RESUMEN
BACKGROUND: Gorham disease is a rare pathological condition characterised by a proliferation of vascular channels of haematic and lymphatic origin in bone and adjacent soft tissues, which results in a progressive destruction of the involved bone segment. AIM: To evaluate expression of the vascular endothelial cell marker CD105/endoglin in Gorham disease of bone. METHODS: An immunohistochemical analysis was conducted on four cases of Gorham disease of bone, and for comparison on eight cases of conventional haemangioma of bone and on normal fetal and adult bone tissue specimens. RESULTS: Diffuse and intense immunostaining of endothelial cells for CD105 was observed in the specimens of fetal bone in areas undergoing ossification and in the growth plate of young adults. In medullary bone, CD105 positivity was limited to sinusoids of haemopoietic marrow, while endothelial cells of capillaries and small arterioles and venules within fatty marrow were either negative or showed weak immunostaining. The mean percentage of positive vessels in Gorham disease was significantly higher than in osseous haemangioma (58.9 (SEM 14.9) vs 17.2 (SEM 12.0); p = 0.03, Mann-Whitney U test). A significant direct correlation was observed between the proliferative activity assessed by MIB-1 immunostaining, and the percentage of CD105 positive vessels in the entire series (r = 0.681; p = 0.01). CONCLUSIONS: Data indicate that the phenotype of proliferating endothelial cells of Gorham disease is similar to that of the endothelial lining of vessels of metabolically active bone characterised by high expression of CD105, while that of conventional haemangioma is more similar to that of metabolically quiescent bone tissue, such as fatty marrow, with low levels of expression of CD105. This may have potential therapeutic and diagnostic applications.
Asunto(s)
Antígenos CD/metabolismo , Osteólisis Esencial/metabolismo , Receptores de Superficie Celular/metabolismo , Adolescente , Biomarcadores/metabolismo , Neoplasias Óseas/metabolismo , Huesos/irrigación sanguínea , Huesos/embriología , Huesos/metabolismo , Proliferación Celular , Endoglina , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Femenino , Feto/metabolismo , Hemangioma/metabolismo , Humanos , Técnicas para Inmunoenzimas/métodos , Masculino , Persona de Mediana Edad , Osteólisis Esencial/diagnóstico por imagen , Osteólisis Esencial/patología , Radiografía , Adulto JovenRESUMEN
A 55-year-old male presented with a 1-month history of localized pain caused by an osteolytic and destructive lesion in the right distal femur. Histologically, the tumour consisted of spindle cells intermingled with epithelioid eosinophilic cells arranged in small cords embedded in a hyalinized-to-chondromyxoid stroma. Electron microscopy and immunohistochemistry showed features of myoepithelial differentiation. RT-PCR failed to demonstrate chimeric transcripts of extraskeletal myxoid chondrosarcoma. The final diagnosis was primary malignant myoepithelioma of bone. The patient is alive with lung metastases 13 months after surgery. Primary malignant myoepithelioma of bone is an exceptionally rare neoplasm that should be considered in the differential diagnosis with the more aggressive myxoid spindle cell sarcomas.
Asunto(s)
Neoplasias Óseas/diagnóstico , Mioepitelioma/diagnóstico , Neoplasias Óseas/patología , Fémur/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mioepitelioma/patologíaRESUMEN
In recent years, classification of soft-tissue sarcomas (STS) has improved with cytogenetic analyses, but their clinical behavior is still not easily predictable. The aim of this study was to detect alterations in the urokinase-type plasminogen system, involved in tumor growth and invasion, by comparing mRNA levels of its components with those of paired normal tissues, and relating them with patient clinical course. Real-time PCR was performed on human STS cell lines and tissues from highly malignant STS, including leiomyosarcomas and malignant fibrous histiocytomas, to evaluate the expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1). Immunohistochemistry of gene products was also performed. Median mRNA values of all genes studied were higher in tumors than in paired normal tissues. In agreement with data on STS cell lines, significant up-regulation for uPA and PAI-1 genes compared to reference values was seen. Moreover, different levels of expression were related to histotype and metastatic phenotype. There was accordance between uPA mRNA and protein expression, while immunodetection of PAI-1 product was weak and scattered. Clearly, the controversial role of PAI-1 protein requires further biological analyses, but evident involvement of uPA/PAI-1 gene overexpression in STS malignancy may highlight a molecular defect useful in discriminating STS high-risk patients.
