Microarray gene expression profiling and analysis of bladder cancer supports the sub-classification of T1 tumours into T1a and T1b stages.

OBJECTIVE: To try and identify a molecular signature for pathological staging and/or grading. through microarray analysis. PATIENTS AND METHODS: We performed a prospective multicentre study between September 2007 and May 2008 that included 108 bladder tumours (45 pTa, 35 pT1 and 28>pT1). Microarray analysis was performed using Agilent Technologies Human Whole Genome 4 × 44K oligonucleotide microarrays (Agilent, Santa Clara, CA, USA). A 'dual colour' method was used vs a reference pool of tumours. From the lists of genes provided by the Biometric Research Branch class comparison analyses, we validated the microarray results of 38 selected differentially expressed genes using reverse transcriptase quantitative PCR in another bladder tumour cohort (n = 95). RESULTS: The cluster 'superficial vs invasive stage' correctly classified 92.9% of invasive stages and 66.3% of superficial stages. Among the superficial tumours, the cluster analysis showed that pT1b tumours were closer to invasive stages than pT1a tumours. We also found molecular differences between low and high grade superficial tumours, but these differences were less well defined than the difference observed for staging. CONCLUSIONS: We confirmed that the histopathological classification into subgroups pTa, pT1a and pT1b can be translated into a molecular signature with a continuous progression of deregulation (overexpression or repression of these genes) from superficial (pTa) to more invasive (pT1a then b) stages.

Comparative evaluation of urinary PCA3 and TMPRSS2: ERG scores and serum PHI in predicting prostate cancer aggressiveness.

It has been suggested that urinary PCA3 and TMPRSS2:ERG fusion tests and serum PHI correlate to cancer aggressiveness-related pathological criteria at prostatectomy. To evaluate and compare their ability in predicting prostate cancer aggressiveness, PHI and urinary PCA3 and TMPRSS2:ERG (T2) scores were assessed in 154 patients who underwent radical prostatectomy for biopsy-proven prostate cancer. Univariate and multivariate analyses using logistic regression and decision curve analyses were performed. All three markers were predictors of a tumor volume≥0.5 mL. Only PHI predicted Gleason score≥7. T2 score and PHI were both independent predictors of extracapsular extension(≥pT3), while multifocality was only predicted by PCA3 score. Moreover, when compared to a base model (age, digital rectal examination, serum PSA, and Gleason sum at biopsy), the addition of both PCA3 score and PHI to the base model induced a significant increase (+12%) when predicting tumor volume>0.5 mL. PHI and urinary PCA3 and T2 scores can be considered as complementary predictors of cancer aggressiveness at prostatectomy.

PCA3 and PCA3-based nomograms improve diagnostic accuracy in patients undergoing first prostate biopsy.

While now recognized as an aid to predict repeat prostate biopsy outcome, the urinary PCA3 (prostate cancer gene 3) test has also been recently advocated to predict initial biopsy results. The objective is to evaluate the performance of the PCA3 test in predicting results of initial prostate biopsies and to determine whether its incorporation into specific nomograms reinforces its diagnostic value. A prospective study included 601 consecutive patients addressed for initial prostate biopsy. The PCA3 test was performed before ≥12-core initial prostate biopsy, along with standard risk factor assessment. Diagnostic performance of the PCA3 test was evaluated. The three available nomograms (Hansen's and Chun's nomograms, as well as the updated Prostate Cancer Prevention Trial risk calculator; PCPT) were applied to the cohort, and their predictive accuracies were assessed in terms of biopsy outcome: the presence of any prostate cancer (PCa) and high-grade prostate cancer (HGPCa). The PCA3 score provided significant predictive accuracy. While the PCPT risk calculator appeared less accurate; both Chun's and Hansen's nomograms provided good calibration and high net benefit on decision curve analyses. When applying nomogram-derived PCa probability thresholds ≤30%, ≤6% of HGPCa would have been missed, while avoiding up to 48% of unnecessary biopsies. The urinary PCA3 test and PCA3-incorporating nomograms can be considered as reliable tools to aid in the initial biopsy decision.

