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1.
Cancer Res ; 52(23): 6705-7, 1992 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-1423318

RESUMEN

A malignant stromal tumor of the testis with an osteosarcoma component and five of its metastases mainly containing osteosarcoma have been analyzed for RB1 and TP53 abnormalities. Whereas in the primary tumor and in some of the metastases loss of heterozygosity could not be detected for RB1 or for the 17p13 region in which TP53 is located, other metastases showed such losses of heterozygosity. By polymerase chain reaction analysis an 18-base pair deletion from exon 5 of the TP53 gene was found in a small proportion of primary tumor cells and in one of the metastases, but not in the other metastases. Therefore, in this case neither RB1 nor TP53 seems to play an essential role in the initiation of osteosarcoma.


Asunto(s)
ADN de Neoplasias/química , Genes de Retinoblastoma/genética , Genes p53/genética , Osteosarcoma/genética , Neoplasias Testiculares/genética , Secuencia de Aminoácidos , Secuencia de Bases , Southern Blotting , Análisis Mutacional de ADN , Humanos , Neoplasias Pulmonares/secundario , Masculino , Datos de Secuencia Molecular , Osteosarcoma/patología , Reacción en Cadena de la Polimerasa , Neoplasias Testiculares/patología
2.
Cancer Res ; 49(2): 439-43, 1989 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-2910461

RESUMEN

A cytogenetic analysis of ten seminomas has been carried out after direct harvesting of the tumor cells. Modal chromosome numbers ranged from 63 to 112. These numbers were in agreement with flow cytometric determination of the DNA content of the tumors. Eight tumors had at least one copy of an i(12p) among other chromosomal abnormalities. Two seminomas lacked the i(12p).


Asunto(s)
Disgerminoma/genética , Neoplasias Testiculares/genética , Adulto , Aberraciones Cromosómicas , Trastornos de los Cromosomas , ADN de Neoplasias/análisis , Humanos , Cariotipificación , Masculino , Persona de Mediana Edad
3.
Cancer Res ; 49(3): 672-6, 1989 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-2910486

RESUMEN

A cytogenetic analysis of 13 mature residual teratomas following chemotherapy revealed modal chromosome numbers ranging from 52 to 85, in agreement with the flow cytometric determination of the DNA content of the tumors. At least one copy of an i(12p) was present in 12 tumors. One tumor, however, lacked that marker. The comparison between the chromosomal abnormalities found in mature residual teratomas following chemotherapy and those from primary testicular nonseminomas suggests that residual teratomas result from selection of clones from the primary tumor with a less abnormal karyotype.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Aberraciones Cromosómicas , Trastornos de los Cromosomas , Teratoma/genética , Neoplasias Testiculares/genética , Adulto , Citometría de Flujo , Humanos , Cariotipificación , Masculino , Persona de Mediana Edad , Teratoma/tratamiento farmacológico , Neoplasias Testiculares/tratamiento farmacológico
4.
Cancer Res ; 56(17): 3948-53, 1996 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-8752162

RESUMEN

This study was undertaken to determine the effects on systemic fibrinolysis of hyperthermic isolated limb perfusion with recombinant tumor necrosis factor alpha (r-TNF-alpha) and melphalan, with or without pretreatment with recombinant IFN-gamma (r-IFN-gamma). Twenty patients were treated with r-TNF-alpha and melphalan; four patients, treated with melphalan only, served as controls. Of the twenty patients treated with both r-TNF-alpha and melphalan, eight received r-IFN-gamma for two days before the perfusion and as a bolus into the perfusion circuit. A significant leak of r-TNF-alpha from the perfusion circuit to the systemic circulation was observed in all r-TNF-alpha-treated patients (mean maximum TNF-alpha, 87,227 ng/liter versus 31 ng/liter in controls; P < 0.002). In these patients, but not in controls, there was an almost instantaneous rise in systemic tissue plasminogen activator activity (from 0.26 to 5.28 IU/ml in 90 min), causing activation of fibrinolysis. After a delay of 90 min, plasminogen activator inhibitor-1 (PAI-1) antigen rose to high levels in the r-TNF-alpha-treated group (mean maximum PAI-1, 1652 ng/ml versus 211 ng/ml in controls; P < 0.02), associated with a sharp decrease of tissue plasminogen activator activity and a slower decrease of plasminogen-antiplasminogen complexes (from 5.28 to 0.02 IU/ml in 2 h and from 1573 to 347 micrograms/liter in 22 h, respectively). No additional effect of IFN-gamma pretreatment on fibrinolysis could be demonstrated. These results suggest that in isolated limb perfusion with r-TNF-alpha and melphalan an initial activation of systemic fibrinolysis, induced by leakage of r-TNF-alpha from the perfusion circuit, is set off by a subsequent inhibition of the fibrinolytic system by PAI-1. This large increase in PAI-1 could place the patient at risk for deposition of microthrombi in the systemic circulation.


