Modeling Mediated Crossover Acute and Subacute Damage to the Pulmonary System During Systemic (Subcutaneous) Administration of Bleomycin in Mice to Test the Potential Therapeutic Effect of Polyphenols / Modelado del Daño Agudo y Subagudo Cruzado Mediado al Sistema Pulmonar Durante la Infección Sistémica (Subcutánea) de Administración de Bleomicina a Ratones para Probar el Posible Efecto Terapéutico de los Polifenoles

SUMMARY: The potential anti-inflammatory and antifibrotic activity of polyphenolic extracts of blueberry and grape was evaluated in a mouse model of lung damage induced by subcutaneous administration of bleomycin. The results of testing the polyphenolic extracts on two different systemic administration variants of bleomycin (intraperitoneal and subcutaneous) were compared. It was found that regardless of the method of bleomycin administration, indirect cross-acute and subacute damage to the pulmonary system was observed. Both patterns exhibited the same prevalence and severity. The administration of polyphenolic extracts of blueberry and grape to mice resulted in a significant decrease in theseverity of acute and subacute patterns of lung damage, suggesting their protective properties for the microcirculatory bed and a pronounced anti-inflammatory effect.

La potencial actividad antiinflamatoria y antifibrótica de los extractos polifenólicos de arándano y uva se evaluó en un modelo de daño pulmonar en ratón inducido por la administración subcutánea de bleomicina. Se compararon los resultados de las pruebas de los extractos polifenólicos en dos variantes diferentes de administración sistémica de bleomicina (intraperitoneal y subcutánea). Se encontró que, independientemente del método de administración de bleomicina, se observaba daño indirecto cruzado, agudo y subagudo al sistema pulmonar. Ambos patrones exhibieron la misma prevalencia y gravedad. La administración de extractos polifenólicos de arándano y uva a ratones dio como resultado una disminución significativa en la gravedad de los patrones agudos y subagudos de daño pulmonar, lo que sugiere sus propiedades protectoras del lecho micro- circulatorio y un efecto antiinflamatorio pronunciado.

Toxicidad pulmonar secundaria a bleomicina. Reporte de un caso / Pulmonary Toxicity Secondary to Bleomycin. A Case Report

La toxicidad pulmonar por antineoplásicos es muy variable dependiente del grupo far-macológico; la bleomicina es uno de los medicamentos en los que se ha reportado este evento. Este citostático puede lesionar el endotelio pulmonar y el epitelio alveolar para llevar a un proceso inflamatorio y fibrótico del intersticio con repercusiones potencial-mente fatales.A continuación, se presenta un caso de enfermedad intersticial tipo neumonía organi-zada asociada a bleomicina en un paciente de 68 años con diagnóstico linfoma Hodg-kin clásico de tipo esclerosis nodular, con estudio imagenológico normal previo al tratamiento

Antineoplastic pulmonary toxicity is highly variable depending on the pharmacological group; bleomycin is one of the drugs in which this event has been reported. This cyto-static can injure the pulmonary endothelium and the alveolar epithelium to lead to an in-flammatory and fibrotic process of the interstitium with potentially fatal repercussions. The following is a case of interstitial disease type organizing pneumonia associated with bleomycin in a 68-year-old patient diagnosed with classical Hodgkin lymphoma of nodular sclerosis type, with imaging study prior to normal treatment

Histopathological changes of lymphatic malformation after bleomycin injection / Alterações histopatológicas da malformação linfática após injeção de bleomicina

ABSTRACT Lymphatic malformation is a rare orbital tumor that used to be treated surgically, with high complication rates, or recently with intralesional bleomycin injection. We report for the first time the histopathological changes of eyelid lymphatic malformation after water-soluble intralesional bleomycin injection in a 20-year-old woman who had unsuccessful orbital surgical debulking during childhood. The changes confirmed the assumption of fibrosis induced by intralesional bleomycin injection. The minimal bleeding during surgical intervention made it much easier than the usual lymphatic malformation bloody procedure, without postoperative recurrences and with favorable aesthetic outcomes.

