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1.
AJR Am J Roentgenol ; 177(4): 807-12, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11566677

RESUMO

OBJECTIVE: The purpose of our study was to evaluate the sensitivity and accuracy of ferumoxides-enhanced MR imaging in comparison with surgery and intraoperative sonography. SUBJECTS AND METHODS: We prospectively evaluated 25 consecutive studies in 24 patients who underwent ferumoxides-enhanced hepatic MR imaging before surgery and intraoperative sonography. Both 1.5-T scanners (13 cases) and 0.2-T scanners (12 cases) were used. Turbo spin-echo T2-weighted sequences were performed before and after the administration of ferumoxides and the images were compared. Lesions were classified as solid or nonsolid and tabulated on standard liver maps. The liver maps from MR imaging were compared with those from surgery and intraoperative sonography. For lesions greater than 1 cm, the regions of interest were measured and contrast-to-noise ratio was calculated. RESULTS: Of 93 solid lesions found at surgery, 69 were seen on unenhanced MR imaging (sensitivity, 74.2%) and 87 were seen on ferumoxides-enhanced MR imaging (sensitivity, 93.5%) (p < 0.05). Of the seven benign lesions (five cysts, two hemangiomas) found at surgery, all were correctly identified as benign on MR imaging. Two lesions identified as solid before surgery were not found at surgery. Mean lesion contrast-to-noise ratio for the unenhanced scans was 22.9 and 34.5 (p < 0.001) for the ferumoxides-enhanced scans. Subanalysis of 1.5- and 0.2-T MR imaging revealed similar results with significant (p < 0.05) increases in sensitivity for both. The average size of the lesions missed before surgery was 0.7 cm. CONCLUSION: Turbo spin-echo T2-weighted ferumoxides-enhanced MR imaging at either 1.5 or 0.2 T has value in preoperative liver assessment.


Assuntos
Meios de Contraste , Cuidados Intraoperatórios , Ferro , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética , Óxidos , Adulto , Idoso , Dextranos , Feminino , Óxido Ferroso-Férrico , Humanos , Neoplasias Hepáticas/cirurgia , Nanopartículas de Magnetita , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ultrassonografia
2.
J Clin Oncol ; 19(13): 3203-9, 2001 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-11432887

RESUMO

PURPOSE: To determine whether treatment-induced pathologic necrosis correlates with local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. PATIENTS AND METHODS: Four hundred ninety-six patients with intermediate- to high-grade extremity soft tissue sarcomas received protocol neoadjuvant therapy. All patients underwent surgical resection after neoadjuvant therapy and had pathologic assessment of tumor necrosis in the resected specimens. RESULTS: The 5- and 10-year local recurrence rates for patients with > or = 95% pathologic necrosis were significantly lower (6% and 11%, respectively) than the local recurrence rates for patients with less than 95% pathologic necrosis (17% and 23%, respectively). The 5- and 10-year survival rates for the patients with > or = 95% pathologic necrosis were significantly higher (80% and 71%, respectively) than the survival rates for the patients with less than 95% pathologic necrosis (62% and 55%, respectively). Patients with less than 95% pathologic necrosis were 2.51 times more likely to develop a local recurrence and 1.86 times more likely to die of their disease as compared with patients with > or = 95% pathologic necrosis. The percentage of patients who achieved > or /= 95% pathologic necrosis increased to 48% with the addition of ifosfamide as compared with 13% of the patients in all the other protocols combined. CONCLUSION: Treatment-induced pathologic necrosis is an independent predictor of both local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. A complete pathologic response (> or = 95% pathologic necrosis) correlated with a significantly lower rate of local recurrence and improved overall survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Recidiva Local de Neoplasia/epidemiologia , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Criança , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Seguimentos , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Los Angeles/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Necrose , Recidiva Local de Neoplasia/diagnóstico , Prognóstico , Risco , Sarcoma/diagnóstico , Sarcoma/epidemiologia , Sarcoma/patologia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/epidemiologia , Neoplasias de Tecidos Moles/patologia , Taxa de Sobrevida
3.
Clin Orthop Relat Res ; (385): 186-91, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11302313

RESUMO

Echinococcosis (hydatid cyst disease) is a zoonotic infection caused by the parasitic tapeworm Echinococcus. The larval stage of this parasite can implant in many organs of the body, most commonly the liver, and create internal budding cystic masses. Echinococcal cysts also can implant in soft tissues; however, a review of the literature revealed no published case with the patient initially presenting with a soft tissue mass. Two such cases are reported in the current study. Physicians who evaluate soft tissue masses, particularly in patients from Echinococcus-endemic areas, need to include echinococcosis in their differential diagnoses. The current treatment of choice for soft tissue echinococcosis is wide resection combined with perioperative medical therapy.


