Thierry Roumeguere

Extraperitoneal laparoscopic radical prostatectomy. Results after 50 cases.

INTRODUCTION After an initial experience using transperitoneal laparoscopic radical prostatectomy as described by Vallancien and Guillonneau, we developed a pure extraperitoneal approach. This approach seems more comparable to the open technique and avoid potential risks of specific complications due to the transperitoneal approach. We evaluated the perioperative parameters (blood loss, operating time, transfusion rate) and postoperative results (oncological results, continence and potency) after our first 50 cases. MATERIAL AND METHOD Between September 1999 and September 2000, we performed 50 laparoscopic radical prostatectomy. On average, patients were 63.3 years old (range 47-71), had preoperative mean PSA values of 9.14 ng/ml (1.1-23). Median Gleason score was 6 (4-10) with 2.5 (1-6) positive biopsies for a mean prostate volume of 40 cm(3) (17.5-95.0). Clinical stage was T1, T2a, T2b and T3 in 46.3, 41.5, 9.8 and 2.4% of the cases, respectively. We used a pure extraperitoneal approach and we performed a descending technique starting with the dissection at the bladder neck. The seminal vesicles dissection is comparable to the open approach. RESULTS 42 extraperitoneal and 8 transperitoneal procedures were performed (2 in the initial experience, 3 because of previous abdominal surgery and 3 because of incidental peritoneal opening). Mean operative time was 317 min, mean blood loss 680 cm(3), transfusion rate of 13%. 1 patient/50 was converted to an open procedure. Pathological stage was pT1a, pT2a, pT2b, pT2c, pT3a and pT3b in 2.2, 8.5, 42.5, 2.2, 34 and 10.6% of cases, respectively. Positive surgical margins were observed in 22% of cases. The potency rate after neurovascular bilateral bundle preservation was 43% at 3 months (n = 7) and 67% at 6 months and (n = 6) without any further treatment. The continence rate (no pad) was 39% at 3 months and 85% at 6 months. Detectable postoperative PSA at 3 month was observed in 2 patients only. Two major complications occurred: one acute transient renal failure one uretrorectal fistula at day 20. CONCLUSIONS The extraperitoneal laparoscopic radical prostatectomy results seem comparable to transperitoneal laparoscopic radical prostatectomy or open surgery. This approach is reproducible and seems to avoid the potential risks of intraperitoneal injury. Long-term follow up and comparative series are however necessary to further evaluate these new techniques.

Erectile Dysfunction Is Associated with a High Prevalence of Hyperlipidemia and Coronary Heart Disease Risk

OBJECTIVES Erectile dysfunction (ED) is frequently of vascular origin. An association between ED and ischemic heart disease has been suggested as a consequence of endothelial disease of penile and coronary arteries. The role of serum lipid levels has been demonstrated in coronary heart disease (CHD), but the relationship with ED is poorly documented. We evaluated undiagnosed hyperlipidemia in ED patients and their coronary heart disease risk. METHODS We prospectively compared a group of patients with ED to matched non-ED patients. Risk factors for ED and CHD were noticed and a serum lipid work up (total cholesterol [TC], triglycerides [TG], HDL-cholesterol [HDL-C], LDL-cholesterol [LDL-C] and TC/HDL-C ratio) was measured. We compared the prevalence of hyperlipidemia in the two groups and its impact as predictor of ED. We calculated the risk to develop CHD in patients with or without ED based upon commonly accepted variables of the Framingham Heart study. RESULTS 215 patients had ED (mean age 57.6+/-9.6 years) and 100 no ED (mean age 59.7+/-8.3 years). The prevalence of hypercholesterolemia (TC >200 mg/dl or 5.17 mmol/l) was 70.6% vs. 52% in ED and non-ED groups respectively (p=0.06). After exclusion of confounding factors, logistic regression analyses showed HDL-C and TC/HDL-C ratio as significant predictors of ED (p=0.011 and 0.000 respectively). Increased 10-year CHD risk was found in 56.6% in the ED group compared to 32.6% in the control group (p<0.05). The median risk was 12.18% vs. 9.07% respectively with a significant age-related risk (p<001). CONCLUSIONS Hyperlipidemia is common in ED patients. HDL-C and TC/HDL-C ratio are predictors of ED. These patients have a high risk of later developing CHD. Erectile dysfunction might therefore serve as sentinel event for coronary heart disease.

