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Xavier Rebillard

Publications and source records attributed to Xavier Rebillard.

14 recordsLinked to original sources
PubMed2006

Seasonality of serum prostate-specific antigen levels: a population-based study.

OBJECTIVE: The measurement of PSA serum levels is central to all early detection programs for prostate cancer. Although individual PSA values were known to fluctuate in the short and long term, the influence of insolation and seasons on PSA had not been addressed to date. To assert the relationship between total and free PSA and meteorological data in 8644 participants (55-70 years) in the French arm of the ERSPC study. METHODS: Blood sample was taken at the local laboratory after informed consent and frozen sera were sent for central testing of total and free PSA. PSA measurement was performed within 7 days on the Access 1.0 automat with Hybritech reagents. Monthly meteorological data -- insolation, daily temperatures and rain precipitations -- were obtained from the local branches of the National Meteorology Agency. RESULTS: Total PSA -- but not free PSA -- was correlated with insolation, that is the monthly accrual in hours of sunshine during which the intensity was higher than 120 Watt x m(-2) (r = 0.05 (95%CI: 0.03-0.07; p < 0.0001)) while no relationships were shown between insolation and percent-free PSA (free PSA divided by the total PSA). Interdependence between total PSA and insolation was also apparent with respect to the 3 ng/mL ERSPC cutoff for recommending biopsies (213.1 vs. 206.2 hours, p = 0.004). Such relationship was even more evident in summer when the tested participants more often had a PSA > 3 ng/mL (17.1% vs. 14.3%, p = 0.0006) than in the rest of the year, resulting in 23% more chances of being referred for biopsies (Odds ratio 1.23, 95%CI: 1.10-1.40). CONCLUSIONS: Total PSA was shown to be strongly associated with insolation and seasons while the percent-free PSA was not influenced.

Aged↗
PubMed2006

DNA-methylation-dependent alterations of claudin-4 expression in human bladder carcinoma.

The expression pattern of tight junction (TJ) proteins is frequently disrupted in epithelial tumors. In particular, isoform- and organ-specific alterations of claudins have been detected in human cancers, highlighting them as interesting tools for the prognosis or treatment of various carcinomas. However, the molecular mechanisms responsible for these alterations are seldom identified. Here, we analyzed the expression and localization of claudins 1, 4, and 7 in human bladder carcinoma. Claudin-4 expression was significantly altered in 26/39 tumors, contrasting with the rare modifications detected in the expression of claudins 1 and 7. Overexpression of claudin-4 in differentiated carcinomas was followed by a strong downregulation in invasive/high-grade tumors, and this expression pattern was associated to the 1-year survival of bladder tumor patients. A CpG island was identified within the coding sequence of the CLDN4 gene, and treatment with a methyl-transferase inhibitor restored expression of the protein in primary cultures prepared from high-grade human bladder tumors. In addition, claudin-4 expression correlated with its gene methylation profile in healthy and tumoral bladders from 20 patients, and downregulation of claudin-4 expression was detected in the urothelium of mice overexpressing DNA methyl transferase 3a (Dnmt3a). Delocalization of claudins 1 and 4 from TJs was observed in most human bladder tumors and in the bladder tumor cell line HT-1376. Although the CLDN4 gene was unmethylated in these cells, pharmacological inhibition of methyl transferases re-addressed the two proteins to TJs, resulting in an increase of cell polarization and transepithelial resistance. These biological effects were prevented by expression of claudin-4-specific siRNAs, demonstrating the important role played by claudin-4 in maintaining a functional regulation of homeostasis in urothelial cells. Results of this study indicate that the TJ barrier is disrupted from early stages of urothelial tumorigenesis. In addition, we identified hypermethylation as the mechanism leading to the alteration of claudin-4 expression, and maybe also localization, in bladder carcinoma.

Animals↗
PubMed2006

Subcutaneous interleukin-2 and interferon-alpha in metastatic renal cell carcinoma: results of a French regional experience in Languedoc.