Assuntos
Equinococose/cirurgia , Infecções dos Tecidos Moles/parasitologia , Infecções dos Tecidos Moles/cirurgia , Adulto , Equinococose/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Infecções dos Tecidos Moles/diagnóstico , Tomografia Computadorizada por Raios X
4.
Cancer Res ; 60(22): 6457-64, 2000 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-11103813

RESUMO

The cytokine interleukin-12 (IL-12) has shown potent antitumor activity in several tumor models. Recently, natural killer (NK) T cells have been proposed to mediate the antitumor effects of IL-12. In this study, the antitumor response of IL-12 was investigated in a gene therapeutic model against s.c. growing mouse hepatocellular carcinomas using an adenoviral vector expressing murine IL-12 (AdVmIL-12). An adenoviral-based system was chosen because of the ability of adenoviruses to transduce dividing and nondividing cells and because of their high transduction efficiencies. Our goals were to examine the efficacy of AdVmIL-12 in a hepatocellular carcinoma model and to investigate the mechanism of the AdVmIL-12-mediated antitumor response with specific interest in the role of NK T cells. Our studies demonstrate that intratumoral AdVmIL-12-mediated regression of s.c. hepatocellular tumors is associated with rapid antitumor responses. AdVmIL-12 treatment was associated with an immune cellular infiltrate consisting of CD4 and CD8 T lymphocytes, macrophages, NK cells, and NK T cells. Antibody ablation of CD4 and CD8 T cells and use of NK cell-defective beige mice failed to abrogate the response to AdVmIL-12. Studies in T-cell- and B-cell-deficient severe combined immunodeficient and recombinase activating gene-2-deficient mice and T-cell-, B-cell-, and NK cell-defective severe combined immunodeficient/beige mice also failed to abrogate this response. AdVmIL-12 retained potent antitumor activity in mice with specific genetic defects in immune cellular cytotoxicity (perforin knockout mice) and costimulation (CD28 knockout mice). Use of mice with specific NK T cell deficiencies, Valpha14 T-cell receptor and CD1 knockout mice, also failed to abrogate the response to AdVmIL-12. Histological and immunohistochemical studies of AdVmIL-12-treated tumors showed extensive inhibition of neovascularization and a marked decrease in factor VIII-stained endothelial cells. Our studies indicate that the antitumor response of AdVmIL-12 is independent of direct cytotoxic cellular immunity (specifically, the function of NK T cells) and suggest that the initial mechanisms of AdVmIL-12-mediated tumor regression involve inhibition of angiogenesis.


Assuntos
Antígenos CD1/imunologia , Interleucina-12/imunologia , Células Matadoras Naturais/imunologia , Neoplasias Hepáticas Experimentais/imunologia , Linfócitos T/imunologia , Adenoviridae/genética , Adenoviridae/imunologia , Animais , Antígenos CD28/imunologia , Citotoxicidade Imunológica , Modelos Animais de Doenças , Humanos , Hospedeiro Imunocomprometido/imunologia , Interleucina-12/genética , Neoplasias Hepáticas Experimentais/terapia , Glicoproteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos SCID , Neovascularização Patológica/prevenção & controle , Perforina , Proteínas Citotóxicas Formadoras de Poros
5.
Surg Oncol ; 9(2): 71-5, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11094326

RESUMO

Gastrointestinal stromal sarcomas, formerly categorized as leiomyosarcomas of gastrointestinal origin, have a common pattern of intraperitoneal dissemination. Despite surgical resection with or without adjuvant systemic chemotherapy the vast majority of these patients succumb to intraperitoneal sarcomatosis and/or hepatic metastases. In an attempt to improve upon the morbidity and mortality associated with this disease we and several other centers have begun treating these patients with intraperitoneal chemotherapy. We have found that aggressive surgical resection with postoperative intraperitoneal chemotherapy has significantly lowered the peritoneal recurrence rate in patients with recurrent gastrointestinal stromal sarcomas as compared to those who have undergone surgical resection alone. However, this treatment approach has proven to be ineffective in preventing hepatic metastases, and thus has had little effect upon overall survival. With the treatment of primary rather than recurrent disease we hope to interrupt the disease process at an earlier stage further decreasing peritoneal recurrences and potentially improving survival.


