Temporal and spatial variability of organotins in an intermittent Mediterranean river.

Organotin compounds (OTs) are exclusively anthropogenic and have been widely used for their biocidal properties and as stabilizers in various industrial applications. Hence organotins are common pollutants. Their high toxicity has led to their entry on the EU water framework's priority substances' list. However, few studies are available regarding their behaviour in surface waters, in particular, in intermittent Mediterranean rivers. The Vène is an intermittent river located in Languedoc-Roussillon, southern France. It is the main tributary of an important shellfish farming site: the Thau lagoon. The present study aims at establishing the presence of OTs on a 1.5 km long reach of the river into which a waste water treatment plant (WWTP) discharges. The study is carried out during steady-state flow conditions over two consecutive years and investigates potential OTs sources in everyday domestic activities. Routine field monitoring was carried out over a 5 month period during the springs of 2008 and 2009. The results establish the presence of butyltins and octyltins throughout the 1.5 km long reach at concentrations exceeding the maximum allowable concentration levels imposed by the water framework directive. The WWTP is recognized as an important OTs point source; however, using trace and rare earth elements as tracers, an urban stormwater sewage gutter is identified as a secondary source. Its impact on the river's pollutant loads is however variable in time because of flow intermittency. The paper discusses the need for specific monitoring and management schemes for intermittent rivers.

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.

Squamous cell carcinoma of the penis: multivariate analysis of prognostic factors and natural history in monocentric study with a conservative policy.

BACKGROUND: Penile carcinoma is uncommon in Western countries. Here we report on a large series of patients with squamous cell carcinoma (SCC) of the penis, describing prognostic factors, survival and therapeutic results. PATIENTS AND METHODS: From 1973 to 1993, 102 patients with invasive SCC of the penis were treated at the Institut Gustave-Roussy. Precancerous lesions and conditions associated with penis cancer were analyzed retrospectively. Survival curves were estimated by the Kaplan-Meier method, and groups were compared for outcome by the log rank test for univariate comparisons and by Cox's proportional hazards model for multivariate analysis. RESULTS: The median age at onset was 58 years. Sixty-nine patients presented with Jackson's stage I disease, 17 with stage II and 15 with stage III. The interval between the manifestation of symptoms and the diagnosis was more than a year in 13.7% of cases. Precancerous lesions were found in 17 (16.6%) patients, and a history of phimosis was noted in 25 (24.5%). In situ and invasive carcinoma were observed together in 17 (16.6%) cases and dysplasia was associated with invasive carcinoma in eight (7.8%) further cases. Conservative treatment was administered whenever feasible. Interstitial brachytherapy was performed alone or associated with limited surgery (local excision or circumcision) in 72 (70.6%) patients. Of the 28 patients with a local relapse, nine have died of their neoplasms (32%) compared to 21 of 28 patients with lymph node relapse (75%). The median follow-up was 111 months. Disease-free survival, disease-specific survival and overall survival were, respectively, 56%, 72% and 63% at five years and 42%, 66% and 50% at 10 years. Age (P = 0.01), the N status (P < 0.00001) or palpable nodes (P < 0.0038), corpus involvement (P = 0.006) and a verrucous histology (P = 0.038) had significant prognostic relevance for survival in the univariate analysis whereas the performance status, T status and Broders' grade did not. In the multivariate analysis only two parameters, involvement of the corpus (P < 0.0001) and palpable nodes (P = 0.009), were singled out as being independent variables influencing survival. A subgroup of nine patients with verrucous histologies were distinguished by their freedom from node involvement. These patients had an excellent prognosis: all are alive and disease-free. Penile integrity was preserved during follow-up in 54 patients (52.9%), 31 of whom are still alive. Of 72 patients treated by a conservative approach including brachytherapy, long-term penile integrity was maintained in 49 (68%). CONCLUSION: Corpus involvement and clinically palpable nodes are highly statistically significant independent factors influencing overall survival. Node relapses remain a major cause of death. Thus, better management of lymph nodes is essential for improving survival even when conservative therapy is used to treat the primary.

A diet moderately enriched in phytosterols lowers plasma cholesterol concentrations in normocholesterolemic humans.

Twelve normolipidic healthy human subjects were fed a diet with or without additional soybean phytosterols for 4 weeks in a crossover design. The order of the treatments was randomized. Phytosterols were added to the diet blended in butter. The dietary ratio cholesterol:phytosterols was 0.7 during the control period (436 mg cholesterol/day and 29 mg phytosterols/day) and 1.88 during the phytosterols period (410 mg cholesterol/day and 740 mg phytosterols/day). Blood cholesterol was 10% lower after subjects consumed the phytosterol-enriched diet than when they consumed the control diet (p < 0.001), which was due to a 15% LDL cholesterol decrease (p < 0.001). The HDL cholesterol:LDL cholesterol ratio was markedly enhanced (+25%) (p < 0.01). These findings suggest that a significant lowering of plasma total and LDL cholesterol can be effected by a modest dietary intake of soybean phytosterols.

