Treatment of low-risk gestational trophoblastic neoplasia comparing biweekly eight-day Methotrexate with folinic acid versus bolus-dose Actinomycin-D, among Brazilian women / Tratamento da neoplasia trofoblástica gestacional de baixo-risco, comparando aplicação quinzenal de oito dias de Metotrexato com ácido folínico versus Actinomicina D em bolo, em mulheres brasileiras

PURPOSE: To compare two single-agent chemotherapy (ChT) regimens evaluating, in first-line treatment, response and side effects and, in final single-agent treatment, the outcomes, among Brazilian patients with low-risk gestational trophoblastic neoplasia (GTN), according to International Federation of Gynecology and Obstetrics (FIGO) 2002. METHODS: Retrospective analysis of two concurrent cohorts with 194 low-risk GTN patients: from 1992 to 2012, as first-line treatment, 115 patients received 4 intramuscular doses of methotrexate alternated with 4 oral doses of folinic acid (MTX/FA) repetead every 14 days and, since 1996, 79 patients received an endovenous bolus-dose of actinomycin D (Act-D), biweekly. At GTN diagnosis, patient opinion was taken into consideration when defining the initial single-agent ChT regimen, and when there was resistance or toxicity to one regimen, the other drug was used preferentially. This study was approved by the Irmandade da Santa Casa de Misericórdia de Porto Alegre Ethical Committee. RESULTS: Both groups were clinically similar (p>0.05). In first-line treatments, frequency of complete response was similar (75.7% with MTX/FA and 67.1% with bolus Act-D); the number of ChT courses -median 3 (range: 1-10) with MTX/FA and 2 (range: 1-6) with bolus Act-D - and the time to remission -median 9 weeks (range: 2-16) with MTX/FA and 10 weeks (range: 2-16) with bolus Act-D) - were not different between the groups. In both groups, first-line side effects frequency were high but intensity was low; stomatitis was higher with MTX/FA (p<0.01) and nausea and vomit with Act-D (p<0.01). Final single-agent ChT responses were high in both groups (94.8% with MTX/FA and 83.5% with bolus Act-D; p<0.01) and 13% higher in the group initially treated with MTX/FA. Rates of hysterectomy and of GTN recurrence were low and similar. No patient died due to GTN. CONCLUSION: The two regimens had similar first-line ChT response. ...

OBJETIVO: Em mulheres brasileiras com neoplasia trofoblástica gestacional (NTG) de baixo-risco, de acordo com a Federação Internacional de Ginecologia e Obstetrícia (FIGO) 2002, comparar dois regimes de quimioterapia (Qt) por agente único avaliando resposta e efeitos colaterais no tratamento de primeira linha, e a eficácia no tratamento final por agente único de Qt. MÉTODOS: Análise retrospectiva de duas coortes concorrentes com 194 pacientes com NTG de baixo risco: de 1992 a 2012; como primeira linha, 115 pacientes receberam 4 doses intramusculares de metotrexato alternado com 4 doses orais de ácido folínico (MTX/FA) repetidos a cada 14 dias e, desde 1996, 79 pacientes receberam quinzenalmente dose em bolo de actinomicina D (Act-D) por via endovenosa. No momento do diagnóstico da NTG, a opinião da paciente foi levada em consideração para definir o regime de Qt por agente único inicial e, quando havia resistência ou toxicidade a um regime, o outro fármaco era usado preferentemente. Este estudo foi aprovado pelo Comitê de Ética da Irmandade da Santa Casa de Misericórdia de Porto Alegre. RESULTADOS: Ambos os grupos eram clinicamente semelhantes (p>0,05). Nos tratamentos de primeira linha, a frequência de resposta completa foi semelhante (75,7% com MTX/FA e 67,1% com Act-D em bolo); não houve diferença entre os grupos quanto ao número de séries de Qt - mediana 3 (intervalo: 1-10) com MTX/FA e 2 (intervalo: 1-6) com Act-D em bolo - e ao tempo para remissão - mediana 9 semanas (intervalo: 2-16) com MTX/FA e 10 semanas (intervalo: 2-16) com Act-D em bolo. Em ambos os grupos, foi elevada a frequência de efeitos colaterais no tratamento de primeira linha, mas com intensidade baixa; estomatite foi mais frequente com MTX/FA (p<0.01) e náuseas e vômitos com Act-D (p<0.01). A resposta final à Qt por agente único foi alta nos dois grupos (94,8% com MTX/FA e 83,5% com Act-D em bolo; p<0,01) e 13% maior no grupo inicialmente tratado com ...