Assuntos
Neoplasias Gastrointestinais/tratamento farmacológico , Mitoxantrona/administração & dosagem , Recidiva Local de Neoplasia/prevenção & controle , Sarcoma/tratamento farmacológico , Antineoplásicos/administração & dosagem , Quimioterapia Adjuvante , Feminino , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/cirurgia , Humanos , Injeções Intraperitoneais , Neoplasias Hepáticas/secundário , Masculino , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Sarcoma/patologia , Sarcoma/secundário , Sarcoma/cirurgia , Taxa de Sobrevida , Resultado do Tratamento
6.
Clin Orthop Relat Res ; (373): 51-61, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10810462

RESUMO

Between September 1984 and January 1996, 32 expandable endoprostheses were used for limb reconstruction after resection of malignant bone tumors in patients who were skeletally immature. The 20 boys and 12 girls ranged in age from 3 to 15 years (mean, 9.7 years). One patient had a Stage IIA tumor, 22 patients had Stage IIB tumors, and seven patients had Stage III tumors according to the classification of the Musculoskeletal Tumor Society. There also were two patients with parosteal osteosarcomas. The histologic diagnosis was osteosarcoma in 23 patients and Ewing's sarcoma in nine. All patients except the patients with parosteal osteosarcoma received standard neoadjuvant therapy. Twenty-two Lewis Expandable Adjustable Prostheses, four modular Wright Medical prostheses, four modular Howmedica prostheses, and two Techmedica expandable prostheses were used. Thirteen patients died, two have no evidence of disease, and 17 are continuously disease free. Sixteen of 32 patients (50%) have not had an expansion procedure because of early death in 10 and early amputation in three. Three patients are waiting to undergo an expansion procedure. Sixteen of the 32 patients (50%) have undergone 32 expansion procedures, to a maximum of 9 cm, without any infection. To maintain range of motion before the expansion procedure, a complete resection of the pseudocapsule was done routinely. Fourteen of the 32 patients did not have complications. Eighteen of the 32 patients had 27 complications. All Lewis Expandable Adjustable Prosthesis endoprostheses and the two nonmodular Techmedica prostheses were associated with a large amount of titanium debris. The children's functional results were similar to the results reported for adults with an average Musculoskeletal Tumor Society rating of good to excellent at the knee, fair to good at the hip, and fair about the shoulder. Rehabilitation of the knee in very young patients (5-8 years) remains problematic and careful selection of patient and family is necessary. The Lewis Expandable Adjustable Prosthesis probably should be reserved for very young patients (5-8 years) and modular systems should be used for large preadolescent and adolescent children.


Assuntos
Neoplasias Ósseas/cirurgia , Osteossarcoma/cirurgia , Implantação de Prótese , Sarcoma de Ewing/cirurgia , Adolescente , Adulto , Neoplasias Ósseas/diagnóstico por imagem , Criança , Pré-Escolar , Análise de Falha de Equipamento , Extremidades/diagnóstico por imagem , Extremidades/cirurgia , Feminino , Humanos , Masculino , Osteossarcoma/diagnóstico por imagem , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/cirurgia , Desenho de Prótese , Ajuste de Prótese , Radiografia , Reoperação , Sarcoma de Ewing/diagnóstico por imagem
7.
Curr Treat Options Oncol ; 1(3): 274-8, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12057171

RESUMO

The approach to the management of retroperitoneal tumors begins with a complete history and physical examination. Imaging of the abdomen and pelvis by computed tomography (CT) provides both an imaging modality and a method by which to obtain tissue for diagnosis. Because a histologic diagnosis is essential in treatment planning, adequate tissue can usually be obtained by a CT-guided core biopsy. If the diagnosis is sarcoma, additional tests necessary for staging include plain chest radiography and evaluation of the liver by either CT scan or magnetic resonance imaging (MRI). The treatment options for primary retroperitoneal sarcomas include chemotherapy, radiation therapy, surgery, or a combination of these modalities; therefore, a multidisciplinary group best manages treatment planning. Primary radiation therapy for cure is seldom effective for retroperitoneal sarcomas but can provide palliation in select cases. Systemic chemotherapy for chemosensitive lesions, such as poorly differentiated liposarcoma, malignant fibrous histiocytoma (MFH), synovial cell sarcoma, and primitive neuroectodermal tumors (PNET), can be useful when used in a neoadjuvant manner. Consequently, surgical resection continues to be the mainstay of treatment for retroperitoneal sarcomas and requires en bloc resection of the primary tumor. Frequently this includes adjacent organs such as colon, small bowel, kidney, adrenal, and pancreas. Postoperative adjuvant therapy with chemotherapy or radiation has not been proven to be of any additional benefit. Overall treatment results are predominantly influenced by tumor stage, grade, size, and margins of surgical resection. Follow-up CT scans at 6-month intervals and surgical resection of recurrences can be valuable.