RESUMO A malformação linfática é um tumor orbital raro que costumava ser tratado cirurgicamente, com alta taxa de complicações. Mais recentemente, passou a ser tratado com uma injeção intralesional de bleomicina. Este é o primeiro relato sobre as alterações histopatológucas da malformação linfática palpebral após uma injeção intralesional de bleomicina hidrossolúvel em uma mulher de 20 anos de idade que sofreu uma cirurgia malsucedida de debulking orbital durante a infância, confirmando a suposição de fibrose induzida por injeções intralesionais de bleomicina. O sangramento mínimo durante a intervenção cirúrgica tornou esta muito mais fácil que o procedimento sangrento habitual, sem recidivas pós-operatórias e com desfechos estéticos favoráveis.

Potential antifibrotic effect of blueberry and grape polyphenol extracts in acute and subacute bleomycin-induced lung tissue injury models in mice / Potencial efecto antifibrótico de los extractos de polifenoles de arándano y uva en modelos de lesión tisular pulmonar aguda y subaguda inducida por bleomicina en ratones

SUMMARY: An experimental morphological and morphometric study of the antifibrotic function of blueberry and grape extracts was carried out on a model of lung injury in mice induced by intraperitoneal administration of bleomycin. During intraperitoneal administration of bleomycin to mice, acute and subacute damage to the pulmonary system was noted. Both patterns had the same prevalence and severity. The administration of polyphenolic extracts of blueberry and grape to mice showed a significant reduction in the severity of the acute and subacute pattern of lung injury. Blueberry and grape extracts reduce the acute phase of damage to the microvasculature, enhance phagocytic function, have an anti-inflammatory effect, reducing the degree of lymphohistiocytic infiltration and locoregional foci of residual inflammatory effects.

Se realizó un estudio experimental morfológico y morfométrico de la función antifibrótica de extractos de arándano y uva en un modelo de lesión pulmonar en ratones inducida por la administración intraperitoneal de bleomicina. Durante la administración intraperitoneal de bleomicina a ratones, se observaron daños agudos y subagudos en el sistema pulmonar. Ambos patrones tuvieron la misma prevalencia y severidad. La administración de extractos polifenólicos de arándano y uva a ratones mostró una reducción significativa en la severidad del patrón agudo y subagudo de lesión pulmonar. Los extractos de arándano y uva reducen la fase aguda del daño a la microvasculatura, mejoran la función fagocítica, tienen un efecto antiinflamatorio, reducen el grado de infiltración linfohistiocítica y los focos locorregionales de efectos inflamatorios residuales.

Use of sirolimus and sclerotherapy for lymphatic malformations in a developing country: a case series / Uso de sirolimus y escleroterapia para malformaciones linfáticas en un país en vías de desarrollo: una serie de casos

Las malformaciones linfáticas y su manejo no han sido bien descritas en República Dominicana. Es por ello, que el objetivo de este artículo es la presentación de tres casos, con diferentes patrones y necesidades de tratamiento, de modo que sirva como referencia para trabajadores de la salud en países en vías de desarrollo.

Lymphatic malformations and its management are not well described in the Dominican Republic. That is why this article's objective is to present 3 cases, with different patterns and treatment needs, so it will work as a reference for healthcare workers in developing countries.

Evaluación del tratamiento de linfangiomas con bleomicina en población pediátrica de 0 a 18 años / Evaluation of the treatment of lymphangiomas with bleomycin in a pediatric population aged 0 to 18 years

INTRODUCCIÓN. Los linfangiomas son una malformación infrecuente a escala mundial y constituye una preocupación para los padres del infante; está asociado a problemas estéticos y a posibles efectos deletéreos debido a la obstrucción o compresión de órganos vitales. Se ha descrito a la escleroterapia como la mejor opción de tratamiento. OBJETIVO. Determinar la eficiencia del tratamiento con bleomicina en linfangiomas en la población pediátrica de 0 a 18 años. MATERIALES Y MÉTODOS. Estudio transversal analítico retrospectivo. Población y muestra conocida de 20 datos de Historias Clínicas electrónicas de pacientes diagnosticados con linfangiomas y tratados con bleomicina en el Hospital de Especialidades Carlos Andrade Marín, desde enero 2015 a enero 2018. Criterios de inclusión: pacientes de 0 a 18 años de edad con diagnóstico de linfangioma mediante ecografía y angiotomografía computarizada. Criterios de exclusión: pacientes mayores de 18 años de edad o sospecha diagnóstica de linfangioma sin estudios de imagen, y/o que no acudieron a la cita de control, pacientes diagnosticados de linfangioma que no recibieron bleomicina para su tratamiento, niños con otras malformaciones vasculares. El análisis de datos se realizó en el programa estadístico International Business Machines Statistical Package for the Social Sciences. RESULTADOS. La mediana de edad en mujeres fue de 6,25 años y 3,8 años en hombres. 10 pacientes fueron hombres. El promedio de seguimiento fue de 26,86 +/- 16,78 meses. El tamaño promedio de los linfangiomas fue de 5,77 +/- 3,73 cm. La localización más frecuente fue cervical con un 52,38%. La mayoría fueron macronodulares con un 85,71%. La respuesta fue buena o excelente en el 81,00% de los casos con la primera infiltración y subió al 95,00% con la segunda y tercera, según requerimiento. CONCLUSIÓN. El tratamiento de los linfangiomas con bleomicina fue muy efectivo en la población estudiada.

