Subclinical Anthracycline-Induced Cardiotoxicity in the Long - Term Follow-Up of Lymphoma Survivors: A Multi-Layer Speckle Tracking Analysis / Cardiotoxicidade Subclínica Induzida por Antraciclina no Seguimento a Longo Prazo de Sobreviventes de Linfoma: Uma Análise Speckle Tracking Multi-Layer

Abstract Background: Anthracycline generates progressive left ventricular dysfunction associated with a poor prognosis. Objectives: The purpose of this study was to evaluate whether layer-specific strain analysis could assess the subclinical left ventricular dysfunction after exposure to anthracycline. Methods: Forty-two anthracycline-treated survivors of large B-cell non-Hodgkin lymphoma, aged 55.83 ± 17.92 years (chemotherapy group) and 27 healthy volunteers, aged 51.39 ± 13.40 years (control group) were enrolled. The cumulative dose of epirubicin in chemotherapy group was 319.67 ± 71.71mg/m2. The time from last dose of epirubicin to the echocardiographic examination was 52.92 ± 22.32 months. Global longitudinal (GLS), circumferential (GCS) and radial strain (GRS), subendocardial, mid and subepicardial layer of longitudinal (LS-ENDO, LS-MID, LS-EPI) and circumferential strain (CS-ENDO, CS-MID, CS-EPI) values were analyzed. Transmural strain gradient was calculated as differences in peak systolic strain between the subendocardial and subepicardial layers. A value of p < 0.05 was considered significant. Results: Conventional parameters of systolic and diastolic function showed no significant difference between two groups. Compared with controls, patients had significantly lower GCS and GLS. Multi-layer speckle tracking analysis showed significant reduction of circumferential strain of subendocardial layer, transmural CS gradient and longitudinal strain of all three layers. In contrast, the two groups did not differ in transmural longitudinal strain gradient and radial strains. Conclusions: It proved the preferential impairment of subendocardial deformation in long-term survivors after exposure to anthracycline. Multi-layer speckle tracking echocardiography might facilitate the longitudinal follow-up of this at-risk patient cohort.

Resumo Fundamentos: A antraciclina gera uma disfunção ventricular esquerda progressiva associada a um prognóstico ruim. Objetivos: O propósito deste estudo foi avaliar se a análise layer específico de strain poderia avaliar disfunção ventricular esquerda subclínica após exposição a antraciclina. Métodos: Foram inscritos quarenta e dois sobreviventes tratados com antraciclina por linfoma não Hodgkin de células B grandes, de 55,83 ± 17,92 anos (grupo de quimioterapia) e 27 voluntários saudáveis, de 51,39 ± 13,40 anos (grupo controle). A dose cumulativa de epirrubicina no grupo de quimioterapia foi de 319,67 ± 71,71 mg/m2. O tempo desde a última dose de epirrubicina até o exame ecocardiográfico foi de 52,92 ± 22,32 meses. Analisaram-se o strain longitudinal global (GLS), o circunferencial (GCS) e o strain radial (GRS), os valores das camadas subendocárdica, média e subepicárdica so strain longitudinal (LS-ENDO, LS-MID, LS-EPI) e do strain circunferencial (CS-ENDO, CS-MID, CS-EPI). O gradiente de strain transmural foi calculado como a diferença no strain sistólico pico entre as camadas subendocárdicas e subepicárdicas. Um valor de p < 0,05 foi considerado significativo. Resultados: Os parâmetros convencionais da função sistólica e diastólica não mostraram diferenças significativas entre dois grupos. Comparados aos controles, os pacientes apresentaram GCS e GLS significativamente menores. A análise de speckle tracking multi-layer mostrou uma redução significativa no strain circunferencial da camada subendocárdica, o gradiente transmural CS e o strain longitudinal das três camadas. Em contraste, os dois grupos não diferiram no gradiente de strain longitudinal transmural e de strain radiais. Conclusões: Provou-se a deterioração preferencial do strain subendocárdico em sobreviventes de longa duração após exposição à antraciclina. O ecocardiograma de speckle tracking multi-layer pode facilitar o acompanhamento longitudinal dessa coorte de pacientes em risco. (Arq Bras Cardiol. 2018; 110(3):219-228)

Outcome of combined modality treatment including neoadjuvant chemotherapy of 128 cases of locally advanced breast cancer: Data from a tertiary cancer center in northern India.

