P. Ballanger

The epithelial-mesenchymal transition-inducing factor TWIST is an attractive target in advanced and/or metastatic bladder and prostate cancers.

PURPOSE Metastasis remains the main cause of death in both bladder (BCa) and prostate (PCa) cancers. The results of chemotherapy did not show any significant improvement of the survival the past years. Cancer research has led to the identification of signaling pathways involved and molecular targets that could change the natural history. The epithelial-mesenchymal transition (EMT), critical during embryonic development, becomes potentially destructive in many epithelial tumors progression where it is inappropriately activated. The cell-cell and cell-extracellular matrix interactions are altered to release cancer cells, which are able to migrate toward metastatic sites. Hallmarks of EMT include the down-regulation of E-cadherin expression, which is the main component of the adherens junctions. The protein TWIST is a transcriptional repressor of E-cadherin, tumor progression, and metastasis, and could be used as a molecular target to restore the chemosensitivity in BCa and PCa. MATERIALS AND METHODS We selected the last 5-year basic research literature on EMT and TWIST but also clinical studies on BCa and PCa in which TWIST is overexpressed and could be considered as an efficient prognostic marker and molecular target. RESULTS TWIST is considered as a potential oncogene promoting the proliferation and inhibiting the apoptosis. TWIST promotes the synthesis of the pro-angiogenic factor, vascular endothelial growth factor (VEGF) involved in tumor progression and metastasis. Apoptosis and angiogenesis are two essential cancer progression steps in many epithelial tumors, including BCa and PCa. CONCLUSIONS With the targeted therapy, oncology has entered into a new era, which is going to be critical in cancer treatment in combination with traditional anticancer drugs.

Complete Histologic Remission after Sunitinib Neoadjuvant Therapy in T3b Renal Cell Carcinoma

The authors present the first case report of complete histologic remission after neoadjuvant sunitinib treatment on primary renal tumour and vena cava thrombus. A 78-yr-old woman with an Eastern Cooperative Oncology Group (ECOG) score of 0 presented with a T3b renal tumour. She refused surgical treatment but agreed to percutaneous biopsy and medical treatment. A Fuhrman III renal cell carcinoma was histologically confirmed on percutaneous biopsy, and sunitinib treatment was administered over 6 mo. A significant objective response was observed for tumour size and thrombus. The patient finally accepted surgical treatment. Pathologic examination concluded with a complete response of primary tumour and thrombus.

Outcome and Cost Analysis of Sacral Nerve Modulation for Treating Urinary and/or Fecal Incontinence

Background:Sacral nerve modulation (SNM) is an established treatment for urinary and fecal incontinence in patients for whom conservative management has failed. Objective:This study assessed the outcome and cost analysis of SNM compared to alternative medical and surgical treatments. Methods:Clinical outcome and cost-effectiveness analyses were performed in parallel with a prospective, multicenter cohort study that included 369 consecutive patients with urge urinary and/or fecal incontinence. The duration of follow-up was 24 months, and costs were estimated from the national health perspective. Cost-effectiveness outcomes were expressed as incremental costs per 50% of improved severity scores (incremental cost-effectiveness ratio). Results:The SNM significantly improved the continence status (P < 0.005) and quality of life (P < 0.05) of patients with urge urinary and/or fecal incontinence compared to alternative treatments. The average cost of SNM for urge urinary incontinence was &OV0556; 8525 (95% confidence interval, &OV0556; 6686–&OV0556; 10,364; P = 0.001) more for the first 2 years compared to alternative treatments. The corresponding increase in cost for subjects with fecal incontinence was &OV0556; 6581 (95% confidence interval, &OV0556; 2077–&OV0556; 11,084; P = 0.006). When an improvement of more than 50% in the continence severity score was used as the unit of effectiveness, the incremental cost-effectiveness ratio for SNM was &OV0556; 94,204 and &OV0556; 185,160 at 24 months of follow-up for urinary and fecal incontinence, respectively. Conclusions:The SNM is a cost-effective treatment for urge urinary and/or fecal incontinence.

Therapeutic Management of De Novo Urological Malignancy in Renal Transplant Recipients: The Experience of the French Department of Urology and Kidney Transplantation from Bordeaux

OBJECTIVES To determine and analyze the incidence, prognosis, and therapeutic strategy of de novo urological malignancies in a series of renal transplant recipients (RTRs). METHODS A retrospective study of 1350 recipients between January 1998 and January 2008 was carried out; we reviewed the data of 42 de novo urological malignancies in 39 recipients. RESULTS There were 21 cases of prostate cancer, 13 cases of renal cell carcinoma in 10 patients, 3 cases of renal graft tumors, and 5 cases of transitional cell carcinoma of the bladder. The overall incidence of urological neoplasms was 3.1%. The mean age of cancer diagnosis was 60 +/- 8.3 years. The mean duration of dialysis before cancer diagnosis was 35 +/- 37.5 months. About 92% of patients underwent hemodialysis (34/39) and the remaining underwent peritoneal dialysis (5/39). All the 39 recipients received cadaveric kidneys. The mean follow-up period for this study was 33 +/- 34.4 months (range 2-160 months). There appears to be a greater risk of urological neoplasm in RTRs. Prostate cancer and renal carcinoma can be treated in a similar manner than in general population with encouraging oncological results and low morbidity. However, the transitional cell carcinoma of the bladder remains particularly aggressive requiring optimal treatment despite the morbidity concerning the intravesical therapy. CONCLUSIONS We can apply the standard medical and surgical treatment in RTRs, with encouraging oncological results if a strict screening program is established and followed by the patients.