INTRODUCTION. Lymphatic malformation is a rare malformation worldwide and is a concern for the parents of the infant; it is associated with aesthetic problems and possible deleterious effects due to obstruction or compression of vital organs. Sclerotherapy has been described as the best treatment option. OBJECTIVE. To determine the efficiency of bleomycin treatment in lymphangiomas in the pediatric population aged 0 to 18 years. MATERIALS AND METHODS. Retrospective analytical cross-sectional study. Population and known sample of 20 data from Electronic Medical Records of patients diagnosed with lymphangiomas and treated with bleomycin at the Carlos Andrade Marín Specialties Hospital, from January 2015 to January 2018. Inclusion criteria: patients aged 0 to 18 years with diagnosis of lymphangioma by ultrasound and computed angiotomography. Exclusion criteria: patients older than 18 years of age or diagnostic suspicion of lymphangioma without imaging studies, and/or who did not attend the control appointment, patients diagnosed with lymphangioma who did not receive bleomycin for treatment, children with other vascular malformations. Data analysis was performed in the statistical program International Business Machines Statistical Package for the Social Sciences. RESULTS. The median age in women was 6,25 years and 3,8 years in men. Ten patients were men. The average follow-up was 26,86 +/- 16,78 months. The average size of the lymphatic malformations was 5,77 +/- 3,73 cm. The most frequent location was cervical with 52,38%. Most were macronodular with 85,71%. The response was good or excellent in 81,00% of cases with the first infiltration and rose to 95,00% with the second and third, as required. CONCLUSION. The treatment of lymphangiomas with bleomycin was very effective in the population studied.

Tratamiento de verruga plantar con bleomicina: presentación de un caso / Plantar wart treatment with bleomycin: presentation of a case

RESUMEN Las verrugas vulgares son proliferaciones benignas producidas por el HPV (virus del papiloma humano) que afectan al 7-10 % de la población en general. Cuando se localizan en la planta del pie generan intenso dolor, interfiriendo en la vida diaria del paciente, y su erradicación suele ser dificultosa. Existen múltiples tratamientos; ninguno es efectivo en su totalidad. La bleomicina es una opción terapéutica en aquellos casos rebeldes y recidivantes.

SUMMARY Common warts are benign proliferations caused by HPV (papilloma virus).When these are in foot generate an intense pain that interferes with daily life of the patient and are difficult to eradicate. There are multiple treatments, none is completely effective. Bleomycin is a therapeutic option for those rebels and recurrent cases.

Tratamiento esclerosante del linfangioma facial. Presentación de un caso / Sclerotherapic treatment of facial lymphangioma

This article details the treatment of lymphangioma of the face with intralesional bleomycin: with a case report and literature review. Surgical treatment of lymphangioma of the face is a difficult task to achieve, due to close vicinity of the lesion to the facial nerve and possibility of scar tissue formation. Inefficient surgical removals generally will give rise to high recurrence rates because of infiltrative and diffuse extension of the lesion. However, complete cure has been described by non-surgical methods with intralesional bleomycin injection under ultrasonographic guidance. Lymphangioma is a rare congenital malformation of the lymphatic system, frequently seen in the head and neck. Percutaneous sclerotherapy of lymphangioma involves the injection of sclerosing substances into the lymphangioma. This study aims to evaluate the effectiveness of intralesional bleomycin sclerotherapy in the treatment of lymphangioma, and to determine the incidence of complications in the treatment. Intralesional bleomycin therapy was very effective in the treatment of lymphangioma. Bleomycin administered as intralesional injection was found to be safe as there was no lesions complicating or side effects observed in the study.