Late Onset of Bladder Urothelial Carcinoma After Kidney Transplantation for End-Stage Aristolochic Acid Nephropathy: A Case Series With 15-Year Follow-up

BACKGROUND Aristolochic acids are nephrotoxins and predispose to upper-tract urothelial carcinoma. The risk of bladder urothelial carcinoma after kidney transplantation and its relationship to upper-tract urothelial carcinoma is not well defined. STUDY DESIGN Case series. SETTING & PARTICIPANTS Single-center cohort of 38 women given kidney transplants for end-stage aristolochic acid nephropathy. OUTCOMES & MEASUREMENTS The prevalence of upper urinary tract urothelial carcinoma was determined by collecting pathological results of specimens obtained by means of bilateral ureteronephrectomy. We also established the cumulative incidence of bladder urothelial carcinoma in biopsies performed during prospective screening cystoscopies during a 15-year follow-up. RESULTS Upper-tract urothelial carcinoma was found in 17 patients with aristolochic acid nephropathy (44.7%). During follow-up, bladder urothelial carcinoma was diagnosed in 15 patients 68 to 169 months after cessation of aristolochic acid exposure (39.5%): 8 urothelial carcinoma in situ, 4 noninvasive low-grade papillary urothelial carcinoma, and 3 infiltrating urothelial carcinoma. 12 of 17 patients (71%) with a history of upper-tract urothelial carcinoma developed bladder urothelial carcinoma during follow-up, whereas this occurred in only 3 of 21 patients (14%) without upper-tract urothelial carcinoma (P < 0.01). Despite local and/or systemic chemotherapy, 3 patients died and 2 radical cystectomies were performed. LIMITATIONS Small sample size of this case series. CONCLUSIONS Upper-tract and bladder urothelial carcinoma are dramatic complications in kidney transplant recipients with aristolochic acid nephropathy, confirming the carcinogenic properties of aristolochic acids. We identified upper-tract urothelial carcinoma as a potent risk factor for the subsequent development of bladder urothelial carcinoma after kidney transplantation for aristolochic acid nephropathy. Because this complication may occur years after aristolochic acid discontinuation, we suggest regular cystoscopies in addition to the bilateral ureteronephrectomy in kidney transplant recipients with aristolochic acid nephropathy.

Is One Set of Sextant Biopsies Enough to Rule Out Prostate Cancer? Influence of Transition and Total Prostate Volumes on Prostate Cancer Yield

Purpose: Although the sextant biopsy technique has been widely used, concern has arisen that this method may not include an adequate sampling of the prostate, especially for large prostate volumes. We conducted a multicenter study in patients with PSA levels <10 ng/ml to determine the influence of the total and transition zone (TZ) volumes of the prostate for predicting whether one single set of biopsies was sufficient to rule out prostate cancer (PCa). These parameters were evaluated in patients in whom PCa was found after one set of systematic sextant biopsies and those in whom PCa was found after a repeat biopsy.Materials and Methods: A total of 1,018 patients were included in this study. All underwent transrectal ultrasound–guided needle sextant and two TZ biopsies of the prostate. Total and TZ volumes of the prostate were measured (prolate ellipsoid method). From this cohort, all patients in whom a benign disease was found after the first set of biopsies underwent a second similar set of biopsies within 6 weeks. Only patients with PCa were included in this study, whether diagnosed on first or repeat biopsy. Uni– and multivariate statistical analysis using the SAS system (Cary, N.C., USA) and ROC curves were used to compare patients in whom the diagnosis was performed after the first set of biopsies and those who required a second set. Results: Of the 1,018 patients, 344 (33.8%) had PCa diagnosed, 285 (28%) after the first set of biopsies, and 59 (8.1%) on repeat biopsy. As compared to patients diagnosed with PCa after the first set of biopsies, patients diagnosed after the second set had larger total prostate and TZ volumes (43.1±13.0 vs. 32.5±10.6 cm3, p<0.0001 and 20.5±8.3 vs. 12.8±6.0 cm3, p<0.0001). ROC curves showed that total and TZ volumes of 45 and 22.5 cm3, respectively, provided the best combination of sensitivity and specificity for discriminating between patients diagnosed with PCa after the first from those diagnosed after a second set. Conclusion: In patients with total prostate volume >45 cm3 and TZ >22.5 cm3, a single set of sextant biopsies may not be sufficient to rule out PCa. In these patients, a repeat biopsy should be considered in case of a negative first biopsy.