Transurethral plasma vaporization of the prostate: 3-month functional outcome and complications.

UNLABELLED: Study Type - Therapy (multi-centre cohort). Level of Evidence 2b. OBJECTIVE: To evaluate the early functional outcomes of transurethral plasma vaporization of the prostate (TUVis) in a multicentre study. PATIENTS AND METHODS: A prospective multicentre observational study was conducted in eight urology departments. The inclusion criterion was benign prostatic hyperplasia (BPH) requiring surgical treatment. Patients on anti-coagulant therapy were not excluded. The TUVis procedure was performed according to a classic transurethral resection of the prostate (TURP) scheme following the manufacturer's recommendations. We evaluated subjective functional outcome using self-questionnaires (International Prostate Symptom Score [IPSS] and five-item International Index of Erectile Function [IIEF-5]) and objective criteria (prostate volume, prostate-specific antigen [PSA], uroflowmetry, post residual volume) at baseline and at 1- and 3-month follow-ups. All types of complications were systematically recorded. RESULTS: Despite 52% of patients receiving anticoagulant therapy before surgery, we reported only 3% with haemorrhagic complications, no blood transfusion, a mean catheterization time of 44 h and a mean postoperative stay of 2.9 nights. No significant change in irrigation time, catheter time or hospital stay was observed in patients with or without anticoagulant therapy. The IPSS and bother scores significantly decreased after the 3-month follow-up (57% and 59%, respectively), but the average remaining prostate volume was 29 cc and the tissue ablation rate was only 0.5 cc/min. Three major complications occurred, consisting of two urinary fistulas and one partial bladder coagulation. CONCLUSIONS: The TUVis procedure has a proven fast postoperative recovery time, good short-term functional outcome and good haemostatic efficiency. However, the tissue ablation rate was lower than expected and we encountered three major complications, the mechanisms of which remain unclear. Considering the high energy level required to create the plasma effect, the generator, cable and resectoscope must be carefully checked before each procedure.

Urinary PCA3 score predicts prostate cancer multifocality.

PURPOSE: The urinary PCA3 gene test has proved helpful for deciding whether to (re)biopsy to diagnose prostate cancer. We searched for pathological features that influence the shedding of PCA3 producing prostate cancer cells in urine after digital rectal examination. MATERIALS AND METHODS: Included in our study were 102 patients with an informative PCA3 score on the Progensa® PCA3 assay who underwent radical prostatectomy. Correlations were evaluated between PCA3 score and histopathological factors on prostatectomy, including tumor site in the prostate and the number of cancer foci. RESULTS: PCA3 score significantly correlated with total tumor volume in prostatectomy specimens (p <0.001) but not with prostatectomy Gleason score or pathological stage. PCA3 score positively correlated with apical and basal invasion, and with bilaterality and multifocality. On multivariate analysis multifocality was an independent factor influencing PCA3 score (p = 0.012). CONCLUSIONS: Site in the prostate gland and the number of cancer foci may explain the observed PCA3 score variation in patients operated on for prostate cancer. The PCA3 test could be helpful in preoperatively selecting patients with unifocal and unilateral cancer who could benefit from active surveillance or focal therapy.

Down-regulation of DcR2 sensitizes androgen-dependent prostate cancer LNCaP cells to TRAIL-induced apoptosis.

BACKGROUND: Dysregulation of many apoptotic related genes and androgens are critical in the development, progression, and treatment of prostate cancer. The differential sensitivity of tumour cells to TRAIL-induced apoptosis can be mediated by the modulation of surface TRAIL receptor expression related to androgen concentration. Our previous results led to the hypothesis that downregulation of TRAIL-decoy receptor DcR2 expression following androgen deprivation would leave hormone sensitive normal prostate cells vulnerable to the cell death signal generated by TRAIL via its pro-apoptotic receptors. We tested this hypothesis under pathological conditions by exploring the regulation of TRAIL-induced apoptosis related to their death and decoy receptor expression, as also to hormonal concentrations in androgen-sensitive human prostate cancer, LNCaP, cells. RESULTS: In contrast to androgen-insensitive PC3 cells, decoy (DcR2) and death (DR5) receptor protein expression was correlated with hormone concentrations and TRAIL-induced apoptosis in LNCaP cells. Silencing of androgen-sensitive DcR2 protein expression by siRNA led to a significant increase in TRAIL-mediated apoptosis related to androgen concentration in LNCaP cells. CONCLUSIONS: The data support the hypothesis that hormone modulation of DcR2 expression regulates TRAIL-induced apoptosis in LNCaP cells, giving insight into cell death induction in apoptosis-resistant hormone-sensitive tumour cells from prostate cancer. TRAIL action and DcR2 expression modulation are potentially of clinical value in advanced tumour treatment.

