Eletroquimioterapia como tratamento de carcinoma espinocelular em felino: relato de caso / Electrochemotherapy as treatment of squamous cell carcinoma in feline: case report / Electroquimioterapia como tratamiento del carcinoma de células escamosas en felino: relato de caso

O carcinoma de células escamosas (CCE) é uma neoplasia maligna resultante da diferenciação de ceratinócitos, que acomete principalmente animais de pelagem clara e pouco pigmentados, decorrente da exposição à radiação ultravioleta. Apresentam evolução lenta e baixo caráter metastático, porém, em alguns mais avançados pode ocorrer acometimento metastático de órgãos adjacentes. Os tratamentos utilizados no CCE incluem cirurgia, radioterapia, quimioterapia, crioterapia e eletroquimioterapia (EQT). A eletroquimioterapia se mostra bastante eficaz no tratamento desse tumor, dentre outros e comumente não apresenta efeito colateral. O presente trabalho tem como objetivo relatar o caso de um felino atendido na Clínica Veterinária Bichos S.A. no município de Foz do Iguaçu, diagnosticado com Carcinoma de Células Escamosas e portador do vírus da imunodefiência felina. O tratamento adotado para a neoplasia foi a eletroquimioterapia, resultando em remissão parcial das lesões, após vinte dias da EQT. Com objetivo de investigar possível acometimento ósseo, foi realizada radiografia de face, onde a mesma apresentou área de lise óssea em arco zigomático e maxila esquerda, indicativo de infiltração neoplásica. A radiografia torácica apontou presença de área nodular sobrepondo lobo pulmonar caudal direito, indicativo de processo metastático. Em virtude do prognóstico reservado, os tutores optaram pela eutanásia do mesmo.(AU)

Squamous cell carcinoma (SCC) is a malignant neoplasm resulting from the differentiation of keratinocytes, which mainly affects light-colored and non-pigmented animals due to exposure to ultraviolet radiation. Although they present slow evolution and low metastatic character, in some more advanced cases, metastatic involvement of adjacent organs may occur. The treatments used in SCC include surgery, radiotherapy, chemotherapy, cryotherapy and electrochemotherapy (ECT). Electrochemotherapy is quite effective in the treatment of this type of tumor, among others, and it usually has no side effect. This work aims at reporting the case of a feline treated at the Veterinary Clinic Bichos S.A. in the city of Foz do Iguaçu diagnosed with Squamous Cell Carcinoma and carrying the feline immunodefense virus (FIV). Electrochemotherapy was the treatment of choice for the neoplasia, resulting in partial remission of the lesions after twenty days of treatment. In order to investigate possible bone involvement, an X-ray of the face was performed, where it presented area of bone lysis in the zygomatic arch and left maxilla, signs of neoplastic infiltration. The chest X-ray showed a nodular area overlapping the right caudal pulmonary lobe, an indication of metastatic process. Due to the reserved prognosis, the tutors chose euthanasia of the subject.(AU)

El carcinoma de células escamosas (CEC) es una neoplasia maligna resultante de la diferenciación de queratinocitos, que afecta principalmente a animales de pelaje claro y de poca pigmentación, resultado de la exposición a la radiación ultravioleta. Tienen una evolución lenta y un carácter metastásico bajo, sin embargo, en algunos más avanzados puede producirse afectación metastásica de órganos adyacentes. Los tratamientos utilizados en el CEC incluyen cirugía, radioterapia, quimioterapia, crioterapia y electroquimioterapia (EQT). La electroquimioterapia es muy eficaz en el tratamiento de ese tumor, entre otros y no suele tener efectos secundarios. Este trabajo tiene como objetivo reportar el caso de un felino atendido en la Clínica Veterinária Bichos S.A. de la ciudad de Foz do Iguaçu, diagnosticado con Carcinoma de Células Escamosas y con el virus de la inmunodeficiencia felina. El tratamiento adoptado para la neoplasia fue la electroquimioterapia, resultando en remisión parcial de las lesiones luego de veinte días de EQT. Con el fin de investigar la posible afectación ósea se realizó una radiografía de rostro, donde se presentó un área de lisis ósea en arco cigomático y maxilar izquierdo, indicativo de infiltración neoplásica. La radiografía de tórax mostró la presencia de un área nodular superpuesta al lóbulo pulmonar caudal derecho, lo que indicaba un proceso metastásico. Debido al pronóstico reservado, los tutores optaron por la eutanasia.(AU)

Dosagem sérica do marcador tumoral CA 15. 3 em cadelas portadoras de neoplasias mamárias pelo método de eletroquimioluminescência / Serum dosage of the tumor marker Ca 15. 3 in bitches presenting mammary neoplasia with the chemiluminescence method