OBJECTIVES: To assess the efficacy and toxicity of an immunotherapy regimen combining subcutaneous (SC) interleukin-2 (IL-2) and interferon-alpha (IFN) in patients with metastatic renal cell carcinoma (MRCC). METHODS: The present study included 86 patients with MRCC. Data on treatment toxicity and efficacy (responses rates and overall survival) were collected on a hospital database. Treatment consisted of 6-week cycles repeated every 2 months for a maximum of 3 cycles. Each cycle included SC IL-2 20 x 10 MIU/m2 3 times/wk on weeks 1 and 4; 5 x 10 MIU/m2 3 times/wk on weeks 2, 3, 5, and 6, in combination with IFN 6 x 10 MIU/m2 once weekly on weeks 1 and 4; and 3 times/wk on weeks 2, 3, 5, and 6. RESULTS: Seventy (82%) and 71 (83%) patients received more than 80% of the planned doses of IL-2 and IFN during the first cycle, respectively. Ten patients had to stop therapy before the end of the first cycle because of excessive toxicity (7 patients) or rapidly progressive disease (3 patients). Only 17 (28%) proceeded to the second cycle. Main toxicities included fever and asthenia in 86 (100%) patients, nausea/emesis in 83 (96%) patients, skin disorders in 69 (80%) patients, hypotension in 56 (65%) patients, and diarrhea in 50 (58%) patients. Sixty-seven (78%) patients developed at least one episode of grade 3 toxicity. Objective responses were observed in 13 patients, including 4 complete and 9 partial responses (15%; 95% confidence interval, 9.5-20.5%). After a median follow-up of 45 months, the median time to progression was 4 months (range, 1-41) and the median survival was 14 months (range, 1-89). CONCLUSIONS: Only a small subset of patients with MRCC is likely to benefit from treatment with IL-2 and IFN. As toxicity is significant, the refinement of predictive variables for sensitivity to immunotherapy is mandatory.

Adult↗
PubMed2006

[Place of contrast imaging in prostate cancer detection].

Contrast imaging of the prostate is based on rapid-sequence MRI after dynamic Gadolinium injection and contrast ultrasound after injection of microbubbles. MRI can be performed routinely on all available machines. Contrast ultrasound requires specific software not yet available on all machines. The two techniques are designed to improve the reliability of imaging, as a complement to MR spectroscopy, to localize prostate cancer MRI can detect suspicious enhancement in the peripheral zone, but especially in the transitional zone after one or a series of negative posterior biopsies to target a new series of biopsies. The sensitivity and specificity of the technique have yet to be determined. The objective of contrast ultrasound is to improve cancer detection on the first series of biopsies by multiplying sextant biopsies in sites where the contrast kinetics are suggestive of a primary lesion. However, this technique cannot yet be recommended in routine practice, as the modalities of injection of the latest generation of microbubbles (bolus or infusion) need to be evaluated.

Contrast Media↗
PubMed2006

[What is the objective of second-line chemotherapy after failure of first-line chemotherapy in hormone-resistant metastatic prostate?].

UNLABELLED: Chemotherapy occupies an increasingly important place in the management of hormone-resistant metastatic prostate cancer. For the first time in this disease, docetaxel increases the survival of patients, with a modest, but definite median gain of about 2 months. In everyday practice, the indication for second-line chemotherapy after immediate or delayed failure of first-line chemotherapy is sometimes considered, although objective data concerning its efficacy are limited. The objective of the present study was to retrospectively evaluate the results obtained with second-line chemotherapy in a patient cohort managed at the Montpellier Regional Cancer Centre. PATIENTS AND METHODS: Clinical characteristics, treatments delivered and outcome of 43 patients who received two successive lines of chemotherapy were retrospectively collected by means of a standardized questionnaire. Three groups of patients were defined as a function of the chemotherapy protocols delivered: docetaxel alone or in combination, mitoxantrone and other protocols not comprising either docetaxel or mitoxantrone. Responses to chemotherapy were analysed according to three criteria: objective responses, laboratory responses and palliative responses. RESULTS: At the time of second-line chemotherapy, the median age of the patients was 69 years (range: 46 to 83). The median interval between the end of first-line chemotherapy and the start of second-line chemotherapy was 3 months (range: 1 to 15). The protocols administered comprised docetaxel alone (12 patients) or in combination with cisplatin (4 patients), mitoxantrone in 13 patients, or other cytotoxic molecules such as vinblastine, doxorubicin or etoposide in combination with a platinum salt (14 patients). The median number of cycles delivered was 4 (range: 1 to 10). No objective response was observed. Six (14%) patients obtained a laboratory response. A palliative response was observed in 16 (37%) patients, 7 of whom were treated with a docetaxel-based protocol, 6 were treated with mitoxantrone and 3 were treated by other protocols. The median duration of palliative response was 3 months (range: 1 to 6). The median survival was 8 months (range: 1 to 24), with no significant difference between the various protocols. CONCLUSION: In 2006, the objective of second-line chemotherapy in patients with hormone-resistant prostate cancer appears to be purely palliative. No reference protocol has been defined among currently available cytotoxic molecules. The indication must therefore take into account the benefit/risk balance to avoid compromising the patients quality of life. Therapeutic trials are essential to develop effective new molecules.