Asunto(s)
Antineoplásicos/efectos adversos , Quimioterapia del Cáncer por Perfusión Regional , Fibrinólisis/efectos de los fármacos , Hipertermia Inducida/efectos adversos , Melfalán/efectos adversos , Factor de Necrosis Tumoral alfa/efectos adversos , Antineoplásicos/uso terapéutico , Terapia Combinada , Extremidades , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Humanos , Interferón gamma/administración & dosificación , Melfalán/administración & dosificación , Neoplasias/sangre , Neoplasias/tratamiento farmacológico , Inhibidor 1 de Activador Plasminogénico/metabolismo , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/sangre , Activador de Tejido Plasminógeno/metabolismo , Factor de Necrosis Tumoral alfa/administración & dosificación , Factor de Necrosis Tumoral alfa/metabolismo
5.
J Clin Oncol ; 5(4): 651-6, 1987 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-3104546

RESUMEN

The gonadal functions were studied in 54 patients with disseminated nonseminomatous testicular tumors who had been subjected to combination chemotherapy (cisplatin, vinblastine, and bleomycin [PVB]) and surgery (hemiorchiectomy, retroperitoneal lymph node dissection or removal of retroperitoneal residual tumor after chemotherapy) and in 17 patients with a stage I tumor subjected to hemiorchiectomy exclusively. In the patients treated with chemotherapy, the plasma testosterone levels remained at the lower limit of normal and the luteinizing hormone (LH) levels remained elevated for 2 years after completion of treatment. The follicle-stimulating hormone (FSH) levels also remained significantly elevated, but showed a tendency to decrease after 2 years. Semen analysis was performed in 25 patients; of the other patients, 18 had no antegrade ejaculation, eight had undergone a vasectomy and three patients did not cooperate. Before treatment, 72% of the patients showed azoo- or oligozoospermia; 2 years after discontinuation of the chemotherapy, 48% had azoo- or oligozoospermia while 28% had more than 60 X 10(6) spermatozoa/mL. However, interestingly the proportion of patients with azoospermia had increased from 4% to 28%. In the course of this study, eight pregnancies occurred; one ended in an early spontaneous abortion; the other seven pregnancies ran an uncomplicated course. Seven healthy children were born. In 17 patients with a stage I tumor treated by hemiorchiectomy only, the testosterone, LH and FSH levels were also observed for 2 years; until 2 years after treatment, the testosterone levels remained lower and the FSH levels remained higher than normal. Insufficiency of the Leydig's cells in the unaffected gonad appeared to be responsible for the altered hormone concentrations in the blood.


Asunto(s)
Neoplasias Testiculares/fisiopatología , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Hormona Folículo Estimulante/sangre , Estudios de Seguimiento , Humanos , Hormona Luteinizante/sangre , Escisión del Ganglio Linfático , Masculino , Estadificación de Neoplasias , Oligospermia/fisiopatología , Orquiectomía , Espermatogénesis , Neoplasias Testiculares/terapia , Testosterona/sangre
6.
J Clin Oncol ; 12(6): 1137-49, 1994 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8201375