A New Modality for the Diagnosis of Bleomycin-induced Toxicity: Ultrasonography.

OBJECTIVE: To evaluate the role of ultrasonography (USG) in the diagnosis of bleomycin-induced pulmonary toxicity (BT). MATERIAL AND METHODS: The study included patients with suspected BT during treatment with bleomycin due to various oncologic diseases between June 2015 and May 2017. The patients initially underwent clinical and high-resolution computed tomography (HRCT) examinations and pulmonary function tests (PFT)-diffusing capacity of the lung for carbon monoxide (DLCO), followed by registration of USG findings-number of comet tail artifact (CTA) images by a different pulmonologist. We compared the findings from USG, HRCT, and PFT-DLCO tests between BT and non-BT groups. With the diagnosis based on clinical-radiologic and PFT-DLCO assessments taken as the gold standard, we determined the sensitivity and specificity of the USG outcomes for diagnosis of BT. RESULTS: The study included a total of 30 patients. Nine patients were diagnosed as having BT according to their clinical and radiologic findings and PFT-DLCO measurements. The mean number of CTA images was 68.7±22 in patients with BT vs 28.2±9.3 in those without BT (P<.001). The difference in CTA images between the patients with and without ground glass density was statistically significant (28.3±9.5 and 64.6±24.5, respectively, P<.001). In patients with BT, there was a negative correlation between the number of CTAs and DLCO% and FVC% values (P=.004; P=.016). USG had a sensitivity of 100%, and a specificity of 95% diagnosing BT in selected patients. CONCLUSION: In bleomycin-induced toxicity, USG findings are correlated with HRCT and PFT-DLCO findings, with a remarkably increased number of CTAs in BT. Thoracic USG examination is a diagnostic tool with a high sensitivity and specificity for diagnosing BT.

Dermatitis flagelada inducida por bleomicina: a propósito de un caso / Bleomycin-induced flagellated dermatitis: a case report

INTRODUCCIÓN: La Dermatitis Flagelada es una patología infrecuente, con lesiones cutáneas características, que se desarrolla por el uso de Bleomicina. Clínicamente se presenta como maculas eritematosas o hiperpigmentadas de disposición lineal con patrón flagelar, en tronco y/o extremidades superiores. Presenta evolución autolimitada por lo que su tratamiento varía desde conducta expectante hasta uso de corticoides tópicos u orales. OBJETIVO: Presentación de un caso clínico de Dermatitis flagelada secundaria a Bleomicina en paciente pediátrico con antecedentes de neoplasia de sistema nervioso central. CASO CLÍNICO: Escolar de 8 años, sexo femenino, con antecedentes de tumor prima rio de células germinales mixto intracraneal (selar y supraselar) y panhipopituitarismo secundario. Recibe tratamiento quimioterapéutico según protocolo PEB, con uso de Bleomicina EV por 3 días. A los 2 días posteriores, inicia prurito intermitente, asociado a máculas eritematosas y pigmentadas de distribución lineal, siguiendo patrón flagelado, con aislados signos de excoriación, en región abdominal y dorso alto. Se indica tratamiento tópico con corticoides de moderada potencia por 10 días, con respuesta clínica satisfactoria. CONCLUSIONES: Se debe tener una alta sospecha diagnóstica en pacientes pediátricos con historia de administración previa del fármaco y aparición de lesiones cutáneas características, lo que permitirá una conducta adecuada respecto a su manejo y a la continuidad de la quimioterapia.