Background: Breast cancer is now the most common cancer in many parts of India and the incidence varies from 12 to 31/100000, and is rising. Locally advanced breast cancer (LABC) accounts for 30 - 35% of all cases of breast cancers in India. LABC continues to present a challenge and imposes a major health impact in our country. Materials and Methods: We carried out a analysis of our LABC patients who received neoadjuvant chemotherapy (NACT) at our hospital over a 10-year period, from January 1995 to December 2004. We analyzed the response to NACT, disease-free survival (DFS), and overall survival (OS). Results: Patients with stages IIIA, IIIB, and IIIC were included. LABC comprised of 26.24% (609 patients) of new patients. One hundred and twenty-eight (31.1%) patients received NACT. Median age was 48 years and estrogen receptor was positive in 64%. Chemotherapy protocol was an FEC (5-Fluorouracil, Epirubicin, Cyclophosphamide) regimen in the following doses: Cyclophosphamide 600 mg/m2, 5-FU 600 mg/m2, and Epirubicin 75 mg/m2 given every three weeks, six doses, followed by modified radical mastectomy (MRM) and locoregional radiotherapy. The overall response rate (complete response (CR) + partial response (PR)) was 84.4%, clinical CR (cCR) was 13.3% and pathological CR (pCR) was 7.8%. Median DFS and OS were 33 and 101 months, respectively. The disease-free survival (DFS) and overall survival (OS) at five years were 41 and 58%, respectively. Conclusions: This study analyzes the outcome in patients who received NACT, in the largest number of LABC patients from a single center in India, and our results are comparable to the results reported from other centers.

A Case of Therapy-related ALL with MLL Gene Rearrangement Following Treatment of Breast Cancer / 대한진단검사의학회지

ALL with MLL gene rearrangement secondary to chemotherapy has been rarely reported. We report a case of therapy-related ALL (t-ALL) with MLL gene rearrangement in a patient who had undergone treatment for breast cancer. A 60-yr-old woman with breast cancer underwent breast-conserving surgery followed by 6 cycles of adjuvant chemotherapy (cyclophosphamide, epirubicin, and fluorouracil) and radiation therapy (dose, 5,040 cGy to the left breast and a 1,000 cGy boost to the tumor bed). A follow-up examination performed 14 months after the chemotherapy revealed no evidence of breast malignancy. However, the patient's complete blood cell count indicated acute leukemia: white blood cell count, 174.1x10(9)/L with 88% blasts; Hb level, 12.5 g/dL; and platelet count, 103.0x10(9)/L. Examination of the bone marrow aspirate smear revealed a high percentage of blasts (85.1% of all nucleated cells); the blasts showed a pro-B immunophenotype and were positive for CD19, CD79a, HLA-DR, CD34, and terminal deoxynucleotidyl transferase (TdT). Cytogenetic and FISH analyses revealed t(4;11)(q21;q23) and MLL gene rearrangement, respectively. The patient received induction chemotherapy with cyclophosphamide, vincristine, doxorubicin, and dexamethasone and achieved complete remission. Following consolidation chemotherapy, she underwent allogenic peripheral blood stem cell transplantation and has been clinically stable. To our knowledge, this is the first reported case of t-ALL with MLL gene rearrangement following treatment of breast cancer in Korea.

Tumor neuroendocrino metastásico: de células grandes KI-67 negativo / Neuroendocrines metastatic tumor: of big cells negative ki-67

Los tumores neuroendocrinos se consideran neoplasias poco frecuentes de las células de los sistemas neuroendocrinos diseminados o localizados. Poseen presentaciones clínicas y comportamientos biológicos muy heterogéneos. Baja tasa de proliferación celular y capacidad de liberar mediadores biológicos responsables de síndromes clínicos específicos. Tal heterogeneidad no permite un tratamiento estándar, siendo la terapia biológica y la quimioterapia efectiva en el control de enfermedad avanzada. Se presenta el caso de un paciente masculino de 60 años de edad, con enfermedad caracterizada por edema en región cervical izquierda, dura, fija y no dolorosa. Se le programaron 3 ciclos con protocolo 5-Fu, dacarbazina y epirrubicina obteniendo respuesta clínica del 60 por ciento. La heterogeneidad de estas entidades limita el consenso de su tratamiento.

Neuroendocrines tumors are considered neoplasm lees frequent of the cells of neuroendocrines systems disseminated or localized. They have clinical presentation and biologically conduct very heterogeneous: Low tease cellular proliferation and capacity of liberty biologically products responsibility of specifically clinically syndrome. These kind of heterogeneity don’t permit the application of standard treatment, the biologically therapy and chemotherapy are effective in the control of advance disease. We present a clinical case of a 60 years old male patient, with a disease characterized foe edema in left cervical region, hard, fix and no painful. We program 3 cycles with protocol 5-FU, dacarbazine, epirrubicine and obtain a clinical response of 60 %. The heterogeneous of this entity limit the consensus of treatment.