Impact of oral anticoagulation on morbidity of transurethral resection of the prostate.

AIM: To assess the impact of oral anticoagulation (OA) on morbidity of transurethral resection of the prostate (TURP). OA included warfarin and platelet aggregation inhibitors (PAI). PATIENTS AND METHOD: Multicenter analysis of patients operated for symptomatic benign prostatic hyperplasia (BPH) by TURP. Patients under OA were compared to those with no OA. RESULTS: Out of 612 patients included in the analysis, 206 (33%) were on OA prior surgery (55 warfarin, 142 PAI, and 9 warfarin and PAI). No patient continued warfarin and clopidogrel during the operating period. Patients under OA were significantly older (75 vs. 71 yo, P < 0.001), had larger prostate volume (56 vs. 49 ml, P = 0.05), and had higher rate of bladder catheter prior surgery (26 vs. 17%, P = 0.02). At 3 months follow-up, patients in the OA group had a higher weight of resected tissue (24 vs. 21.7 g, P < 0.001), a longer duration of hospitalization (6.4 vs. 4.7 days P < 0.001), a higher rate of bladder clots (13 vs. 4.7%, P < 0.001), red cell transfusion (1.9 vs. 1.0%, P = 0.026), late hematuria (15.0 vs. 8.4%, P = 0.004), and thromboembolic events (2.4 vs. 0.7, P = 0.02). In multivariable analysis, OA status was the sole independent parameter associated with bladder clots (P = 0.004) and with late hematuria (P = 0.03). CONCLUSION: OA had a significant and independent impact on TURP outcome in terms of bleeding complications. This data could be used for treatment decision and for patient's information prior BPH surgery.

Surgical management of BPH in patients on oral anticoagulation: transurethral bipolar plasma vaporization in saline versus transurethral monopolar resection of the prostate.

INTRODUCTION: To compare postoperative outcomes of patients on oral anticoagulation (OA) treated with transurethral plasma vaporization of the prostate in saline water (TUVis) and transurethral resection of the prostate (TURP). MATERIALS AND METHODS: Between January and December 2009, 111 patients on OA therapy were treated with either TURP or TUVis in eight centers. Types of OA and perioperative management were collected. Postoperative outcomes were statistically compared between the two groups. RESULTS: A total of 57 (51%) and 54 (49%) patients were treated with TURP and TUVis, respectively. Types of OA were not significantly different between the two groups, but bladder catheterization prior to surgery was more frequently observed in the TUVis group. Before surgery, 28 patients were treated with warfarin alone, 74 with a platelet aggregation inhibitor (PAI) alone, and 9 with a combination of both. PAI was withdrawn preoperatively in 50 patients. All treatments with warfarin were switched for heparin. Comparison of the two groups showed significantly less hemorrhagic complications after TUVis. Patients treated with TUVis experienced less bladder washouts (2% versus 18%, p = 0.008), less late hematuria (4% versus 19%, p = 0.02), and lower decrease of serum hemoglobin (mean decrease of 0.66 versus 1.47 g/dL, p = 0.02). Postoperative bladder catheterization and hospital stay were significantly shorter, whereas the rate of urinary retention was significantly higher. Three months after surgery, functional results were not significantly different between the two groups. CONCLUSIONS: In patients on OA, TUVis led to significantly less bleeding, as well as shorter bladder catheterization and hospital stay than TURP.

