Human renal cell carcinoma xenografts in SCID mice: tumorigenicity correlates with a poor clinical prognosis.

To establish human renal cell carcinoma (RCC) xenografts for preclinical studies, 55 renal tumors (33 primary and 22 metastatic lesions) were transplanted subcutaneously into severe combined immunodeficient mice. Twenty of 49 evaluable tumors (40.8%) grew with a median latency period of 89 days (36 to 209 days) from the day of engraftment. Tumor growth was stabilized after the fifth passage with a median time between passages of 38 days (19 to 80 days). Tumorigenicity was correlated with the metastatic phenotype of the tumor (54% success rate, p = 0.007) and with reduced survival of patients. Despite a possible evolution of histological features and tumor grading, established RCC xenografts were comparable to parental tumors, as assessed by karyotype and DNA-ploidy analyses. Molecular cytogenetic analysis also revealed specific genetic alterations characterizing distinct RCC types that were constant in parental and corresponding xenografts. In addition, this xenograft model has permitted the selection of minor tumor subclones with a proliferative advantage and minimal overexpressed chromosomal regions. We conclude that severe combined immunodeficient mice are useful recipients for the establishment of long-term RCC xenografts that can be used as valuable tools to evaluate the activity of new therapeutic approaches and to study biological parameters determining in vivo aggressiveness of human RCC.

Evaluation of primary standard cisplatin-based chemotherapy for clinical stage II non-seminomatous germ cell tumours of the testis.

OBJECTIVE: To evaluate the use of primary cisplatin-based chemotherapy before retroperitoneal lymph node dissection (RPLND) in patients with clinical stage II non-seminomatous germ cell tumours of the testis. PATIENTS AND METHODS: Between 1984 and 1992, 55 patients with clinical stage II testicular cancer (12 with stage IIA. 33 stage IIB and 10 stage IIC disease) were treated at Institut Gustave Roussy with primary chemotherapy using three conventional regimens including cisplatin. Patients were assessed 4 weeks after the end of chemotherapy and depending on the response, underwent RPLND; the overall survival and disease progression were monitored. RESULTS: Sixteen (29%) patients achieved a sustained complete remission after chemotherapy only, while 30 (55%) patients required subsequent RPLND for persistent residual tumour masses: nine other patients obtained a clinical partial remission. Six patients who initially had achieved either a clinical complete response (three) or a surgical complete response (one) or a clinical partial response (two) subsequently relapsed. Overall, 52 of 55 (95%) patients remained free of disease 33 to 111 months after the end of treatment. CONCLUSION: These results show that primary cisplatin-based chemotherapy can effect a cure of the tumour in all subgroups of patients with stage II disease.

[Uro-intestinal fistulas of cancerous origin]. / Fistules uro-digestives d'origine cancéreuse.

Malignant entero-vesical fistulas are uncommon. Colonic malignancy is the main cause although fistula are present in just 1%. Pneumaturia and fecaluria are pathognomonic for entero-vesico-fistula and are present in half of cases. By combining the results of cystoscopy, barium enema and urine culture, fistula can be identified in almost all the cases. Escherichia coli, Streptococcus faecalis and Proteus mirabilis are very often isolated from the urine cultures. The management of entero-vesical-fistula depends of the etiology. The treatment requires in most of the case resection of the diseased bowel with partial cystectomy and primary anastomosis. But sometimes, is necessary to perform a diverting colostomy and urinary diversion.

[Therapeutic strategy in metastatic renal cancer]. / Stratégie thérapeutique dans le cancer du rein métastatique.

Prognostic factors have been described in metastatic renal cell cancer: performance status, weight loss, elevated erythrocyte sedimentation rate, presence of liver metastases. The treatment for a patient with good prognosis consists of: surgical exeresis of solitary metastasis, immunotherapy by either interferon or interleukin 2. Treatment in case of a rom prognosis is a combination of supportive care, orthopedic surgery for pathologic fracture or medullar compression, antalgic radiotherapy, embolization, nephrectomy for hematuria, and analgesic treatments.

[Cancer of the bladder after treatment with cyclophosphamide. Apropos of a case and a review of the literature]. / Cancer de la vessie après traitement par cyclophosphamide. A propos d'un cas et revue de la littérature.

A case of cancer of the bladder is reported in a patient treated 5 years previously with cyclophosphamide for membranoproliferative glomerulonephritis. The responsibility of cyclophosphamide for this type of tumour is well documented in the literature and should lead to a limitation of its use in disease with a favourable prognosis and to close surveillance via regular cystoscopy and blind biopsy in patients who receive more than 50 g of the drug.

Phase II trial of combination chemotherapy with dacarbazine, cyclophosphamide, cisplatin, doxorubicin, and vindesine (DECAV) in advanced renal cell cancer.

Eighteen patients with advanced renal cell cancer were evaluated for objective response to a combination chemotherapy regimen twenty-eight-day (d) cycles, with dacarbazine (200 mg/sq m/d, d1,2,3); cyclophosphamide (400 mg/sq m/d, d1); cisplatin (100 mg/sq m/d, d1); doxorubicin (50 mg/sq m/d, d1); vindesine (1.5 mg/sq m/d, d1,2) (DECAV). One response in 16 patients was observed (6.25%; 95% confidence limits are 0-30%). No major toxicity occurred. An important point is that the only complete remission was observed in a patient with sarcomatoid cell renal cancer. At this dose with this schedule this combination regimen appears to have no activity in renal cell carcinoma.

Prognostic factors in advanced nonseminomatous testicular cancer. A multivariate logistic regression analysis.

In order to define prognostic factors for advanced stage of nonseminomatous germ cell tumors (NSGCT) of the testis, the authors reviewed 84 patients treated from 1978 through 1985. The survival rate was 51% at 3 years. Patients with elevated seric levels of human chorionic gonadotropin (HCG) and/or alpha-fetoprotein (AFP), or the presence of an abdominal mass had significantly worse survival. Only HCG and AFP levels retained their significance when multivariate Cox analysis was performed. The probability that a patient achieves a complete remission (CR) was assessed by a function of certain patient characteristics using a multivariate logistic regression analysis. The significant variables were a function of HCG and AFP values. Since both variables are related to the CR rate and survival the authors define the obtention of a CR as a unique outcome of interest. The probability of a CR greater than 70% adequately separates the patients into two prognostic subgroups. This model currently is being used to enrole NSGCT patients in a prospective modulated clinical trial according to these prognostic factors.