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N Thiounn

Publications and source records attributed to N Thiounn.

At least 19 recordsLinked to original sources
PubMed2006

[PSA bounce after permanent implant prostate brachytherapy may mimic a biochemical failure].

PURPOSE: To assess the frequency of the PSA "bouncing" phenomenon after a significant follow-up in a series of patients treated by permanent implant brachytherapy for a prostate cancer. To look for the clinical and dosimetric parameters possibly linked to this transitory secondary PSA increase. To evaluate in which percentage of cases this bouncing could have mimicked a biochemical relapse according to the ASTRO consensus criteria. PATIENTS AND METHODS: From January 1999, to December 2001, 295 patients were treated by a permanent prostate implantation (real-time technique, with free (125)I seeds- Isoseed Bebig-) by the Institut Curie-Hôpital Cochin-Hôpital Necker Paris group. The mean follow-up is 40.3 months (9-66 months). The PSA level was regularly checked, at least every 6 months. We defined as a "bouncing" all increase in PSA, starting at 0.1 ng/ml, subsequently followed by a spontaneous (without any treatment) decrease, with return to the previous level or lower. We particularly focused on the patients fulfilling the criteria for a biochemical relapse according to the ASTRO consensus (Three successive increases in PSA). A multivariate analysis tried to identify independent factors among the usual clinical and dosimetric parameters. RESULTS: In our series, 161 patients (55%) showed a transitory PSA increase (bouncing) of at least 0.1 ng/ml; 145 patients (49%) a bouncing of 0.2 ng/ml, 93 patients (32%) a bouncing of 0.4 ng/ml and 43 patients (15%) a bouncing of at least 1 ng/ml. Mean PSA bounce was 0.8 ng/ml (0.1-4.1), and mean time to bounce was 19 months. Thirty-two patients (11% of the total number) presented three successive PSA increases with a significant (3 months) interval between the dosages, and therefore were to be considered as being in biochemical relapse according to the ASTRO consensus criteria. Actually, among those 32 patients, 18 (56%) subsequently showed a complete normalization of their PSA, without any treatment. Ten patients went on increasing their PSA, and were considered to be really in biochemical relapse. For the last 4 patients, the situation still remains ambiguous. In multivariate analysis, age<70 years (P<0.00001) and D90>200 Gy (P<0.003) were identified as independent factors for a PSA bouncing of at least 0.4 ng/ml. CONCLUSIONS: The observed rate of 32% of patients showing a PSA bouncing of at least 0.4 ng/ml in our series is in good agreement with what has been previously reported in the literature. Age<70 years and D90>200 Gy were found to be independent factors predicting for such a secondary transitory increase in PSA. Interestingly, among 32 patients fulfilling the classical criteria of the ASTRO for a biochemical relapse, 18 (56%) subsequently showed a spontaneous PSA decrease, demonstrating that the ASTRO consensus is not well adapted to the biochemical follow-up of our patients undergoing permanent implant prostate Brachytherapy.

Age Factors↗
PubMed2006

[Brachytherapy for prostate cancer: old concept, new techniques].

Whereas it has been proposed almost one century ago, brachytherapy for prostate cancer has only recently emerged, especially thanks to endorectal echography, allowing to visualize seed implantation, to the development of seeds for permanent delivery and of micro-sources for high-dose rate delivery, and also to the development of three-dimension dosimetry programs allowing real-time implantations. For selected patients with localized prostate cancer (PSA < 10, Gleason < 7, no extracapsular extension, volume < 50-60 g), prostate brachytherapy with permanent implants (iodine 125 or, less frequently, palladium 103) gives results which appear at 10-15 years comparable to those of surgery. Incontinence and impotence rates appear lower than those of classical surgery. However, the first post-implant months are usually accompanied by urinary toxicity that should not be minimized. High-dose rate brachytherapy (HDR) could find its indications, in combination with conformal radiotherapy, in the treatment of more advanced forms, presenting an intermediate risk. It could also be an alternative to brachytherapy with permanent implants for the low-risk forms mentioned above, especially in developing countries where the cost of radioactive seeds slows down the use of this technique. Brachytherapy for prostate cancer should, therefore, find more and more indications, because of the increased incidence of prostate cancer, due to population ageing, of the increased proportion of localized forms, due to better detection, of the patient's request for less toxicity, and of the expecting lowering of the costs, which are now equivalent to those of surgery and should further lower.

