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Purpose: The main goal of treatment of soft-tissue sarcomas is achieving wide negative margins to improve local control and prevent recurrence. The role of radiation therapy (RT) is well established in sarcomas of the extremities; however, its role in unplanned surgery of soft-tissue sarcoma (when a mass presumed to be benign is resected and the pathology comes back as sarcoma, usually referred to as an "oops" operation) is inconclusive. This article reports on the effect of RT after an unplanned surgery before the reresection. Methods and Materials: A total of 65 patients who had undergone an unplanned resection of a postoperatively diagnosed soft-tissue sarcoma were treated with RT and/or surgery and retrospectively evaluated for disease progression. Treatment started with RT in 49 cases (75.4%), including 8 cases of no further surgery. A repeat wide resection was performed directly after the initial surgery in 16 patients, followed by RT in 15 of them. Results: The disease recurred in 7 out of 49 patients (14.3%) who received RT first and in 9 out of 16 (56.25%) who underwent reoperation before RT (P = .001). Disease-free progression was higher in cases of low-grade malignancy (P = .049). A clinical diagnosis of lipoma was associated with a better outcome than a diagnosis of nonlipoma (P = .034). The presence of residual tumor at reoperation did not affect disease control. Patient age, time between symptom onset and diagnosis, hospital level of initial diagnosis (tertiary versus nontertiary), anatomic site, tumor size, and margin status at the initial excisional biopsy were not significantly correlated with the outcome. Conclusion: Initiating treatment with RT followed by unplanned "oops" resection of soft-tissue sarcoma before the reresection improved disease-free survival as opposed to vice versa.
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BACKGROUND: Most benign active and latent lesions of proximal femur do not predispose a patient to a pathologic fracture. Nonetheless, there is a tendency to perform internal fixation due to the lack of accurate clinical tools that may reliably confirm low risk of pathologic fracture. As many as 30% of these surgeries may be unnecessary. A patient-specific CT-based finite element analysis may quantify bone strength and risk of fracture under normal weight-bearing conditions. METHODS: The clinical relevance of such finite element analysis was investigated in a retrospective study on a cohort of 17 patients. Finite element analysis results (high risk = indication for surgery, low or moderate risk = follow-up) were compared to actual clinical decisions (surgery vs follow-up). All patients predicted by the finite element analysis as high risk underwent internal fixation and had good outcomes (n = 6). FINDINGS: Four of the 11 low- and moderate-risk finite element analysis patients (36%) were operated immediately, and seven (64%) were either operated after a delay of at least 6 months or were never operated. None sustained a pathologic fracture. Patients who were predicted as low fracture risk by finite element analysis remained fracture-free for a minimal period of 6 months. Prediction of high risk of pathologic fracture by finite element analysis was in complete agreement with the conventional clinical evaluation. INTERPRETATION: We consider finite element analysis a promising decision support system for the management of patients with benign tumors of femur, and that it may reliably endorse the decision to withhold surgery for patients at low fracture-risk.
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Fêmur/diagnóstico por imagem , Fêmur/lesões , Análise de Elementos Finitos , Fraturas Ósseas/diagnóstico por imagem , Adulto , Idoso , Estudos de Coortes , Feminino , Fêmur/patologia , Fêmur/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Tomografia Computadorizada por Raios X/métodos , Suporte de CargaRESUMO
