoscintigraphy and patent blue allows for the precise localization of the sentinel lymph node, with a fast learning curve for surgeons, and low operative morbidity.

A incidência do melanoma vem aumentando em todo o mundo. O status do linfonodo sentinela é o fator prognóstico mais importante para o melanoma localizado. Este estudo teve como objetivo avaliar a sistematização da técnica de identificação anatômica do linfonodo sentinela com o uso de linfocintigrafia e azul patente. Método: Foram estudados 12 casos no período de março de 2009 a março de 2012. O protocolo de tratamento seguiu os critérios do Grupo Brasileiro de Melanoma. Os pacientes foram avaliados quanto a idade, sexo, espessura da lesão primária, localização dos sítios de drenagem do linfonodo sentinela, e presença de metástases. Resultados: A maioria dos pacientes era do sexo masculino e a média de idade era de 49,7 anos. Em relação à espessura, os tipos mais encontrados foram 0-1 mm de Breslow e nível II de Clark. Todos os linfonodos dissecados foram corados por azul patente. A análise histológica e imuno-histoquímica dos linfonodos foi negativa para metástases. Conclusões: O uso combinado de linfocintigrafia e azul patente permite a localização precisa do linfonodo sentinela, com rápida curva de aprendizado e baixa morbidade operatória.

Sentinel Lymph Node Biopsy in Thyroid Cancer / 대한내분비외과학회지

The role of sentinel lymph node biopsy (SLNB) in thyroid cancer is still debatable. The primary goals of SLNB are to facilitate accurate identification of lymph node (LN) metastasis without formal lymphadenoectomy to reduce morbidity associated with LN dissection. SLN in thyroid cancer can be identified using either vital blue dye, radioactive tracer, or a combination of these methods. Here, 26 selected studies of SLNB for thyroid cancer are analyzed and reviewed. For the vital blue dye, radioisotope, and combined methods, the overall sentinel node identification rates (SNIRs) were 84.0, 98.4 and 97.9%, the overall sensitivities were 86.1, 66.7 and 90.7% and the overall false negative rates were 11.4, 16.3, and 11.4%, respectively. The combined blue dye and radioisotope method had superior SNIRs, sensitivities, and false negative rates than the single vital blue dye technique. New tracers such as carbon nanoparticles can be used in SLNB. Lateral compartment SLNB studies employing a radioisotope technique can be useful for evaluation of the occult lateral neck LN status in patients with papillary thyroid cancer (PTC), especially in cases of central neck node metastasis. Lateral SLNB may also provide useful information for medullary thyroid cancer (MTC) treatment.

Patent-blue-liposomes for lymphography and the detection of their biological property / 国际外科学杂志

Objective To prepare patent-blue-lipesomes(PB-LPS),a lymph-mapping developer.Methods PB was encapsulated in the liposomes using the passive loading method.The female Wistar rats were injected subcutaneously with the PB-LPS,PB,blank liposomes or isotonic rmtrium chloride at the heel solos,to study the stained situation of the lymph nodes and chemical analysis oftheir ALT,AST,BUN,Cr.Results The lymph nodes were obviously blue staining after injected PB-LPS or PB,the blue smimng ratios were 40%,20%(P<0.05),and the effect of PB-LPS on tracing of lymphy nodes was better than PB.No significant difference was found in ALT,AST,BUN and Cr.Conclusion The PB-LPS can be successfully prefabricated with such advantage as avirulence and high entrapment efficiency by passive loading method.