Brachytherapy↗
PubMed2005

ICSI outcomes in obstructive azoospermia: influence of the origin of surgically retrieved spermatozoa and the cause of obstruction.

BACKGROUND: Spermatozoa can be retrieved from the testis and epididymis of men with obstructive azoospermia (OA) and used for ICSI. However, it is unknown whether the outcome of ICSI depends on the cause of obstruction or the origin of surgically retrieved spermatozoa. METHODS: A cohort of 171 men with OA and normal spermatogenesis were included in this retrospective study. They were divided into three groups according to the site and origin of obstruction: 83 men had congenital bilateral absence of vas deferens; 55 and 33 had acquired epididymal and deferent duct obstructions, respectively. The outcome of 368 ICSI cycles was determined and compared according to the origin of spermatozoa: epididymal (n = 253) or testicular (n = 115). RESULTS: Fertilization and clinical pregnancy rates did not differ between spermatozoa of different origin (58.9% versus 51.9% and 22.1% versus 24.3% with epididymal and testicular spermatozoa, respectively). However, the miscarriage rate was significantly higher for testicular spermatozoa (35.7% versus. 12.5% P < 0.05, chi2 test). Findings were similar whatever the aetiology of the OA. CONCLUSION: This study suggests that the use of testicular spermatozoa, even those generated during normal spermatogenesis, alters embryonic development and that epididymal spermatozoa should be preferentially used, irrespective of the aetiology of OA.

Adult↗
PubMed2004

[Iodin 125 seed migration after prostate brachytherapy: a study of 170 patients].

PURPOSE: To study the number of migrating seeds, the anatomical site of migration and possible predictive parameters of migration, after prostate cancer brachytherapy using a loose-seed (I125) implantation technique. PATIENTS AND METHODS: The charts of the 170 patients consecutively treated by the Institut Curie/Hospital Cochin/Hospital Necker Group between September 1, 2001 and August 31, 2002, were analysed. All seeds having migrated to the lungs and seen on the chest X-ray systematically performed at 2 months, have been recorded, as well as the seeds lost by the urines (after sieving) or in the sperm (condom). RESULTS: Among 12,179 implanted seeds, 44 were found to have migrated (0.36%). Most of the migrating seeds (32/44; 73%), were found in the lungs. Overall, one or several seed migrations were observed in 35 patients (21% of the total number of patients in this series). In the majority of cases (77%), only one seed migrated. A significant relationship (P = 0.04) was found between the number of migrating seeds and the number of implanted ones (or with the prostate volume, but those two parameters were closely linked in our series). More specifically, a significant relationship (P = 0.02) could be demonstrated between the number of seeds implanted at the periphery of the prostate and the number of seeds migrating to the lungs. CONCLUSION: The percentage of migrating seeds observed in this series is low, actually one of the lowest found in the literature when using the loose-seed technique. There was no clinical consequences and the loss of-usually-only one seed is very unlikely to alter the quality of the dose distribution. However, the predominance of pulmonary migrations in our series led us to slightly modify our implantation technique. We now try to avoid too "peripheral" seed implantations, due to the risk of migration towards the periprostatic veins, and subsequently to the lungs.

Aged↗
PubMed2004

Risk factors for adult renal cell carcinoma.

This study confirmed several independent risk and protective factors for RCC identified in the authors' previous study. Protective factors such as oral contraceptive use and moderate alcohol consumption were identified only in women. Tobacco consumption and severe obesity were the main independent risk factors. There were other modifiable risk markers, however, such as occupational exposure, thiazidic drug intake, and urinary tract infections. The associations between risk factors and RCC were weak, even for tobacco, for which the association was weaker than that for lung cancer. The identified risks involve a large proportion of the population, however, and the risk attributable to these types of exposure is high. The authors' recommendations for the prevention of RCC are therefore similar to those for the prevention of cardiovascular disease and cancer, and should be disseminated to the general population. The high-risk groups identified are too large for a specific early-screening program for RCC, but such screening might be appropriate if restricted to selected age groups.