PURPOSE: We report the unexpected absence of early relapse (before 30 months) in 24 consecutive patients with isolated limb primary Ewing sarcoma treated with an intensified pilot protocol, SCMCIE94. METHODS: Clinical data for the study were collected retrospectively from the patient files. The protocol included 6 courses of chemotherapy, split radiation, and limb salvage surgery. This SCMCIE94 protocol had been used in almost all the patients described in an earlier report, in whom those with non-pelvic isolated tumors and low/absent CD56 expression in Ewing sarcoma tumor cells were all long-term survivors. RESULTS: The 5-year (10-year) event-free survival rate for the patients with isolated limb primary Ewing sarcoma was 78.95 ± 8.3% (68.6 ± 10.0%) and the overall survival rate was 90.7 ± 6.2% (71.1 ± 11.2%). There were no relapses before 30 months in any of these patients. CONCLUSION: The intensified SCMCIE94 pilot protocol has been shown previously to cure patients with localized CD56-negative non-pelvic Ewing sarcoma. The present study shows that among all patients with localized extremity disease who were treated with this protocol, there were no cases of early relapse. Although our cohort was small, the difference in results from studies using other protocols is so striking, that it would seem reasonable to assume it is attributable to the changes made in the protocol itself rather than risk factors. Late relapses of isolated limb CD56-positive Ewing sarcoma suggest minimal residual disease warranting additional therapeutic approaches such as autologous stem cell rescue after Busulfan Melfelan.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Ósseas/terapia , Sarcoma de Ewing/terapia , Neoplasias Ósseas/patologia , Antígeno CD56/metabolismo , Terapia Combinada , Intervalo Livre de Doença , Humanos , Salvamento de Membro/métodos , Recidiva Local de Neoplasia , Projetos Piloto , Estudos Retrospectivos , Sarcoma de Ewing/patologia , Taxa de SobrevidaRESUMO
This study evaluated the effect of an intensified pilot protocol, SCMCIE 94, on the outcome of Ewing sarcoma (EWS). The cohort included 121 patients with local or metastatic EWS treated at a tertiary pediatric medical center with the SCMCIE 94 (protocol 3, 1994 to 2011) or an earlier protocol (protocol 2, 1988 to 1994; protocol 1, 1985 to 1988). All protocols included 4 to 6 courses of chemotherapy, radiation, and surgery. Clinical data were collected retrospectively by chart review. Survival rates for protocol 3 were as follows: all patients-5-year event-free survival (EFS): 52.5%±5.6%, 10-year EFS: 49.3%±5.8%, 5-year overall survival (OS): 68.8%±5.3%, and 10-year OS: 51.1%±6.3%; patients with localized disease (any site)-5-year EFS: 63.5%±6.0% and 5-year OS: 77.2%±5.3%; patients with localized extremity disease-5-year EFS: 78.95%±8.3%, 10-year EFS: 68.6%±10.0%, 5-year OS: 90.7%±6.2%, and 10-year OS: 71.1%±11.2%. Protocol 3 was associated with an increase in 10-year EFS of 16% overall and 33% in patients with localized extremity disease compared with protocols 1+2, and a significant improvement in 5-year EFS and OS in patients with any localized disease (P=0.001). No survival benefit was found for metastatic disease. On multivariate analysis, protocol and metastatic disease were significantly independent prognostic factors. The intensified SCMCIE 94 protocol seems to increase survival in patients with localized but not metastatic EWS.
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Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/terapia , Adolescente , Adulto , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Metástase Neoplásica , Projetos Piloto , Sarcoma de Ewing/patologia , Taxa de SobrevidaRESUMO
Ewing Sarcoma (ES) is the second most common primary malignant bone tumor in children and adolescents. microRNAs (miRNAs) are involved in cancer as tumor suppressors or oncogenes. We studied the involvement of miRNAs located on chromosomes 11q and 22q that participate in the most common translocation in ES. Of these, we focused on 3 that belong to the let-7 family.We studied the expression levels of let-7a, and let-7b and detected a significant correlation between low expression of let-7b and increased risk of relapse. let-7 is known to be a negative regulator of the RAS oncogene. Indeed, we detected an inverse association between the expression of let-7 and RAS protein levels and its downstream target p-ERK, following transfection of let-7 mimics and inhibitors. Furthermore, we identified let-7 as a negative regulator of HIF-1α and EWS-FLI-1. Moreover, we were able to show that HIF-1α directly binds to the EWS-FLI-1 promoter. Salirasib treatment in-vitro resulted in the reduction of cell viability, migration ability, and in the decrease of cells in S-phase. A significant reduction in tumor burden and in the expression levels of both HIF-1α and EWS-FLI-1 proteins were observed in mice after treatment.Our results support the hypothesis that let-7 is a tumor suppressor that negatively regulates RAS, also in ES, and that HIF-1α may contribute to the aggressive metastatic behavior of ES. Moreover, the reduction in the tumor burden in a mouse model of ES following Salirasib treatment, suggests therapeutic potential for this RAS inhibitor in ES.