Assuntos
Neoplasias Retroperitoneais/terapia , Sarcoma/terapia , Antineoplásicos/uso terapêutico , Biópsia/métodos , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Recidiva Local de Neoplasia/patologia , Radioterapia , Neoplasias Retroperitoneais/mortalidade , Neoplasias Retroperitoneais/patologia , Sarcoma/mortalidade , Sarcoma/patologia , Taxa de Sobrevida
8.
Clin Cancer Res ; 5(11): 3516-22, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10589766

RESUMO

Solid tumors depend on angiogenesis for growth and metastasis. It has been shown that blood vessel density, as determined by counting the number of capillaries in clustered bursts, is a significant prognostic factor in carcinomas. It is unclear, however, whether vessel density is a prognostic factor in sarcomas. In this study, we examined angiogenesis in sarcomas of various grades and compared their vascular patterns to those of carcinomas. Microvessels were identified by von Willebrand factor staining. The matrix of multiple sarcoma and breast carcinoma specimens were extracted and subjected to Western analysis of various angiogenic factors and inhibitors. Metalloproteinase inhibitor presence was also determined by in situ hybridization. In breast carcinomas, capillaries were clustered in bursts within the stroma of the tumor, whereas the sarcoma capillaries were homogeneously distributed in the tumor stroma. Random blood vessel density per high power field in sarcomas did not correlate with patient prognosis. The matrix of sarcomas and carcinomas contained both angiogenic stimulators and inhibitors. Tissue inhibitor of metalloproteinase-1 was found predominantly in fibroblasts and myofibroblasts in the matrix of carcinoma specimens. The difference in the pattern of angiogenesis in sarcomas and carcinomas may be attributable to the presence of fibroblasts and myofibroblasts in carcinomas, resulting in the compartmentalization of bursts of angiogenic factors. The homogeneous appearance of vessel density in sarcomas observed in the present study would be the consequence of the influence of a single compartment.


Assuntos
Carcinoma/irrigação sanguínea , Neovascularização Patológica/patologia , Sarcoma/irrigação sanguínea , Inibidores da Angiogênese/análise , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/patologia , Carcinoma/patologia , Endotélio Vascular/patologia , Endotélio Vascular/fisiopatologia , Feminino , Substâncias de Crescimento/análise , Humanos , Hibridização In Situ , Leiomiossarcoma/irrigação sanguínea , Leiomiossarcoma/patologia , Microcirculação/patologia , Modelos Cardiovasculares , Neovascularização Patológica/fisiopatologia , Prognóstico , Estudos Retrospectivos , Sarcoma/patologia , Inibidor Tecidual de Metaloproteinase-1/genética , Fator de von Willebrand/análise
9.
Ann Surg Oncol ; 6(7): 645-50, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10560849

RESUMO

BACKGROUND: Recurrent abdominal sarcomas have an extremely high rate of recurrence and poor overall survival. A prospective study was initiated to assess the feasibility, toxicity, and benefit of surgical resection and intraperitoneal chemotherapy for improving local control of disease and overall survival. METHODS: Fifty-four patients underwent surgical excision of all gross disease and postoperative intraperitoneal chemotherapy with mitoxantrone. Thirty-five patients had peritoneal disease only (stage II), and 19 patients had peritoneal disease with hepatic metastases (stage III). RESULTS: Nine (17%) patients remain free of disease with a mean follow-up of 37 months. The remaining 45 patients (83%) have had recurrence, with a mean interval to recurrence of 11 months. Stage (P = .001) and grade (P = .005) were the only two variables found to significantly affect recurrence. There was an overall peritoneal recurrence rate of 48% and an overall hepatic failure rate of 69%. Nineteen (35%) of the patients are alive, with a mean follow-up of 46 months. The overall 5-year survival was 31%. The 5-year survival for stage II patients was 46%; for stage III patients, it was only 5%. Stage (P = .001) and grade (P = .056) were the only two variables found to significantly affect survival. There were no treatment-related deaths, and only 5 patients (9%) developed local complications. CONCLUSIONS: Aggressive surgical resection and intraperitoneal chemotherapy for recurrent abdominal sarcomas is a feasible treatment approach with minimal toxicity. Although this treatment had little effect on the hepatic spread of this disease and thus overall survival, it appears to have significantly lowered the rate of peritoneal recurrence and may provide a survival benefit for patients with disease limited to the peritoneum.


Assuntos
Neoplasias Abdominais/tratamento farmacológico , Neoplasias Abdominais/cirurgia , Antineoplásicos/uso terapêutico , Mitoxantrona/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/cirurgia , Sarcoma/tratamento farmacológico , Sarcoma/cirurgia , Adulto , Idoso , Terapia Combinada , Estudos de Viabilidade , Feminino , Humanos , Infusões Parenterais , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de Sobrevida
10.
Radiology ; 212(3): 682-6, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10478232