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PubMed2005

Effects of long-term finasteride treatment on prostate cancer morphology and clinical outcome.

OBJECTIVES: To examine the morphologic alterations of finasteride therapy on prostate cancer compared with no treatment or treatment with a luteinizing hormone-releasing hormone (LHRH) agonist and the clinical outcomes of patients treated with finasteride. METHODS: The data of 56 patients with prostate cancer who had taken finasteride for at least 6 months were reviewed. A central pathology review was performed in a blinded manner comparing these patients with 56 matched controls and 44 patients who received a 3-month course of LHRH agonist before radical prostatectomy. The histologic hormonal treatment effects included apoptosis, vacuolated cytoplasm, pyknotic nuclei, and small irregular glands. An overall consensus was scored using a three-tiered system: no apparent effect (score = 0), suspicious for hormonal effect (score = 1), and highly suggestive of hormonal treatment (score = 2). A Gleason score was assigned to all prostatectomy specimens. RESULTS: The mean hormonal treatment score for the prostatectomy specimens was 0.4, 0.5, and 1.6 for the control, finasteride, and 3-month LHRH groups, respectively. Surprisingly, 20% of control patients had suspicious or highly suggestive hormonal effects and 26% of the finasteride-treated patients did so. For the LHRH-treated group, only 23% did not demonstrate classic features of hormonal treatment. Similar clinical outcomes were observed between the finasteride and control groups. CONCLUSIONS: No consistent hormonal therapy effects with finasteride treatment were observed compared with LHRH agonists. The hormonal effect was observed in the control group. Therefore, although other aspects of the Prostate Cancer Prevention Trial design might account for the greater percentage of Gleason grade tumors in the study arm, morphologic changes due to long-term finasteride treatment were not a likely cause.

Adult↗
PubMed2005

Technology insight: High-intensity focused ultrasound for urologic cancers.

The growing interest in high-intensity focused ultrasound (HIFU) technology is mainly due to its many potential applications as a minimally invasive therapy. It has been introduced to urologic oncology as a treatment for prostate and kidney cancers. While its application in the kidney is still at the clinical feasibility phase, HIFU technology is currently used in daily practice in Europe for the treatment of prostate cancer. Literature describing the results of HIFU for prostate cancer is mainly based on several series of patients from clinical development teams. The latest published results suggest that HIFU treatment is a valuable option for well-differentiated and moderately-differentiated tumors, as well as for local recurrence after external-beam radiation therapy.

Humans↗
PubMed2005

[PSA doubling time and method of calculation].

Prostate Specific Antigen (PSA) is currently the best marker for prostate cancer, although it is not very specific for this disease. The use of the PSA kinetic, in addition to its absolute value, is theoretically very attractive in a large number of clinical situations. Based on a review of the literature, the authors report the various methods used to study this kinetic, with particular emphasis on the most reliable method: the PSA doubling time. After describing the definitions and the methods used to calculate this parameter, the authors discuss the various clinical situations in which it could be useful: surveillance of prostatic tumours after the initial diagnosis in high-risk patients or patients refusing treatment, prognostic factor before curative treatment, evaluation of the efficacy of curative treatment, prognostic factor of tumour aggressiveness at the time of biochemical recurrence after curative treatment or during endocrine therapy.