[Brachytherapy in prostatic adenocarcinoma]. / Curiethérapie dans les adénocarcinomes prostatiques.

Brachytherapy can represent the exclusive treatment of localized prostatic adenocarcinoma. Several techniques have been described: permanent implantations with 125-iodine or 198-gold seeds or temporary implantations with 192-iridium. These implantations are performed either via a retropubic approach, often combined with pelvic lymphadenectomy, or via a transperineal approach, with or without ultrasound guidance. The largest clinical experience is from Memorial Sloan-Kettering Cancer Center, with 1119 patients treated from 1970 to 1985 for stage B or C prostatic adenocarcinoma with pelvic lymph node dissection and interstitial iodine-125 brachytherapy. The 15-year overall local control is 51%. One of the strongest prognostic factors is lymph node involvement. The comparison between brachytherapy and other treatment modalities such as radical prostatectomy or external irradiation or even expectant management in localized tumors has never been performed prospectively. This type of randomized trial appears to be necessary in the assessment of the results published with brachytherapy.

[Brachytherapy in cancer of the penis]. / La curiethérapie des cancers du pénis.

Brachytherapy can play an essential role in the conservative treatment of penile cancer limited to the glans. This treatment is usually performed using hypodermic needles with templates which are subsequently loaded with iridium wires. Various studies, particularly French reports, show a local control rate of 80%, penis preservation in 75% of cases and a specific survival rate of 60%.

Penile cancer chemotherapy: twelve years' experience at Institut Gustave-Roussy.

Between 1980 and 1992, 14 patients (median age 50 years) with penile carcinoma were treated with multidrug combination chemotherapy in our institution. Twelve patients had Stage IV (Jackson classification) tumor, 1 patient each had Stage III and Stage II. All patients received cisplatin-based chemotherapy. Cisplatin was associated with either 5-fluorouracil (4 patients), methotrexate and bleomycin (4 patients), methotrexate (3 patients), Adriamycin (1 patient), bleomycin and vinblastine (1 patient), or bleomycin and epirubicin (1 patient). Thirteen patients were evaluable for response. Objective response was encountered in 2 patients (15%) with 1 complete response and 1 partial response. Response duration was difficult to determine because of additive radio-therapy or patient was lost to follow-up. There were 2 patients with long-term evidence of no disease among 12 patients with Stage IV disease. These 2 patients received complementary irradiation in association with the chemotherapy. The response rate was dismal in our series. Methotrexate-based regimens seem to be the most active. The bimodality treatment with multidrug chemotherapy and radiotherapy for advanced penile cancer could offer a survival advantage in the management of these patients.

Sarcoidosis and testicular germ cell tumor. Case report.

The authors describe the case of a patient with stage II non seminomatous germinal cell tumor of the testis with a generalized sarcoidosis. They review the existing literature and discuss the problem of diagnosis.

[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.

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.

[Cancer of the prostate: technics of curietherapy. Review of the literature and experience at the Institut Gustave-Roussy]. / Cancer de la prostate: techniques de curiethérapie. Revue de la littérature et expérience de l'Institut Gustave-Roussy.

Pasteau and Degrais in Paris used radium to treat prostatic cancer in 1907, radium was further used with different techniques including radium needles and radon seeds during twenty years. In 1951, Flock advocated colloidal radioactive gold with interesting palliative results. Permanent gold seeds implant was also used. But until 1970 with the appearance of Iodine 125 grain, brachytherapy was not widely employed. Hilaris and Whitmore treated almost 1000 cases until now, with few immediate complications. Survivals at 5 years are T1 96%, T2 76%, T3 69%. Conservation of potency and absence of late complications are the main benefits. However, the technique is a somewhat complex surgical procedure and the cases have to be carefully selected. Many others centers used iodine technique and Holm recently proposed an ingenious per-operative echography to improve the safety and accuracy of the permanent implantation. Removable implants with 192Ir wire (or nylon ribbon seeds) are obviously simpler and safer to implant through perineal route. For us, flexible plastic tubes is the technique of choice. In ten cases irradiated at 70 Gy level, no recurrences and no complications except one pulmonary embolism, but the patients were highly selected. For Syed rigid needles through perineal template is the technique of choice. External radiation is added after the implant, which delivered a dose of about 30 Gy. The results are satisfactory in the first 100 cases, but with a high level of complication. Comparative series and more follow-up are evidently requested, to know the exact place of brachytherapy in the treatment of prostatic adenocarcinoma.

Treatment of malignant bladder tumors by iridium-192 wiring.

Small tumors of the mobile portion of the bladder may be treated by means of interstitial irradiation by iridium-192 wiring. Twenty-six tumors (mostly T1, but also T2 and T3) were treated by this procedure. Good results are attained in 89 per cent of 19 cases followed over three years. This method has the benefit of avoiding irradiation to the surgeon's hands, and of delivering to a specific site a dose of 6,000 rads. No bladder contraction was observed.