RESUMO

PURPOSE: To analyze the effectiveness of core-needle biopsy for evaluation of possible primary musculoskeletal neoplasms, which often are evaluated with open biopsy. MATERIALS AND METHODS: Core-needle biopsy was performed at a tertiary care institution in 141 patients suspected of having a mesenchymal neoplasm. In 85 patients, the lesion was in soft tissue; in 56 patients, the lesion was in bone. Eighty-nine patients had a malignant lesion, and 52 had a benign lesion. Twenty-eight patients had undergone previous surgery. RESULTS: In 105 (74%) patients, core-needle biopsy results were concordant with results from specimens subsequently obtained at surgery with respect to tumor histologic features and grade, or they provided sufficient diagnostic information to obviate surgery. In 36 (26%) patients, inaccurate core-needle biopsy results were obtained: In nine, results were imprecise about exact histologic features; in three, results were correct about histologic features but incorrect about tumor grade. In 25 (18%) patients, open biopsy was performed after core-needle biopsy. The accuracy and rate of performance of open biopsy for soft-tissue lesions were not significantly different from those for bone lesions. CONCLUSION: Percutaneous core-needle biopsy can be an effective alternative to open biopsy in the evaluation of possible mesenchymal neoplasms of either bone or soft tissue. Needle biopsy of such lesions, however, is best performed as part of a multidisciplinary team approach to tumor management.


Assuntos
Biópsia por Agulha , Neoplasias Ósseas/patologia , Neoplasias Musculares/patologia , Biópsia , Osso e Ossos/patologia , Diagnóstico Diferencial , Humanos , Mesenquimoma/patologia , Músculos/patologia , Sensibilidade e Especificidade , Neoplasias de Tecidos Moles/patologia
11.
Cancer Res ; 59(17): 4369-74, 1999 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-10485485

RESUMO

An E1B gene-attenuated adenovirus (dl1520) has been proposed to have a selective cytolytic activity in cancer cells with a mutation or deletion in the p53 tumor suppressor gene (p53-null), a defect present in almost half of human hepatocellular carcinomas (HCCs). In this study, the in vitro and in vivo antitumor activity of dl1520 was investigated focusing on two human HCC cell lines, a p53-wild type (p53-wt) cell line and a p53-null cell line. dl1520 was tested for in vitro cytopathic effects and viral replication in the human HCC cell lines Hep3B (p53-null) and HepG2 (p53-wt). The in vivo antitumor effects of dl1520 were investigated in tumors grown s.c. in a severe combined immunodeficient mouse model. In addition, the combination of dl1520 infection with systemic chemotherapy was assessed in these tumor xenografts. At low multiplicities of infection, dl1520 had an apparent p53-dependent in vitro viral growth in HCC cell lines. At higher multiplicities of infection, dl1520 viral replication was independent of the p53 status of the target cells. In vivo, dl1520 significantly retarded the growth of the p53-null Hep3B xenografts, an effect augmented by the addition of cisplatin. However, complete tumor regressions were rare, and most tumors eventually grew progressively. dl1520 had no effect on the in vivo growth of the p53-wt HepG2 cells, with or without cisplatin treatment. The E1B-deleted adenoviral vector dl1520 has an apparent p53-dependent effect in HCC cell lines. However, this effect is lost at higher viral doses and only induces partial tumor regressions without tumor cures in a human HCC xenograft model.


Assuntos
Adenoviridae/fisiologia , Proteínas E1B de Adenovirus/fisiologia , Carcinoma Hepatocelular/terapia , Genes p53/fisiologia , Neoplasias Hepáticas/terapia , Replicação Viral , Animais , Humanos , Masculino , Camundongos , Camundongos SCID , Transplante de Neoplasias , Transplante Heterólogo , Células Tumorais Cultivadas
12.
Cancer Res ; 59(13): 3064-7, 1999 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-10397245

RESUMO

The majority of human hepatocellular carcinomas overexpress alpha-fetoprotein (AFP). Two genetic immunization strategies were used to determine whether AFP could serve as a target for T-cell immune responses. Dendritic cells engineered to express AFP produced potent T-cell responses in mice, as evidenced by the generation of AFP-specific CTLs, cytokine-producing T cells, and protective immunity. AFP plasmid-based immunization generated less potent responses. These novel observations demonstrate that this oncofetal antigen can serve as an effective tumor rejection antigen. This provides a rational, gene therapy-based strategy for this disease, which is responsible for the largest number of cancer-related deaths worldwide.


