Clinicopathological characteristics of incidental prostate cancer discovered from radical cystoprostatectomy specimen: a multicenter French study.

PURPOSE: The present study assessed the incidence and histopathological features of incidentally diagnosed prostate cancer (PCa) in specimens from radical cystoprostatectomy (RCP) for bladder cancer. The patient outcomes also were evaluated. METHODS: We retrospectively reviewed the histopathological features and survival data of 4,299 male patients who underwent a RCP for bladder cancer at 25 French centers between January 1996 and June 2012. No patients had preoperative clinical or biological suspicion of PCa. RESULTS: Among the 4,299 RCP specimens, PCa was diagnosed in 931 patients (21.7%). Most tumors (90.1%) were organ-confined (pT2), whereas 9.9% of them were diagnosed at a locally advanced stage (≥pT3). Gleason score was <6 in 129 cases (13.9%), 6 in 575 cases (61.7%), 7 (3 + 4) in 149 cases (16.0%), 7 (4 + 3) in 38 cases (4.1%), and >7 in 40 cases (4.3%). After a median follow-up of 25.5 months (interquartile range 14.2-47.4), 35.4% of patients had bladder cancer recurrence and 23.8% died of bladder cancer. Only 16 patients (1.9%) experienced PCa biochemical recurrence during follow-up, and no preoperative predictive factor was identified. No patients died from PCa. CONCLUSIONS: The rate of incidentally diagnosed PCa in RCP specimens was 21.7%. The majority of these PCas were organ-confined. PCa recurrence occurred in only 1.9% of cases during follow-up.

[Long-term morbidity of living donor kidney harvesting]. / Prélèvement rénal chez le donneur vivant: morbidité et suivi à long terme.

OBJECTIVE: To evaluate the morbidity of living donor kidney harvesting and the long-term medical consequences and impact on quality of life (QoL). MATERIAL AND METHODS: Retrospective analysis of medical and surgical data for 114 living kidney donors in a single teaching hospital between 1977 and 2005. Complications were evaluated in relation to the surgical approach and body mass index (BMI) using a Chi-square test or Fisher's exact test. Changes in renal function (serum creatinine, creatinine clearance), proteinuria and blood pressure (BP) were studied by Student's t test or a Mann-Whitney U or Wilcoxon nonparametric test. Long-term QoL was evaluated by the MOS SF-36 questionnaire and a local questionnaire and was then compared to that of the French general population. RESULTS: The median follow-up was 63 months. The morbidity of kidney harvesting was significantly correlated with the surgical approach (p = 0.018) and a BMI > or = 25 kg/m2 (p = 0.014). No mortality was observed in this series. A moderate elevation of serum creatinine was observed during follow-up (mean serum creatinine increased from 82.2 micromol/l [+/- 16.3] to 104.5 micromol/l [+/- 19.9]), and mean creatinine clearance decreased from 113.4 ml/min [+/- 27.6] to 76 ml/min [+/- 29.9]. Little impact was observed on proteinuria and BP and QoL was not altered by kidney harvesting. CONCLUSION: The perioperative complication rate is correlated with BMI and a flank incision. Kidney harvesting lowers glomerular filtration, but clearance remained stable during follow-up. Macroalbuminuria or hypertension may be observed, but their frequency is not higher than in the general population. The QoL of living donors is not altered. Clear information for the general public would allow promotion of living donor transplantation.

Prognostic factors for first recurrence in patients with retroperitoneal sarcoma.