Asunto(s)
Expresión Génica , Inhibidor 1 de Activador Plasminogénico/metabolismo , Sarcoma/metabolismo , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Adulto , Anciano , Estudios de Casos y Controles , Técnicas de Cultivo de Célula , Línea Celular Tumoral , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Inhibidor 1 de Activador Plasminogénico/genética , Reacción en Cadena de la Polimerasa , ARN Mensajero/metabolismo , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Receptores del Activador de Plasminógeno Tipo Uroquinasa , Factores de Riesgo , Sarcoma/clasificación , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/patología , Sarcoma/radioterapia , Sarcoma/cirugía , Factores de Tiempo , Activador de Plasminógeno de Tipo Uroquinasa/genéticaRESUMEN
AIMS: Evaluation of pattern of recurrences of 290 patients with an Ewing's sarcoma family tumor (ESFT), who relapsed after adjuvant or neoadjuvant chemotherapy. METHODS: Retrospective analysis at a median follow-up of 16.6 years (range: 5-32) from the primary therapy. RESULTS: There were 378 recurrences, treated by surgery, and/or chemotherapy, radiotherapy, or only palliative treatments. At the last control 18 patients were alive and free of disease 2.5 to 20 years (median 12.1 year) from the last treatment, 4 were alive with uncontrolled disease, 2 died of second line chemotherapy-related toxicity, and 266 died of the tumor 4 months to 20.5 years from the first relapse (median 3.2 years). The 5-year event free survival after the last relapse and overall survival were 5.1 and 7.9%, respectively, and resulted significantly correlated with the time of first relapse, the site of first metastases, the treatment performed after relapse (all patients presently free of disease had been treated by surgery alone or combined with a second line chemotherapy) and for patients treated with neoadjuvant chemotherapy and locally by surgery, with the histologic response to preoperative chemotherapy. CONCLUSIONS: We confirm that the post-relapse outcome of patients with ESFT who relapse after conventional treatment is very poor. Nonetheless specific subgroups of patients may be cured even after 2 or 3 relapses: patients who relapse 2 or more years after primary treatment, patients who relapse with only lung metastases, and patients whose recurrences can be surgically treated.
Asunto(s)
Neoplasias Óseas/tratamiento farmacológico , Sarcoma de Ewing/tratamiento farmacológico , Adolescente , Adulto , Neoplasias Óseas/patología , Neoplasias Óseas/terapia , Quimioterapia Adyuvante , Distribución de Chi-Cuadrado , Niño , Preescolar , Terapia Combinada , Femenino , Humanos , Lactante , Masculino , Terapia Neoadyuvante , Recurrencia Local de Neoplasia , Pronóstico , Estudios Retrospectivos , Sarcoma de Ewing/patología , Sarcoma de Ewing/terapia , Resultado del TratamientoRESUMEN
The authors describe a rare form of pseudotumor of the muscle tissue of an inflammatory nature with an unknown etiology that occurred in a boy aged 13 years, characterized by the occurrence of rapidly-developing swelling, no pain symptoms, with degeneration of the myofibers, evident eosinophilia and lymphomonoplasmacellular infiltrate. Surgical excision of the lesion is the treatment of choice.
Asunto(s)
Miositis , Adolescente , Humanos , Masculino , Miositis/diagnóstico , Miositis/cirugíaRESUMEN
Elastofibroma dorsi is a pseudotumoral fibroproliferative lesion characterized by polymorphic fiber-like deposits of elastinophilic material. Several theories have been reported explaining the pathogenesis of elastofibroma. Recent cytogenetic studies have demonstrated chromosomal instability in elastofibromas, not normally observed in non-neoplastic tissues. These chromosomal defects are commonly observed in aggressive fibromatosis too. Such clinical observations suggest a multistage pathogenetic mechanism for the onset of elastofibroma. This study, using histochemical, immunohistochemical staining techniques, and ultrastructural examination, describes the detection of an otherwise typical elastofibroma contextual to a high grade sarcoma. Hence, the coexistence of elastofibroma and high-grade sarcoma may suggest a causal link between the two pathological entities. The results obtained suggest that the coexistence of the two pathological entities is conceivably coincidental.