RESUMEN

PURPOSE: To evaluate the benefit of adjuvant chemotherapy in adult patients with soft tissue sarcomas. The principal end points were freedom from local recurrence and/or metastases and overall survival. PATIENTS AND METHODS: Between January 1977 and June 1988, 468 patients entered this randomized study and 317 were considered eligible. Following complete surgical resection with or without radiotherapy, outcome in 145 eligible patients receiving cyclophosphamide 500 mg/m2 intravenously (IV) bolus on day 1, vincristine 1.4 mg/m2 IV bolus on day 1, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) 50 mg/m2 IV bolus on day 1, and dacarbazine (DTIC) 400 mg/m2 by 1-hour infusion on days 1 to 3 (CYVADIC) cycles repeated every 28 days for eight courses was compared with that in 172 control patients. RESULTS: With a median follow-up duration of 80 months (range, 39 to 165), actuarial percentage survival figures at 7 years were compared. Relapse-free survival rates were higher for CYVADIC, 56% versus 43% (P = .007), and local recurrence was significantly reduced in the CYVADIC arm at 17% versus 31% (P = .004). In contrast, distant metastases occurred with similar frequency in both arms, 32% for CYVADIC versus 36% for control patients (P = .42), and overall survival rates were not significantly different at 63% versus 56% (P = .64). A reduction in local recurrence was only apparent in the group of head, neck, and trunk sarcomas (P = .002), but not in limb tumors (P = .31). CONCLUSION: Adjuvant chemotherapy with CYVADIC cannot be recommended outside the context of a clinical trial. Experience from this study has been used to plan a trial of neoadjuvant chemotherapy with doxorubicin/ifosfamide, which is currently in progress.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Sarcoma/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Adolescente , Adulto , Anciano , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Dacarbazina/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Sarcoma/mortalidad , Sarcoma/patología , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/mortalidad , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/terapia , Tasa de Supervivencia , Vincristina/administración & dosificación
7.
J Clin Oncol ; 13(5): 1188-94, 1995 May.
Artículo en Inglés | MEDLINE | ID: mdl-7537802

RESUMEN

PURPOSE: A wait-and-see policy for patients with stage I nonseminomatous testicular germ cell tumors (NSTGCT) was evaluated in a prospective study. The frequency and time of recurrence, detection of recurrence, and presence of unfavorable prognostic factors were investigated. PATIENTS AND METHODS: During the period 1982 to 1992, 154 patients with stage I NSTGCT (median age, 29 years) underwent orchidectomy and were monitored at follow-up evaluation with physical examinations, alfafetoprotein (AFP) and beta-human choriogonadotropin (hCG) levels, chest x-rays (CXR), and computed tomographic (CT) scans of the abdomen and chest. Multivariate logistic regression analyses were performed to identify prognostic factors. RESULTS: During a median follow-up period of 7 years (range, 2 to 12), recurrence was found in 42 patients (27.3%). All cases of recurrence were detected within 2 years, 90% in the first year after orchidectomy. In 29 patients (69.0%), recurrence was detected in the abdominal lymph nodes. Nine patients (21.4%) had metastases in the retroperitoneum and mediastinum and/or lungs, and four patients (9.6%) had metastases only in the mediastinum or lungs. The majority of recurrences (97.6%) were detected by tumor markers and CT scans. Recurrence was related to the presence of vascular invasion, embryonal carcinoma (E), elevated preoperative hCG level, and absence of mature teratoma (M). Only vascular invasion was an independent risk factor. After polychemotherapy treatment for recurrence, the survival rate for the total group was 98.7%. CONCLUSION: The wait-and-see policy is a reliable method for follow-up monitoring of patients with stage I NSTGCT. Even in patients with unfavorable prognostic factors, it is justified to await the possible appearance of metastases. For the future, it is recommended that CXR be omitted from the schedule, and it might be feasible to discontinue follow-up evaluations after 5 years.


Asunto(s)
Germinoma/diagnóstico , Germinoma/secundario , Metástasis de la Neoplasia/diagnóstico , Neoplasias Testiculares/patología , Adolescente , Adulto , Anciano , Análisis de Varianza , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Gonadotropina Coriónica/análisis , Estudios de Seguimiento , Germinoma/terapia , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Orquiectomía , Estudios Prospectivos , Recurrencia , Análisis de Regresión , Inducción de Remisión , Neoplasias Testiculares/terapia , Tomografía Computarizada por Rayos X , alfa-Fetoproteínas/análisis
8.
J Clin Oncol ; 14(10): 2653-65, 1996 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8874324