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Regulação Neoplásica da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , MicroRNAs/metabolismo , Sarcoma de Ewing/metabolismo , Proteínas ras/metabolismo , Adolescente , Adulto , Animais , Antineoplásicos/uso terapêutico , Ciclo Celular , Movimento Celular , Sobrevivência Celular , Criança , Pré-Escolar , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 22/genética , Intervalo Livre de Doença , Farneseno Álcool/análogos & derivados , Farneseno Álcool/uso terapêutico , Feminino , Inativação Gênica , Genes Supressores de Tumor , Humanos , Lactente , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Transplante de Neoplasias , Proteínas de Fusão Oncogênica/metabolismo , Proteína Proto-Oncogênica c-fli-1/metabolismo , Proteína EWS de Ligação a RNA/metabolismo , Distribuição Aleatória , Salicilatos/uso terapêutico , Sarcoma de Ewing/patologia , Transdução de Sinais , Adulto JovemRESUMO
PURPOSE: Aggressive chemotherapy protocols for non-metastatic limb osteosarcoma have improved histological response without affecting prognosis. This study evaluated the toxicity and outcome of a dose-intensive, high-dose 3- to 5-drug pilot protocol, SCOS 89. METHODS: The cohort included 26 patients (14 male; ages 6.5-22 years) with non-metastatic limb osteosarcoma treated at a tertiary pediatric medical center between 1989 and 2013. Preoperatively, patients received two courses of once-weekly pulses of high-dose methotrexate (12-30 g/m(2)) for 2 weeks; doxorubicin (90 mg/m(2)) with dexrazoxane, combined with cisplatin (200 mg/m(2)), was added in week 3. Following methotrexate, 760 mg/m(2) of folinic acid was administered. Postoperative chemotherapy was continued to a total of 14 courses of methotrexate, doxorubicin (up to a total dose of 360 mg/m(2)), and cisplatin (up to a total dose of 560 mg/m(2)). If toxicity occurred or <90 % tumor necrosis, ifosfamide (12 g/m(2)) plus etoposide (500 mg/m(2)) was substituted for doxorubicin, cisplatin, or methotrexate. Toxicity and death rates were calculated. RESULTS: All patients underwent definitive limb salvage surgery. Six patients died of infection, recurrent disease, or secondary malignancy. Median follow-up was 100 months (range 2-290). Event-free and overall survival rates, respectively, were 88 and 96 % at 2 years, 80 and 87.6 % at 5 years, 80 and 78 % at 10 years. Eleven patients required ifosfamide/etoposide substitution. One patient had a transient decreased left ventricular ejection fraction. Two patients developed acute nephrotoxicity during therapy, but no neurotoxicity. Seven patients had hearing impairment. CONCLUSIONS: The SCOS 89 yields a high event-free survival rate with reduced nephro-/neuro-/cardiotoxicity in patients with non-metastatic limb osteosarcoma.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/cirurgia , Criança , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Terapia Combinada , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Substituição de Medicamentos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Seguimentos , Perda Auditiva/induzido quimicamente , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Nefropatias/induzido quimicamente , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Osteossarcoma/cirurgia , Projetos Piloto , Volume Sistólico/efeitos dos fármacos , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Four hundred and twenty-six participants volunteered to participate in this study. A total of 159 men and 281 women comprised the sample. The sample was composed of 99 cancer stricken patients, 97 caregivers, 124 participants from the general population, and 126 people who were related to them in a similar manner that caregivers were related to patients (i.e. spouse, intimate partner, child, family member, etc.). Utilizing the Loneliness Questionnaire, the Multidimensional Scale of Perceived Social Support (MPSS), and the Sense of Coherence (SOC) questionnaires, it was found that significant differences among the four groups were found on Reflection and Acceptance, Self-development and Understanding, Social Support Network, Distancing and Denial, and on the Increased Activity subscales. Significant differences were not found on the Religion and Faith subscale. The findings are interpreted in light of the analyses of the other two measures which address the social support that patients and caregivers received and their SOC.