Laparoscopic Radical Prostatectomy in Renal Transplant Recipients

OBJECTIVES To report our experience with 9 consecutive laparoscopic radical prostatectomy (LRP) on renal transplant recipients (RTR) and to compare it with other LRPs performed during the same period by the same surgeons. Retropubic radical prostatectomy has widely been described in RTR, whereas LRP has rarely been studied. METHODS Between January 2007 and December 2008, all clinical data from patients undergoing radical prostatectomy were prospectively collected in a database. The database was searched to find information of LRP on RTR. We compared RTR and other patients for all relevant clinical data and for surgical complications. RESULTS A total of 9 LRP on RTR (5.8%) and other 164 LRP were performed. LRP on RTR were compared with other LRP. No statistically relevant difference was observed in patient characteristics, biopsy core pathologic analysis, prostate specimen pathologic analysis, and oncologic outcomes. Surgical procedure was also achieved under the same conditions in RTR than in other patients (surgical time, blood loss, transfusion rate, bladder injury). Rectal injury rate was significantly higher in RTR than in other patients (22.2% vs 1.8%, P = .022). CONCLUSIONS LRP in RTR is feasible. The procedure can be managed the same way as LRP on other patients, but special care must be taken to avoid rectal injury. In our experience, the dissection of the posterior side of the prostate was more difficult on RTR than on other patients.

Salvage Radiotherapy After High-Intensity Focussed Ultrasound for Recurrent Localised Prostate Cancer

BACKGROUND Radiotherapy is a treatment option in the case of local failure following treatment for localised prostate cancer with high-intensity focussed ultrasound (HIFU). OBJECTIVE Our aim was to evaluate tolerance and oncologic control with salvage radiotherapy (SRT) after HIFU failure and to identify predictive factors of success. DESIGN, SETTING, AND PARTICIPANTS From March 1995 to March 2008, all patients who presented with histologically proven persistent local disease following HIFU and were treated with curative intent SRT (with or without hormonal treatment) were included in this single-centre retrospective study. INTERVENTION Patients underwent conformal radiotherapy. The median dose of conformal treatment was 72 Gy (65-78 Gy). MEASUREMENTS The primary outcome measure was progression-free survival (PFS) defined as no biochemical relapse (three consecutive rises in prostate-specific antigen [PSA] with a velocity >0.4 ng/ml per year or PSA >1.5 ng/ml) and no additional treatment. Predictive factors of failure were examined in univariate and multivariate analyses. Adverse events in terms of urinary and digestive toxicity, urine incontinence, and erectile dysfunction (ED) were reported. RESULTS AND LIMITATIONS The median (range) and mean (standard deviation) follow-up of the 100 patients analysed was 33 mo (5-164 mo) and 37.2 mo (23.6 mo), respectively. Eighty-three patients received SRT alone, and 17 received SRT and androgen-deprivation therapy. For the 83 patients treated with exclusive radiation therapy, PFS was 72.5% at 5 yr and 93%, 67%, and 55% for the low-, intermediate-, and high-risk groups, respectively. In the univariate analysis, PSA level prior to SRT, risk status, PSA nadir after SRT, PSA nadir after SRT >0.2 ng/ml, and time to achieve this nadir were all predictive of failure. In the multivariate analysis, PSA nadir post-SRT with a threshold at 0.2 ng/ml and time to achieve this nadir were the significant predictive factors of failure. Gastrointestinal toxicity was low; urinary toxicity grade < or =2 was 34.5%. Four were grade 3 (4.7%), one was grade 4 (1.2%), and one was grade 5 (1.2%). The incidence of severe ED (International Index of Erectile Dysfunction-5 score 5-10) was 14% pre-HIFU, and 51.9% and 82.3% pre- and post-SRT, respectively. Because our study was retrospective, results have to be interpreted cautiously. CONCLUSIONS SRT provides satisfactory oncologic control after HIFU failure with little (or mild) additional toxicity. These results warrant further investigation.

Clinical and Urodynamic Repercussions after TVT Procedure and How to Diminish Patient Complaints

OBJECTIVES Analysis of changes in voiding patterns after sub-urethral TVT procedure: urodynamic variations and clinical repercussions. METHODS 112 women included in an ethics committee protocol (CCPPRB ) with a mean follow-up of 22 months underwent complete urodynamic testing before and after TVT procedure and filled in pre- and post-operative questionnaires. RESULTS Analysis of the questionnaires showed that two clinical symptoms were predominant post-operatively: dysuria and micturitional urge. The urodynamic profiles showed that TVT banding led to infravesical obstruction but not to significant detrusor overactivity. CONCLUSION Our results show that clinical changes induced by the TVT procedure were due to infravesical obstruction, and that there was no progression of detrusor overactivity. We suggest two ways to avoid, or diminish, this post-operative obstruction, or to detect patients at risk from obstruction: training for women who use their abdominal muscles for voiding rather than their detrusor, or pre-operative screening of hypotonic bladders.