BACKGROUND: Retroperitoneal sarcomas are characterized by a high local recurrence rate despite optimal surgical treatment. The definition of prognostic factors for recurrence could help offer high-risk patients a closer follow-up and a multidisciplinary therapeutic approach. PATIENTS AND METHODS: A cohort of 40 patients treated for a primary retroperitoneal sarcoma was retrospectively analyzed. Median follow-up was 24 months. Patient (sex and age), tumor (maximal size, histologic type, tumor localization, and histologic grade), and treatment (complete vs. incomplete surgery) characteristics were included in univariate and multivariate prognostic factor analyses. RESULTS: After a median follow-up of 24 months (range 3-121), the overall recurrence rate was 65%. Median time between initial surgery and recurrence was 15 months (range 11.5-29.5). In univariate analysis, surgical positive margins (P = 0.011), bilateral tumors (P = 0.0034), nonliposarcoma histologic subtypes (P = 0.043), and a high histologic grade (P = 0.0072) were associated with an increased recurrence rate. All these factors except the histologic subtypes retained an independent prognostic value in the multivariate analysis. Death was strongly related to recurrence (P = 0.0033). CONCLUSION: The optimal treatment of patients with primary retroperitoneal sarcoma should be based on radical surgery, with en bloc organ resection if necessary, to minimize the risk of positive margins. In high-risk patients, close follow-up is mandatory to offer optimal subsequent surgical procedures. The impact of a multidisciplinary therapeutic approach remains to be proved.

[What is the objective of second-line chemotherapy after failure of first-line chemotherapy in hormone-resistant metastatic prostate?]. / Chimiothérapie de deuxième ligne après échec d'une chimiothérapie de première ligne dans le cancer de la prostate métastatique hormono-résistant. Pour quel objectif?

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.

Potential action of IGF-1 and EGF on androgen receptor nuclear transfer and transactivation in normal and cancer human prostate cell lines.

This work was designed to determine whether IGF-1 and EGF modulate nuclear transfer and transactivation of the androgen receptor (AR) in human prostate cell lines (PNT1A and DU-145). We first characterized the IGF-1 and EGF receptors by ligand-binding assays with [125I] IGF-1 and [125I] EGF in a normal human prostate epithelial cell line, PNT1A. We then evaluated the effects of these growth factors on AR nuclear transfer and transcriptional activation in this cell line and in DU-145, a human prostate tumor cell line. The cell lines were cotransfected with an AR expression vector and an androgen-responsive luciferase gene driven by the mouse mammary tumor virus (MMTV-luciferase) promoter. Neither IGF-1 nor EGF could activate reporter gene in the absence of androgens. Conversely, both enhanced the magnitude of the AR response in the presence of low levels of androgen (10(-11)-10(-9) M) and this response, increased by twofold, was inhibited by hydroxyflutamide. No effect of IGF-1 and EGF was observed on the intracellular localization of the fusion protein EGFP-AR in either cell line. The fluorescence stayed cytoplasmic even after 24 h of IGF-1 or EGF treatment. Taken together, these data indicate that growth factors are unable to initiate the nuclear translocation of AR in the absence of androgens or to induce ligand-independent transcriptional activity. We observed only cross-talk in the presence of androgens and IGF-1 or EGF, leading to an over-activated AR. In conclusion, the cross-talk between AR and growth factor signaling pathways may sensitize AR to suboptimal stimulation by low levels of androgens.

[Erectile dysfunction: knowledge, wishes and attitudes. Results of a French study of 5.099 men aged 17 to 70]. / Dysfonction érectile: connaissances, souhaits et attitudes. Résultats d'une enquête française réalisée auprès de 5.099 hommes âgés de 18 ans à 70 ans.

OBJECTIVE: Although erectile dysfunction is today considered as a frequent disease, few patients actually seek for medical advice and take medication. The purpose of the study was therefore to analyse use and behaviour of men with erectile dysfunction. MATERIAL AND METHODS: The study, performed between the 12th April and the 21st May 2002, involved 10,000 men 18 to 70 years old and consisted in self-administered questionnaires including 55 items (5099 questionnaires were eligible for analyse). RESULTS: Despite a high prevalence of erectile dysfunction (25%), increased with age (44% in the men aged 45 and over), the study showed that only 22.2% of men with erectile dysfunction take medical advice with 36.9% of them take medication. Men generally think erectile dysfunction is not very common in comparison to other diseases, and correlate it with stress and tiredness. However, men with erectile dysfunction (particularly those over 45) mention diseases as hypertension, prostatic and cardiovascular diseases. 94% of men would take medical advice if their problems should repeat. However, obstacles to consultation still remain for men presenting with erectile dysfunction and especially the difficulty to talk about sexuality with their physician (for 63% of men). CONCLUSION: This study confirms the high prevalence of erectile dysfunction and that few men concerned actually seek for professional assistance and take medication. Moreover, it demonstrates the major contribution of the physician in opening the dialogue on sexual problems because men are frequently embarassed or afraid to discuss this sensitive topic.