The objective of the present study was to analyze the serum levels of the tumor marker Ca15.3 in healthy bitches and those with mammary neoplasms, correlating results with tumor type, clinical staging, time until presentation, and presence of ulceration and vascularization. For the study, 30 bitches with mammary tumors and 30 healthy bitches (control group) were selected. Histopathology was performed for identification of tumor type, and blood was collected for measurement of serum concentration of the marker via the chemiluminescence method using a commercial kit. A higher frequency of malignant neoplasms was observed (76.7%), with a higher quantity of carcinoma in mixed tumor (26.7%). Regarding serum concentration of the marker Ca15.3, there was no difference in serum values when comparing the means from bitches with neoplasia and healthy bitches, nor when comparing the other characteristics. The majority of results for serum concentration of Ca15.3, whether in bitches with neoplasia or in healthy bitches, was zero. It is concluded that the measurement of the marker Ca15.3 using the chemiluminescence method and commercial kits for humans did not offer significant results that would make this method or this marker a useful tool for patient monitoring and evaluation of the prognosis of bitches with mammary neoplasms.(AU)

Efectos de la corriente eléctrica de baja intensidad en ratones sanos / Effects of low-intensity electric current on healthy mice

Introducción: El conocimiento de los efectos de la terapia electroquímica, en los organismos puede ser importante para el tratamiento de diferentes enfermedades. Objetiv:o Evaluar los efectos de la corriente eléctrica directa de baja intensidad en ratones sanos. Métodos: 80 ratones C57BL/6/Cenp sanos (40 machos y 40 hembras) fueron distribuidos aleatoriamente en ocho grupos experimentales (cuatro grupos controles y cuatro grupos tratados). La corriente eléctrica directa (10 mA durante 5 min) o tensión constante (10 V durante 5 min) fue aplicada a los ratones. Fueron realizadas observaciones clínicas, macroscópicas, microscópicas y mediciones de los parámetros hematológicos y bioquímicos de la sangre. Resultados: Se indujeron cambios reversibles en los parámetros hematológicos, bioquímicos de la sangre e histológicos estudiados en ratones C57BL/6/Cenp machos y hembras cuando se usó 10 mA o 10 V y diferentes arreglos de electrodos, siendo menos notable para el modo de tensión constante. Conclusiones: Las alteraciones inducidas en los ratones C57BL/6/Cenp sanos por la corriente eléctrica directa de baja intensidad son reversibles y el proceso inflamatorio sistémico es dominado por los linfocitos(AU)

Introduction: Knowledge about the effects of electrochemotherapy on organisms may be important for the treatment of various diseases. Objective: Evaluate the effects of low-intensity direct electric current on healthy mice. Methods: Eighty healthy C57BL/6/Cenp mice (40 male and 40 female) were randomly distributed in eight experimental groups (four control and four treated). Direct electric current (10 mA during 5 min) or constant voltage (10 V during 5 min) was applied to the mice. Clinical, macroscopic and microscopic observation was performed, and measurements were taken of hematological and biochemical parameters of the blood. Results: Reversible changes were induced in hematological, biochemical and histological parameters of the blood of male and female C57BL/6/Cenp mice when 10 mA or 10 V and various electrode arrays were used. These changes were less noticeable in the constant voltage mode. Conclusions: The alterations induced by low-intensity direct electric current in healthy C57BL/6/Cenp mice are reversible. The systemic inflammatory process is dominated by the lymphocytes(AU)

Avaliação comparativa de dosagem do marcador tumoral CA 15-3 em cadelas hígidas ou com neoplasia mamária / Comparative evaluation of tumor marker CA 15-3 dosage in dogs, healthy or with breast cancer

O antígeno CA 15-3 é uma proteína presente no soro utilizado no acompanhamento de mulheres com câncer de mama, essencialmente na detecção de metástases. Os objetivos deste estudo foram avaliar a efetividade e a viabilidade da utilização do marcador tumoral CA 15-3 em cadelas, comparando-se os valores do marcador entre cadelas sem e com neoplasia mamária, avaliando-se alterações nos valores do marcador após a mastectomia, e suas correlações entre o tipo histológico. Foi realizada a quantificação sérica do marcador tumoral CA 15-3 (teste de eletroquimioluminescência), em vinte cadelas hígidas (grupo controle) e vinte cadelas com neoplasia mamária (grupo teste). Os animais com neoplasia tiveram a dosagem do marcador realizada antes e 10 dias após a mastectomia. Ainda, foi realiza a citologia vaginal no momento da mastectomia e foram estabelecidos três grupos de acordo com a fase estral de cada cadela, Diestro, Proestro e Anestro. As massas tumorais foram encaminhadas para exame histopatológico. A avaliação dos dados de citologia vaginal entre os grupos Diestro, Proestro e Anestro pelo teste de ANOVA não demonstrou diferença estatística significativa entre os valores encontrados. E na análise para a comparação dos valores do marcador tumoral com os tipos histológicos de neoplasias, divididas em dois grupos, benignas e malignas, utilizando o teste de Mann-Whitney Rank Sum Test, o teste não demonstrou diferença estatística significativa visto que p>0,05. Os valores encontrados do marcador no grupo controle foram uma média de 0,19+0,39 U/mL, no grupo pré-mastectomia 1,56+0,39 U/mL e pós-mastectomia 0,66+0,27 U/mL. Em análise estatística com a comparação de grupo pré e pós-mastectomia, e do grupo controle com o grupo pré e pós-mastectomia observou-se significância com p< 0,005. Assim, observou-se diferença nos valores do marcador antes e depois da remoção cirúrgica da neoplasia, sugerindo seu possível uso como controle de crescimento tumoral pós-mastectomia individual. Porém há muita variação dos resultados nos diferentes métodos existentes, e não há ainda um padrão dos valores de referência para cada método, sendo necessários mais estudos sobre o uso dos marcadores.(AU)