Neuromodulation sacrée avec le système InterStim™ : résultats du registre national français

AIM To analyse current practice patterns and to evaluate (long-term) effectiveness and adverse events of sacral neuromodulation with InterStim™ Therapy based on data collected in a national register and to discuss the strengths and weaknesses of the register. PATIENTS AND METHODS This is a French multicenter prospective observational trial including patients with a permanent implant (2003-2009). Voiding diary variables and patient satisfaction were analysed based on last follow-up visit since implantation. RESULTS One thousand four hundred and eighteen patients (median age: 63 years, 1206 females) were included in the database (median follow-up: 12 months). One thousand and eighty-nine patients had non-neurological disease. The principal diagnosis was overactive bladder syndrome ([OAB], n=1170) and retention (n=151). Implantation occurred in 1358 patients; 1172 patients had greater than or equal to one registered follow-up. Clinical improvement of greater than or equal to 50% was seen in 447/527 patients with OAB at 12 months follow-up (median number of voids per 24 hours decreased from 15 at baseline to 8 at 12 months) and in 42/54 of patients with retention (median number of catheterization per 24 hours dropped from 5 at baseline to 0 at 12 months). Clinical improvement remained relatively stable up to 60 months. Median patient satisfaction with treatment was between 60 and 80%. Five hundred and twenty-four patients had at least one adverse event; loss of efficacy (n=244) occurred most frequently. CONCLUSIONS In this large database sacral neuromodulation with InterStim™ Therapy seems to be an effective treatment through routine practice in the long-term (up to 60 months) for patients refractory to medical treatment.

Targeted therapies in non-muscle-invasive bladder cancer according to the signaling pathways.

With 300,000 annually new cases worldwide, urothelial-cell carcinoma of the bladder (UCCB) is the second most common urologic neoplasm after prostate carcinoma. Non-muscle-invasive bladder cancer (NMIBC), which is not immediately life-threatening, represents 70% to 80% of these initial cases. Despite optimal treatment (transurethral resection with intravesical chemo- or immunotherapy), 70% of these NMIBC will recur, and 10% to 20% will progress, highlighting the need for a new therapeutic approach. Indeed, the identification of patients at high risk of disease recurrence and progression would be beneficial in predicting which patients with NMIBC would benefit from strict follow-up and which would benefit from a more aggressive therapy. To date, conventional treatment remains disappointing in terms of oncologic results and morbidity. The growing understanding in tumor biology has enabled the signaling pathways involved in bladder tumorigenesis and progression to be identified, but few molecular targets have been available until now. The encouraging results seen in various human carcinomas suggests that these new agents should become part of the arsenal of drugs available in the treatment of NMIBC, alone or in combination with already known agents. In this article, we have tried to highlight the main molecular signaling pathways involved in NMIBC tumorigenesis and progression, and the potential targets useful for improving the treatment of NMIBC.

Real-Time Heart Rate Variability and Its Correlation with Plasma Catecholamines During Laparoscopic Adrenal Pheochromocytoma Surgery

BACKGROUND:We studied sympathovagal activity using real-time heart rate variability (HRV) and determined its relationship with plasma catecholamines to characterize short-term cardioregulatory mechanisms during laparoscopic adrenal pheochromocytoma surgery. METHODS:We recruited 20 patients with pheochromocytoma (Group P) and 20 with incidentaloma (Group I). HRV, systolic blood pressure and heart rate were continuously monitored. The low frequency and high frequency spectra denoted, respectively, sympathetic and parasympathetic activity. The low frequency/high frequency (LF/HF) ratio represented sympathovagal balance. Blood samples for epinephrine and norepinephrine assays were collected before, during, and after surgery. After log transformation of the repeated measures, a linear regression model was applied on their mean values. The correlation coefficients among variables were calculated using the Spearman rank test. RESULTS:No significant changes were observed in Group I. In Group P, epinephrine and norepinephrine increased in all patients during peritoneal insufflation and tumor resection. In 16 patients, systolic blood pressure, heart rate, low frequency, and LF/HF ratio increased concurrently. In four patients, low frequency and LF/HF ratio decreased. Three of these patients had normal systolic blood pressure and heart rate, and the fourth patient had hypotension and tachycardia. The high frequency component was enhanced in 15 patients and was stable in five. Low frequency was correlated with norepinephrine (r = 0.68, P < 0.001), systolic blood pressure (r = 0.66, P < 0.01), and heart rate (r = 0.62, P < 0.05). CONCLUSION:This study demonstrated a strong correlation between low frequency HRV, plasma norepinephrine, arterial blood pressure, and heart rate during pheochromocytoma surgery.