Adult↗
PubMed2003

Intermittent androgen suppression in patients with prostate cancer.

OBJECTIVES: To evaluate intermittent androgen suppression (IAS) in patients with prostate cancer and to try to define predictive factors for biochemical progression. PATIENTS AND METHODS: From 1989 to 2001, 146 patients received IAS as a primary treatment for localized, advanced or metastatic prostate cancer (72 men) or as a treatment for prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP) and/or radiation therapy (74 men). Androgen-deprivation treatment (ADT) was continued up to 6 months after PSA became undetectable or a nadir PSA level was reached. ADT was then re-instituted when the PSA level was> 4 ng/mL for patients who had RP or> 10 ng/mL for the others. RESULTS: After a mean (range) follow-up of 45.6 (12-196.9) months, 24 patients had biochemical progression. These patients were younger than those with no biochemical progression (67 vs 72 years, P = 0.004) and had a statistically higher Gleason score (7.21 vs 6.52, P = 0.01) and PSA level (111.1 vs 32.1 ng/mL, P = 0.05), and a shorter first phase without treatment (7.6 vs 11.2 months, P = 0.05). Overall 5-year metastatic disease free survival of 91.3%. The overall 5-year biochemical recurrence-free survival was 68%. Using multivariate analysis, a Gleason score of >or= 8 (P = 0.021), first-phase duration with no treatment of < 1 year (P = 0.044), positive lymph nodes or metastatic disease at the time of starting IAS (P = 0.023) and age < 70 years (P = 0.037) were the strongest predictors of biochemical progression. CONCLUSION: IAS appeared to be a feasible treatment; the best candidates being those aged> 70 years with localized prostate cancer and a Gleason score of <or= 7.

Aged↗
PubMed2002

[Indications for curietherapy of the prostate using permanent implants].

In the last decade, brachytherapy emerged as a particularly appealing new way ot treating localized prostate cancer. Recently published 10-12 years biochemical control results appear to be superimposable to the best percentages achieved by surgery or conformal radiotherapy, with a small percentage of complications. This applied to severely patients. Only patients with T1/T2, PSA < 10 ng/mL, and Gleason score < 7 should be proposed such a treatment. The potential benefit of exploring patients with a endorectal coil MRI is being evaluated. The number of positive biopsies is also a parameter which should probably be considered in the therapeutic choice. Moreover, a prostate volume > 60 g, hip mobility limitations, a urinary obstructive syndrome and previous transurethral resection lead to difficulties in technical implantation and therefore must be taken into account when discussing brachytherapy. In conclusion, for adequately selected patients, brachytherapy offers a particularly applied alternative to surgery and external radiotherapy, with satisfactory long term biochemical control rates and limited complications.

Adenocarcinoma↗
PubMed2002

Local immunostimulation induced by intravesical administration of autologous interferon-gamma-activated macrophages in patients with superficial bladder cancer.

We conducted a phase I/II clinical trial of the safety and efficacy of intravesical administration of autologous IFN-gamma-activated macrophages (MAK) in patients with superficial bladder cancer. Monocyte-derived MAK cells were prepared in vitro and patients received six instillations of 1.4 x 10(8) to 2.5 x 10(8) cells, once a week, for five consecutive weeks. Treatment was well tolerated, with seven grade 1 and five Grade 2 protocol-related adverse effects. Nine out of 17 included patients had no recurrences during the year following the first instillation of MAK. The aim of the present study was to search for immune parameters related to local immunostimulation induced by MAK. Monitoring of the patients showed that urinary IL-8, GM-CSF and, to a lesser extent, IL-18 were increased following MAK instillations, with inter-individual differences. The urinary IL-8 level was about 10-fold higher than that observed for other cytokines, and its biological activity was reflected by a concomitant increase of urinary elastase, indicating neutrophil activation and degranulation. We also showed that nine out of 12 patients investigated presented an increase of urinary neopterin, a marker of IFN-gamma-activated macrophages, 7 days after MAK instillation, while serum neopterin levels were almost stable. These results are in line with persistence of activated macrophages in the bladder wall after infusions. Moreover, there was evidence of macrophages in urine smears 2 months after the sixth MAK instillation, and the score of macrophages correlated with the quantity of neutrophils in the urine. Overall, this study provides evidence of a local immunostimulation induced by this novel and safe immunotherapeutic approach of MAK instillations in patients with superficial bladder cancer.