RESUMEN

PURPOSE: To determine the efficacy of isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNF) in combination with interferon-gamma (IFN) and melphalan as induction therapy to render tumors resectable and avoid amputation in patients with nonresectable extremity soft tissue sarcomas (STS). PATIENTS AND METHODS: Among 55 patients with 30 primary and 25 recurrent sarcomas, there were 48 high-grade and seven grade 1 sarcomas (very large, recurrent, or multiple). The composition of this series of patients is unusual: 13 patients (24%) had multifocal primary sarcomas or multiple recurrent tumors; tumors were very large (median, 18 cm); and nine patients (16%) had known systemic metastases. IFN was administered subcutaneously on the 2 days before ILP with TNF, IFN, and melphalan. A delayed marginal resection of the tumor remnant was usually performed 2 to 3 months after ILP. RESULTS: A major tumor response was seen in 87% of patients and rendered the sarcomas resectable in most cases. Clinical response rates were as follows: 10 (18%) completes responses (CRs), 35 (64%) partial responses (PRs), and 10 (18%) no change (NC). Final outcome was defined as follows by clinical and pathologic response: 20 (36%) CRs, 28 (51%) PRs, and seven (13%) NC. Limb salvage was achieved in 84% (follow-up duration, 20+ to 50+ months). In 39 patients, resection of the tumor remnant (n = 31) or of two to eight tumors (n = 8) after ILP was performed; local recurrence developed in five (13%). When no resection was performed (multiple tumors or systemic metastases), local recurrences were frequent (five of 16), but limb salvage was often achieved as patients died of systemic disease. Regional toxicity was limited and systemic toxicity minimal to moderate with no toxic deaths. Histology showed hemorrhagic necrosis; angiographies showed selective destruction of tumor-associated vessels. CONCLUSION: ILP with TNF, IFN, and melphalan is a safe and highly effective induction biochemotherapy procedure that can achieve limb salvage in patients with nonresectable extremity STS. TNF is an active anticancer drug in humans in the setting of ILP.


Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Extremidades , Interferón gamma/uso terapéutico , Melfalán/uso terapéutico , Sarcoma/terapia , Factor de Necrosis Tumoral alfa/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Alquilantes/efectos adversos , Quimioterapia del Cáncer por Perfusión Regional , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Interferón gamma/efectos adversos , Masculino , Melfalán/efectos adversos , Persona de Mediana Edad , Inducción de Remisión , Terapia Recuperativa , Sarcoma/irrigación sanguínea , Sarcoma/patología , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/efectos adversos
9.
J Clin Oncol ; 14(2): 490-6, 1996 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8636762

RESUMEN

PURPOSE: The value of high-dose methotrexate (HD-MTX)-based neoadjuvant chemotherapy was evaluated in patients with malignant fibrous histiocytoma (MFH) of bone. PATIENTS AND METHODS: Since 1977, MFH of bone was diagnosed in 17 patients (12 males and five females). Ten patients (59%), completed treatment with four courses of neoadjuvant chemotherapy as follows: HD-MTX, vincristine, doxorubicin, cyclophosphamide, bleomycin, and dactinomycin, or HD-MTX, 4(1)-epidoxorubicin, and carboplatin followed by local tumor resection (n = 3), curettage-cryosurgery (n = 2), amputation (n = 2), or tumor resection-endoprosthetic replacement or allograft (n = 3). After recovery from surgery, an additional six courses of polychemotherapy, including HD-MTX in nine patients, were administered. One patient changed to cisplatin- instead of HD-MTX-containing chemotherapy postoperatively. One additional patient received only adjuvant HD-MTX-containing polychemotherapy. Neoadjuvant MTX-containing chemotherapy was contraindicated in five patients (29%) due to age, cardiac insufficiency, or mental disorder. In one patient, neoadjuvant chemotherapy was cancelled after one course due to renal failure. Treatment consisted of amputation (n = 2), one course of chemotherapy and amputation (n = 1), hyperthermic isolated limb perfusion (HILP; n = 1), intraarterial chemotherapy, radiotherapy, and endoprosthetic replacement (n = 1), and a combination of chemotherapy and radiation treatment (n = 1). RESULTS: Five of six patients who received no HD-MTX-based neoadjuvant chemotherapy developed metastatic disease (83%); the median time to metastatic disease was 17 months (range, 3 to 44). In contrast, in 10 patients who completed treatment with HD-MTX-based neoadjuvant chemotherapy, with a mean follow-up time of 9.8 years (range, 2.3 to 15.7) and a median follow-up time of 10.8 years (range, 2.3 to 15.7) after diagnosis, no local recurrence or distant metastases were diagnosed (P < .005). CONCLUSION: Neoadjuvant HD-MTX-containing chemotherapy in addition to surgery has dramatically improved the prognosis of patients with MFH of bone.


Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias Óseas/tratamiento farmacológico , Histiocitoma Fibroso Benigno/tratamiento farmacológico , Metotrexato/administración & dosificación , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Óseas/mortalidad , Quimioterapia Adyuvante , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Histiocitoma Fibroso Benigno/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Resultado del Tratamiento
10.
J Clin Oncol ; 7(8): 1099-104, 1989 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-2474060

RESUMEN

This 10-year follow-up study of 91 patients with disseminated testicular nonseminomatous cancer, treated with cisplatin, vinblastine, and bleomycin (PVB) induction chemotherapy and vinblastine plus bleomycin maintenance chemotherapy for a planned period of 2 years, shows a 63% cure rate. The predominant long-term sequelae are neurological and sexual dysfunction in 68% and 40% of patients, respectively. Two patients died of myocardial infarction. Sixteen percent of patients developed hypertension, 23% Raynaud's phenomenon, and 25% ototoxicity. Despite the long-term side effects, 90% of the patients who responded to a questionnaire are fully employed. This study shows that the maintenance chemotherapy has contributed to the incidence and/or degree of neurotoxicity, hypertension, and renal function disturbance.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bleomicina/administración & dosificación , Cisplatino/administración & dosificación , Neoplasias Testiculares/tratamiento farmacológico , Vinblastina/administración & dosificación , Creatinina/sangre , Empleo , Estudios de Seguimiento , Humanos , Hipertensión/etiología , Riñón/efectos de los fármacos , Riñón/fisiología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Aptitud Física , Pronóstico , Enfermedad de Raynaud/etiología , Conducta Sexual/efectos de los fármacos
11.
J Clin Oncol ; 6(4): 701-8, 1988 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-3357008

RESUMEN

The use of isolated regional perfusion in an adjuvant setting for stage I melanoma of the extremity continues to be controversial. The present retrospective study evaluates the past 20 years' experience by comparing 227 perfused patients from Groningen with 238 matched controls from five hospitals in The Netherlands and Westphalia (a region of West Germany bordering the Netherlands). All patients underwent wide local excision for a primary extremity melanoma of 1.5 mm or greater in thickness. A proportional hazards regression analysis for recurrence of disease and survival identified the significant prognostic factors, of which tumor thickness was the most important. Corrected for these factors, it was not possible to demonstrate a statistically significant effect for perfusion in terms of time to limb recurrence (P = .61), time to regional lymph node metastasis (P = .11), time to distant metastasis (P = .73), disease-free interval (P = .42), and survival (P = .90). No statistically significant differences were seen for adjuvant perfusion in any of the subgroups.


Asunto(s)
Melanoma/tratamiento farmacológico , Melfalán/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Melanoma/patología , Melanoma/cirugía , Melfalán/administración & dosificación , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Perfusión , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía
12.
J Clin Oncol ; 13(5): 1177-87, 1995 May.
Artículo en Inglés | MEDLINE | ID: mdl-7537801

RESUMEN

PURPOSE: To develop a statistical model that predicts the histology (necrosis, mature teratoma, or cancer) after chemotherapy for metastatic nonseminomatous germ cell tumor (NSGCT). PATIENTS AND METHODS: An international data set was collected comprising individual patient data from six study groups. Logistic regression analysis was used to estimate the probability of necrosis and the ratio of cancer and mature teratoma. RESULTS: Of 556 patients, 250 (45%) had necrosis at resection, 236 (42%) had mature teratoma, and 70 (13%) had cancer. Predictors of necrosis were the absence of teratoma elements in the primary tumor, prechemotherapy normal alfa-fetoprotein (AFP), normal human chorionic gonadotropin (HCG), and elevated lactate dehydrogenase (LDH) levels, a small prechemotherapy or postchemotherapy mass, and a large shrinkage of the mass during chemotherapy. Multivariate combination of predictors yielded reliable models (goodness-of-fit tests, P > .20), which discriminated necrosis well from other histologies (area under the receiver operating characteristic (ROC) curve, .84), but which discriminated cancer only reasonably from mature teratoma (area, .66). Internal and external validation confirmed these findings. CONCLUSION: The validated models estimate with high accuracy the histology at resection, especially necrosis, based on well-known and readily available predictors. The predicted probabilities may help to choose between immediate resection of a residual mass or follow-up, taking into account the expected benefits and risks of resection, feasibility of frequent follow-up, the financial costs, and the patient's individual preferences.