Asunto(s)
Fibroma/ultraestructura , Leiomiosarcoma/ultraestructura , Recurrencia Local de Neoplasia/ultraestructura , Neoplasias de los Tejidos Blandos/ultraestructura , Femenino , Fibroma/diagnóstico , Fibroma/cirugía , Humanos , Inmunohistoquímica/métodos , Leiomiosarcoma/diagnóstico , Leiomiosarcoma/cirugía , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/cirugía , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/cirugíaAsunto(s)
Neoplasias Óseas/patología , Osteosarcoma/patología , Sarcoma de Ewing/patología , Biomarcadores de Tumor , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/tratamiento farmacológico , Protocolos Clínicos , Humanos , Necrosis , Osteosarcoma/diagnóstico , Osteosarcoma/tratamiento farmacológico , Pronóstico , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/tratamiento farmacológicoRESUMEN
AIMS: To describe the outcomes of a large number of patients with pelvic osteosarcoma, and to define the guidelines for appropriate treatment. METHODS: We reviewed 60 consecutive patients with primary pelvic high-grade osteosarcoma. The tumour involved the whole hemipelvis in 15 cases, while the most common location was the iliac wing in 29 cases (48.3%): 25 of these adjacent to or passing the sacroiliac joint. RESULTS: Thirty patients underwent surgery; there were 16 hindquarter amputations and 14 internal hemipelvectomies. All the patients who presented with metastasis died of their disease. In 18 cases wide margins were achieved, however, eight patients experienced local recurrence. Of the series, only eight patients are still alive. CONCLUSION: The use of intense chemotherapy and surgical wide margin, hardly seems to achieve local control, however, tumour necrosis was correlated with positive prognosis. When internal hemipelvectomy it is not safe enough, amputation must be considered, particularly for cases with sacrifice of the sciatic nerve roots or for older patients where a shorter surgical procedure can be less risky.
Asunto(s)
Neoplasias Pulmonares/terapia , Osteosarcoma/terapia , Neoplasias Pélvicas/terapia , Adolescente , Adulto , Anciano , Amputación Quirúrgica/métodos , Niño , Terapia Combinada , Femenino , Humanos , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Osteosarcoma/secundario , Neoplasias Pélvicas/patología , Guías de Práctica Clínica como Asunto , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Effective adjuvant or neoadjuvant regimens of chemotherapy have dramatically improved the prognosis of patients with high-grade osteosarcoma of the extremity, localized at diagnosis. Currently, little is known about patients with metastatic disease at presentation. PATIENTS AND METHODS: From May 1995 to May 2000, 57 patients with osteosarcoma of the extremity, metastatic at presentation, were treated according to the following scheme: primary chemotherapy, restaging, simultaneous resection of primary tumor and metastatic lesions, and maintenance chemotherapy. RESULTS: Thirty-five patients achieved remission. At a follow-up ranging from 2 to 7 years, seven remained continuously free of disease, one died of chemotherapy-related toxicity and 27 patients relapsed. Twenty-one of the 22 patients who never achieved remission died as a result of the tumor, as well as 20 of the 27 who achieved remission but then relapsed. Of the remaining seven relapsing patients, six are alive with uncontrolled disease, while one is alive and free of disease 24 months after the last post-relapse treatment. Two-year event-free survival (EFS) and overall survival (OS) were 21% and 55%, respectively. These results are significantly poorer than those achieved in 128 contemporary patients with non-metastatic disease at presentation, treated with the same chemotherapy protocol (2-year EFS and OS of 75% and 94%, respectively). CONCLUSIONS: The results of our study confirm that the prognosis of patients with osteosarcoma of the extremity, metastatic at presentation, remains poor, despite the use of aggressive treatments.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Osteosarcoma/tratamiento farmacológico , Adolescente , Adulto , Brazo/patología , Neoplasias Óseas/patología , Neoplasias Óseas/cirugía , Niño , Preescolar , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Humanos , Ifosfamida/administración & dosificación , Pierna/patología , Masculino , Metotrexato/administración & dosificación , Terapia Neoadyuvante , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Osteosarcoma/patología , Pronóstico , Resultado del TratamientoRESUMEN
Elastofibroma is a benign lesion occurring almost exclusively in the chest wall, parascapular region being the most frequent site. Rare lesions have been reported in other anatomic locations, but there are no reports about the co-existence of an elastofibroma with a malignant sarcoma. The purpose of the authors is to describe histologically and ultrastructurally the synchronous detection of an elastofibroma and a high grade leiomyosarcoma, speculating on eventual links between the two pathological states.