Long-Term Survivals of Stage IIB Osteosarcoma: A 20-Year Experience in a Single Institution

BACKGROUND: The purpose of this study is to evaluate the disease-free survival (DFS) and overall survival (OS) of patients with stage IIB osteosarcoma at a single institution for 20 years and to compare the results according to the chemotherapy protocols. METHODS: From Jan 1988 to Nov 2008, 167 patients with osteosarcoma were treated at our hospital and among them, 117 patients (67 males and 50 females) with stage IIB osteosarcoma were evaluable. Their mean age was 22.6 years (range, 8 months to 71 years). Seventy-eight cases underwent the modified T10 (M-T10) protocol (group 1), 23 cases underwent the T20 protocol (group 2) and 16 cases underwent the T12 protocol (group 3). The DFS and OS were calculated and compared according to the chemotherapy protocols. RESULTS: At a mean follow-up of 78.9 months, 63 patients were continuously disease-free (63/117), 6 patients were alive after having metastatic lesions, 7 patients died of other cause and 41 patients died of their disease. The 5- and 10-year OS rates were 60.2% and 44.8%, respectively and the 5- and 10-year DFS rates were 53.5% and 41.4%, respectively. There was no significant difference of the OS and DFS between the chemotherapy protocols (p = 0.692, p = 0.113). CONCLUSIONS: At present, we achieved success rates close to the internationally accepted DFS and OS. We were able to achieve the higher survival rates using the M-T10 protocol over the 20 years. However, there was no significant difference of results between the chemotherapy protocols. We think the M-T10 protocol will achieve more favorable results in the near future.

Intracaval and intracardiac extension of Wilms' tumor: the influence of preoperative chemotherapy on surgical morbidity

OBJECTIVES: The aim of this retrospective study is to compare surgical complications and long-term survival in children with Wilms' tumor (WT) and tumor thrombus receiving or not preoperative chemotherapy MATERIALS AND METHODS: Review of the charts of 155 children with WT treated between 1983 and 2005, and analysis of 16/155 (10.3 percent) children with WT who presented cavoatrial tumor extension, being 8/16 IVC and 8/16 atrial thrombus RESULTS: Median age was 54 months. 2/16 had cardiac failure as the first symptom. 11/16(7 IVC and 4 atrial extension) (67 percent) were submitted to preoperative chemotherapy with vincristine plus actinomycin D, and 5/16(1 IVC and 4 atrial) (33 percent) underwent initial nephrectomy and thrombus resection. So, 11 patients were submitted to preoperative VCR/ACTD and 2/11 (18.1 percent) had complete regression of the thrombus, 6/11(54.5 percent) partial regression and 3/11 (27 percent) had no response. Among the partial responders, nephrectomy with thrombus removal was performed in all, including one patient with previous intracardiac involvement, without extracorporeal circulation procedures. In two of the three non-responders, cardiopulmonary bypass was necessary for thrombus removal. There were no surgical related deaths. Long-term survival is 91 percent in the group submitted to preoperative chemotherapy and 100 percent in the group who had surgery as first approach CONCLUSION: Preoperative chemotherapy was able to reduce thrombus extension in 8/11 (73 percent) treated patients and cardiopulmonary bypass was avoided in 2 patients with atrial thrombus. Surgical resection of tumor and thrombus was successful in all cases, receiving or not preoperative chemotherapy and overall survival was similar in both groups.

Cytogenetical effects of sonication in mice and their modulations by actinomycin D and a homeopathic drug, Arnica 30.

Experiments were designed to examine if Actinomycin D, an antibiotic, and Amica 30, a homeopathic drug used against shock and injury, can ameliorate cytogenetic damage induced by single or multiple exposures to ultrasonication. Separate sets of healthy mice were directly exposed to sonication for two minutes either once or they received multiple exposures at an interval of 20 days. The mice were then assessed at different intervals, against suitable controls, using parameters like chromosome aberrations (CA), mitotic index (MI), sperm head anomaly (SHA) and micronucleated erythrocytes (MNE). Separate groups of sonicated mice were either orally administered with Arnica 30 (alcohol 30 in control) or injected intramuscularly with Actinomycin-D (AMD). Elevated frequencies of CA, MI, MNE and SHA were noted in sonicated series. AMD had genotoxic effects of its own and also had additive effects on sonication induced genotoxicity. Sonicated mice fed with Arnica 30 showed appreciably reduced genotoxicity as against alcohol 30 and distilled water fed controls, thereby showing ameliorating effect which may have human application.