Asunto(s)
Germinoma/patología , Germinoma/secundario , Neoplasias Retroperitoneales/patología , Neoplasias Retroperitoneales/secundario , Teratoma/patología , Neoplasias Testiculares/patología , Análisis de Varianza , Gonadotropina Coriónica/sangre , Estudios de Seguimiento , Germinoma/sangre , Germinoma/terapia , Humanos , L-Lactato Deshidrogenasa/sangre , Modelos Logísticos , Masculino , Análisis Multivariante , Necrosis , Neoplasia Residual , Valor Predictivo de las Pruebas , Probabilidad , Curva ROC , Reproducibilidad de los Resultados , Neoplasias Retroperitoneales/sangre , Neoplasias Retroperitoneales/terapia , Teratoma/secundario , Neoplasias Testiculares/sangre , Neoplasias Testiculares/tratamiento farmacológico , alfa-Fetoproteínas/análisis
13.
Eur J Cancer ; 34(9): 1363-7, 1998 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9849418

RESUMEN

Development of second testicular tumours, i.e. bilateral testicular cancer, is influenced by systemic chemotherapy for the first tumour. The prevalence of bilateral testicular cancer was studied in patients with initial stage I disease, in which no systemic treatment was given after orchidectomy. All stage I testicular cancer patients entered a surveillance study with an intensive follow-up since 1982. We hypothesised that after 1982, bilateral testicular cancer was diagnosed at an earlier stage of disease. The prevalence of bilateral testicular cancer was 4.7% (8/170) in stage I patients treated between 1967 and 1981, and 2.9% (8/275) in stage I patients treated between 1982 and 1997 (P > 0.5 chi 2-test). In the period 1967-1981, 6 patients had stage I second tumours and 2 patients had stage III second tumours. The former 6 patients are alive with no evidence of disease and the 2 patients with metastatic tumours died of disease or treatment. In the period 1982-1977, all 8 patients had stage I second tumours and all are alive with no evidence of disease. The overall prevalence of bilateral testicular cancer in stage I patients was 3.6% and has slightly decreased over the past three decades. Intensive follow-up, improvement of radiodiagnostic computed tomography techniques, availability of serum tumour markers, and patient education have resulted in earlier diagnosis and lower stage of contralateral testicular tumours, contributing to improved prognosis.


Asunto(s)
Germinoma/epidemiología , Germinoma/patología , Neoplasias Testiculares/epidemiología , Neoplasias Testiculares/patología , Adulto , Anciano , Estudios de Seguimiento , Germinoma/terapia , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Primarias Secundarias , Países Bajos/epidemiología , Prevalencia , Pronóstico , Neoplasias Testiculares/terapia , Factores de Tiempo
14.
Eur J Cancer ; 26(9): 969-72, 1990.
Artículo en Inglés | MEDLINE | ID: mdl-1703772

RESUMEN

To establish whether alpha-fetoprotein (AFP) produced in the early post-treatment phase of a patient with a germ cell tumour of the testis or the ovary originates from the tumour or is due to an underlying disturbance in liver function, the binding of AFP to concanavalin A (Con A) was investigated as a discriminative variable. A two-step assay is described that can distinguish the type of AFP produced at levels as low as 10 ng/ml. A Con A-binding ratio of 12-43% was found in the patients with disseminated germ cell tumours and in patients with AFP-positive gastrointestinal carcinomas. AFP from the liver gives ratios below 10%.


Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias Hepáticas/sangre , Neoplasias de Células Germinales y Embrionarias/sangre , Neoplasias Ováricas/sangre , Neoplasias Testiculares/sangre , alfa-Fetoproteínas/metabolismo , Carcinoma Hepatocelular/sangre , Concanavalina A/farmacología , Femenino , Neoplasias Gastrointestinales/sangre , Humanos , Masculino , Métodos , Unión Proteica
15.
Eur J Cancer ; 32A(3): 550-2, 1996 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-8814706

RESUMEN

We examined whether cisplatin-induced nephrotoxicity augmented bleomycin-induced pulmonary toxicity in patients with testicular cancer treated with etoposide and cisplatin with (BEP) or without bleomycin (EP). Before and at 3-week intervals during chemotherapy, creatinine clearance and lung functions were measured. In patients receiving BEP, deterioration of renal function correlated with a decrease in transfer factor of the lungs for carbon monoxide (TLCO) and vital capacity (VC), parameters known to reflect bleomycin-induced pulmonary effects. Other lung functions did not correlate with renal function. In the EP group, no relationships were observed at all. These observations suggest enhanced pulmonary effects of bleomycin when combined with cisplatin. Therefore, attention should be paid to the potential development of bleomycin-induced pulmonary toxicity in patients treated with BEP.