INTRODUCTION: Flagellated dermatitis is an infrequent pathology, with characteristic skin lesions, which is developed due to the use of bleomycin. Clinically it occurs as erythematous or hyperpigmented maculae of linear disposition with flagellar pattern, in trunk and/or upper extremities. It presents self-limited evolution, therefore, its treatment varies from expectant management to the use of topical or oral corticosteroids. OBJECTIVE: Presentation of a clinical case of flagellated dermatitis secondary to bleomycin in a pediatric patient with history of central nervous system neoplasia. CLINICAL CASE: 8 years, schoolchild, female, with a history of primary intracranial mixed germ cell tumor (sellar and suprasellar) and secondary panhypopituitarism. She receives chemotherapeutic treatment according to the PEB protocol, with use of IV bleomycin during three days. After two days, intermittent pruritus begins, associated with erythematous and pigmented maculae of linear distribution, followed by a flagellated pattern, with isolated signs of excoriation, in the abdominal region and upper back. Topical treatment with mild potency corticosteroids is indicated for ten days, with a satisfactory clinical response. CONCLUSIONS: There should be a high diagnostic suspi cion in pediatric patients with a history of prior administration of the drug and the appearance of characteristic skin lesions, which will allow adequate behavior regarding its management and the continuity of chemotherapy.

Chemotherapy-induced response of liver hemangiomas in a patient with a germ cell tumor: a case report. / Respuesta de los hemangiomas hepáticos inducida por la quimioterapia adyuvante empleada en el tratamiento de los tumores germinales.

Liver hemangiomas are the most common benign primary tumors of the liver. Due to their high prevalence, incidental finding of hemangiomas during radiological workup of oncologic patients is not uncommon. We present the case of a patient diagnosed of an ovarian immature teratoma and hepatic lesions with typical radiological appearance of hemangiomas that decreased in size during adjuvant chemotherapy with BEP regimen (cisplatin, etoposide and bleomycin). Chemotherapy-induced shrinkage of hepatic hemangiomas can mimic the response of liver metastases to chemotherapy and may induce erroneous interpretations. The purpose of this report is to describe a chemotherapy-induced response of liver hemangiomas, especially when BEP combination is used. To date this observation has been barely reported in the literature and, to our knowledge, this is the first documented case of chemotherapy-induced response of liver hemangiomas in a patient diagnosed of an ovarian immature teratoma.

Tratamento de verrugas virais com bleomicina intralesional / Treatment of viral warts with intralesional bleomycin

A verruga viral representa uma das dermatoses mais prevalentes. O quadro clínico varia de lesão única com cura espontânea até múltiplas lesões recalcitrantes. O sulfato de bleomicina é uma droga de ação citotóxica, aprovada para o tratamento quimioterápico de algumas malignidades. Há mais de 45 anos existem trabalhos demonstrando sua utilidade na dermatologia, em especial na terapia intralesional para verrugas virais, que constitui excelente opção para as lesões em topografias de difícil manejo e para os casos não responsivos a outras abordagens.

Viral warts are one of the most prevalent dermatoses. The clinical picture varies from a single lesion with spontaneous cure to multiple recalcitrant lesions. Bleomycin sulfate is a cytotoxic action drug approved for the chemotherapeutic treatment of some malignancies. There are a number of studies that have been carried out during the last 45 years demonstrating its usefulness in dermatology, especially in intralesional therapy for viral warts, meaning it is an excellent option for lesions in difficult-to-handle topographies and for cases that do not respond to other approaches.

Electrochemotherapy as palliative treatment in patients with thyroid papillary carcinoma / Eletroquimioterapia como tratamento paliativo em pacientes com carcinoma papilar da tireoide

ABSTRACT INTRODUCTION: Local progression of papillary thyroid carcinoma (PTC) after failure of standard therapies may cause pain, ulceration, and bleeding. As patients are fully aware of the tumor growth, they might suffer high grade anxiety. Electrochemotherapy (ECT) is a new local palliative treatment for skin metastases of malignant melanoma or other tumors, including squamous head e neck cancer patients. OBJECTIVE: To evaluate the impact of ECT in patients with local progression of PTC. METHODS: Four patients with local progression of PTC were treated with ECT based on Bleomycin, and evaluated according to tumor response, local pain and side effects. RESULTS: In all cases, some grade of tumor response was observed, lasting 6, 7, 12 and 8 months, respectively. Also, reduction of local pain and anxiety was registered in all patients. Tumor infiltrated skin necrosis was the only collateral effect of the treatment. ECT induced a tumor response in all PTC patients with improvement of symptoms. CONCLUSIONS: ECT may be an option for local palliative treatment in PTC patients with local tumor progression.