Laparoscopic radical prostatectomy: The learning curve

Purpose of review Laparoscopic radical prostatectomy is now an accepted treatment option for the management of localized prostate cancer. Numerous studies have demonstrated the feasibility and the reproducibility of this procedure. Expert teams in high-volume centres routinely carry out laparoscopic radical prostatectomy but for the novice the obstacle to success is how to learn and gain proficiency in this procedure. In this review, we will present our views on how this can be done. Recent findings A learning curve includes the necessity for continuous self-evaluation in terms of cancer control, continence and potency. Many different methods can be used to acquire the technique: dry lab, animal live lab, cadaveric laparoscopic dissection or mentoring with an expert. All of these steps may not be essential as laparoscopic radical prostatectomy is not too dissimilar to open prostatectomy. However, one must understand that the physiological consequences of anaesthesia during laparoscopy and basic laparoscopic suturing technique should be perfected prior to taking on laparoscopic radical prostatectomy. The training then must continue under the supervision of a mentor. The opportunity for discussion with an expert allows the novice to learn the pitfalls and the tips and tricks of laparoscopic radical prostatectomy, thus reducing the length of the learning curve and negating the need to reinvent the wheel. Summary Laparoscopic radical prostatectomy is similar to any other new surgical procedure and as with open surgery we learn and gain experience with each procedure; the learning curve is never completely finished.

Low-Density Lipoprotein Modified by Myeloperoxidase in Inflammatory Pathways and Clinical Studies

Oxidation of low-density lipoprotein (LDL) has a key role in atherogenesis. Among the different models of oxidation that have been studied, the one using myeloperoxidase (MPO) is thought to be more physiopathologically relevant. Apolipoprotein B-100 is the unique protein of LDL and is the major target of MPO. Furthermore, MPO rapidly adsorbs at the surface of LDL, promoting oxidation of amino acid residues and formation of oxidized lipoproteins that are commonly named Mox-LDL. The latter is not recognized by the LDL receptor and is accumulated by macrophages. In the context of atherogenesis, Mox-LDL accumulates in macrophages leading to foam cell formation. Furthermore, Mox-LDL seems to have specific effects and triggers inflammation. Indeed, those oxidized lipoproteins activate endothelial cells and monocytes/macrophages and induce proinflammatory molecules such as TNFα and IL-8. Mox-LDL may also inhibit fibrinolysis mediated via endothelial cells and consecutively increase the risk of thrombus formation. Finally, Mox-LDL has been involved in the physiopathology of several diseases linked to atherosclerosis such as kidney failure and consequent hemodialysis therapy, erectile dysfunction, and sleep restriction. All these issues show that the investigations of MPO-dependent LDL oxidation are of importance to better understand the inflammatory context of atherosclerosis.

The importance of measuring the prostatic transition zone: an anatomical and radiological study.

 To assess the accuracy and reliability of measurements of the volume of the transition zone (TZ, representing the hypertrophied benign component) and whole prostate by TRUS in patients with BPH or cancer, by comparing the radiological with pathological findings after surgery.