[Value of PCA3 urinary test for prostate biopsy decision: the Lyon-Sud University Hospital experience]. / Intérêt du test urinaire PCA3 dans la décision de biopsie prostatique : l'expérience du Centre hospitalier Lyon-Sud.

The poor specificity of diagnostic strategy for prostate cancer (digital rectal examination and seric PSA) induces both a great number of useless prostate biopsies and diagnosis of non evolutive cancers. A urinary test (Progensa PCA3(®), Gen-Probe) measuring the expression of PCA3, a prostate cancer-specific gene, has recently be proposed to indicate re-biopsy. The aim of this prospective study was to evaluate diagnostic value of urinary PCA3 test for prostate cancer. In the urines of 245 patients submitted to prostate biopsy, expression of the PCA3 gene was measured and reported to that of PSA to calculate PCA3 score using a method amplifying and detecting RNA. Patients with informative samples (98%) were classified depending of the presence (n = 126) or absence (n = 114) of cancer tissue on biopsies. The median PCA3 score was significantly higher in the group with positive biopsies (p < 0.0001). Area under ROC curve was 0.70 for PCA3 as compared to that of PSA (0.53) and free/total PSA ratio (0.65). At the best threshold of 38, PCA3 test had a 59%-sensitivity and a 72%-specificity, as compared to 66% and 32% for total PSA (threshold 4 ng/mL) and 81% and 28% for free/total PSA ratio (threshold 25%). These performances were maintained in patients with seric PSA within the grey zone (4-10 ng/mL) and those with previous prostate biopsies. This study confirms the clinical value of PCA3 urinary test in helping decision for biopsies in patients with suspected prostate cancer.

Impact of lower urinary tract symptoms on discomfort in men aged between 50 and 80 years.

BACKGROUND/AIMS: There are only a few surveys on the prevalence of lower urinary tract symptoms (LUTS) among the general population. The aim of this survey was to assess the prevalence of LUTS and their impact on discomfort in men. METHODS: A questionnaire was mailed to 3,877 men aged 50-80 years, which included questions on their medical history, demographic and sociological status, and also the International Prostate Symptom Score (IPSS) with additional questions on discomfort related to urinary symptoms. RESULTS: The response rate was 81.5%. Prevalence of mild and severe IPSS was 89.2%. Specific bother for each urinary symptom depended on symptom frequency: urgency, frequency, weak stream, nocturia, incomplete emptying, intermittency and straining 1 time out of 5 were responsible for discomfort in respectively 4.9, 6.1, 7.1, 7.5, 8.7 and 9.9%; the same symptoms more than half of the time were responsible for discomfort in respectively 32.8, 38, 45.3, 45.6, 53.2 and 58.7%. Urgency was much more deeply implicated in discomfort than frequency of nocturia. CONCLUSIONS: Urinary symptoms in men are very common. Nocturia is the most frequent but has a low impact on discomfort. Urgency has a higher impact on discomfort and should therefore be considered in treatment decision-making.

Laser treatment of benign prostatic hyperplasia in patients on oral anticoagulant therapy: a review.

We assessed the therapeutic efficacy and safety of laser prostatectomy (LP) for treating benign prostatic hyperplasia (BPH) in patients on oral anticoagulation. We systematically reviewed previous reports, using the Pubmed database and bibliographies of retrieved articles and reviews. The oral anticoagulation included coumarin derivatives and platelet-aggregation inhibitors (PAI). Previous studies do not allow the establishment of definitive conclusions for managing patients on oral anticoagulation and who require BPH surgery. No randomized studies are available. Nevertheless, compared to transurethral resection of the prostate (TURP), LP seems to decrease the risk of haemorrhage in patients taking PAI or coumarin derivatives. Therefore, LP is a useful alternative to TURP for managing patients on oral anticoagulation, and could be proposed as the first intention for those patients. Continuing PAI during the procedure is feasible. A replacement of coumarin derivatives by low molecular weight heparin is preferable. No conclusion can be reached on the preferred type of laser technique to treat these patients, but data on laser enucleation is much less abundant and conclusive than that on laser vaporization.