[Non-typhus Salmonella urinary tract infections]. / Infections urinaires à salmonella non typhique.

Non-typhus Salmonella urinary tract infections are rare. Based on a clinical case and a review of the recent literature, the authors analyse the diagnostic setting and discuss the necessary investigations and treatment modalities. Non-typhus Salmonella urinary tract infections generally occur in a predisposed clinical setting, such as immunodepression or acquired (stones, schistosomiasis) or congenital uropathy. As in the present case, it can also be the first clinical expression of AIDS, which must be systematically investigated. Antibiotic therapy must be continued for at least two weeks and consists of a third generation cephalosporin or fluoroquinolones, but the prognosis is directly related to the underlying clinical condition.

[Solitary fibrous tumours of the kidney]. / Tumeur fibreuse solitaire du rein.

Solitary fibrous tumours (SFT) are mesenchymal tumours that usually arise from the pleura. Renal SFT are exceptional (9 cases reported in the literature). The authors report a new case discovered during assessment of HT and treated by radical right nephrectomy. The histological appearance is characteristic: a tumour with a fibrous centre, composed of a monomorphic proliferation of spindle cells, with positive CD 34, CD 99, and bcl 2 labelling. The prognosis after complete resection is generally favourable.

[Calculous renal failure and pregnancy]. / Insuffisance rénale lithiasique et grossesse.

Obstructive renal failure is a rare but serious complication of pregnancy. Although most cases are due to extrinsic compression, renal tract obstruction can also be due to intraluminal precipitation of sulfadiazine prescribed for maternofoetal toxoplasmosis. The diagnosis is suggested by clinical history, ultrasound (radiolucent stones situated anywhere in the renal tract) and especially analysis of the urine pellet (wheat sheaf formation of yellowish crystals). Urinary drainage by double J stent or percutaneous nephrotomy is indicated in the absence of clinical improvement in response to symptomatic treatment and adequate alkaline rehydration. The risk of sulfadiazine crystallization must be systematically prevented by a sufficient water intake and urinary alkalinization right from the start of treatment.

[Prostate cancer and acute disseminated intravascular coagulation. Therapeutic management based on three cases]. / Cancer de la prostate et coagulation intra vasculaire disséminée aiguë. Prise en charge thérapeutique: à propos de trois cas.

Acute DIC is a rare, but life-threatening complication of metastatic prostate cancer. The authors discuss the treatment modalities in the light of three cases and a review of the recent literature. The key to treatment of DIC is treatment anti of the tumour. Androgen blockade is indicated in hormone-dependent tumours. This treatment can sometimes be completed by low-dose oral anticoagulants. Chemotherapy is the treatment of choice of acute DIC during the hormone resistance phase.

[Efficacy of suburethral TVT in cases of stress urinary incontinence associated with severe sphincter insufficiency. Report of 22 cases]. / Efficacité de la bandelette sous urétrale TVT en cas d'incontinence urinaire d'effort associée à une insuffisance sphinctérienne sévère. A propos de 22 cas.