The CA 15-3 antigen is a protein present in the serum, used to monitor women with breast cancer, mainly in metastatic disease detection. The objective of this study was to evaluate the effectiveness and feasibility of the CA 15-3 tumor marker in dogs, comparing the marker values between dogs with or without breast cancer, to estimate changes in marker values after mastectomy, and their correlation between the histological types. Serum quantification of the tumor marker CA 15-3 (electrochemiluminescence test) was performed in twenty healthy bitches and twenty others with mammary neoplasia. Bitches with cancer had the content of the tracer performed before and 10 days after mastectomy. The vaginal cytology was performed at the moment of the mastectomy, dividing the animals into three different groups (diestrus, proestrus and anestrus). All the mammary tumors were examined histopathologically. The evaluation of the vaginal cytology data of the groups Diestro, Proestro and Anestro by the ANOVA test did not show a statistically significant difference between the values ​​found. In the analysis histological types of tumor marker values of neoplasms, divided into two groups, benign and malignant, using the Mann-Whitney Rank Sum Test, there was no statistical significant difference at p>0.05. The values of the marker in the control group had an average of 0.19+0.39 U/mL, of the pre-mastectomy group 1.56+0.39 U/mL, and of the post-mastectomy group 0.66+0.27 U/mL. The statistic was performed comparing groups pre- and post-mastectomy, and the control group with group pre- and post-mastectomy with a statistical significance p< 0.005 in both tests. There was a difference of marker values ​​before and after surgical removal of the neoplasia, suggesting its possible use in post-mastectomy tumor control. But exist variation of results with the different existing methods, and there will be still a standard reference value for each method.(AU)

Assessment of electrochemotherapy effects on the development of Ehrlich solid tumor in swiss mice using a novel electroporator device / Avaliação dos efeitos da eletroquimioterapia sobre o desenvolvimento do tumor sólido de Ehrlich em camundongos Swiss utilizando um novo eletroporador

Electrochemotherapy is a local anticancer treatment in which non-permeant chemotherapeutic drugs are associated with electric pulses of well-established parameters. The electric pulses cause pores to open on the plasma membrane and facilitate drug transport, enhancing cytotoxicity and reducing side effects. Assessment of electrochemotherapy effects on Ehrlich solid tumor development in this work aims to evaluate in vivo usage of the electroporator device developed by the Department of Electrical Engineering of Engineering School of UFMG. Therefore, 40 Swiss mice were inoculated with Ehrlich tumor cells, and developed the tumor in solid form. After 21 days, mice were subjected to specific treatment protocols (control, bleomycin, electric pulses and electrochemotherapy); 17 days later they were euthanized and the tumors collected for histopathology analysis. Electrochemotherapy induced discrete weight loss and an inflammatory response in the tumor, which was not seen on the other treatment groups. Bleomycin alone induced necrosis. Both groups showed lower cellular proliferation rates. From this study, it was concluded that the animals tolerated electrochemotherapy treatment under anesthesia and the electroporator device developed by the Engineering School of UFMG was adequate when used in an electrochemotherapy protocol.(AU)

Eletroquimioterapia é uma modalidade de tratamento local contra o câncer em que a administração de quimioterápicos não penetrantes à membrana plasmática é associada à aplicação de pulsos elétricos com parâmetros bem estabelecidos, que abrem poros na membrana plasmática e facilitam a entrada desses fármacos nas células, aumentando sua citotoxicidade e reduzindo efeitos colaterais. A avaliação dos efeitos da eletroquimioterapia sobre o desenvolvimento do tumor sólido de Ehrlich em camundongos Swiss neste trabalho teve como objetivo testar o uso in vivo do aparelho eletroporador desenvolvido pelo Departamento de Engenharia Elétrica da Escola de Engenharia da UFMG. Para tanto, foram utilizados 40 camundongos fêmeas da linhagem Swiss, nos quais foram inoculadas células de tumor de Ehrlich, para o desenvolvimento do tumor na forma sólida. Após 21 dias, os camundongos foram submetidos ao protocolo de tratamento específico (controle, bleomicina, pulsos elétricos e eletroquimioterapia); 17 dias depois foram eutanasiados e seus tumores coletados para análise histopatológica e imuno-histoquímica. A eletroquimioterapia induziu perda de peso discreta e uma resposta inflamatória no tumor que não foi observada nos outros grupos. O grupo bleomicina apresentou maior porcentagem de necrose. Ambos os grupos apresentaram menor índice de proliferação celular. Com este estudo, pode-se concluir que o tratamento sob anestesia foi bem tolerado pelos animais e que o aparelho eletroporador desenvolvido pela Escola de Engenharia da UFMG é adequado para utilização em um protocolo de eletroquimioterapia.(AU)