Silodosin in the treatment of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS) are highly prevalent in older men. Medical therapy is the first-line treatment for LUTS due to BPH. Alpha-adrenergic receptor blockers remain one of the mainstays in the treatment of male LUTS and clinical BPH. They exhibit early onset of efficacy with regard to both symptoms and flow rate improvement, and this is clearly demonstrated in placebo-controlled trials with extensions out to five years. These agents have been shown to prevent symptomatic progression of the disease. The aim of this article is to offer a critical review of the current literature on silodosin, formerly known as KMD-3213, a novel alpha-blocker with unprecedented selectivity for α1A-adrenergic receptors, as compared with both α1B- and α1D -adrenoceptors, exceeding the selectivity of all currently used α1-blockers, and with clinically promising effects.

Effects of Phosphodiesterase Inhibitors on the Inflammatory Response of Endothelial Cells Stimulated by Myeloperoxidase-Modified Low-Density Lipoprotein or Tumor Necrosis Factor Alpha

BACKGROUND Sildenafil, vardenafil, and tadalafil are phosphodiesterase type 5 inhibitors (PDE5-Is) usually used in the treatment of erectile dysfunction (ED). Previously, we have shown the presence of myeloperoxidase-modified low-density lipoprotein (Mox-LDL) in the penises of patients with ED, and we have shown the impact of Mox-LDL on cyclic monophosphate (cGMP) level. In vitro, Mox-LDL triggered the inflammatory response by increasing the release of both interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-alpha) by endothelial cells (ECs) and monocytes respectively. OBJECTIVE To determine whether or not the three therapeutically PDE5-Is protect against the proinflammatory effects of Mox-LDL or TNF-alpha on ECs. DESIGN, SETTING, AND PARTICIPANTS ECs (EA.hy926) were incubated in the presence of either TNF-alpha (100 pg/ml) or Mox-LDL (200 microg/ml) with each of the three PDE5-Is (1 microM, 5 microM, and 10 microM) respectively. IL-8 production was measured in the supernatant after 48 h of incubation. MEASUREMENTS All experiments were repeated at least three times. Statistical analysis was performed with an ANOVA. RESULTS AND LIMITATIONS Two-way ANOVA analysis showed that TNF-alpha alone (p<0.001) or Mox-LDL alone (p<0.001) increased IL-8 production. Sildenafil, vardenafil, or tadalafil alone did not generate an increase of IL-8 production. Tadalafil in combination with Mox-LDL and TNF-alpha showed a decrease of IL-8 (p<0.05) compared with sildenafil and vardenafil. CONCLUSIONS Among the three available PDE5-Is, tadalafil showed an additional potentially anti-inflammatory effect on relaxation. Those data could be considered for the chronic use of PDE5-Is, but extrapolations of experimental evidence to the clinical setting should be made cautiously.

Current management of erectile dysfunction after cancer treatment

Purpose of review Erectile dysfunction has a major impact on quality of life. Treating sexual dysfunction after cancer treatment requires special concern because of specific medical, psychological and social factors. This article presents the relevant experimental and clinical recent literature on rehabilitation of erectile function after surgery, external beam radiotherapy, brachytherapy or hormonal deprivation therapy for prostate cancer as it is the most studied model for erectile dysfunction management. Recent findings Counseling and reeducation with a multidisciplinary approach seems to be both mandatory and effective in achieving erectile function recovery. Administration of proerectile drugs nightly or on-demand early after cancer treatment is probably the key factor of erectile rehabilitation. Several studies have highlighted the presumption of a potential role for phosphodiesterase type 5 inhibitors (PDE5-Is) in the prevention of endothelial damage related to ischemia-reperfusion and denervation following surgery or pelvic radiation. Larger multicancer, randomized, controlled trials are needed to assess the role of PDE5-Is in erectile dysfunction pharmacological prophylaxis and rehabilitation strategy. Summary Erectile dysfunction postcancer treatment requires multimodal management with early administration of PDE5-Is, combined therapy to maintain erectile tissue oxygenation if necessary with PDE5-Is, intracavernosal injection and transurethral alprostadil or even vacuum erect device, psychological counseling considering erectile dysfunction as a couples issue. The best modality to optimize postcancer erectile dysfunction management has not yet been standardized and is still challenging.