Serum human chorionic gonadotropin regression pattern in persistent trophoblastic disease during chemotherapy.

The objective of this study was to identify the regression pattern of serum beta-hCG in persistent trophoblastic disease patients after initiating chemotherapy. Eighty-nine women who were diagnosed as persistent trophoblastic disease in King Chulalongkorn Memorial Hospital between January 1985 and December 1998, and received single agent chemotherapy were included. The incidence was 20.2 per cent of total gestational trophoblastic disease patients. Seventy-two (80.9%) from 89 patients were recruited in our study. Sixty-four (88.9%) patients responded to first-line chemotherapy and 8 patients (11.1%) resisted. Suction curettage was done as initial treatment in 61 (84.7%) cases. Most of them (95.8%) received actinomycin-D as first line treatment. Total courses of chemotherapy averaged 4 courses, but increased to 8.5 courses in the resistant group. Mean time of serum beta-hCG to remission was 16.7 and 21.5 weeks in the chemo-sensitive and chemo-resistant group, respectively. Average time to start chemotherapy was in the tenth week, and in the resistant group it was started in the sixth week. Chemotherapy regimen was changed in the fifteenth week. Initial serum beta-hCG levels were not significantly different between the two groups. The reduction rates of beta-hCG were significantly different from the third to the seventh week in the chemo-sensitive and chemo-resistant groups, which was during the second and third course of chemotherapy (P<0.05). In conclusion, by using the reduction rate, the regression pattern of serum beta-hCG level in persistent trophoblastic disease patients was significantly different between the chemosensitive and chemoresistant group from the third to the seventh week after starting chemotherapy.

Detection of early apoptosis and cell death in T CD4+ and CD8+ cells from lesions of patients with localized cutaneous leishmaniasis

Human localized cutaneous leishmaniasis (LCL), induced by Leishmania braziliensis, ranges from a clinically mild, self-healing disease with localized cutaneous lesions to severe forms which can present secondary metastatic lesions. The T cell-mediated immune response is extremely important to define the outcome of the disease; however, the underlying mechanisms involved are not fully understood. A flow cytometric analysis of incorporation of 7-amino actinomycin D and CD4+ or CD8+ T cell surface phenotyping was used to determine whether different frequencies of early apoptosis or accidental cell death occur at different stages of LCL lesions. When all cells obtained from a biopsy sample were analyzed, larger numbers of early apoptotic and dead cells were observed in lesions from patients with active disease (mean = 39.5 + or - 2.7 per cent) as compared with lesions undergoing spontaneous healing (mean = 17.8 + or - 2.2 per cent). Cells displaying normal viability patterns obtained from active LCL lesions showed higher numbers of early apoptotic events among CD8+ than among CD4+ T cells (mean = 28.5 + or - 3.8 and 15.3 + or - 3.0 per cent, respectively). The higher frequency of cell death events in CD8+ T cells from patients with LCL may be associated with an active form of the disease. In addition, low frequencies of early apoptotic events among the CD8+ T cells were observed in two patients with self-healing lesions. Although the number of patients in the latter group was small, it is possible to speculate that, during the immune response, differences in apoptotic events in CD4+ and CD8+ T cell subsets could be responsible for controlling the CD4/CD8 ratio, thus leading to healing or maintenance of disease.

Wilm's tumour with WAGR complex.

WAGR Syndrome is an acronym for a rare constellation of congenital abnormalities which include Wilms' tumor, Aniridia, Genito-urinary malformations and mental Retardation. Fewer than fifty patients of this complex have been described in the literature. We report a case of WAGR syndrome, with Stage-IV Wilms' tumor and intracaval extension, treated by multimodal therapy.