Impact of Grade, Hormone Receptor, and HER-2 Status in Women with Breast Cancer on Response to Specific Chemotherapeutic Agents by in vitro Adenosine Triphosphate-based Chemotherapy Response Assay

This study was designed to assess whether histological and biological factors of breast cancer can predict chemoresponse to specific agents. Adenosine triphosphate-based chemotherapy response assay (ATP-CRA) was employed to retrieve chemoresponse to 5-fluorouracil (5-FU), doxetaxel, doxorubicin, epirubicin, and paclitaxel in 49 patients. Tumors with high histologic and nuclear grade have higher response rate to doxorubicin (P<0.05) and palitaxel (P<0.05). Estrogen receptor (ER)-negative tumors respond well to doxorubicin (P=0.038), and progesterone receptor (PR)-negative tumors to 5-FU (P=0.039), doxetaxel (P=0.038), doxorubicin (P=0.000), epirubicin (P=0.010), and paclitaxel (P=0.003). Among the breast cancer subtypes determined by ER, PR, and HER-2 immunohistochemical stains, the HER-2+/ER- subtype has a higher response rate to doxorubicin (P=0.008). This in vitro result suggests that the combination of histologic and nuclear grade, hormone receptor, and HER-2 status can be a predictive factor of response to specific chemotherapy agents. Further in vivo study should be followed for clinical trials.

Accessory breast tissue in axilla masquerading as breast cancer recurrence.

Ectopic or accessory breast tissue is most commonly located in the axilla, though it may be present anywhere along the milk line. Development is hormone dependent, similar to normal breast tissue. These lesions do not warrant any intervention unless they produce discomfort, thus their identification and distinction from other breast pathologies, both benign and malignant, is essential. We report a case with locally advanced breast cancer who presented with an ipsilateral axillary mass following surgery, radiotherapy, and chemotherapy. Subsequent evaluation with excision biopsy showed duct ectasia in axillary breast tissue and the patient was continued on hormone therapy with tamoxifen.

Chemoreduction Followed by Local Therapy and Adjuvant Chemotherapy for Advanced Intraocular Retinoblastoma: A Pilot Study in a Single Center

Intraocular (IO) retinoblastoma (RB) has traditionally been treated with enucleation (ENU) or external beam radiotherapy (EBRT). Recently, clinical trials are in progress to cure RB without ENU or EBRT in order to salvage the globe and to avoid unacceptable side effects of EBRT. We performed a pilot study to treat patients with advanced Reese-Ellsworth (RE) stage IO RB with initial chemotherapy (CRx) followed by local therapy (LT) and adjuvant CRx. Ten eyes (8 RE group V, 2 RE group IV) from 9 patients were enrolled from March 2001 to November 2001. All tumors responded to CRx. In 5 of 10 eyes, the RB was enough to be treated with LT after chemoreduction. One patient who underwent LT is waiting for ENU due to post-cryotherapy complication. For a median follow-up of 13 months (8-16 mo), 4 eyes that received LT and adjuvant CRx were relapse-free. A patient with bilateral RB who failed to be a candidate for LT was rescued with high-dose CRx and hematopoietic stem cell transplantation. Consequently, by treating patients according to our strategy, we were able to salvage 6 out of 10 eyes without ENU or EBRT. These results suggest that chemoreduction followed by LT and adjuvant CRx might offer the opportunity to salvage the globe and vision even in patients with advanced stage IO RB.

Princípios do tratamento do câncer de mama localmente avançado / Principles of the treatment of locally advanced breast cancer

Câncer de mama localmente avançado é uma forma clínica, que se caracteriza por tumor volumoso, geralmente maior que 5cm, e extenso comprometimento axiliar. Tem importante impacto social devido à sua alta incidência, aproximadamente 40 por cento dos casos diagnosticados no Brasil, e por sua elevada mortalidade. A quimioterapia primária ou neoadjuvante trouxe uma série de benefícios teóricos e práticos, incluindo melhores condiçöes de operatividade e permitindo cirurgias conservadoras. O desenvolvimento de novos quimioterápicos, assim como medidas de suporte hematológico e antiinfeccioso têm permitido o uso de drogas antineoplásticas em altas doses, com melhores resultados no intervalo livre de doença e sobrevida global. A intensificaçäo de doses de quimioterápicos e o tratamento autólogo de medula óssea abrem grande perspectiva de melhor controle dessa doença