Terapia electroquímica: relación del patrón espacial del daño tisular con la forma del arreglo de electrodos / Electrochemical therapy: relationship of the tissular damage space pattern with the form of electrodes repair

Se realizó una investigación en la Escuela Superior de Ingeniería Mecánica y Eléctrica del Instituto Politécnico Nacional de Ciudad de México, desde mayo hasta junio de 2016, con el objetivo de determinar cómo cambia el patrón espacial del daño tisular con la forma del arreglo de electrodos en piezas tridimensionales de papa (Solanum tuberosum L) bajo la acción de 10 mA durante 30 min para los arreglos de electrodos con formas colineal, circular, elíptica, parabólica e hiperbólica). Los resultados mostraron la estrecha relación entre el daño tisular y la forma del arreglo de electrodos, así como algunos hallazgos que se observan también en tumores, tales como: necrosis circular alrededor de todos los electrodos, daño tisular extensivo en espacio y en tiempo, burbujeo alrededor del cátodo, zona blanca alrededor del ánodo; igualmente, se observó que las regiones alejadas de los electrodos no se afectaron

An investigation in the Mechanical and Electric Engineering Higher School of the National Polytechnic Institute of Mexico City, was carried out from May to June, 2016, aimed at determining how the tissue damage space pattern changes with the electrodes position form in three-dimensional pieces of potato (Solanum tuberosum L) under the 10 MA action during 30 minutes for electrodes position with cholineal, round, elliptic, parabolic and hyperbolic forms). The results showed a close relationship between the tissue damage and the electrodes position form, as well as some findings that are also observed in tumors, such as: circular necrosis around all the electrodes, extensive tissue damage in space and time, bubbling around the cathode, white area near the anode; likewise, it was observed that the regions far from the electrodes were not affected

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.

Utilização de eletroquimioterapia para carcinoma de células escamosas tegumentar em felino / Employment of electrochemotherapy for cutaneous squamous cell carcinoma in cats

A eletroquimioterapia compreende a utilização conjunta de fármacos antineoplásicos e aplicação regional de pulsos elétricos (eletroporação), maximizando a concentração intracelular destes fármacos, assim propiciando maior ação citotóxica. A bleomicina, fármaco antimicrobiano dotado de propriedade antineoplásica, apresenta restrita penetrabilidade na membrana celular, dada a sua hidrossolubilidade. Todavia, uma vez administrada via intralesional ou intravenosa associada à eletroporação, demonstra citotoxicidade potencializada. Foram utilizados 21 felinos acometidos por carcinoma de células escamosas tegumentar. Padronizou-se o protocolo eletroquimioterápico empregando-se sulfato de bleomicina, pela via intravenosa, na dose de 15U/m2 de superfície corpórea. A eletroporação foi perfilada com eletrodo composto por agulhas, pulsos elétricos com tensão de 1000 V, em onda quadrada unipolar, com duração de 100 microsegundos, totalizando oito ciclos. Verificou-se remissão neoplásica integral em 21 felinos inclusos no estudo (100%). Inexistiram complicações e/ou efeitos adversos decorrentes do procedimento. O protocolo avaliado neste trabalho revelou-se exequível, eficaz e seguro na terapêutica antineoplásica de carcinoma de células escamosas tegumentar felino.

Electrochemotherapy is characterized as a protocol which combines the use of antineoplastic agents and localized application of electric pulses (electroporation) to improve the intracellular concentration of these agents, increasing its cytotoxic action. Bleomycin, an antibiotic agent with antineoplastic properties, is a hydrophilic molecule, having a restricted transport through the cellular membrane. However, when it is administered intralesionally or intravenously and associated to electroporation, its cytotoxicity is maximized. There were utilized 21 cats affected by cutaneous squamous cell carcinoma. The electrochemotherapy protocol was standardized using intravenous bleomycin sulfate at a dose of 15U/m2 body surface area. Electroporation was performed using an electrode composed of needles and electric pulses with 1000 V voltage, in unipolar square wave and 100 microseconds duration, totalizing eight cycles. There was complete neoplastic remission in 21 cats (100%). There were no complications or side effects associated with the procedure. The protocol studied in this work showed to be feasible, effective and safe for antineoplastic therapy in feline cutaneous squamous cell carcinoma.

Cutaneous metastasis of unknown primary presenting as massive and invasive abdominal lesion: an elective approach

Abstract: We describe herein what is to our knowledge the first reported case of an invasive cutaneous metastasis with unknown primary, electively treated solely with electrochemotherapy. We describe a female patient with a large, invasive and painful lesion in her hypogastric region, extending up to the pubic area. The cutaneous biopsy and instrumental and laboratory analyses, all failed to reveal the primary site. A final diagnosis of cutaneous metastasis with unknown primary was made and treatment was performed with electrochemotherapy. Our case highlights the importance of interdisciplinary choices in clinical practice to cope with the lack of a primary site and to improve quality of life, since no standardized therapy exists for these classes of patients.