Resumo Introdução: A progressão local do carcinoma papilífero de tireoide (CPT) após a falha da terapia de rotina pode causar dor, ulceração e sangramento. Considerando que os pacientes estão perfeitamente cientes do crescimento tumoral, podem apresentar um alto grau de ansiedade. A eletroquimioterapia (EQT) é um novo tratamento paliativo para metástases de pele de melanoma maligno ou de outros tumores, inclusive em pacientes com carcinoma escamoso de cabeça e pescoço. Objetivo: Avaliar o impacto da EQT em pacientes com progressão local de CPT. Método: Quatro pacientes com progressão local de CPT foram tratados com EQT com base em bleomicina, e avaliados em relação ao grau de resposta tumoral, dor local, efeitos colaterais. Resultados: Em todos os casos, foi observado algum grau de resposta tumoral, que perdurou por 6, 7, 12 e 8 meses, respectivamente. Da mesma forma, foi registrada diminuição da dor local e da ansiedade em todos os pacientes. Necrose cutânea na infiltração tumoral foi o único efeito colateral do tratamento. EQT induziu resposta tumoral em todos os pacientes com CPT, com melhora dos sintomas. Conclusões: EQT pode ser uma opção para o tratamento paliativo tópico em pacientes com CPT com progressão tumoral local.

Construcción de un modelo animal de fibrosis pulmonar inducido por Bleomicina / Making an animal model of Bleomycin-induced pulmonary fibrosis

La fibrosis pulmonar es una enfermedad crónica, progresiva y letal, cuya etiología se desconoce. El modelo de fibrosis pulmonar inducida por Bleomicina en ratas es útil para ilustrar la patobiología in vivo de la enfermedad, así como para identificar nuevos blancos farmacológicos y estimar la eficiencia de nuevas moléculas o procedimientos Objetivo: El objetivo de este trabajo fue construir un modelo animal de fibrosis pulmonar secundaria a Bleomicina, en ratas Wistar, como herramienta que pueda servir de base para futuros diseños experimentales. Materiales y métodos: Se trabajó con dos grupos de ratas Wistar para la administración del medicamento por vía intratraqueal. El grupo experimental recibió una dosis única (2.0 U/Kg) de Bleomicina, mientras que el grupo control recibió un volumen equivalente de solución salina. A los 14 o 28 días se realizó un lavado broncoalveolar con recuento total y diferencial celular y análisis histopatológico pulmonar. Resultados: La histología de una parte del grupo experimental tratado con Bleomicina y sacrificado a los 14 días reveló daño pulmonar caracterizado por inflamación aguda, hemorragia intraalveolar y proliferación fibroblástica intersticial incipiente; en el resto del grupo experimental la histología a 28 días reveló además alteración de la arquitectura pulmonar debida a fibrosis y aumento en el número de macrófagos intraalveolares e inflamación linfocitaria. Conclusiones: Se implementó satisfactoriamente un modelo de fibrosis pulmonar inducido farmacológicamente por Bleomicina en ratas Wistar.

Pulmonary fibrosis is a chronic, progressive and fatal disease, whose etiology is unknown. The model of Bleomycininduced pulmonary fibrosis in rats is useful to illustrate the pathobiology of the disease in vivo as well as to identify new drug targets and to estimate the efficacy of new promising molecules or procedures. Objective: The aim of this work was to make an animal model of pulmonary fibrosis secondary to bleomycin, in Wistar rats, as a tool that can serve as a basis for future experimental designs. Materials and methods: We worked with two groups of Wistar rats which were anesthetized and intubated for intratracheally drug administration. The experimental group received a single dose (2.0 U / kg) of Bleomycin, while the control group received an equivalent volume of saline. At 14 or 28 days after treatment, a bronchoalveolar lavage with total and differential cellular count were performed. Additionally, the lungs were dissected for histopathogical analysis. Results: In the experimental group treated with Bleomycin and sacrificed at 14 days, histology revealed lung damage characterized by acute inflammation, intra-alveolar hemorrhage and fibroblast proliferation; in sacrificed animals at 28 days, alteration of lung architecture due to fibrosis evidenced by trichrome stain, increase in the alveolar macrophages number and lymphocytic chronic inflammation were observed. Conclusions: In this study, a model of pharmacologically induced pulmonary fibrosis by Bleomycin has been successfully implemented.