Asunto(s)
Tejido Elástico/ultraestructura , Fibroma/patología , Leiomiosarcoma/patología , Neoplasias de los Tejidos Blandos/patología , Biopsia con Aguja , Supervivencia sin Enfermedad , Femenino , Fibroma/cirugía , Humanos , Leiomiosarcoma/cirugía , Microscopía Electrónica , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Neoplasias Primarias Múltiples , Neoplasias de los Tejidos Blandos/cirugía , Tomografía Computarizada por Rayos XRESUMEN
Malignant giant cell tumor is a confusing term that in the past has been used to describe different types of giant cell-rich tumors. We try to clarify this term in this report. We consider two types of malignancy in giant cell tumor of bone: "primary" when it arises in juxtaposition to a benign giant cell tumor and 'secondary' when it arises at the site of a previously treated giant cell tumor. Here we present a case of primary malignancy in giant cell tumor that was initially not recognized as a malignancy. On radiography and histology of frozen sections the lesion had the appearance of a conventional giant cell tumor of bone. After curettage, the permanent histology slides showed areas of highly malignant osteosarcoma juxtaposed to areas of benign giant cell tumor. The patient was treated with chemotherapy and wide resection of the tumor.
Asunto(s)
Neoplasias Femorales/patología , Tumor Óseo de Células Gigantes/patología , Osteosarcoma/patología , Adulto , Neoplasias Femorales/diagnóstico por imagen , Neoplasias Femorales/terapia , Fémur/patología , Tumor Óseo de Células Gigantes/diagnóstico por imagen , Tumor Óseo de Células Gigantes/terapia , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Masculino , Osteosarcoma/diagnóstico por imagen , Osteosarcoma/terapia , RadiografíaRESUMEN
The results achieved in 157 patients with non-metastatic Ewing's sarcoma of the bone treated at a single institution between 1991 and 1997 according to a new protocol (REN-3) are reported. Induction chemotherapy consisted of two cycles of 'VAC': vincristine (V), doxorubicin (A), cyclophosphamide (C) alternated with one cycle of 'VIAc': V, ifosfamide (I), actinomycin (Ac). After local treatment, patients received three more cycles of VAC, two of VIAc, three cycles of I plus etoposide (E) and two cycles with V, C and Ac. Local treatment was surgery in 53% of patients, surgery+radiotherapy in 25% and radiotherapy only in 22%. With a follow-up ranging between 4 and 10 years (mean: 7 years), 110 patients (70%) remained continuously event-free, 2 patients died of toxicity and 45 patients relapsed: 33 due to metastases and 12 due to local recurrence always associated with metastases. The 5-year event-free survival (EFS) and overall survival (OS) were 71.0 and 76.5% respectively. These results are significantly better that the ones achieved in our previous three studies in which a three-drug VAC regimen (REA-1), and 4-drug VACAc regimen (REA-2 and REN-1) was used, and in our most recent study (REN-2) which was based on a six-drug regimen as in the present study, but where I and Ac were used only after the local treatment. However, since REN-3 surgery was used in a significantly larger number of patients, we cannot say whether the better outcome of this study was due to the use of a six-drug regimen with an early delivery of ifosfamide and actinomycin, or to the wider use of surgery as local treatment or both.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Sarcoma de Ewing/tratamiento farmacológico , Adolescente , Neoplasias Óseas/radioterapia , Neoplasias Óseas/cirugía , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Masculino , Terapia Neoadyuvante/métodos , Recurrencia Local de Neoplasia/etiología , Cooperación del Paciente , Prohibitinas , Sarcoma de Ewing/radioterapia , Sarcoma de Ewing/cirugíaRESUMEN
This retrospective study examined 10 patients with osteoid osteoma and 11 patients with osteoblastoma localized in the sacrococcyx. In the sacrum, the diagnosis was delayed compared to other sites. Curettage through a posterior approach is the treatment of choice. Radiotherapy as well as embolization of feeding arteries may be used for the most aggressive lesions. Prognosis is generally good with a low incidence of local recurrence (<10%).