Asunto(s)
Antibióticos Antineoplásicos/efectos adversos , Antineoplásicos/efectos adversos , Bleomicina/efectos adversos , Cisplatino/efectos adversos , Enfermedades Renales/inducido químicamente , Enfermedades Pulmonares/inducido químicamente , Adolescente , Adulto , Bleomicina/uso terapéutico , Cisplatino/uso terapéutico , Sinergismo Farmacológico , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pruebas de Función Respiratoria , Neoplasias Testiculares/tratamiento farmacológico
16.
Eur J Cancer ; 31A(1): 58-63, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-7695980

RESUMEN

The aim of this study was to investigate the role of mild hyperthermia (39-40 degrees C) in isolated cytostatic perfusion for patients with recurrent melanoma of the extremities. A total of 218 patients treated with mild hyperthermic perfusion was compared to 166 patients perfused under controlled normothermic conditions (37-38 degrees C). Only patients whose lesions had been excised before or at the moment of perfusion were eligible for this study. A variety of prognostic factors was controlled for in a Cox proportional hazards analysis. The application of mild hyperthermia did not influence limb recurrence-free interval nor survival (corrected P values 0.46 and 0.18, respectively). In this retrospective comparative study, no benefit for mild hyperthermia in regional isolated perfusion could be identified.


Asunto(s)
Quimioterapia del Cáncer por Perfusión Regional/métodos , Hipertermia Inducida , Melanoma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adolescente , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Melanoma/mortalidad , Melanoma/cirugía , Melfalán/administración & dosificación , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos
17.
Semin Oncol ; 24(5): 547-55, 1997 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9344321

RESUMEN

The unique property of high dose recombinant tumor necrosis factor alpha (rTNF alpha) is to activate and selectively destroy the tumor-associated microvasculature. For the systemic application of rTNF alpha it has been shown that the maximum tolerated dose (MTD) is 10 times less than the effective dose in animals. The main toxicity corresponds to systemic inflammatory response syndrome with a decrease in vascular resistance and hypotension. We found that it is possible to administer rTNF alpha at 10 times the MTD in an isolated limb perfusion (ILP) system with heart-lung machine, for locally advanced extremity soft tissue sarcomas. One hundred forty patients received an ILP with high-dose TNF alpha. In 55 patients treated with the combination of high-dose rTNF alpha + interferon-gamma + melphalan an overall objective response rate of 87% with 36% complete responses was observed; it was 81% and 28%, respectively, in a group treated with TNF alpha and melphalan (n = 85). Angiographic and immunohistological studies showed the selective and early damage of the sarcoma-associated microvasculature preceded by the upregulation of adhesion molecules and intratumoral leak of von Willebrand factor. Tumor invasion by platelets and, in some cases, by polymorphonuclear cells, appeared within hours after the application of rTNFa long before the lysis of the tumor. Thus, ILP with high-dose TNF alpha and chemotherapy seems to act through a dual targeting: TNF hits the tumor associated vasculature, and chemotherapy attacks the tumor cells. Therefore, ILP with TNF is a new option in the management of locally advanced soft tissue sarcoma of the extremities.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Quimioterapia del Cáncer por Perfusión Regional , Sarcoma/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Esquema de Medicación , Extremidades , Femenino , Máquina Corazón-Pulmón , Humanos , Hipertermia Inducida , Interferón gamma/administración & dosificación , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Análisis de Supervivencia , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/uso terapéutico
18.
Int J Radiat Oncol Biol Phys ; 40(4): 807-14, 1998 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-9531364