Assuntos
Células Dendríticas/imunologia , Terapia Genética , Imunoterapia , Neoplasias Hepáticas Experimentais/terapia , Neoplasias Hepáticas/terapia , Linfócitos T/imunologia , alfa-Fetoproteínas/genética , Animais , Citotoxicidade Imunológica , Feminino , Vetores Genéticos , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas Experimentais/imunologia , Linfoma/imunologia , Complexo Principal de Histocompatibilidade , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Baço/imunologia , Transcrição Gênica , alfa-Fetoproteínas/imunologia
13.
Clin Orthop Relat Res ; (360): 207-20, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10101327

RESUMO

Between December 1980 and December 1992, 59 patients underwent 60 reconstructions with endoprostheses after resection of malignant tumors in the upper extremity. There were 32 male patients and 27 female patients, with a mean age of 33 years (range, 3-83 years). The type of reconstruction was based on the location of the primary tumor site. The histologic diagnoses included osteosarcoma, chondrosarcoma, Ewing's sarcoma, malignant fibrous histiocytoma, soft tissue sarcoma, and fibrosarcoma of bone. Most of the patients had Stage IIB disease (N = 38), as established by the Musculoskeletal Tumor Society classification. An additional six patients had metastatic tumors to the upper extremity. Twenty-seven of 59 patients died of disease progression. Two patients died of other causes (chronic leukemia, human immunodeficiency virus infection). The 30 survivors had a mean followup of 90 months (range, 60-170 months). The Musculoskeletal Tumor Society functional analysis for the patients with a minimum 2-year followup (N = 41) averaged 74%. Sixteen of the 59 (27%) patients had local complications. Problems related to mechanical failure and infection were managed successfully with second operation. Amputation was rare, occurring in three of 60 (5%) patients and was related only to local recurrence. Endoprosthetic reconstructions of the upper extremity after tumor resections have proven to be successful.


Assuntos
Neoplasias Ósseas/cirurgia , Próteses e Implantes , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/secundário , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Resultado do Tratamento
14.
Cancer ; 85(5): 1077-83, 1999 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-10091791

RESUMO

BACKGROUND: Leiomyosarcoma of the inferior vena cava (IVC) is an uncommon tumor that many believe portends a poor prognosis compared with leiomyosarcoma with similar histology at other anatomic sites. Because of the limited international experience with this disease, the optimal management of these patients is unknown. METHODS: From October 1978 to January 1997, 14 patients with leiomyosarcoma of the IVC were treated at the University of California-Los Angeles Medical Center. Wide resection was attempted in all patients. The characteristics of each patient were documented and compared with those of patients with leiomyosarcoma of the stomach (n = 13), small intestine (n = 18), retroperitoneum (n = 19), and uterus (n = 10) who were treated during the same time period. RESULTS: Age, gender, tumor size, tumor grade, and lymph node status did not impact survival of patients with leiomyosarcoma of the IVC. Patients with positive surgical margins fared significantly worse (P < 0.03) compared with those who underwent complete resection. Radiation therapy diminished local recurrence and may improve median survival (6 months [n = 2] vs. 51 months [n = 12]) in this patient population. Patients who received combined chemotherapy and radiation lived longer than those who did not (P < 0.05). The 5-year cumulative survival rate (Kaplan-Meier method) was 53% for patients with leiomyosarcoma of the IVC, 47% for those with leiomyosarcoma of the stomach, 43% for those with leiomyosarcoma of the small intestine, 56% for those with leiomyosarcoma of the retroperitoneum, and 65% for those with leiomyosarcoma of the uterus. CONCLUSIONS: Despite having a tumor that originates from the IVC, patients with this tumor type can enjoy reasonably long term survival. It appears that these patients benefit from radiation therapy to control local disease. Survival of these patients is no worse than of patients with leiomyosarcomatous lesions of other origin. Aggressive surgical management combined with adjuvant therapy offers the best treatment for patients with leiomyosarcoma of the IVC.


Assuntos
Leiomiossarcoma/diagnóstico , Leiomiossarcoma/terapia , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/terapia , Veia Cava Inferior , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Neoplasias Intestinais/diagnóstico , Neoplasias Intestinais/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Retroperitoneais/diagnóstico , Neoplasias Retroperitoneais/terapia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Análise de Sobrevida , Resultado do Tratamento , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/terapia
15.
Clin Orthop Relat Res ; (358): 64-74, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9973977

RESUMO

From December 1980 to December 1995, 278 patients underwent primary custom endoprosthesis replacements for neoplastic disease at the University of California, Los Angeles and have been followed up for a minimum of 2 years or to death. The endoprosthesis reconstruction failed in 64 patients, including 10 additional patients referred for revision of their replacements. Failure was defined as the complete removal of a prosthesis for any reason. The cause of failure were aseptic loosening (44%), fatigue fracture (16%), local recurrence (14%), infection (13%), and failure of the expansion mechanism (6%). Forty-eight of 64 failed endoprostheses were managed by endoprosthesis reconstruction with most being revised using the same type of prosthesis. Nine of these patients with failed replacements experienced a second failure and four went on to require an amputation. Aseptic loosening and mechanical failure accounted for most of the failures and they were revised successfully. Sixty percent of the infected cases were salvaged satisfactorily by endoprosthetic revision, whereas, 89% of the local recurrences resulted in amputation. Based on endoprosthesis survival the 7-year failure rates were 31% and 34% for primary and revision reconstructions, respectively. The functional results for the patients with endoprosthesis revisions either were better, unchanged, or on average only slightly lower than results of patients with a surviving endoprosthesis.