Asunto(s)
Neoplasias Óseas/diagnóstico , Osteoblastoma/diagnóstico , Osteoma Osteoide/diagnóstico , Sacro , Adolescente , Adulto , Distribución por Edad , Biopsia con Aguja , Neoplasias Óseas/epidemiología , Neoplasias Óseas/cirugía , Niño , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Italia/epidemiología , Masculino , Osteoblastoma/epidemiología , Osteoblastoma/cirugía , Osteoma Osteoide/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Distribución por Sexo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Relatively little is known about the biologic relevance of numerical chromosomal changes in relation to DNA content in osteosarcoma. In this study, by using a series of human osteosarcoma cell lines, we standardized a method for the assessment, on the same nuclei specimen, of both specific chromosome copy numbers by fluorescence in situ hybridization (FISH) and the DNA content by static cytofluorometry or image cytometry. On the same cell lines, we also evaluated the DNA content by using flow cytometry and the chromosome number distribution by metaphase analysis. Comparison between these different methods showed that DNA ploidy level as determined by FISH or metaphase analysis is frequently lower than the ploidy pattern as defined by cytometric methods. By using comparative genomic hybridization, we were able to demonstrate that these discrepancies were due to the presence of several unbalanced chromosome aberrations, specifically gains and high-level amplifications, which affect the total DNA content with less effect on the total chromosome number. Thus, evaluation of DNA ploidy in osteosarcoma cells is needed for a correct interpretation of FISH or cytogenetic data concerning numerical chromosomal changes. Evaluation of tumor ploidy in a series of clinical samples demonstrated that in high-grade osteosarcoma, flow cytometry sometimes may give false results because of the presence of high proportions of contaminating, nonneoplastic cells that cannot be excluded from the flow cytometric assessment but that do not interfere with the evaluation of DNA ploidy by static cytofluorometry or image cytometry, in which only tumor cells are selected for the analysis. The possibility of using this method to evaluate, on the same nuclei sample, both specific chromosomal aberrations and DNA ploidy may allow a better determination of numerical chromosomal changes that may be relevant for the biologic behavior of osteosarcoma.
Asunto(s)
Neoplasias Óseas/genética , Aberraciones Cromosómicas/genética , ADN de Neoplasias/metabolismo , Osteosarcoma/genética , Neoplasias Óseas/patología , ADN de Neoplasias/genética , Citometría de Flujo , Humanos , Hibridación Fluorescente in Situ , Osteosarcoma/patología , Ploidias , Células Tumorales CultivadasRESUMEN
A case of cellular schwannoma originating in the left lumbar paraspinal region is described. The diagnosis was originally made on needle biopsy material. The histological examination is usually not sufficient to correctly diagnose this benign neoplasm. Bone erosion, neurological symptoms, caused by compression of the spinal roots, together with hypercellularity, pleomorphism and an occasional increase in mitotic activity, may lead to an erroneous diagnosis of malignancy. Immunohistochemistry and ultrastructural analysis are helpful in confirming the diagnosis. The recognition of this entity avoids unnecessary overtreatment of these patients.