Estudio comparativo de dos métodos para la cuantificación del antígeno carcinoembrionario / Comparative study of two methods for carcinoembryonic antigen quantification / Estudo comparativo de dois métodos para a quantificação do antígeno carcinoembrionário

El antígeno carcinoembrionario (CEA) es una glicoproteína ampliamente utilizada como complemento del diagnóstico, monitoreo de tratamiento y evolución del cáncer colorrectal. El objetivo del presente trabajo fue realizar un análisis comparativo entre dos métodos para la determinación de CEA: electroquimioluminiscencia y quimioluminiscencia, en muestras de suero de 57 pacientes con diagnóstico de cáncer, principalmente colorrectal. Cuando se analizaron los datos totales se obtuvo una elevada correlación (r=0,9135, p<0,00001). Al realizar un corte de los resultados tomando como límite el valor de 4 ng/mL se observó que las mayores discrepancias entre métodos estuvieron en los valores considerados dentro del rango normal (r=0,5716, p<0,0014, n=29). Por el contrario, en concentraciones mayores al límite de corte, la correlación fue elevada (r=0,9453, p<0,00001, n=28). Estos resultados sugieren que, a diferencia de lo descripto por los fabricantes, los valores de CEA obtenidos por ambos métodos son comparables. La menor correlación observada en concentraciones inferiores a 4 ng/mL no sería tan relevante debido a que estos niveles se consideran dentro del rango de normalidad y, por lo tanto, su importancia desde el punto de vista clínico es relativa. Sin embargo, debido a que pueden detectarse con baja frecuencia diferencias individuales (atribuidas probablemente a diferencias en los epitopes detectados por cada método), para los casos con fuerte presunción clínica y un valor de CEA incongruente, se sugiere repetir la determinación por medio de otra metodología.

The carcinoembryonic antigen (CEA) is a glycoprotein widely employed in colorectal cancer, mainly as evolutive marker and as measure of therapy's ef-ficacy. The goal of this work was to perform a comparative study between two analytical methods to measure serum CEA levels: electrochemiluminescence (ECL) and chemilumines-cence (CL) in serum samples of 57 patients with diagnosis of cancer, mainly colorectal. On the whole, an elevated correlation between ECL and CL (r=0.9135; p<0.00001) was obtained. When data was analyzed with a cut-off value of 4 ng/mL, the main discrepancy between methods occurred in the range of normal values (r=0.5716; p<0.0014; n=29). On the contrary, in concentrations higher than the cut-off, the cor-relation was very high (r=0.9453; p<0.00001; n=28). These results suggest that, in spite of the reports of manufacturers, the CEA values obtained by both methods are comparable. The lower correlation observed in values below 4 ng/mL would not be significant because those values are in the normal range and, for that reason, their clinical importance is minor. However, due to the individual differences that could be detected in some patients (probably resulting from the differences in epitopes detected by each method), in cases with strong clinical evidence without concordance with the CEA result, it could be necessary to repeat the determination using another methodology.

O antígeno carcinoembrionário (CEA) é uma glicoproteína amplamente usada como complemento do diagnóstico, monitoração de tratamento e evolução do câncer colorretal. O objetivo deste trabalho foi realizar uma análise comparativa entre dois métodos para a detecção do CEA: eletroquimioluminescência e quimio-luminescência em amostras de soro de 57 pacientes com diagnóstico de câncer, principalmente colorretal. Quando analisados os dados totais, houve uma correlação elevada (r=0,9135, p<0,00001). Quando realizado um corte dos resultados tomando como valor limite 4 ng/mL, observou-se que as maiores diferenças entre ambos os métodos estiveram nos valores considerados dentro da faixa dos valores normais (r=0,5716, p<0,0014, n=29). No entanto, nas concentrações superiores respeito do limite de corte, a correlação foi elevada (r=0,9453, p<0,00001, n=28). Estes resultados sugerem que, comparado com o descrito pelos fabricantes, os valores de CEA obtidos por ambos os métodos são comparáveis. A menor correlação observada nas concentrações inferiores a 4 ng/mL não seria tão relevante devido a que estes níveis consideram-se dentro da faixa de normalidade e, portanto, sua importância, do ponto de vista clínico, é relativa. Contudo, devido a que podem ser detectados com baixa frequência diferenças individuais (atribuídas provavelmente a diferenças nos epitopos detectados por cada método), para os casos com forte suspeita clínica e um valor de CEA incongruente, sugere-se repetir a determinação através de outra metodologia.