Association between sarcoidosis and testicular carcinoma: a diagnostic pitfall.

BACKGROUND AND AIM OF THE WORK: Sarcoidosis is a multisystemic, non-caseous, benign granulomatous disease of unknown etiology that is sometimes associated with testicular cancer. This association, which does not appear to be accidental, can give rise to diagnostic problems because adenopathies or parenchymatous pulmonary nodules related to sarcoidosis can lead to the presumption of metastatic testicular cancer. The objective of this article was to assess the clinical, histological, and radiological characteristics of the association between sarcoidosis and testicular cancer to help clinicians avoid potentially fatal diagnostic traps and management errors. METHODS: Literature review. RESULTS: A total of 64 cases of sarcoidosis concomitant with testicular cancer were described in the literature. In more than 50% of the cases (35/64), testicular cancer was diagnosed before sarcoidosis or sarcoid-like reaction. Cancer was diagnosed concomitantly in 31% of cases (20/64). Every anatomopathological type of testicular tumor was described in association with sarcoidosis. Seminoma was the most frequent tumor, occuring in 62% (40/64) of patients. In 80% of the cases (51/64) sarcoidosis regressed spontaneously. CONCLUSIONS: Testis cancer may be accompanied by a sarcoid-like reaction or can be associated with real sarcoidosis. The association of testicular cancer with sarcoidosis did not change the therapeutic management of either of these two pathologies. The presence of sarcoidosis does not change the cancer prognosis. Sarcoidosis is a benign disease that resolved favorably and spontaneously in 80% of the cases.

[Value of urinary markers in the diagnosis and follow-up of urothelial bladder tumours]. / Intérêt des marqueurs urinaires dans le diagnostic et le suivi des tumeurs urothéliales de vessie.

Urothelial bladder tumours require regular surveillance: cystoscopy associated with urine cytology are reference examinations. Several new markers currently under evaluation or already validated have recently been proposed to replace cytology and potentially reduce or even replace unnecessary cystoscopies. The biological fluid studied for all of these markers is the same as that of urine cytology, i.e. urine. The authors review the results of recent studies on these new urinary markers. The results of these markers demonstrate a better global sensitivity than urine cytology, but often a lower specificity. In the majority of cases, these tests are performed during patient follow-up (NMP22, BTA, CYFRA 21-l., etc.), but do not replace cystoscopy, due to a large number of false-positives. Other techniques, such as FISH, uCyt+ or microsatellites appear to be more promising, especially for the diagnosis of low-grade tumours. The best solution in practice may consist of a combination of several markers to further improve sensitivity and to decrease the false-positive rate responsible for unnecessary cystoscopies.

[Value of antidiuretic, anticholinergic, and anti-inflammatory drugs and botulinum toxin for the treatment of voiding disorders related to BPH (CTMH-AFU forum 2005)]. / Intérêts des antidiurétiques, des anticholinergiques, des anti-inflammatoires et de la toxine botulinique pour le traitement des troubles mictionnels liés à l'HBP (forum CTMH-AFU 2005).

New therapeutic approaches have recently been investigated in order to improve the voiding disorders of patient with lower urinary tract symptoms related to benign prostatic hyperplasia. The purpose of this article is to provide a review of these treatments: anti-inflammatory, antidiuretic, anticholinergic and botulinum toxin. Anticholinergic drugs associated with a risk of urinary retention, appear to be effective for irritative disorders in combination with an alpha-blocker. Antidiuretics can be proposed in patients younger than 65 with disabling polyuria confirmed by a voiding diary, related to BPH and refractory to conventional treatment of BPH. The interaction between inflammation and BPH has not yet been clarified, but anti-inflammatory drugs appear to improve symptoms and may have a place in short-term treatment of BPH, as their long-term use is not recommended and COX-2 inhibitors have been withdrawn from the market. Finally, botulinum toxin could have a place in the treatment of disorders related to BPH if clinical studies confirm the recently published promising results. These new approaches will probably be integrated into guidelines and flow-charts for the treatment of voiding disorders related to BPH.

