Aplasia pura adquirida crônica da série vermelha secundária à quimioterapia em paciente com adenocarcinoma endometrioide invasivo / Chronic acquired pure aplasia of the red series secondary to chemotherapy in a patient with invasive endometrioid adenocarcinoma

O presente relato de caso descreve a apresentação atípica de uma paciente com adenocarcinoma endometrioide invasivo que evoluiu com aplasia pura adquirida crônica da série vermelha secundária à quimioterapia. Paciente de 71 anos, sexo feminino, procurou atendimento médico por quadro de metrorragia com três meses de evolução. A curetagem uterina evidenciou adenocarcinoma endometrioide invasor moderadamente diferenciado. Iniciou-se uma abordagem com esquema quimioterápico composto por Carboplatina e Paclitaxel interrompido ao quinto ciclo para evitar progressão de aplasia medular constatada por biópsia de medula óssea. A possível hematotoxicidade do protocolo Paclitaxel e Carboplatina foi observada na conduta terapêutica da paciente, por sua progressão para uma apresentação atípica de aplasia pura adquirida crônica da série vermelha após administração desta associação de drogas.

The present case report describes the atypical presentation of a patient with invasive endometrioid adenocarcinoma that evolved with chronic acquired pure aplasia of the red series secondary to chemotherapy. A seventy-one-yearold patient, female, sought medical care for a three-month-old metrorrhagia evolution. The uterine curettage showed moderately differentiated invasive endometrioid adenocarcinoma. It was initiated an approach with chemotherapy regimen consisting of Carboplatin and Paclitaxel interrupted at the fifth cycle to prevent progression of spinal aplasia found by bone marrow biopsy. The possible hematoxicity of the patient, for its progression to an atypical presentation of chronic acquired aplasia of the red series after administration of this combination of drugs.

Oral health status before, during and after antineoplastic treatment at a cancer institute in Barranquilla, Colombia / Estado de salud oral antes, durante y después del tratamiento antineoplásico en un instituto de cáncer en Barranquilla, Colombia

Chemotherapy and radiotherapy are aggressive treatments for cancer management. Both therapies make the stomatogatic system vulnerable to adverse effects on the oral mucosa and hard tissues. This may result in severe oral complications that can affect the quality of life of the oncologic patient. Consequently, oral diagnosis and interdisciplinary management by the stomatologist are critical for cancer treatment, regardless of its location. Objective. To determine the oral health status of cancer patients before, during and after antineoplastic treatment at a cancer institute in the city of Barranquilla, Colombia. Materials and Methods. A descriptive, longitudinal and prospective study of 131 cancer patients, was conducted. The study consisted of initial stomatological assessment of the antineoplastic therapy; classification according to the antineoplastic therapy given by the oncologist; a second stomatological assessment during treatment; and a final stomatological assessment or evaluation forty days after the end of therapy. Descriptive statistics, chi-square and MacNemar test were used to compare and identify variances at the different stages. Results. Female patients accounted for 69%, and breast cancer had 24% prevalence among the included subjects. At the initial stomatological assessment, high frequency lesions were identified, such as generalized biofilm-associated gingivitis in 69% of the cases, followed by oral candidiasis in 61%. The specific prevalence of lesions was 10.65%. In the second stomatological assessment, a greater frequency of periodontal abscesses was observed in 31%, and oral mucositis type II in 18%. The third clinical assessment showed significant changes in oral health status; an increase in the frequency of gingivitis was found in 9.9% (p<0.001); unlike before and during, there was an increment in dental caries of 26.73% (p<0.00000) at this last stage, root remains increased by 39.53% (p<0.00000), and finally, xerostomia increased by 45%. Oral candidiasis was the only lesion that showed improvement. Conclusion. An increase in the number of lesions was observed during and after antineoplastic treatment. The oral cavity is susceptible to antineoplastic treatments; gingivitis, candidiasis, xerostomia, and mucositis were observed, among others conditions.