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Adaptação Psicológica , Cuidadores/psicologia , Solidão/psicologia , Neoplasias/enfermagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Escolaridade , Saúde da Família , Feminino , Humanos , Israel , Masculino , Estado Civil , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/psicologia , Religião , Senso de Coerência , Apoio Social , Inquéritos e Questionários , Adulto JovemRESUMO
OBJECTIVE: Chondrosarcomas (CS) represent a heterogeneous group of rare sarcomas, poorly responsive to chemotherapy or radiotherapy. When local therapies in recurrent or metastatic disease are exhausted, chemotherapy plays a marginal role. Different molecular pathways have been shown to be activated in CS. In this retrospective study, we summarize our experience in treating a cohort of patients with recurrent unresectable CS with a combination of sirolimus (SIR) and cyclophosphamide (CTX). PATIENTS AND METHODS: Ten consecutive patients with unresectable CS were offered off-label treatment with SIR and CTX between 2007 and 2012. Tumor response, progression-free survival (PFS), adverse events, and other relevant clinical data were analyzed. RESULTS: The median patients' age was 49 (range 28-68). Median disease-free interval since the primary diagnosis was 22.5 months. Median time from the disease recurrence to initiation of SIR and CTX treatment was 21.7 months due to additional local surgical treatments, excision of metastases, or slow asymptomatic progression. One (10 %) objective response was observed, and six (60 %) patients had stabilization of disease for at least 6 months. Three patients had progressive disease. Median PFS was 13.4 months (range 3-30.3). No significant adverse events were observed. CONCLUSIONS: Although advanced CS remains an incurable disease, our experience suggests that a combination of SIR and CTX is well tolerated and may have meaningful clinical activity with disease control rate of 70 %. Further prospective studies are warranted.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Condrossarcoma/tratamento farmacológico , Condrossarcoma/patologia , Sirolimo/administração & dosagem , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adulto , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/efeitos adversos , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Neoplasias Ósseas/metabolismo , Condrossarcoma/metabolismo , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sirolimo/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Ketamine induces a short-term effect on postoperative pain when administered intravenously immediately before or during acute pain. Repeated administration of low-dose ketamine may induce long-term pain relief in chronic pain syndromes. OBJECTIVE: The aim of our study was to determine whether ketamine's effect on acute postoperative pain could be enhanced and prolonged and analgesia consumption reduced if it was administered intramuscularly in repeated and escalating subanesthetic doses many hours before surgery. METHODS: Patients who were scheduled for tumor resection under general anesthesia were randomly and blindly given preoperative IM ketamine (K) or normal saline (placebo [P]) following 1 of 3 consecutive protocols (2 groups/protocol, 20 patients/group): 1 dose (25-mg ketamine or 1-mL saline) at 4 hours preoperatively (K1 or P1); 2 doses (10- and 25-mg ketamine or 1-mL saline twice) at 11 and 4 hours (K2 or P2); or 3 doses (5-, 10-, and 25-mg ketamine or 1-mL saline thrice) at 17, 11, and 4 hours preoperatively (K3 or P3). No other preoperative medications were given. Postoperatively, all patients received morphine (1.5 mg/bolus) via an intravenous patient-controlled analgesia (PCA) device. RESULTS: A total of 120 patients took part in the study. Patients' ages ranged from 15 to 75 years; mean weight (76 [14] kg; range, 50-120), gender (69 men, 51 women), and race were equally distributed among the groups. There were no significant differences in intraoperative parameters among the groups. The patients' mean self-rated 48-hour pain scores on a numerical rating scale were lower in the K2 and K3 groups than in their corresponding placebo groups (K2: 1.67 [1.04] vs P2: 3.62 [1.93] [P = 0.0004]; K3: 2.22 [1.37] vs P3: 3.25 [1.76] [P = 0.046]). These groups also used â¼35% less morphine compared with the placebo groups (K2: 28.4 [20.4] mg, K3: 26.6 [16.0] mg vs P2: 42.4 [30.4] mg, P3: 40.9 [21.2] mg [P ≤ 0.02]). Intravenous PCA usage among K2 and K3 patients was â¼50% less than the usage among their placebo counterparts (P < 0.05). The 1-ketamine-injection patients' pain scores and analgesic consumption were similar to those of their placebo groups. The 25-mg-ketamine injections caused dizziness that lasted up to 2 minutes. CONCLUSIONS: Our 48-hour data suggest that 2 or 3 escalating subanesthetic doses of IM ketamine injected consecutively hours before surgery attenuated postoperative pain and reduced morphine consumption in these subjects.