[Thermal distribution in ablation of squamous cell carcinoma skin tumors using irreversible electroporation]

Irreversible electroporation is a new treatment modality for skin tumors ablation. In order to successful treatment, all of tumoral tissues must be exposed to intense electric field. In addition, the heat that produced during the surgery has adverse effect on recovery procedure. This study was done to evaluate the thermal distribution in ablation of squamous cell carcinoma skin tumors using irreversible electroporation. In this study numerical modeling by finite element was used for determination of electrical and thermal distribution in healthy and tumoral tissues. Three-Dimensional Model was done using MR imaging of patient with squamous cell carcinoma in FEMLAB v3.5a software. Electric field distribution determined using Laplace equation and distribution of thermal damage calculated using bioheat equation and Arrhenius equation. This calculation was done for different geometry parameters of needle and plate electrodes. Thermal damage of first-degree burn was not observed in any cases. However in high voltage, volume with temperature above 43[degree sign]C reach to 10% of tumoral tissue and 3% of healthy tissue. The study show that the voltage applied to the electrodes and the distance between the electrodes can have the greatest impact on the thermal and electrical distributions. Although needle electrode showed better electric coverage in tumoral area. This study showed that it can be possible to select optimized electric and geometric parameter to select electrode for complete tumor ablation, control of thermal damage in tumoral and healthy tissues

Effect of electrochemotherapy in treating patients with venous malformations / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of electrochemotherapy in treating venous malformations.</p><p><b>METHODS</b>Electrochemotherapy was applied to 665 patients with venous malformations of limbs and trunk, and 505 cases were followed up for half to 6 years. In this study, 228 male and 277 female patients were involved. Diagnosis was made by clinical manifestations and magnetic resonance imaging. The platinum electrodes were inserted into tumor through a trocar with plastic insulating cannula percutaneously and connected with the electrochemical therapeutic apparatus in anodes and cathodes separately. Then electricity was given. The treating voltage is 6-12 V and volume 100-180 mA, the total electricity used is in general 80-100 coulombs per 1.0 square centimeter of tumors' area. The treating time was usually from several dozen minutes to over 2 h depending on the size of the tumor. The severe cases which needed to be treated once again usually were operated after 6 months.</p><p><b>RESULTS</b>The primary efficacy end point was defined as an improvement of patients' symptoms and a reduction in size of tumor 6 months after treatment. Effects were divided into 4 grades, and the efficacy rate decreased from grade 1 to grade 4. The efficacy turned out that 30.1% (152/505) of patients was classified as grade 1; 46.3% (234/505) as grade 2; 19.0% (96/505) as grade 3 and 4.6% (23/505) as grade 4.</p><p><b>CONCLUSIONS</b>Electrochemotherapy shows special superiorities in treating venous malformations. It might bring a confirmed clinical efficacy with the advantages of less injury, quick recovery, simple operation and less complications.</p>

Antitumor efficiency of electrochemotherapy by high and low frequencies and repetitive therapy in the treatment of invasive ductal carcinoma in Balb/c Mice

In electrochemotherapy [ECT], there is an unpleasant sensation of muscle contraction when using a low frequency [1 Hz]. Therefore, by increasing the pulse frequency above the tetanic frequency this painful sensation can be reduced. The aim of the present study is to compare the treatment efficiencies of low and high frequency ECT, and estimate the effect of its repeated sessions. We transplanted invasive ductal carcinoma into the flanks of female Balb/c mice. ECT was performed on the mice by the use of 8 pulses, 1000 v/cm, of 100 micro s duration at 1 Hz and 5 kHz repetition frequencies along with intra-tumoral injections of bleomycin. We also used this ECT protocol for the second therapy session six days after tumour regrowth. The effect of treatment was measured by calculating the tumor volumes for 24 days following treatment. Statistical analysis was performed with ANOVA. ECT at 1 Hz and 5 kHz pulse frequencies demonstrated significant inhibition of tumor growth, but after the first treatment the tumours began to regrow. Repetitive ECT sessions increased the curability of tumors up to 40% in the group treated by 1 Hz frequency and 60% in the group treated with 5 kHz frequency. Our results demonstrate that the effects of 1 Hz and 5 kHz pulse repetition frequencies are comparable for inhibited tumour growth. Repetitive treatment can improve the effectiveness of ECT

Eletroquimioterapia em adenocarcinoma perianal canino / Electrochemotherapy in canine perianal adenocarcinoma

Objetivo - Este estudo objetivou avaliar a aplicabilidade, eficácia e segurança da eletroquimioterapia em neoplasias perianais caninas, no intuito da caracterização das vantagens intrínsecas ao protocolo. Métodos - Foram utilizados dez cães acometidos por neoformações perianais, admitidos junto ao Serviço de Cirurgia do Hospital Veterinário do Curso de Medicina Veterinária da Universidade Paulista, São Paulo-SP, no período compreendido entre janeiro de 2009 a fevereiro de 2010. Todas estas lesões foram submetidas a exame histopatológico, através do qual se estabeleceu o diagnóstico definitivo de adenocarcinoma perianal. Padronizou-se o protocolo eletroquimioterápico utilizando-se sulfato de bleomicina, via intralesional, na dose de 1U/cm3 de tumor. Três minutos após a aplicação do fármaco pela mencionada via, administraram-se pulsos elétricos sobre toda extensão das neoformações. Os cães foram reavaliados sete, 14, 21 e 30 dias após a realização do protocolo. Constatada a remissão tumoral total, os pacientes foram monitorados através de retornos bimestralmente aprazados, por período de 12 meses. Resultados - Todos os cães (n = 10) (100%) exibiram regressão neoplásica completa. Todos os pacientes foram reavaliados a cada 60 dias através da execução de minucioso exame físico e subsidiários pertinentes por período de 12 meses, não exibindo sintomas, achados laboratoriais, radiográficos e/ou sonográficos de recidiva neoplásica e/ou metástases adjacentes ou distantes neste intervalo de tempo. Conclusão - O protocolo demonstrou-se aplicável, eficaz e seguro na terapêutica antineoplásica para adenocarcinoma perianal canino. Não houve toxicidade relacionável ao fármaco utilizado, observando-se ainda, manutenção da integridade anátomo-fisiológica do tecido acometido pela afecção.