La quimioterapia y la radioterapia son tratamientos agresivos para el manejo del cáncer, producen susceptibilidad en el sistema estomatogático causando efectos adversos en mucosa bucal y tejidos duros. Esto se traduce a complicaciones bucales agresivas, que afectan la calidad de vida del paciente oncologico, por lo que es fundamental el diagnostic bucal y manejo interdisciplinario que incluya el estomatologo en manejo del cáncer, indistintamente de su localizacion. Objetivo. Determinar el estado de salud bucal antes, durante y después del tratamiento antineoplásico en un instituto oncológico de la ciudad de Barranquilla. Materiales y Métodos. Estudio descriptivo prospectivo longitudinal, con una muestra de 131 pacientes con cáncer. Constó de: valoración estomatológica inicial a la terapia antineoplásica, clasificación según la terapia antineoplásica asignada por el oncólogo, una segunda valoración estomatológica durante los tratamientos, y finalmente una última valoración estomatológica cuarenta días de culminadas las terapias. Se empleó estadística descriptiva, chi cuadrado y prueba de MacNemar para comparar e identificar varianzas en las diferentes fases. Resultados. Un 69% eran del género femenino con frecuencia de cáncer de mama en un 24%. A la valoración estomatológica inicial se identificó alta frecuencia de lesiones como gingivitis asociada a biofilm generalizada en un 69%, seguida de candidiasis oral en un 61%. La prevalencia puntual de lesiones fue de 10,65%. En el segundo examen estomatológico se observó mayor frecuencia de abscesos periodontales en un 31% y mucositis oral tipo II en un 18%, entre otras. La tercera valoración clínica mostró cambios significativos en la salud bucal; se encontró un aumento de la frecuencia de gingivitis en un 9,9% (p<0,001) a diferencia del antes y el durante, igualmente para la caries dental se encontró aumentada en un 26,73% (p<0,00000), restos radiculares aumentó en un 39,53% (p<0,00000) y finalmente la xerostomía aumentando en un 45%, entre otras; la única lesión que mostró mejoria fue la candidiasis oral. Conclusión. Se observó un aumento de las lesiones, durante y después del tratamiento antineoplásico. La cavidad oral es susceptible a los tratamientos antineoplásicos, se relacionan con: gingivitis, candidiasis, xerostomía, mucositis entre otras.

Evaluation of the antioxidant potential of Copaifera multijuga in Ehrlich tumor-bearing mice

Copaifera multijuga, commonly known as copaiba, is popularly used in the form of tea for various conditions due to the presence of antioxidant substances in its composition, which protect cells against damage caused by free radicals. Its oleoresin is also used as an anti-inflammatory and antitumoral agent. The present study investigated the antioxidant effect of the ethanolic extract of copaiba stem bark on Swiss mice inoculated with solid Ehrlich tumors. Mice were inoculated subcutaneously with 1x106 Ehrlich's tumor cells and treated via gavage with ethanolic extract of copaiba for thirty days, with doses varying between 100 and 200 mg kg-1. Biochemical analyses of enzymatic antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST)], non-enzymatic antioxidants [reduced glutathione (GSH) and ascorbic acid (ASA)], substances reactive to thiobarbituric acid (TBARS) and protein carbonylation (carbonyl) in different tissues were significantly affected. The extract administered at 200 mg kg-1 presented higher antioxidant capacity in the liver, increased CAT, GST, GSH and decreased TBARS, as well as increased CAT activity and protein carbonylation in brain tissue. The results showed that the copaiba extract was able to reverse the oxidative stress caused by solid Ehrlich tumor, probably due to the presence of antioxidant compounds, and had potential antineoplasic effect after a 30-day treatment. (AU)

Glioblastoma: approach to treat elderly patients / Glioblastoma: enfoque no tratamento de pacientes idosos

Treating elderly cancer patients is a challenge for oncologists, especially considering the several therapeutic modalities in glioblastoma. Extensive tumor resection offers the best chance of local control. Adequate radiotherapy should always be given to elderly patients if they have undergone gross total resection and have maintained a good performance status. Rather than being ruled out, chemotherapy should be considered, and temozolomide is the chosen drug. A comprehensive geriatric assessment is a valuable tool to help guiding treatment decisions in elderly patients with glioblastoma.

O tratamento de idosos com câncer é um desafio para a prática oncológica, especialmente no que se refere à terapêutica multimodal do glioblastoma. Nessa população, a ressecção ampla do tumor oferece a melhor chance de controle local e, naqueles pacientes que mantenham um bom performance status, a radioterapia complementar deve sempre ser levada em consideração. A quimioterapia também tem um papel no tratamento, sendo a temozolomida a droga de eleição. Frente à heterogeneidade desses pacientes, uma avaliação geriátrica ampla é um instrumento valioso no auxílio da decisão terapêutica em idosos com glioblastoma.