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Analgésicos/uso terapêutico , Ketamina/uso terapêutico , Neoplasias/cirurgia , Dor Pós-Operatória/tratamento farmacológico , Adolescente , Adulto , Idoso , Analgesia Controlada pelo Paciente/métodos , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Analgésicos Opioides/administração & dosagem , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Morfina/administração & dosagem , Cuidados Pré-Operatórios/métodos , Adulto JovemRESUMO
Radiotherapy (RT) is our preferred modality for local palliation of metastatic soft tissue sarcoma (STS). A short and intense course of RT is usually needed for rapid palliation and local control of metastatic disease. Seventeen patients at a median age of 61 had symptomatic metastatic sarcoma and required rapid palliation. The symptoms related to the metastases were either pain or discomfort. All patients were treated by a short and intensive course of administration: 39 Gy were given in 13 fractions of 3 Gy/day, 5 times a week. Median follow-up period was 25 weeks. The treatment was well tolerated. Acute side effects included grade one skin toxicity. No wound complications were noted among those undergoing surgery. Late side effects included skin pigmentation and induration of irradiated soft tissues. Durable pain control was achieved in 12 out 15 cases treated for gross metastases. Tumor progression was seen in the 3 other cases within a period of two to nine months. Among 5 lesions which were irradiated as an adjunctive treatment following resection, no local recurrence was observed. The results of this series, although limited in size, point to the safety and feasibility of hypofractionated RT for palliation of musculoskeletal metastases from sarcoma.
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PURPOSE: Most children today with bone sarcomas undergo limb-sparing surgery. When treating children younger than 12 years of age, the result is significant limb length discrepancy (LLD). One of the solutions is the use of an expandable endoprosthesis. METHODS: A retrospective analysis of 38 skeletally immature patients with bone sarcoma of the lower limb in whom different types of expandable endoprostheses were used from January 1988 to December 2005 were included. All patients were under the age of 14 years. There were 26 osteosarcoma and 12 Ewing's sarcomas. The data collected included the tumor characteristics, the surgical and other treatment modalities, complications and their treatment, and the final LLD and functional results. RESULTS: Fifty-five percent of the patients survived and had a mean follow-up of 113 months. All survivors reached skeletal maturity at the time of last follow-up. Seventy-one percent of the survivors had satisfactory function and 29% had a poor result. There were three secondary amputations due to local recurrence. Complications were documented in 58% of patients; the most common was infection that was diagnosed 56 times (primary 16% and secondary 84%). A significant correlation was found between function and final LLD (greater than 5 cm = inferior function), the number of complications, and the number of surgical procedures performed other than prosthesis elongation. The younger the patient was at definitive surgery, the shorter the time it took for the prosthesis to fail. CONCLUSION: In order to improve results, the number of operations must be reduced. This can be achieved by the use of novel non-invasive expandable endoprostheses or biological reconstruction.
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The authors describe a 6-year-old boy diagnosed with alveolar rhabdomyosarcoma located in the thigh, with distal metastases to lungs, bones, and bone marrow. A very good partial response to first-line chemotherapy was obtained, but the child developed fatal leptomeningeal dissemination immediately after complete resection of the primary tumor. This case demonstrates the rapidity with which leptomeningeal spread of extracranial metastatic alveolar rhabdomyosarcoma can occur and underscores the importance of diagnostic lumbar puncture and brain radiological investigations at diagnosis, even when the tumors are not in the parameningeal location.