Humans↗
PubMed2003

[Urologic cancer at the Hérault department: 14 years of continuous registration].

OBJECTIVE: The objective of this study is to present the characteristics of urological cancers in the Hérault department based on data of this department's cancer registry. METHODOLOGY: We analysed the course of all urological data over a 14-year period, from 1987 to 2000, based on the Hérault cancer registry database. Incidence and mortality chronological trends, the risk of cancer before the age of 75 years, and regional estimations were calculated for each cancer site. Data for each cancer site were also compared to French, European and international data. RESULTS: 9,556 urological cancers were reported over a period of fourteen years: 8,779 in males and 777 in females. Urological cancers represented 30.1% of all male cancers and 3.6% of all female cancers. The probability of developing a genital cancer before the age of 75 years for a man was 12.6% and the probability of a urinary tract cancer was 3.2% in males and 0.8% in females. The incidence of prostate cancer has more than tripled over this 14-year period, while the mortality has remained stable. The incidence of renal cancers in both sexes is also increasing, while that of bladder cancers is decreasing. The incidence of cancers of the penis, testis and upper urinary tract has remained stable over time.

Adult↗
PubMedDate not supplied

Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer.

The literature concerning the efficacy and safety of transrectal high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer still comprises a relatively small number of articles. The main studies have been published by four teams using an apparatus available in Europe for several years. The recently presented results of the European Multicentre Study and the study by Gelet and associates based on 242 patients with a follow-up of more than 1 year show that HIFU is a valid alternative for the management of welldifferentiated and moderately differentiated localized prostate cancer with an initial PSA </=15 ng/mL in men with a life expectancy >10 years. In two studies, the combination of transurethral resection of the prostate and HIFU limited the risk of postoperative urinary retention without inducing a higher complication rate. In a series of patients presenting recurrence after external-beam radiotherapy, HIFU was found to be a useful therapy, with >80% negative biopsies. The best indications for HIFU are men over the age of 65, those who are not candidates for radical prostatectomy, obese patients, or patients with comorbidities likely to make surgery more difficult. The learning curve for this technique is relatively short, between 10 and 15 patients, for urologists experienced in transrectal ultrasonography. One of the advantages of HIFU is that it can be repeated in the case of recurrence or to re-treat a prostatic site, it involves no radiation, and patients do not suffer from long-term irritative urinary symptoms.

Aged↗
PubMedDate not supplied

Gemcitabine and oxaliplatin in advanced transitional cell carcinoma of the urothelium: a pilot study.

BACKGROUND: Despite the fact that new drugs have emerged from clinical research in urothelial cancer during the last decade, the prognosis of patients with advanced disease remains poor with a median survival of 12 to 14 months. We designed a feasibility study of gemcitabine and oxaliplatin (GO) in patients with advanced urothelial cancer. PATIENTS AND METHODS: Twenty patients received bimonthly cycles of gemcitabine 1500 mg/m2 and oxaliplatin 85 mg/m2. The cycles were given at 2-week intervals without G-CSF support. Thirteen patients were treated with the GO combination as first-line chemotherapy because of a poor performance status or a creatinine clearance < 1 ml/s. RESULTS: The median number of cycles of GO was 5 (1-7). The median number of days between cycles was 14 throughout the treatment. Seven (8%) out of 87 cycles had to be delayed because of neutropenia or asthenia. A 25% dose reduction in the doses of cytotoxic drugs was necessary in 2 patients. Chemotherapy was stopped before the sixth cycle because of an early death related to a myocardial infarction in 1 patient, a grade 3 neuropathy in 1 patient and a progressive disease in 9 patients. CONCLUSION: Using these doses and schedules, the GO regimen appears a safe therapy for patients with advanced urothelial cancer. Phase II studies are required to assess the possible role of this combination in advanced urothelial cancer.

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