Objective - The purpose of this study was to evaluate the applicability, effectiveness and safety of electrochemotherapy in canine perianal adenocarcinoma, aiming the characterization of benefits intrinsic the protocol. Methods - Ten dogs presenting perianal adenocarcinoma were admitted at the Surgery Service of the Veterinary Hospital from University Paulista, São Paulo, during the period from January 2009 to February 2010. All injuries were subjected to histopathological examination, through which established the definitive diagnosis of perianal adenocarcinoma. The electrochemotherapy protocol was standardized using intralesional bleomycin sulfate at a dose of 1U/cm3 of tumoral area. Three minutes after intralesional administration of the antineoplastic agent, electric pulses were applied all over the neoplastic extension. Dogs were reevaluated seven, 14, 21 and 30 days after the protocol performance. Once observed the complete tumoral remission, patients were monitored every two months for a 12-month-period. Results - All dogs (n = 10) (100%) presented complete neoplastic remission. All patients were reevaluated every two months through a detailed physical examination and pertinent complementary exams for a 12-month period, showing no clinical, laboratorial, radiological and/or sonographic manifestations of neoplastic recidivating, adjacent and/or distant metastasis within this period. Conclusion - The studied protocol revealed to be applicable, effective and safe for antineoplastic therapy in canine perianal adenocarcinoma. There was no toxicity related to the employed agent. Nevertheless, anatomophysiological integrity of the involved tissue was preserved.

ETM study of electroporation influence on cell morphology in human malignant melanoma and human primary gingival fibroblast cells

<p><b>OBJECTIVE</b>To estimate electroporation (EP) influence on malignant and normal cells.</p><p><b>METHODS</b>Two cell lines including human malignant melanoma (Me-45) and normal human gingival fibroblast (HGFs) were used. EP parameters were the following: 250, 1 000, 1 750, 2 500 V/cm; 50 µs by 5 impulses for every case. The viability of cells after EP was estimated by MTT assay. The ultrastructural analysis was observed by transmission electron microscope (Zeiss EM 900).</p><p><b>RESULTS</b>In the current study we observed the intracellular effect following EP on Me-45 and HGF cells. At the conditions applied, we did not observe any significant damage of mitochondrial activity in both cell lines treated by EP. Conversely, we showed that EP in some conditions can stimulate cells to proliferation. Some changes induced by EP were only visible in electron microscopy. In fibroblast cells we observed significant changes in lower parameters of EP (250 and 1 000 V/cm). After applying higher electric field intensities (2 500 V/cm) we detected many vacuoles, myelin-like bodies and swallowed endoplasmic reticulum. In melanoma cells such strong pathological modifications after EP were not observed, in comparison with control cells. The ultrastructure of both treated cell lines was changed according to the applied parameters of EP.</p><p><b>CONCLUSIONS</b>We can claim that EP conditions are cell line dependent. In terms of the intracellular morphology, human fibroblasts are more sensitive to electric field as compared with melanoma cells. Optimal conditions should be determined for each cell line. Summarizing our study, we can conclude that EP is not an invasive method for human normal and malignant cells. This technique can be safely applied in chemotherapy for delivering drugs into tumor cells.</p>

Application of electrochemical therapy in high-flow vascular malformation in maxillofacial region / 中华整形外科杂志

<p><b>OBJECTIVE</b>To explore the therapeutic effect of electrochemical therapy(ECT) for high-flow vascular malformation in maxillofacial region.</p><p><b>METHODS</b>38 patients with high-flow vascular malformation in maxillofacial region were treated with ECT. The voltage was 6-8 V, and the electric current was 80-100 mA. The electric quantity was 10-20 C/cm2.</p><p><b>RESULTS</b>Among the 38 cases, 32 cases received only one treatment, 5 cases received two treatments and one case received three treatments. The patients were followed up for 2 months to 3 years. The total effective rate was 100% with 55.26% of cure rate and 44.74% of partial cure rate. No hemolysis happened during follow-up period.</p><p><b>CONCLUSIONS</b>ECT is a simple and effective method for high-flow vascular malformation with less morbidity.</p>

Utilização de eletroquimioterapia em neoplasias de origem epitelial ou mesenquimal localizadas em pele ou mucosas de cães / Employment of electrochemotherapy in canine neoplasms of epithelial or mesenchymal origin located in the skin or mucosal membranes