Early administration of peroxisomicine A1 (T-514 extracted from K. parvifolia seeds) causes necrosis of implanted TC-1 cells without affecting target organs in a murine model / La administración temprana de peroxisomicina A1 (T-514 extraída de las semillas de K. parvifolia)causa necrosis de células TC-1 implantadas sin afectar órganos blanco en un modelo murino

Peroxisomicine A1 (PA1), one of the toxins isolated from seeds of plants of the Karwinskia genus, whose targets organs are the liver, kidney, and lungs. There is a selective toxicity in vitro to cancer-cell lines derived from the lungs, liver, and colon, compared to normal cell lines. PA1 caused apoptosis in several cancer-cell lines in culture. In toxic doses to rodents, it causes extensive apoptosis in the liver, kidney, and lungs. In our study we were interested in evaluating, for the first time, the morphological effects of administration of PA1 to implanted TC-1 cells and in the target organs in vivo. The TC-1 cells were cultured and injected into the hind limb of C57BL-6 mice. The animals were divided into 3 groups; those treated with four doses of 1 mg/kg each of PA1, the untreated control, and the vehicle-control groups. All mice were killed 10 days after cell implantation. Samples were obtained from TC-1 cells at the implantation site and from the liver, kidney, and lungs. The samples were processed for examination under light and electron microscopy. In the PA1-treated group, the TC-1 cells had necrosis, whereas in the control groups the tumor cells were undamaged. The target organs did not show any lesions. We demonstrated for the first time that there is a selective toxic effect of PA1 on the TC-1 cells in vivo.

Peroxisomicina A1 (PA1), una de las toxinas aisladas de las semillas de plantas del género Karwinskia, cuyos órganos blanco son hígado, riñón y pulmón. Hay una toxicidad selectiva in vitro contra líneas celulares cancerosas derivadas de pulmón, hígado y colon, comparadas con líneas celulares normales. PA1 causa apoptosis en varias líneas celulares malignas en cultivo. En dosis tóxicas a roedores, causa extensa apoptosis en hígado, riñón y pulmón. En nuestro estudio, estuvimos interesados en evaluar por primera vez los efectos morfológicos de la administración temprana de PA1 sobre células TC-1 implantadas y los órganos blanco in vivo. Las células TC-1 fueron cultivadas e implantadas en la extremidad posterior de ratones C57BL-6. Los animales fueron divididos en tres grupos: tratado con cuatro dosis de 1 mg/kg de peso de PA1, control sin tratamiento y control vehículo. Todos los animales fueron sacrificados 10 días posterior al implante de las células. Se colectaron muestras del sitio del implante de las células TC-1 y de hígado, riñón y pulmón. Las muestras fueron procesadas para su análisis a microscopía de luz y microscopia electrónica de transmisión. En el grupo tratado con PA1, las células TC-1 presentaron necrosis, mientras que en los grupos control las células tumorales se observaron sin daño. Los órganos blanco no mostraron lesión alguna. Demostramos por primera vez que existe un efecto tóxico selectivo de PA1 sobre las células TC-1 in vivo.

Uso neoadjuvante do mesilato de imatinibe no tratamento de GIST retal volumoso: relato de caso / Neoadjuvant use of imatinib mesylate for treatment of large rectal GIST: case report

Tem sido relevante o papel das drogas que interferem na atividade tirosina-quinase dos receptores c-kit, no tratamento dos tumores derivados do estroma gastrintestinal (GISTs), sobretudo em tumores volumosos. Relata-se o caso de um paciente do sexo masculino, 56 anos, obeso, com quadro de peso retoanal associado a tenesmo e à sensação de evacuação incompleta. Foi diagnosticado volumoso GIST de reto inferior de localização posterior, visualizado por ressonância magnética e confirmado por estudo imunoistoquímico em punção-biópsia parassacral, guiada por tomografia. A impressão inicial foi de necessidade de amputação abdômino-perineal do reto, pois havia importante compressão do canal anal e do aparelho esfincteriano. Optou-se, então, por indicação de neoadjuvância com mesilato de imatinibe (Glivec®) na tentativa de preservação esfincteriana. Após quatro meses de tratamento, apresentava, ao toque retal, redução significativa (cerca de 50 por cento) do volume da massa e em menor grau à ressonância magnética. Paciente foi submetido à excisão total do mesorreto e anastomose colo-anal manual, com ileostomia protetora. Evoluiu com necrose do cólon abaixado, tendo sido realizada ressecção do mesmo e colostomia terminal ilíaca. O paciente recusou a se submeter a uma nova tentativa de abaixamento colo-anal, tendo sido fechada a ileostomia e restabelecido trânsito pela colostomia ilíaca. No tratamento dos GISTs de reto muito volumosos ou irressecáveis, deve-se avaliar a indicação pré-operatória do imatinibe, uma vez que a cirurgia radical deve ser sempre indicada, a fim de minimizar a possibilidade de recorrência local.