Administration, Intravesical↗
PubMed2002

Predictive factors of radiation therapy for patients with prostate specific antigen recurrence after radical prostatectomy.

OBJECTIVE: To assess the efficacy of salvage/adjuvant radiation therapy (RT) for patients with prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). PATIENTS AND METHODS: Between 1997 and 2001, 52 patients were treated in our institution with RT for PSA recurrence after RP. The mean (range) delay between RP and RT was 30.5 (0.16-105.6) months. Eighteen patients received no hormonal therapy before RT. The failure of RT was defined as three consecutive increases in PSA levels with intervals of > or = 6 weeks. RESULTS: Within a mean (range) follow-up of 27.7 (6-69) months, 18 patients presented with biochemical progression. The 3-year biochemical progression-free survival was 51%. Using univariate analysis, an age < 65 years (P = 0.0262), a Gleason score on the RP specimen of > or = 8 (P = 0.0024), stage pT3 (P = 0.02), a detectable nadir PSA after RT (P < 0.001) and the absence of hormonal therapy (P = 0.0359) were associated with a lower biochemical progression-free survival. However, only the Gleason score (P = 0.0395) and nadir serum PSA after RT (P = 0.028) remained independent predictive factors on multivariate analysis. CONCLUSION: Half of the present patients treated with RT for an isolated high serum PSA level after RP were free of biochemical relapse at 3 years of follow-up. RT may be proposed to selected patients with mild morbidity. However, definitive evidence of the beneficial effect of adjuvant RT for patients with PSA recurrence after RP awaits the conclusion of randomized clinical trials.

Aged↗
PubMed2001

Bisulfite genomic sequencing of microdissected cells.

Mapping of methylation patterns in CpG islands has become an important tool for understanding tissue-specific gene expression in both normal and pathological situations. However, the inherent cellular heterogeneity of any given tissues can affect the outcome and interpretation of molecular studies. In order to analyse genomic DNA methylation on a pure cell population from tissue sample, we have developed a simple technique of single-cell microdissection from cryostat sections which can be combined with bisulfite-mediated sequencing of 5-methylcytosine. We report here our results on the methylation status of the androgen receptor gene studied by bisulfite genomic sequencing on purified cells isolated from human testis.

Cells, Cultured↗
PubMed2001

Identification of p53 peptides recognized by CD8(+) T lymphocytes from patients with bladder cancer.

In many types of cancer, p53 frequently accumulates in tumor cells and anti-p53 antibodies can be detected. However, only four CD8(+) T-cell epitopes from p53 have been identified in humans so far. To further analyze the development of a T-cell response against p53, peptides having binding motifs specific for HLA-A1, -A2, -A3, -A24, -B7, -B35, -B44, and -B51 molecules have been defined. The HLA-binding capacity of those peptides was tested, and the stability of formed complexes was defined. Thirteen peptides that bound to HLA-A24 and -B44 molecules are presented. The positive peptides were then used to detect the anti-p53 response of CD8(+) T lymphocytes from patients with bladder cancer. Six peptides, presented by HLA-A2, -B51, or -A24, were able to stimulate T cells from two patients (among 16) with tumor cells that strongly accumulated p53. On the contrary, p53 peptides systematically failed to stimulate T cells from healthy donors or patients with low or undetectable levels of p53 in their tumor cells. These results have led to the identification of four new potential T CD8(+) epitopes from p53: 194-203 associating with HLA-B51 and 204-212, 211-218, and 235-243 associating with HLA-A24.

CD8-Positive T-Lymphocytes↗
PubMed2001

Analysis of interleukin-18, interleukin-1 converting enzyme (ICE) and interleukin-18-related cytokines in Crohn's disease lesions.