Assuntos
Artroplastia de Substituição , Neoplasias Ósseas/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Falha de Prótese , Infecções Relacionadas à Prótese/cirurgia , Reoperação , Resultado do Tratamento
16.
Surg Oncol ; 8(4): 211-4, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11128835

RESUMO

Limb salvage is now possible for the majority of patients with extremity sarcomas. Although overall prognosis is primarily based on tumor size and histologic grade, complete surgical excision and local control is essential for cure. There are, however, certain anatomic locations such as the flexor fossae in which a complete surgical margin is difficult to attain, and surgery without adjuvant therapy has a high local failure and amputation rate. We have found that preoperative adjuvant therapy consisting of chemotherapy and radiation followed by surgical excision with tumor-free margins has been successful in treating flexor fossa sarcomas with high limb salvage (96%), local control (89%) and overall survival rates (70%). These results are comparable to patients with similar large, high-grade extremity tumors in other compartmental locations.


Assuntos
Sarcoma/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Axila/cirurgia , Terapia Combinada , Fracionamento da Dose de Radiação , Doxorrubicina/administração & dosagem , Cotovelo/cirurgia , Virilha/cirurgia , Humanos , Ifosfamida/administração & dosagem , Joelho/cirurgia , Terapia Neoadjuvante , Sarcoma/tratamento farmacológico , Sarcoma/radioterapia , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/radioterapia
17.
Am J Clin Oncol ; 21(6): 584-90, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9856660

RESUMO

The authors compare the progression-free survival of patients with unresected or partially resected desmoid tumors treated with radiotherapy with those not given radiotherapy. A retrospective analysis and pathologic review was performed on 14 patients treated at the University of California Los Angeles School of Medicine from 1965 through 1992. Median follow-up was 6 years. The 6-year progression-free survival for irradiated patients was 100%, compared with 50% for those not irradiated (p = 0.04). Of the seven patients irradiated, only two had a complete response and one had a partial response. There was no difference in disease-specific survival between patients irradiated and those not irradiated, because only 1 of 14 patients died of desmoid tumor progression, which caused airway obstruction. This data suggest that radiotherapy may improve the progression-free survival of patients with unresected or partially resected desmoid tumor; however, the number of patients in this series is small. Most patients did not have a complete response to radiotherapy. For patients with tumor adjacent to the airway in the neck or upper thorax, the authors recommend radiotherapy because of the potential for mortality. Otherwise, because tumor progression rarely causes death, one must consider whether the morbidity of treatment would outweigh the morbidity of disease progression.


Assuntos
Fibromatose Agressiva/radioterapia , Adolescente , Adulto , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Feminino , Fibromatose Agressiva/tratamento farmacológico , Fibromatose Agressiva/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia Adjuvante , Estudos Retrospectivos , Análise de Sobrevida
18.
J Vasc Surg ; 28(1): 75-81; discussion 82-3, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9685133

RESUMO

PURPOSE: Invasion of the inferior vena cava (IVC) by tumor is generally considered a criterion of unresectability. This study was designed to review the outcomes of a strategy of aggressive resection of the vena cava to achieve complete tumor resection coupled with prosthetic graft placement to re-establish caval flow. METHODS: Retrospective review of patients treated at a university referral center. Ten patients (mean age 54; eight females, two males) underwent tumor resection that involved circumferential resection of the IVC and immediate prosthetic replacement with ringed polytetrafluoroethylene (PTFE) grafts ranging in diameter from 12 to 16 mm. RESULTS: Seven patients had replacement of the infrarenal IVC, two of their suprarenal IVC, and one had reconstruction of the IVC bifurcation. Four of the 10 patients received preoperative chemotherapy, and none received radiotherapy. The most common (7/10) pathologic diagnosis was leiomyosarcoma arising from the IVC or retroperitoneum. Additional diagnoses included teratoma (one), renal cell carcinoma (one), and adrenal lymphoma (one). There were no perioperative deaths, and one complication (prolonged ileus) occurred. Mean length of stay was 8.1 days. Anticoagulation was not routinely used intraoperatively or postoperatively. Follow-up (mean duration = 19 months) demonstrated that survival was 80% (8/10) and 88% (7/8) of patients were free of venous obstructive symptoms. CONCLUSION: Resection of the IVC with prosthetic reconstruction allows for complete tumor resection and provides durable relief from symptoms of venous obstruction.