The role of drugs that intervene with the tirosine kinase activity on the c-kit receptors in the treatment of gastrointestinal stromal tumors (GISTs) has been considered very important, mainly in large tumors. We report a case of a male patient, 56 years-old, obese, presenting with feeling of rectal pressure and incomplete evacuation. Work-up revealed a large inferior rectal GIST located in the posterior wall, suspected on MRI and confirmed by immunohistochemical study of a parasacral biopsy guided by tomography. The supposed initial approach was an abdominoperineal resection, since tumor was compressing anal canal and sphincter complex. In order to save the sphincters, we have decided to refer patient to neoadjuvant treatment with imatinib mesylate (Glyvec®). After four months of treatment, a down staging of tumor was observed during rectal exam (about 50 percent), which was smaller on pelvic RNM. Patient was undergone to total mesorectal excision with manual coloanal anastomosis and protective ileostomy. He presented necrosis of mobilized left colon and underwent to resection, and terminal iliac colostomy. Subsequently, patient refused to undergo through a new coloanal anastomosis and remain with iliac colostomy after ileostomy takedown. In the treatment of unresectable or large rectal GISTs, the use of imantinib should be strongly considered, since that radical surgery is the main approach to reduce the possibility of local recurrence.

Neoadjuvância sistêmica / Systemic neoadjuvance

A neoadjuvância sistêmica é a aplicação de terapia antineoplásica como primeiro tratamento em pacientes sem evidência de metástases e com intenção plena de controle da doença. É tambem chamada de primária, pré-operatória, perioperatória, basal ou de indução. Cada vez mais pacientes estão sendo tratados com quimioterapia (QT), hormonioterapia (HT) e imunoterapia (IT) antes do tratamento cirúrgico e em estágios mais precoces da doença. A chamada Estratégia de Tratamento Multidisciplinar consiste no tratamento sistêmico primário ou adjuvante associada ao tratamento locorregional, através da cirurgia e radioterapia (RT). O tratamento do câncer de mama, em especial o localmente avançado, é baseado nesse planejamento, e a QT com antracíclicos e taxanos ocupa o papel central. Entretanto, a utilização de dados histológicos e marcadores imuno-histoquimicos relacionados a biologia molecular e a expressão genética tumoral conduzem a individualização do tratamento, que consiste na obtenção do máximo de informações disponíveis sobre o tumor para oferecer o tratamento mais adequado para cada paciente. Em relação à IT, ou terapia alvo, muitos ensaios clínicos tem mostrado bons índices de resposta em pacientes HER 2 positivo com esquemas quimioterapicos contendo Trastuzumab. Outras drogas anti-HER 2 também tem sido testadas. A HT neoadjuvante como tratamento único pode ser uma opção adequada em pós-menopáusicas com receptores hormonais (RH) positivo, e os inibidores da aromatase (IA) são a opção de escolha. As principais vantagens do tratamento sistêmico primario consistem na melhora das condições cirúrgicas, uma melhor avaliação do potencial de resposta tumoral a terapia sistêmica e uma possivel melhora da sobrevida.

Systemic neoadjuvant therapy is the first line treatment in patients without evidence of metastasis and with a good control of the disease. It is also named as primary, preoperative, perioperative, basal or induction. Chemotherapy (CT), hormone therapy (HT) and immunotherapy (IT) have been increasingly used before the surgical treatment and in early stages of the disease. The so-called Multidisciplinary Treatment Strategy consists in a primary or adjuvant systemic treatment associated to locoregional treatment through surgery and radiotherapy (RT). Breast cancer treatment, specially the locally advanced, is mainly based on this planning, and CT with anthracyclics and taxanes has the central role. Nevertheless, histologic data and tumor markers, related to molecular biology and tumor genetic expression, have been used to individualize the treatment for breast cancer, by obtaining the maximum available information about the tumor in order to offer the proper treatment for each patient. There are many clinical trials with IT, or target therapy, demonstrating good response rates in patients HER 2positive who used chemotherapy with Trastuzumab. Other anti-HER 2 drugs have been tested. The neoadjuvant HT as single agent can be used as an option in post-menopausal women with positive hormone receptor, and aromatase inhibitors are the drug of choice. The main advantages of primary systemic treatment are better surgical conditions, better evaluation of the potential of the tumor to respond to systemic therapy and, consequently, a better survival rate.