A local increase of interleukin-18 (IL-18) expression has been recently demonstrated in Crohn's disease (CD), suggesting a role for mature IL-18 (cleaved by ICE protease) in the induction of proinflammatory cytokines and Th1 polarization observed in CD lesions. The aim of this study was to investigate IL-18 modulation and its potential immune consequences in CD lesions. We showed increased IL-18 production in chronic CD lesions and identified epithelial cells and macrophages as IL-18-producing cells. A twofold increase in ICE alpha, beta, and/or gamma mRNA that encodes for the complete mature peptide was required for ICE activity, and a marked increase in IL-18R-positive immune cells was observed in chronic lesions compared to uninvolved areas or normal control samples. Chronic lesions also displayed intense transcription of IL-18-induced cytokines, IFN-gamma, IL-1beta, TNF-alpha, and IL-8. By contrast, when neither IL-18 nor ICE mRNAs were enhanced (early asymptomatic CD lesions), IL-18-induced cytokines were not up-regulated. These results are in accordance with a putative role of mature IL-18 in the pathogenesis of CD.

Base Sequence↗
PubMed2001

[Chromophobe cell renal cancer, a distinct entity. Report of a series of 35 cases].

OBJECTIVE: To describe the clinical and histological characteristics and natural history of clear cell renal carcinoma. PATIENTS AND METHODS: The case files of 35 patients (22 men and 13 women, with a mean age of 58 +/- 13.8 years) operated for clear cell renal carcinoma were reviewed. The circumstances of diagnosis and the histological features of the tumour were analysed. The outcome of the patients was studied with a mean follow-up of 70 +/- 20.2 months. RESULTS: The diagnosis was incidental in 66% of cases. The macroscopic appearance of the tumour was characteristic: homogeneous and beige or white colour. On light microscopy, tumours were composed of variable proportions of clear cells and eosinophilic cells. The were classified as 15 predominantly eosinophilic tumours (43%), 9 predominantly clear cell tumours (26%) and 11 tumours composed of equal number of clear cells and eosinophilic cells (31%). Nuclei were irregular and indented. Hale stain was positive in every case. The majority of tumours were confined to the kidney (T1: 65% and T2: 29%) with a low nuclear grade (91% of grades 1 and 2). No patient developed local recurrence or metastasis during follow-up. The overall 5-year survival rate was 92%. No death related to the disease was reported. CONCLUSION: The histological diagnosis of clear cell renal cancer is now easy and can be suggested even on macroscopic examination of the operative specimen. This tumour appears to have a good prognosis, as it is usually confined to the kidney with a low nuclear grade.

Adenocarcinoma↗
PubMed2000

Endorectal color doppler sonography and endorectal MR imaging features of nonpalpable prostate cancer: correlation with radical prostatectomy findings.

OBJECTIVE: The purpose of this study was to describe endorectal sonography and color Doppler sonography features of nonpalpable prostate cancer and to assess the value of endorectal MR imaging for the preoperative local staging of these tumors. MATERIALS AND METHODS: Ninety-four patients with nonsuspicious findings on digital rectal examination and a mean prostate-specific antigen level of 16.3 +/-10 ng/mL (median, 13 ng/mL) underwent endorectal sonography, color Doppler sonography, sextant endorectal sonographically guided biopsy, and endorectal MR imaging before radical prostatectomy. RESULTS: Tumors were visible in 48 cases and not visible in 46. The mean Gleason biopsy score, the frequency of tumors involving three sextants or more of the prostate gland at biopsies, and the frequency of stage pT3 tumors were significantly higher in patients with visible tumors (5.9+/-0.9, 42%, and 37.5%) than in those with invisible tumors (5.4+/-1.1, 17%, and 17%). The 42 hypervascular tumors were hypoechoic in every case and had a higher rate of Gleason tumor grades 4 and 5 at biopsy than did the 52 hypovascular tumors (33% versus 11.5%). Six hypovascular tumors (6/52, 11.5%, two visible) had an insignificant tumor volume. Established extraprostatic tumor spread was detected on MR imaging in six of 18 cases (sensitivity, 33%; specificity, 100%0, all of which had the following four features: hypervascularity, prostate-specific antigen level greater than 20 ng/mL, three or more sextants of the gland having positive findings at biopsy, and seminal vesicle invasion. CONCLUSION: Endorectal sonography and color Doppler sonography are useful to differentiate low-risk invisible and hypovascular tumors from high-risk visible and hypervascular tumors. However, MR imaging has a poor sensitivity for the detection of extraprostatic spread and is accurate only in a minority of highly selected high-risk hypervascular tumors.

Aged↗