Technique of Injection of Hyaluronic Acid as a Prostatic Spacer and Fiducials Before Hypofractionated External Beam Radiotherapy for Prostate Cancer.

OBJECTIVE: To describe a technique combining the implantation of fiducials and a prostatic spacer (hyaluronic acid [HA]) to decrease the rectal toxicity after an image-guided external beam radiotherapy (EBRT) with hypofractionation for prostate cancer and to assess the tolerance and the learning curve of the procedure. MATERIALS AND METHODS: Thirty patients with prostate cancer at low or intermediate risk were included in a phase II trial: image-guided EBRT of 62 Gy in 20 fractions of 3.1 Gy with intensity-modulated radiotherapy. A transrectal implantation of 3 fiducials and transperineal injection of 10 cc of HA (NASHA gel spacer, Q-Med AB, Uppsala, Sweden) between the rectum and the prostate was performed by 1 operator. The thickness of HA was measured at 10 points on magnetic resonance imaging to establish a quality score of the injection (maximum score = 10) and determine the learning curve of the procedure. RESULTS: The quality score increased from patients 1-10, 11-20, to 21-30 with respective median scores: 7 [2-10], 5 [4-7], and 8 [3-10]. The average thicknesses of HA between the base, middle part, and apex of the prostate and the rectum were the following: 15.1 mm [6.4-29], 9.8 mm [5-21.2], and 9.9 mm [3.2-21.5]. The injection of the HA induced a median pain score of 4 [1-8] and no residual pain at mid-long term. CONCLUSION: Creating an interface between the rectum and the prostate and the implantation of fiducials were feasible under local anesthesia with a short learning curve and could become a standard procedure before a hypofractionated EBRT for prostate cancer.

[REMEEX: A possible treatment option in selected cases of sphincter incompetence]. / REMEEX: une option thérapeutique envisageable dans des cas sélectionnés d'insuffisance sphinctérienne.

OBJECTIVE: To evaluate the functional results and morbidity of adjustable tension suburethral tape (REMEEX) in the treatment of urinary incontinence due to severe sphincter incompetence (MUCP < 40 cm H2O) in patients presenting a contraindication to artificial sphincter operated between December 2001 and May 2004. Twelve patients (66.7%) had already undergone incontinence surgery. Ten patients (55.5%) had mixed urinary incontinence. The efficacy of the tape was considered to be good when incontinence resolved completely, partial when incontinence was decreased by > 50% and/or PVR > 100 ml. All other cases were considered to be failures. In April 2005, after a mean follow-up of 26.3 months, retrospective evaluation of the functional results was performed by means of a pad-test and a questionnaire comprising an MHU (urinary disability) score and a Ditrovie score. Complications after each intercurrent event were recorded. RESULTS: The initial efficacy of the tape was considered to be good in 13 patients (72.2%) and partial in 4 patients (22.2%) with only one initial failure. Eight patients (44.4%) required secondary adjustment after a mean interval of 5.2 months, with a failure rate of 62.5%. In April 2005, 10 patients (55.5%) had a good result, 2 patients (11.1%) required self-catheterization (partial efficacy) and 6 patients (33.4%) were considered to be failures. In terms of morbidity, we observed 2 bladder injuries (11.1%), 6 superinfections of the device (33.3%), 2 (11.1%) of which required removal of the material. Fifteen patients (83.3%) answered the questionnaire: 6 patients (40%) had an MHU score greater than 3. The mean Ditrovie score was 2.1. 9 patients (60%) had a score less than 2 and 4 patients (26.6%) had a score greater than 3. CONCLUSION: The results of this series, in patients in whom artificial sphincter was contraindicated, are satisfactory at the price of acceptable morbidity. Before defining the place of this device in the range of treatment options for sphincter incompetence, our results must be confirmed by a longer series.

[Management of corpus cavernosum trauma]. / Prise en charge des traumatismes des corps caverneux du pénis.