Asunto(s)
Neurilemoma/diagnóstico , Sarcoma/diagnóstico , Neoplasias de la Médula Espinal/diagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Vértebras Lumbares , Persona de Mediana EdadRESUMEN
Between April 1990 and December 1994, we treated 24 patients with telangiectatic osteosarcoma (TO) of the extremities with neoadjuvant chemotherapy using 2 protocols. Surgery consisted of limb salvage in 21 patients and amputation or rotation plasty in 3. The histologic response to chemotherapy was good (90% or more tumor necrosis) in 23 patients, of whom 12 had total necrosis. With a mean follow-up of 74 (60-96) months, 20 patients remained continuously free of disease and 4 relapsed with lung metastases. There were no local recurrences. Comparing these results to the ones achieved in 269 contemporary patients with conventional osteosarcoma of the extremities using the same protocols for chemotherapy, we found a significantly better histologic response to chemotherapy (96% vs 68% of good histologic response; p = 0.004) and disease-free survival (83% vs 55%; p = 0.01) in the TO group. We conclude that TO, once considered a lethal tumor, seems to be even more sensitive to chemotherapy than conventional osteosarcoma, and that most of these patients may be cured without amputation.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Terapia Neoadyuvante , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Telangiectasia , Adolescente , Neoplasias Óseas/cirugía , Quimioterapia Adyuvante , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Osteosarcoma/cirugía , Resultado del TratamientoRESUMEN
In 510 patients with osteosarcoma of the extremity treated at the authors' institute between March 1983 and June 1995 with different regimens of neoadjuvant chemotherapy, factors that influenced the histologic response were investigated. The rate of total necrosis was not related to the patients' gender, age, site, size of tumor, serum of alkaline phosphatase values, or route of cisplatin administration. The histologic response significantly and independently correlated with the number of drugs administered before surgery and with the histologic subtype of the tumor. According to the number of drugs used, the percentage of total necrosis was 31% for a four-drug regimen, 18% for a three-drug regimen, and only 1.5% for a two-drug regimen. According to the histologic type, the rates of total necrosis were 41% for telangiectatic tumors, 36% for fibroblastic tumors, 15% for osteoblastic tumors, and 3% for chondroblastic tumors. The authors concluded that in neoadjuvant therapy of osteosarcoma, the histologic response to preoperative treatment, which correlates with prognosis, depends on the effectiveness of the chemotherapy regimen and on some features intrinsically inherent to the tumor. These data should be considered when selecting the type of treatment (adjuvant or neoadjuvant) and the combinations of drugs to be used in preoperative treatment of patients with osteosarcoma.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Osteonecrosis/patología , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Adolescente , Adulto , Amputación Quirúrgica/métodos , Neoplasias Óseas/mortalidad , Neoplasias Óseas/cirugía , Niño , Preescolar , Cisplatino/administración & dosificación , Terapia Combinada , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Extremidades , Femenino , Humanos , Ifosfamida/administración & dosificación , Modelos Logísticos , Masculino , Metotrexato/administración & dosificación , Análisis Multivariante , Osteosarcoma/mortalidad , Osteosarcoma/cirugía , Cuidados Preoperatorios , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
AIM: Our experience of pre-operative intraarterial (i.a.) vs intravenous (i.v.) infusion of cisplatinum (CDP) in a multiagent neo-adjuvant chemotherapy for osteosarcoma of the extremity is reported. METHODS: Two successive randomized studies were performed. In the first, pre-operatively, CDP i.a. vs CDP i.v. was applied in combination with high-dose methotrexate (HDMTX) and adriamycin (ADM) within a three-drug regimen. In the second, a combination of HDMTX, ADM and IFO, within a four-drug regimen was tested. RESULTS: The rate of responses to chemotherapy (tumour necrosis > or = 90%) was significantly higher (P<0.04) for the 142 patients treated with the four-drug regimen than in the 79 patients treated with a three-drug regimen (76%vs 62%). According to the route of CDP infusion, in the three-drug regimen the rate of responses was significantly higher (P=0.004) in patients treated with i.a. CDP (77%) than in patients treated i.v. (46%); with the four-drug regimen the rate of response was not significantly different in patients treated i.a. (81%) and in patients treated i.v. (71%). No significant differences in the rates of limb salvages, local recurrence and event-free survival (EFS) were seen between the i.a. and the i.v. groups. CONCLUSION: In the treatment of osteosarcoma of the extremity, the i.a. infusion of CDP does not offer any significant advantage when this drug is used within an aggressive, multiagent, pre-operative four-drug regimen.