Electrochemotherapy as palliative treatment in patients with thyroid papillary carcinoma.

INTRODUCTION: Local progression of papillary thyroid carcinoma (PTC) after failure of standard therapies may cause pain, ulceration, and bleeding. As patients are fully aware of the tumor growth, they might suffer high grade anxiety. Electrochemotherapy (ECT) is a new local palliative treatment for skin metastases of malignant melanoma or other tumors, including squamous head e neck cancer patients. OBJECTIVE: To evaluate the impact of ECT in patients with local progression of PTC. METHODS: Four patients with local progression of PTC were treated with ECT based on Bleomycin, and evaluated according to tumor response, local pain and side effects. RESULTS: In all cases, some grade of tumor response was observed, lasting 6, 7, 12 and 8 months, respectively. Also, reduction of local pain and anxiety was registered in all patients. Tumor infiltrated skin necrosis was the only collateral effect of the treatment. ECT induced a tumor response in all PTC patients with improvement of symptoms. CONCLUSIONS: ECT may be an option for local palliative treatment in PTC patients with local tumor progression.

Uso de bleomicina em queloides e cicatrizes hipertróficas: revisão da literatura / Use of bleomycin in keloids and hypertrophic scars: a literature review

Queloides e cicatrizes hipertróficas resultam da cicatrização anormal de feridas, com crescimento excessivo de tecido fibroso. Apesar da elevada ocorrência na população, das altas taxas de recidivas e do importante comprometimento psicossocial, o tratamento continua sendo um desafio para os dermatologistas. O objetivo deste trabalho foi revisar publicações sobre aspectos clínicos, etiológicos e terapêuticos de queloides e cicatrizes hipertróficas, com ênfase em sua terapêutica com bleomicina, demonstrando seu uso eficaz e seguro. A busca foi realizada nas bases de dados Scopus e MEDLINE, utilizando-se, para o período de 1995 a 2016, as palavras-chave: queloide/keloid; cicatriz hipertrófica/cicatrix, hypertrophic; e bleomicina/bleomycin.

Keloids and hypertrophic scars result from abnormal wound healing with excessive growth of fibrous tissue. Despite the high incidence in the population, the high rates of relapse and the significant psychosocial impairment, treatment remains a challenge for dermatologists. The objective of this study was to review literature on clinical, etiological and therapeutical aspects of keloids and hypertrophic scars, emphasizing its therapy with bleomycin, demonstrating its effective and safe use. The search was conducted in Scopus and MEDLINE databases, for the period from 1995 to 2016, using the key words: queloide/keloid; cicatriz hipertrófica/cicatrix, hypertrophic; and bleomicina/bleomycin

Electrochemotherapy in the treatment of melanoma skin metastases: a report on 31 cases.

INTRODUCTION AND OBJECTIVES: Electrochemotherapy is indicated for the treatment of unresectable cutaneous and subcutaneous tumors. The technique involves the synergistic use of electroporation of cell membranes to increase the cytotoxicity of anticancer drugs delivered to the tumor cells. The aim of this study was to analyze the clinical effectiveness and safety of electrochemotherapy in the treatment of unresectable locoregional recurrent or metastatic melanomas. MATERIAL AND METHODS: We studied 31 patients treated between January 2007 and December 2012. The European Standard Operating Procedures of Electrochemotherapy (ESOPE) were applied in all cases. Treatment response was analyzed as overall patient response (mean response based on results for all lesions treated in a given patient). RESULTS: Response was classified as partial in 49% of patients and complete in 23%. At 1 year, the level of response achieved had been maintained in 17 patients. Disease progression was observed in 28% of the series. Immediate local complications (pain, swelling, erythema) were mild and resolved within 48hours in most cases. Eight patients developed subsequent local complications, such as ulcers and secondary infections associated with necrosis of the lesions. These complications were brought under control with topical treatments. CONCLUSIONS: Electrochemotherapy is a very effective, safe, and efficient treatment for advanced locoregional disease in patients with unresectable melanoma lesions.