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Neoplasias da Medula Óssea/secundário , Neoplasias Encefálicas/secundário , Neoplasias Pulmonares/secundário , Neoplasias Meníngeas/secundário , Rabdomiossarcoma Alveolar/secundário , Neoplasias de Tecidos Moles/patologia , Neoplasias da Medula Óssea/tratamento farmacológico , Neoplasias Encefálicas/tratamento farmacológico , Criança , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Neoplasias Meníngeas/tratamento farmacológico , Coxa da PernaRESUMO
BACKGROUND: Ewing sarcoma (ES) is the second most common solid bone and soft tissue malignancy in children and young adults with low cure rates indicating the need to identify further prognostic markers. The importance of methylation in the inactivation of key tumor suppressor genes including RASSF1A has begun to be appreciated in context of cancer development, prognosis and therapy. However there is lack of similar broad based studies in ES. The objective of this study was to analyze RASSF1A methylation and assess its clinical significance in ES. PROCEDURE: The methylation of RASSF1A was determined 31 ES tumor samples and 4 ES cell lines. ES cell lines were also treated with demethylating agent 5-aza-2'-deoxycytidine to ascertain its effect on methylation. RASSF1A expression was studied in 12 ES tumors. The association between RASSF1A methylation, clinical parameters and outcome was also analyzed. RESULTS: Methylation of RASSF1A was observed in 21/31 (68%) tumors and in 3/4 ES cell lines. A significant correlation of methylation to reduced expression of RASSF1A was observed in 12 ES tumors analyzed (P = 0.0013) and in all cell lines. ES patients with methylated RASSF1A had worse prognosis compared to the unmethylated group (P = 0.049). Treatment with 5-aza-2'-deoxycytidine resulted in the re-expression of the unmethylated form of RASSF1A in two ES cell lines. CONCLUSION: RASSF1A is frequently methylated in ES.
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Metilação de DNA , Inativação Gênica , Sarcoma de Ewing/genética , Proteínas Supressoras de Tumor/genética , Linhagem Celular Tumoral , Criança , Humanos , Proteínas Supressoras de Tumor/metabolismoRESUMO
BACKGROUND: Postoperative pain in patients with bone and soft tissue cancer is different from that of other surgical patients due to the severity of the pain generated during surgery and because many of them have already been in pain preoperatively. The search for optimal intravenous pharmacologic management for this population is an ongoing one. We conducted a 10-month prospective, randomised, double blind study to compare the effects of a standard morphine dose to a 35%-lower dose plus a subanaesthetic dose of ketamine for postoperative pain control in patients undergoing bone and soft tissue cancer surgery under standardised general anaesthesia. METHODS: After extubation, when objectively awake (>or=5/10 on a 0-10 visual analogue scale (VAS)) and complaining of pain (>or=5/10 VAS), patients were connected to an intravenous patient-controlled analgesia (IV-PCA) device that delivered 1.5 mg morphine/bolus (MO group) or 1 mg morphine+5mg ketamine/bolus (MK group), with a 7 min lockout time. Rescue intramuscular diclofenac 75 mg was available Q4/day. Follow-up lasted 96 h. RESULTS: Fifty-seven patients (24 males, aged 18-74 years) completed the study. Pain scores were lower in the MK group compared to the MO patients, although MO patients (n=29) used 32.9+/-24.9 mg/patient morphine during the first 24 postoperative h compared to 14.6+/-11.4 mg/patient (P<0.05) for the MK patients (n=28). At that time point, 11 MO versus 4 MK patients still required IV-PCA (P<0.05). Diclofenac was also used more in the MO group. All vital signs were similar between the groups. The physiotherapy score was 35% higher for the MK patients (P<0.05). No patient had hallucinations. Postoperative nausea and vomiting rates were higher in the MO group. CONCLUSIONS: The use of subanaesthetic ketamine plus 2/3 the standard dose of morphine following bone and tissue resections results in 1) lower and more stable pain score, 2) approximately 60% morphine sparing effect, 3) a shorter period of postoperative IV-PCA dependence. Such therapy is also associated with better early physical performance.
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Analgésicos/administração & dosagem , Neoplasias Ósseas/cirurgia , Ketamina/administração & dosagem , Morfina/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Neoplasias de Tecidos Moles/cirurgia , Adolescente , Adulto , Idoso , Análise de Variância , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Infusões Intravenosas , Ketamina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Morfina/efeitos adversos , Medição da Dor , Modalidades de Fisioterapia , Náusea e Vômito Pós-Operatórios/induzido quimicamente , Estudos ProspectivosRESUMO
BACKGROUND: Simple resection of diffuse pigmented villonodular synovitis of the ankle joint is associated with local recurrence rates as high as 50%. Thus, adjuvant treatment modalities, such as radiation or intra-articular isotope injection, are sometimes used after tumor resection. Our initial and highly satisfactory experience with the injection of radioactive yttrium 90 to treat pigmented villonodular synovitis of the ankle joint eroded with time so much so that we discontinued its use in the ankle and believe that it is important to alert our colleagues to the complications that we observed. METHODS: Between 1989 and 2006, we treated seven patients who had diffuse pigmented villonodular synovitis of the ankle joint with subtotal synovectomy followed by intra-articular injection of 15 mCi of yttrium 90. RESULTS: Two of the study patients had full-thickness skin necrosis develop around the injection site, necessitating free muscle flap transfer within three months of treatment, and a third patient had development of a draining sinus that was associated with chronic severe pain. The other four patients reported pain after the injection that was reasonably controlled by the use of nonsteroidal anti-inflammatory drugs. At the most recent follow-up evaluation, no study patient had recurrent disease. CONCLUSIONS: Because of the unacceptably high rate of serious complications associated with the injection of yttrium 90 into the ankle joint following subtotal synovectomy, we discontinued its use as a local adjuvant in the management of diffuse pigmented villonodular synovitis of the ankle.