Mono and polichemotherapy in the treatment of metastatic and invasive gestational trophoblastic disease: analysis of 50 cases

Fifty patients with metastatic or invasive gestational trophoblastic disease (GTD) were admited at the "Hospital das clínicas" of the Ribeiräo Preto School of Medicine of the Säo Paulo University between January 1980 and December 1990. Of these 50 patients, 44 (88 per cent) had GTD folliwing abortion, 5 (10 per cent) after term pregnancies and one (2 per cent) after an ectopic pregnancy. Thirty five (70 per cent) had invasive GTD and 15 (30 per cent) metastatic GTD). The sites of metastases were: lung, 8 (53.3 per cent), pelvis, 4 (26,6 per cent), central nervous system, 2 (13.3 per cent) and right auricle, 1 (6.6 per cent). Human chorionic gonadotropin, pelvic arteriography and ultrasonography were used in the diagnosis of invasive GTD. 25 of the 41 patients with low-risk metastatic and invasive GTD were treated with monochemotherapy. There were 6 (24 per cent failures and the remining 19 patients (76 per cents had complete remission of the disease after 3.89 meancycles. Sixteen patients were treated with polichemotherapy, there were 2 (12.5 per cent) failure and the remaining 14 had complete remission after a 2.3 mean cycles. No statistical differences between the two types of chemotherapy were observed. Four (8 per cent)deaths were recorded

Infantile malignant mesenchymoma: limb salvage therapy.

The case of malignant mesenchymoma on the right knee in a 3-month-old infant girl was reported. Combination of treatment, including preoperative radiation, tumor resection, and chemotherapy was given. The patient had been free of the disease for 17 months after diagnosis. Review and emphasis on giving combined modality of treatment and the possibility of saving the extremities for patients with sarcoma were given.

Treatment of advanced seminoma dactinomycin, cyclophosphamide,vinblastine, bleomycin and cisplatinum the VAB-6 protocol

Eighteen ppatients with advanced seminoma (stages IIc-III) were with: cytoxan 600 mg/m2, vinblastine 4 mg/m2, actinomycin D 1 mg/m2, bleomycin 30 mg, i. v. on day 1, followed by bleomycin 30 mg/day by infusion, days 1-3, and cis-platinum 120 mg/m2 on day 4. 9/18 pts. achieved complete remission and have been followed clinically; no recurrences have occurred in this group. The other 9 pts. had residual masses after 3 cycles of chemotherapy; they were taken to surgery and no viable tumor was found on surgical specimens. Thera were 3 recurrences in this group, always distant from the site of original disease. These patients were successfully treated with salvage chemotherapy and radiotherapy. One of these patients died of hepatic failure un related to his seminoma. All the other patients are alive, at a median follow-up of 50 months. This chemotherapy regimen is effective in curing advanced seminoma

Tumores testiculares primarios en niños / Primary testicular tumors in children

Se analizan 37 niños con tumores testiculares de células germinales atendidos en el Hospital Luis Calvo Mackenna entre l968-1984. Los tipos histológicos fueron 26 carcinomas embrionarios infantiles (C.E.I.) 7 teratomas inmaduros y 4 teratomas maduros. Los 26 carcinomas embrionarios se trataron con orquiectomía total, 5 con orquiectomía exclusiva, 5 con orquiectomía y linfadenectomía (histología negativa) y 16 con orquiectomía y quimioterapia M.A.C. (metotrexato, actinomicina D y ciclofosfamida). Los últimos 12 pacientes ingresados se controlaron con alfafetoproteina. De los 7 teratomas inmaduros la orquiectomía fue exclusiva en 2, en 2 se agregó linfadenectomía y en 3 quimioterapia (M.A.C.). En los 4 teratomas maduros se utilizó orquiectomía exclusiva. Fallecieron 4/33 pacientes con tumores malignos de células germinales todos CEI, de estos 2 eran Estadio II y se trataron con orquiectomía exclusiva. 2 Estadio I tratados con orquiectomía y linfadenectomía recayeron y fallecieron. Los 29 restantes están vivos sin evidencia de enfermedad entre a y 16 años, a pesar de que recayeron 5 CEI, 3 de los cuales se trataron con PVB (cis-platinum, vinblastina y bleomicina) con buen resultado. Los tumores de células germinales testiculares malignos, en Estadio I pueden ser tratados solo con cirugía y controlados con niveles de alfafetoproteina y radiografía de tórax. Si recidivan (menos del l5%), pueden ser curados con quimioterapia (PBV)