Assuntos
Implante de Prótese Vascular , Neoplasias Retroperitoneais/patologia , Neoplasias Vasculares/cirurgia , Veia Cava Inferior/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Politetrafluoretileno/uso terapêutico , Neoplasias Retroperitoneais/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Neoplasias Vasculares/diagnóstico por imagem , Neoplasias Vasculares/patologia , Veia Cava Inferior/patologia
19.
Cancer ; 82(9): 1704-8, 1998 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-9576292

RESUMO

BACKGROUND: The sentinel lymph node is defined as the first lymph node to receive drainage from a primary tumor. Based on this concept, the authors set out to evaluate whether the status of the sentinel lymph node can accurately predict whether breast tumor cells have metastasized to the axillary lymphatic basin. METHODS: Radiolabeled dextran was injected into the site of the breast tumor. In the operating room, a portable gamma detector probe was used to identify the exact location of the sentinel lymph node(s). After identifying and excising the radioactive sentinel lymph node specimens, a routine axillary lymph node dissection was performed. All lymph nodes were then subjected to hematoxylin and eosin (H & E) staining, and the sentinel lymph nodes were subjected to additional cytokeratin immunohistochemistry. RESULTS: Of the 41 patients who participated in the study, 18 had tumor metastasis to their axillary lymph nodes. In all 18 of these cases, the sentinel lymph node(s) contained cancer detected by either H & E staining or cytokeratin immunohistochemistry. CONCLUSIONS: The status of the sentinel lymph node(s) appears to predict accurately whether breast tumor cells have metastasized to the axillary lymphatic basin. This new, minimally invasive technique for staging breast carcinoma should be further validated in a large, multi-institutional clinical trial.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Dextranos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Feminino , Humanos , Linfonodos/cirurgia , Metástase Linfática , Estadiamento de Neoplasias , Cintilografia
20.
Int J Radiat Oncol Biol Phys ; 39(3): 659-65, 1997 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-9336146

RESUMO

PURPOSE: Desmoid tumors have a high propensity for local recurrence with surgical resection. There are many reports describing good responses of desmoid tumors to irradiation, but none have clearly established the indications for adjuvant radiotherapy in treating resectable desmoid tumors. METHODS AND MATERIALS: A retrospective analysis was performed on 61 patients with resectable desmoid tumor(s) who were treated at our institution from 1965 to February of 1992. Five patients had multifocal disease and are analyzed separately. Fifty-six patients had unifocal disease, of which 34 had positive surgical margins. Forty-five of the 56 patients with unifocal disease were treated with surgery alone, while 11 were treated with surgery plus adjuvant radiotherapy. Median follow-up was 6 years. Local control was measured from the last day of treatment, and all cases were reviewed by our Department of Pathology. RESULTS: Multivariate analysis of the 56 patients with unifocal disease revealed that positive margins independently predicted for local recurrence (p < or = 0.01). Only 3 of 22 patients with clear margins experienced a local recurrence, with a 6-year actuarial local control of 85%. Multivariate analysis of the 34 patients with positive margins revealed that adjuvant radiotherapy independently predicted for improved local control (p = 0.01), and patients with recurrent disease had a slightly higher risk of local recurrence (p = 0.08). The 6-year actuarial local control determined by Kaplan-Meier for patients with unifocal disease and positive margins was 32% (+/-12%) with surgery alone, and 78% (+/-14%) with surgery plus adjuvant radiotherapy (p = 0.02). Subgroup analysis of the patients with positive margins and recurrent disease revealed that those treated with surgery alone had a 6-year actuarial local control of 0% vs. 80% for those treated with surgery plus radiotherapy (p < or = 0.01). Patients with positive margins and primary disease had a trend towards improved local control with adjuvant radiotherapy, but this was not statistically significant. None of the patients treated with radiotherapy developed serious complications or a secondary malignancy. CONCLUSIONS: Margin status is the most important predictor of local recurrence for patients with resectable, unifocal desmoid tumor. Adjuvant radiotherapy is indicated in the treatment of patients with positive margins following wide excision of recurrent disease. The role of adjuvant radiotherapy in patients with positive margins following resection of primary disease is controversial, and should be based on a balanced discussion of the potential morbidity from radiotherapy compared to the potential morbidity of another local recurrence. Adjuvant radiotherapy is less likely to benefit those with clear margins due to the excellent results for these patients treated with surgery alone. The local control of desmoid tumor in the adjuvant setting is excellent with total doses ranging from 50-60 Gy, with acceptable morbidity. Field sizes should be generous to prevent marginal recurrences, and large volume MRIs of patients with extremity lesions should be used to identify those patients with multifocal disease.


Assuntos
Fibromatose Agressiva/radioterapia , Fibromatose Agressiva/cirurgia , Adolescente , Adulto , Análise de Variância , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasia Residual , Radioterapia Adjuvante , Estudos Retrospectivos , Falha de Tratamento
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