Assuntos
Compostos Radiofarmacêuticos/efeitos adversos , Sinovite Pigmentada Vilonodular/radioterapia , Radioisótopos de Ítrio/efeitos adversos , Adulto , Articulação do Tornozelo , Artralgia/etiologia , Doença Crônica , Feminino , Humanos , Injeções Intra-Articulares , Masculino , Pessoa de Meia-Idade , Necrose , Complicações Pós-Operatórias , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Compostos Radiofarmacêuticos/administração & dosagem , Radioterapia Adjuvante/efeitos adversos , Pele/patologia , Sinovectomia , Sinovite Pigmentada Vilonodular/cirurgia , Radioisótopos de Ítrio/administração & dosagemRESUMO
OBJECTIVE: The incidence of musculoskeletal tumors during pregnancy is very low. The aim of this study was to summarize our experience in treating a large cohort of pregnant patients diagnosed with these rare tumors. METHODS: Women diagnosed with musculoskeletal tumors during pregnancy or immediately after delivery were identified retrospectively in our database between 1996 and 2006. Relevant maternal and neonatal data were collected. RESULTS: Twenty patients, 8 with bone sarcomas (BS) and 12 with soft tissue sarcomas (STS) were identified. Two women were treated by wide excision of mass during pregnancy. In all other cases oncological treatment was delayed until delivery or termination of pregnancy. Vaginal delivery was possible in 9 patients, cesarean section was performed in 7, spontaneous abortion occurred in 1, and 3 underwent termination of pregnancy. Three newborns were premature, but normal growth and development were observed. Different techniques of fertility preservation were used in our patients. Five patients with BS and 5 patients with STS received preoperative chemotherapy, with different grades of toxicity. The degree of tumor necrosis tended to correlate with dose-intensity of chemotherapy. Seven patients with BS received adjuvant chemotherapy. Two patients with STS received adjuvant chemotherapy, two - radiotherapy, and four - both modalities. Median disease-free survival was 15.1 months, median overall survival - 25.4 months. CONCLUSIONS: Musculoskeletal tumors diagnosed during pregnancy, or after delivery, do not appear to have a significant impact on the prognosis. A multidisciplinary team should tailor the oncological approach individually.
Assuntos
Neoplasias Ósseas/terapia , Parto Obstétrico , Complicações Neoplásicas na Gravidez/terapia , Sarcoma/terapia , Neoplasias de Tecidos Moles/terapia , Aborto Induzido , Adulto , Neoplasias Ósseas/complicações , Neoplasias Ósseas/mortalidade , Estudos de Coortes , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Gravidez , Complicações Neoplásicas na Gravidez/mortalidade , Resultado da Gravidez , Prognóstico , Estudos Retrospectivos , Sarcoma/complicações , Sarcoma/mortalidade , Neoplasias de Tecidos Moles/complicações , Neoplasias de Tecidos Moles/mortalidade , SobrevidaRESUMO
PURPOSE: Despite advances in therapy, >50% of patients with Ewing sarcoma will relapse. The current prognostic factors are not optimal for risk prediction. Studies have shown that telomere length could predict outcome in different malignancies. Our aim was to evaluate whether telomere length could be a better prognostic factor in Ewing sarcoma and correlate the results with clinical variables, outcome, and chromosomal instability. EXPERIMENTAL DESIGN: Telomere length was determined in the primary tumor and peripheral blood of 32 patients with Ewing sarcoma. Chromosomal instability was evaluated by combining classical cytogenetics, comparative genomic hybridization and random aneuploidy. Telomere length was correlated to clinical variables, chromosomal instability, and outcome. RESULTS: In 75% of the tumors, changes in telomere length, when compared with the corresponding peripheral blood lymphocytes, were noted. The majority of changes consisted of a reduction in telomere length. Patients harboring shorter telomeres had a significantly adverse outcome (P = 0.015). Chromosomal instability was identified in 65% of tumors, significantly correlating with short telomeres (P = 0.0094). Using multivariate analysis, telomere length remained the only significant prognostic variable (P = 0.034). Patients with short telomeres had a 5.3-fold risk of relapse as compared to those with unchanged or longer telomeres. CONCLUSION: We have shown that tumors with telomere length reduction result in genomic instability. In addition, telomere length reduction was the only significant predictor of outcome. We suggest that reduction of telomere length in tumor cells at diagnosis could serve as a prognostic marker in Ewing sarcoma.