Experiencia en uso de epirrubicina endovesical para el tratamiento del cáncer vesical superficial recidivante / Experience in use of endovesical epirubicin for the treatment in superficial relapse bladder cancer

Frente a nuestros pobres resultados con otras alternativas terapéuticas de manejo de Ca vesical superficial recidivante, y basados en Literatura Internacional, hicimos una experiencia con el uso de la Epirrubicina endovesical (post RTU inmediata) en el tratamiento de estos pacientes. Se trata de un grupo de 10 pacientes. Se presentan los resultados, que nos alientan a continuar su uso como terapéutica adyuvante a la resección endoscópica, dado sus efectos favorables, la buen tolerancia y de escasa toxicidad sistémica

Estudo com 4'-epirubicina em linfomas näo-Hodgkin / Study with 4'-epirubucin in non-Kodgkin's lymphomas

Com o objetivo de avaliar a eficácia e a toxicidade da 4'-epirubicina em poliquimioterapia no tratamento de linfomas näo-Hodgkin de alto grau, foram estudados 14 pacientes, sendo nove do sexo masculino e cinco do sexo feminino. A idade mediana dos homens foi de 52 anos e das mulheres, 32 anos. Linfoma histiocítico difuso foi o diagnóstico mais freqüente, representando 50 por cento dos casos. Nove oacientes haviam sido submetidos à cirurga antes do tratamento e um paciente foi submetido à radioerapia antes do início da quimioterapia. Dos 14 pacientes avaliáveis, 10 apresentaram resposta completa (91 por cento) e um apresentou resposta parcial (9 por cento). Dois pacientes faleceram durante o tratamento quimioterápico e um abandonou o tratamento por toxicidade. A duraçäo mediana da resposta foi de 17 meses após o início do tratamento. Com relaçäo à toxicidade, mucosite foi o sintoma mais freqüente, sendo observada em oito pacientes (73 por cento); náuseas e vômitos foram observados em três pacientese diarréia e alopecia, cada uma, em dois pacientes. Quatro pacientes apresentaram contagem plaquetária inferior a 150.000 plaquetas/mm3; nenhum paciente apresentou contagem leucocitária inferior a 2.000 leucócitos/mm3. Concluímos que este protocolo 4'epi é altamente eficaz no tratamento dos L.N.H. de alto grau, embora apresente expressiva toxicidade

5-fluorouracil, 4'-epirubicina, ciclofosfamida (FEC) e acetato de medroxiprogesterona A. D. no tratamento de carcinoma metastático de mama / 5-Fluorouracil, 4'-epirubicin, cyclophosphamide and medroxyprogesterone acetate H. D. in metastic breast cancer

Foram estudados 25 pacientes portadores de carcinoma de mama avançaod, estádio IV, diagnosticado clínica e laboratorialmente por métodos convencionais. O grau de desempenho demonstrado em 48% dos pacientes no início do tratamento foi 1(um), sendo que ao término do mesmo 14% apresentaram grau 0(zero). A mastectomia, como cirurgia prévia, foi realizada em 92% dos pacientes, sendo que em 70% como tratamento inicial. A radioterapia prévia foi realizada em 68% dos pacientes, como também a quimioterapia prévia em 56%. Entre as várias combinaçöes de quimioterapia utilizadas, o esquema FEC (5-fluorouracil, 4'/epirubicina e ciclofosfamida) tem demonstrado ser um dos que obtêm melhores resultados terapêuticos, juntamente com a associaçäo de acetato de medroxiprogesterona A.D. (MAP), resultando em aumento significativo do índice de resposta, duraçäo, tempo livre de doença e melhoria da qualidade de sobrevida. Todos os pacientes incluídos no estudo receberam a combinaçäo fluorouracil 500mg/m2 i.v., 4'/epirubicina 50mg/m2 i.v. e ciclofosfamida 500mg/m2 i.v. no primeiro dia do ciclo. O ciclo repetiu-se a cada três semanas, com um total de 12 ciclos. Acetato de medroxiprogesterona foi administrado na dose de 1.000mg/I.M./dia durante cinco dias em cada semana, por um total de três semanas e, posteriormente, 1.000mg/I.M./semana. Dos pacientes que concluíram o estudo, 28% apresentaram Resposta Completa(RC), 40% Resposta Parcial (RP), 16% Progressäo da Doença (PD) e 16% Resposta Inalterada (IN)...