INTRODUCTION: The TVT system has revolutionized the management of female stress urinary incontinence (SUI). Less favourable results have been observed in patients with urinary incontinence associated with a low maximum urethral closing pressure (MUCP). The objective of this prospective study was to evaluate the efficacy of TVT in this situation. MATERIAL AND METHODS: From October 1999 to June 2001, 22 patients between the ages of 53 and 84 years (median: 66.7 years) were operated for SUI with an MUCP < 25 cm H2O (mean: 17.6 cm H2O, range: 6 to 22 cm H2O) present for more than 8 months (range: 8 to 48 months). Three patients also had associated urgency. The Ulmstem manoeuvre was positive in every case and the Bonney manoeuvre was positive in 19 patients. Insertion of TVT was associated with sacral colpopexy in two patients. Success of treatment was defined by complete absence of incontinence and voiding disorders after the operation. RESULTS: One patient was lost to follow-up. The median follow-up was 7.5 months (range: 3 to 27 months). The mean duration of bladder catheterization was 1.3 days (range: 1 to 5 days). Fifteen patients were completely cured by TVT (71.4%). In these cases, uroflowmetry and post-voiding volume were not affected by the operation. Treatment was ineffective in 6 patients (4 cases of uncontrolled leaks, one case of de novo urge incontinence, one case of postoperative dysuria with a post-voiding residue of 120 ml). CONCLUSION: The TVT system appears to be an effective method for the treatment of most patients with SUI associated with severe manometric sphincter incompetence. However, these favourable results need to be confirmed by a longer follow-up.

Initial management of testicular cancer: practice survey among urologists and pathologists.

INTRODUCTION: The objective of this study was to conduct a declarative professional practices survey among urologists of the French Association of Urology (AFU) and French pathologists concerning their management of testicular cancer. MATERIALS AND METHODS: A questionnaire was sent to all urologists, members of the AFU, and another questionnaire was sent to French pathologists, members of the International Academy of Pathology, French Division, in June 2010. A total of 289 urologists (29%) and 84 pathologists (19%) returned the questionnaires. RESULTS: Fifty-seven percent of urologists declared that they performed fewer than 5 orchidectomies per year. Pathologists declared that they examined less than 5 orchidectomy specimens per year in 24% of cases. The laboratory work-up (only alpha fetoprotein [AFP], lactate dehydrogenase [LDH], and total human chorionic gonadotropin [hCG]) and the radiological work-up (only testicular ultrasound and chest, abdomen, and pelvis computed tomography [CT] scan) were performed strictly according to guidelines in 15.9% and 65.7% of cases, respectively. A total of 31.8% of urologists declared that they performed the minimum assessment required by guidelines (AFP, LDH, total hCG, testicular ultrasound and chest, abdomen, and pelvis CT scan plus other examinations not recommended). Prognostic factors of stage I tumors, to define the indications for adjuvant therapy, were correctly declared in 7.3% of nonseminomatous germ cell tumors (vascular and/or lymphatic emboli) and in 13.8% of seminomas (tumor size >4 cm and rete testis invasion). CONCLUSION: This survey demonstrated that clinical practice did not comply with guidelines, which raises the question of the measures that can be taken to ensure better application of guidelines or how to develop expert centers for the management of these rare tumors.

Abrogation of de novo lipogenesis by stearoyl-CoA desaturase 1 inhibition interferes with oncogenic signaling and blocks prostate cancer progression in mice.

Increased de novo fatty acid (FA) synthesis is one hallmark of tumor cells, including prostate cancer. We present here our most recent results showing that lipid composition in human prostate cancer is characterized by an increased ratio of monounsaturated FA to saturated FA, compared with normal prostate, and evidence the overexpression of the lipogenic enzyme stearoyl-CoA desaturase 1 (SCD1) in human prostate cancer. As a new therapeutic strategy, we show that pharmacologic inhibition of SCD1 activity impairs lipid synthesis and results in decreased proliferation of both androgen-sensitive and androgen-resistant prostate cancer cells, abrogates the growth of prostate tumor xenografts in nude mice, and confers therapeutic benefit on animal survival. We show that these changes in lipid synthesis are translated into the inhibition of the AKT pathway and that the decrease in concentration of phosphatidylinositol-3,4,5-trisphosphate might at least partially mediate this effect. Inhibition of SCD1 also promotes the activation of AMP-activated kinase and glycogen synthase kinase 3alpha/beta, the latter on being consistent with a decrease in beta-catenin activity and mRNA levels of various beta-catenin growth-promoting transcriptional targets. Furthermore, we show that SCD1 activity is required for cell transformation by Ras oncogene. Together, our data support for the first time the concept of targeting the lipogenic enzyme SCD1 as a new promising therapeutic approach to block oncogenesis and prostate cancer progression.