Associação de técnicas para manejo efetivo dos queloides / Association of techniques for effective management of keloids

Queloides constituem uma proliferação anormal de fibroblastos após injúria da pele que ultrapassam bordas da ferida, causando aparência inestética e grande prejuízo à qualidade de vida destes pacientes. Atualmente não há uma terapêutica combinada eficaz para redução das massas queloidianas, inibindo sua recidiva. Neste trabalho apresentamos uma série de casos tratados com uma associação de técnicas (excisão cirúrgica pela técnica de shaving, injeção intralesional de corticosteroide e/ou bleomicina, aplicação de placa de gel de silicone, luz intensa pulsada, laser de CO2 fracionado, laser Nd:YAG, laser Erbium:Glass e LED vermelho e infravermelho), atuando na fisiopatologia do queloide, que demonstraram resultados satisfatórios e duradouros...

Effect of early treatment with transcutaneous electrical diaphragmatic stimulation (TEDS) on pulmonary inflammation induced by bleomycin / Efeito do tratamento precoce com estimulacao diafragmatica eletrica transcutanea (EDET) na inflamacao pulmonar provocada pela Bleomicina

BACKGROUND : Bleomycin (B) is an antineoplastic drug that has pulmonary fibrosis as a side effect. There are few experimental studies about the effects of physical therapy treatment in this case. OBJECTIVE: The objective was to study rat lungs treated with B and precocious intervention by transcutaneous electrical diaphragmatic stimulation (TEDS). METHOD : Wistar rats were divided into 4 groups (n=5): a control group (C); a stimulated group (TEDS); a group treated with a single dose of B (intratracheally, 2.5 mg/kg) (B); and a group treated with B and electric stimulation (B + TEDS). After the B instillation, the electrical stimulation was applied for 7 days, for a duration of 20 minutes. Lung fragments were histologically processed with hematoxylin and eosin (HE) and 8-isoprostane-PGF2α (8-iso-PGF2α). The density of the alveolar area was determined by planimetry, the inflammatory profile was defined by the number of cells, and the level of oxidative stress in the pulmonary tissue was evaluated by 8-iso-PGF2α. For statistical analysis of the data, the Shapiro-Wilk test was used, followed by a one-way ANOVA with the post-hoc Bonferroni test (p≤0.05). RESULTS : The B group exhibited a significant reduction in the area density, and the acute treatment with B + TEDS prevented this reduction. There were increased numbers of fibroblasts, leukocytes, and macrophages in the B group, as well as increased lipid peroxidation, which was observed only in this group. CONCLUSION : B promoted a reduction in the alveolar density area, thereby inducing the inflammatory process and increasing the production of free radicals. These effects were minimized by the application of TEDS at the initial treatment stage. .

CONTEXTUALIZAÇÃO: A bleomicina é um antineoplásico que tem como efeito colateral fibrose pulmonar. Há poucos estudos experimentais dos efeitos do tratamento fisioterapêutico nesse quadro. OBJETIVO: Estudar pulmões de ratos tratados com bleomicina e intervenção precoce com estimulação diafragmática elétrica transcutânea (EDET). MÉTODO: Ratos Wistar foram divididos em quatro grupos (n=5): controle; estimulado; tratado com dose única de bleomicina 2,5 mg/Kg, via intratraqueal, e tratado com bleomicina e estimulação elétrica 24 horas após a instilação da bleomicina, durante sete dias, por 20 minutos. Fragmentos de pulmão foram tratados para coloração em hematoxilina e eosina (HE) e 8-isoprostane-PGF2α (8-iso-PGF2 α). A densidade de área alveolar foi obtida por planimetria; o perfil inflamatório, por quantificação do número de células, e os níveis de estresse oxidativo no tecido pulmonar, pela análise do marcador 8-iso-PGF2 α. Utilizou-se teste de normalidade Shapiro-Wilk seguido de ANOVA one-way+Bonferroni (p<0,05). RESULTADOS: O tratamento com bleomicina promoveu redução significativa na densidade de área da parte aérea, e o tratamento agudo de bleomicina associado com a EDET evitou essa redução. Houve aumento no número de fibroblastos, leucócitos e macrófagos e aumento da peroxidação lipídica no grupo tratado com bleomicina, fato não encontrado no grupo bleomicina+EDET. CONCLUSÃO: A bleomicina promoveu diminuição na densidade de área alveolar por induzir processo inflamatório e aumento na produção de radicais livres, efeitos esses minimizados com a intervenção da EDET na fase precoce do tratamento. .