A eletroquimioterapia é caracterizada como um protocolo que agrega o uso de fármacos antineoplásicos à aplicação regional de pulsos elétricos, maximizando a concentração intracelular destes agentes, assim propiciando maior ação citotóxica dos mesmos. A bleomicina, um antimicrobiano dotado de propriedade antineoplásica, demonstra restrição no transporte através da membrana celular dada sua composição molecular hidrofílica. Todavia, uma vez administrada via intralesional ou endovenosa associada à eletroporação, exibe citotoxicidade potencializada. Foram utilizados 34 cães acometidos por neoformações solitárias de origem epitelial ou mesenquimal, situadas em pele ou membranas mucosas. Padronizou-se o protocolo eletroquimioterápico empregando-se sulfato de bleomicina, pela via intralesional, na dose de 1U/cm3 de tumor. A eletroporação foi perfilada com eletrodo composto por agulhas, pulsos elétricos com tensão de 1000 V, em onda quadrada unipolar, com duração de 100 microsegundos, totalizando-se oito ciclos. Constatou-se remissão neoplásica integral em 30 cães (88,3%) e refratariedade ao protocolo em apenas quatro animais (11,7%). Inexistiram complicações e/ou efeitos adversos decorrentes do procedimento. O protocolo neste trabalho estudado revelou-se aplicável, eficaz e seguro na terapêutica antineoplásica em cães.

Electrochemotherapy is characterized as a protocol which combines the use of antineoplastic agents with localized application of electric pulses to improve the intracellular concentration of these agents, increasing, thus, its cytotoxic action. Bleomycin, an antibiotic agent with antineoplastic properties, is a hydrophilic molecule, having a restricted transport through the cellular membrane. However, when it is administered intralesionally or intravenously and associated to electroporation, its cytotoxicity is maximized. There were utilized 34 dogs affected by a single lesion of epithelial or mesenchymal origin, located in the skin or mucosal membranes. The electrochemotherapy protocol was standardized using intralesional bleomycin sulfate at a dose of 1U/cm3of tumoral area. Electroporation was performed using an electrode composed of needles and electric pulses with a 1000 V voltage, in unipolar square wave and 100 microseconds duration, totalizing eight cycles. There was complete neoplastic remission in 30 dogs (88.3%) and refractoriness to the protocol in four animals (11.7%). There were no complications or side effects associated with the procedure. The protocol studied in this work showed to be feasible, effective and safe for antineoplastic therapy in dogs.

Establishment of animal model for electroporation-mediated gene therapy in distraction osteogenesis of rabbit mandible / 中华整形外科杂志

<p><b>OBJECTIVE</b>To evaluate the feasibility of electroporation-mediated transfection of recombinant plasmid to mandibular distraction area of rabbit in vivo.</p><p><b>METHODS</b>New-Zeland rabbit were employed. The mandible was distracted 3 days after operation at a rate of 0.8 mm per day for 7 days. The rabbits were randomly divided into 3 groups as group A (recombinant plasmid pIRES-VEGF165-EGFP), group B (recombinant plasmid plRES-VEGF165-EGFP) and group C (normal saline). The rabbits were sacrified at 3 hours, 1, 3, 7 and 14 d after injection respectively. The tissue at the distraction area was taken out for frozen section. The gene expression was assessed by the detection of expression of green fluorescence protein (GFP) using fluorescence microscope. The liver and kidney function test (ALT, AST, BUN, Scr) and the histological examination of heart, liver and kidney were also performed.</p><p><b>RESULTS</b>GFP was seen in the distraction area in group A and group B 3 hours after injection, which increased at the 1st day, reached peak value at the 3rd day, decreased at the 7th day and was very lower at 14th day. The GFP expression was much stronger in group A than in group B. GFP was not expressed in group C. There was no statistical difference in the concentration of ALT, AST, BUN and Scr in serum of rabbits among the three groups.</p><p><b>CONCLUSIONS</b>Electroporation-mediated transfection of recombinant plasmid can be expressed in the distraction area of rabbits, and there was no toxicity to the liver and kidney of rabbits. Electroporation could obviously improve transfection efficiency in vivo. It indicates that electroporation-mediated transfection of recombinant plasmid to distraction area tissue of rabbits is feasible.</p>

Studies on inhibitive effect of low-voltage electrochemotherapy on head and neck cancer-bearing nude mice / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To analyse the therapie effect of low-voltage electrochemotherapy (EP) on the head and neck cancer.@*METHOD@#YCU-N861 human head and neck cancer cells were subcutaneously inoculated in the neck of nude mice to establish tumor-bearing models. Then the mice were treated with bleomycin (BLM, 20 microg per mouse), accompanied with electric stimulation (50 V or 100 V).@*RESULT@#BLM treatment applied with EP can significantly inhibit the proliferation of tumor cells than BLM or EP treatment separately (P < 0.01). The tumor volume, the mitotic index (MI) and the labeling index (LI) of Ki67 in BLM+EP group were all obviously decreased than BLM group, EP group and control group (P < 0.01).@*CONCLUSION@#Low-voltage electrochemotherapy can offer promising method in the local treatment of head and neck cancer.