Rupture of the tunica albuginea of the corpus cavernosum of the penis is a rare disease, usually occurring in young adults during sexual intercourse. In Western countries, the most frequent causes is coital injuries. Ultrasound, cavernography or magnetic resonance imaging of the penis can be performed to determine the exact site of the fracture. Treatment is usually elective surgery and consists of evacuating the subcutaneous haematoma and suturing the tear of the tunica albuginea. An associated rupture of the urethra must be excluded. Complications of these fractures of the tunica albuginea especially comprise erectile dysfunction, deviation of the erect penis, development of plaques resembling those of La Peyronie disease, urethro-cavernous or urethro-cutaneous fistula or dysuria secondary to urethral stricture.

[Role of prostatic stents and transurethral microwave thermotherapy in the treatment of voiding disorders related to benign prostatic hyperplasia (CTMH-AFU forum 2005)]. / Place des endoprothèses prostatiques et de la thermothérapie micro-ondes transuréthrales dans le traitement des troubles mictionnels liés à l'HBP? (Forum CTMH-aFU 2005).

Prostatic stents and microwave thermotherapy are minimally invasive techniques for the treatment of voiding disorders related to benign prostatic hyperplasia. A review of the literature evaluates the place of these treatments in 2006. Permanent prostatic stenting is rarely used, but remains a treatment option for patients with obstructive disorders and a formal anaesthetic contraindication. Temporary stenting can be used to predict the effect of resection in selected patients. Finally, microwave thermotherapy, not widely used in France, has a promising clinical efficacy and occupies a place between medical treatment and surgery.

Activation of caspases-3, -6, and -9 during finasteride treatment of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) results from an increase in both epithelial and stromal compartments of the human prostate. Although inhibitors of 5alpha-reductase such as finasteride have been shown to reduce the size of BPH tissues by inducing apoptosis, their mechanisms of action still remain unknown. The present study supports that such a process triggered by finasteride is caspase dependent with a possible involvement of two effector caspases (caspase-3 and 6) and two initiator caspases (caspase-8 and 9). Indeed, by using tissues from patients affected by BPH and treated by finasteride (5 mg/d) for 2-3, 6-8, or 27-32 d, we observed that the 5alpha-reductase inhibitor induced apoptosis in epithelial cells (evaluated through cell number positive for terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) as early as 2-3 d of treatment, with a maximal activity (250-fold increase, P < 0.0001) at 6-8 d of treatment. However, after 27-32 d of treatment, the number of apoptotic cells was reduced and was close to control. Caspases-3, -6, -8, and -9 were immunolocalized to (basal and secretory) epithelial cells and to a lesser extent to stromal cells. Activated caspase-3 immunoexpression was restricted to epithelial secretory cells, and its immunostaining intensity appeared to be higher in BPH tissues from patients treated for 2-3 or 6-8 d. Consistently, in Western blotting analyses, activated caspases-3 and -6 were detected as early as 2-3 d of treatment in BPH tissues, and their levels were increased after 6-8 d of treatment. In real time quantitative PCR experiments, caspase-3 and -6 mRNA levels were found to be unchanged after finasteride treatment. Activated caspase-8 was not detected in the different conditions tested, whereas activated caspase-9 protein levels were maximally enhanced after 2-3 d of finasteride treatment. In conclusion, we report here that finasteride treatment of BPH tissues induced a caspase-dependent apoptotic process restricted to epithelial cells by activating effector caspases-3 and -6 and exhibited a transient action because the apoptotic process was no longer observed after 27-32 d of treatment.

[Well differentiated paratesticular liposarcoma in adults]. / Liposarcome paratesticulaire bien différencié chez l'adulte.

The authors report a case of well differentiated paratesticular liposarcoma in a 41-year-old patient. This is a rare tumour (about one hundred cases have been reported in the literature), which essentially arises from the spermatic cord. Clinical and radiological signs are nonspecific and the diagnosis is generally based on histological examination of the operative specimen. Due to the histological similarities, all specimens of benign lipoma must be examined for the presence of well differentiated liposarcoma. Treatment consists of transinguinal radical orchidectomy, sometimes with resection of adjacent structures. The prognosis is generally better than that of other paratesticular sarcomas. Adjuvant radiotherapy may be indicated in locally advanced masses or in the case of incomplete resection.