Assuntos
Sarcoma de Ewing/genética , Sarcoma de Ewing/patologia , Telômero/ultraestrutura , Adolescente , Adulto , Criança , Pré-Escolar , Instabilidade Cromossômica , Cromossomos/ultraestrutura , Feminino , Humanos , Lactente , Masculino , Análise Multivariada , Hibridização de Ácido Nucleico , Prognóstico , Recidiva , Risco , Fatores de Risco , Sarcoma de Ewing/diagnóstico , Resultado do TratamentoRESUMO
BACKGROUND: Dedifferentiated chondrosarcoma has a very poor prognosis. Because of its rarity, there are few large studies of outcome which might identify potential prognostic factors. In particular there remains uncertainty about the value of chemotherapy for this condition. METHOD: A retrospective study was done using data supplied by members of the European Musculo Skeletal Oncology Society (EMSOS). We obtained data on 337 patients from nine European centres with this rare condition, with details on patients, treatment and outcome which were then analysed in an attempt to identify prognostic features. RESULTS: The median age was 59 years and there was a slight predominance of males (53%). The most common sites were the femur and pelvis. Twenty-nine percent of patients with a long bone tumour had a pathological fracture. 71 patients (21%) had metastases at the time of diagnosis and these patients had a median survival of 5 months with a 10% chance of survival at 2 years. For the 266 patients without metastases at diagnosis, 254 underwent surgery with 79% having limb salvage. Thirty-one percent of these 266 patients had chemotherapy with 47% of those under 60 receiving it. In this group of 266 patients, overall survival was 28% at 10 years and poor prognostic factors were the presence of a pathological fracture at diagnosis, a pelvic location and increasing age. Local recurrence and overall survival were related to inadequate margins of excision. We did not find that the histological subtype, size of the tumour or the use of chemotherapy significantly affected outcome. For all patients the overall survival was 24% at 5 years. CONCLUSIONS: The prognosis for patients with dedifferentiated chondrosarcoma remains dismal. Surgery with clear margins remains the principal treatment for this condition. Further use of chemotherapy should be within a trial or treatment protocol.
Assuntos
Neoplasias Ósseas/mortalidade , Condrossarcoma/mortalidade , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Condrossarcoma/tratamento farmacológico , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Tumors of the axilla are rare and pose a surgical challenge because they are usually large at presentation and in close proximity to the major neurovascular bundle of the upper extremity. The use of detailed preoperative evaluation studies and extensile surgical exposure for these tumors enabled us to determine tumor resectability and proceed with a safe resection or perform an amputation when required. We retrospectively reviewed 27 patients who underwent resection of an axillary tumor from 1989 to 2004 and analyzed their presenting symptoms, results of preoperative studies, type of surgery, and functional outcome. Tumors were exposed using a utilitarian shoulder approach that revealed no tumor invasion of the neurovascular bundle in 19 patients and invasion in eight. The former group was treated with tumor resection and the latter with forequarter amputation. Neurologic deficit, limb edema, and angiographic observation of arterial narrowing were associated with amputation. Good function was achieved in 15 of 19, shoulder range of motion was preserved in 14 of 19, and local tumor control was maintained in 16 of 19 patients who underwent a limb-sparing resection.