RESUMEN

PURPOSE: Hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and melphalan is associated with a dramatic antitumor effect in locally advanced extremity soft-tissue sarcomas (STS). The aim of this study was to demonstrate the feasibility and efficacy of adjuvant radiotherapy after HILP with TNF-alpha, IFN-gamma, and melphalan and delayed surgical resection. METHODS AND MATERIALS: Between 1991 and 1995, 34 patients--16 males and 18 females, median age 50 (range 18-80) years--underwent HILP for locally advanced extremity STS. Resection of the residual tumor mass was performed in most patients after 6-8 weeks. Fifteen patients with histopathological viable tumor after resection received adjuvant 60-70 Gy external beam radiotherapy (EBRT) (44%, HILP + EBRT group). Nineteen patients received HILP without adjuvant EBRT (56%, HILP-only group). Five patients in the HILP-only group had also distant metastases (15%) and received HILP as a palliative treatment. Treatment morbidity, local recurrences, and regional and distant metastases were scored. RESULTS: During a median follow-up of 34 months (range 8-54), limb salvage was achieved in 29 patients (85%): 14 patients after HILP + EBRT and 15 patients after HILP only. None of the patients from the HILP + EBRT group developed local recurrences; however, five patients from the HILP-only did (26%) (p < 0.05). Regional metastases were observed in one patient from the HILP + EBRT group (7%) and in two patients from the HILP-only group who were treated with curative intent (14%). Distant metastases occurred in four patients after HILP + EBRT (27%) and in four patients after HILP only with curative intent (29%). The mean morbidity (subjective, objective, medical management, and analytical evaluation) score in both groups was, respectively, 0.33 for skin and subcutaneous tissue and for muscle and soft tissue, 0.34 (HILP + EBRT group) and 0.33 (HILP-only group). CONCLUSION: Adjuvant EBRT after HILP with TNF-alpha, IFN-gamma, and melphalan and delayed tumor resection of locally advanced extremity STS is feasible and may increase local tumor control without increasing treatment morbidity.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia del Cáncer por Perfusión Regional , Extremidades , Hipertermia Inducida/métodos , Sarcoma/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Amputación Quirúrgica , Terapia Combinada , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Interferón gamma/administración & dosificación , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Radioterapia Adyuvante , Sarcoma/tratamiento farmacológico , Sarcoma/radioterapia , Sarcoma/cirugía , Factor de Necrosis Tumoral alfa/administración & dosificación
19.
J Nucl Med ; 35(1): 90-2, 1994 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-8271067

RESUMEN

METHODS: The treatment of a patient with soft-tissue sarcoma was evaluated with FDG-PET. A limb-saving complete remission of a locally advanced liposarcoma of the left thigh was achieved with isolated regional perfusion of the limb with tumor necrosis factor alpha, interferon gamma and melphalan. RESULTS: PET with 18F-FDG before perfusion showed high glucose consumption in the tumor. After perfusion, glucose metabolism in the tumor was absent. Subsequent excision confirmed complete necrosis of the tumor. CONCLUSION: FDG-PET may be useful in evaluating the results of isolateral regional limb perfusion for soft-tissue sarcomas.


Asunto(s)
Quimioterapia del Cáncer por Perfusión Regional , Desoxiglucosa/análogos & derivados , Pierna , Liposarcoma/diagnóstico por imagen , Liposarcoma/terapia , Neoplasias de los Tejidos Blandos/diagnóstico por imagen , Neoplasias de los Tejidos Blandos/terapia , Tomografía Computarizada de Emisión , Medios de Contraste , Fluorodesoxiglucosa F18 , Humanos , Interferón gamma/administración & dosificación , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/administración & dosificación
20.
J Nucl Med ; 38(2): 191-5, 1997 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9025733

RESUMEN

UNLABELLED: We studied the potential of PET with L-[1-11C]-tyrosine (TYR) to visualize tumors outside the central nervous system and to quantify their protein synthesis rates (PSRs). METHODS: Twenty-two patients suspected of having a malignant tumor underwent a PET study with TYR before biopsy. The PSR in nanomoles per milliliter tumor tissue per minute as well as the PSR in contralateral normal tissue, standardized uptake values (SUVs) and tumor-to-nontumor-ratios (T/N ratios) were calculated. RESULTS: Fifteen of the 16 malignancies (94%) were correctly visualized as a hot spot. A chondrosarcoma of the sacrum was not visualized. Of the six patients with benign lesions, cold spots were correctly identified in four (67%). A benign schwannoma and an intramuscular hemangioma of the forearm were visualized as hot spots. PSR in tumor tissue was higher than in the corresponding contralateral normal tissues. PSR and SUV in malignant tumors were higher than in benign tumors. CONCLUSION: TYR appears to be a good tracer for imaging malignancies. The PSR, which was higher in malignant tumors than in normal tissue and the studied benign lesions, could be quantified and correlated with the SUV.


Asunto(s)
Radioisótopos de Carbono , Neoplasias/diagnóstico por imagen , Neoplasias/metabolismo , Tomografía Computarizada de Emisión , Tirosina , Adulto , Anciano , Radioisótopos de Carbono/farmacocinética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biosíntesis de Proteínas , Sensibilidad y Especificidad , Tirosina/farmacocinética
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