Maurice Stephan Michel

Can pre-operative contrast-enhanced dynamic MR imaging for prostate cancer predict microvessel density in prostatectomy specimens?

The aim of this study was to correlate quantitative dynamic contrast-enhanced MRI (DCE MRI) parameters with microvessel density (MVD) in prostate carcinoma. Twenty-eight patients with biopsy-proven prostate carcinoma were examined by endorectal MRI including multiplanar T2- and T1-weighted spin-echo and dynamic T1-weighted turbo-FLASH MRI during and after intravenous Gd-DTPA administration. Microvessels were stained on surgical specimens using a CD31 monoclonal antibody. The MVD was quantified in hot spots by counting (MVC) and determining the area fraction by morphometry (MVAF). The DCE MRI data were analyzed using an open pharmacokinetic two-compartment model. In corresponding anatomic locations the time shift (Δt) between the beginning of signal enhancement of cancer and adjacent normal prostatic tissue, the degree of contrast enhancement and the contrast exchange rate constant (k21) were calculated. The MVC and MVAF were elevated in carcinoma (p<0.001 and p=0.002, respectively) and correlated to k21 (r=0.62, p<0.001 and r=0.80, p<0.001, respectively). k21-values of carcinoma were significantly higher compared with normal peripheral but not central zone tissue. Δt was longer in high compared with low-grade tumors (p=0.025). The DCE MRI can provide important information about individual MVD in prostate cancer, which may be helpful for guiding biopsy and assessing individual prognosis.

Impact of Lymph Node Dissection on Cancer Specific Survival in Patients With Upper Tract Urothelial Carcinoma Treated With Radical Nephroureterectomy

PURPOSE We examined the impact of lymphadenectomy on the clinical outcomes of patients with upper tract urothelial cancer treated with radical nephroureterectomy. MATERIALS AND METHODS Data were collected on 1,130 consecutive patients with pT1-4 upper tract urothelial cancer treated with radical nephroureterectomy at 13 centers worldwide. Patients were grouped according to nodal status (pN0 vs pNx vs pN+). The choice to perform lymphadenectomy was determined by the treating surgeon. All pathology slides were reevaluated by dedicated genitourinary pathologists. Univariable and multivariable Cox regression models measured the association of nodal status (pN0 vs pNx vs pN+) with cancer specific survival. RESULTS Overall 412 patients (36.5%) had pN0 disease, 578 had pNx disease (51.1%) and 140 had pN+ disease (12.4%). The 5-year cancer specific survival estimate was lower in patients with pN+ compared to those with pNx disease (35% vs 69%, p <0.001), which in turn was lower than that in those with pN0 disease (69% vs 77%, p = 0.024). In the subgroup of patients with pT1 disease (345) cancer specific survival rates were not different in those with pN0 and pNx. In pT2-4 cases (813) cancer specific survival estimates were lowest in pN+, intermediate in pNx and highest in pN0 (33% vs 58% vs 70%, p = 0.017). When adjusted for the effects of standard clinicopathological features pN+ was an independent predictor of cancer specific survival (p <0.001). pNx was significantly associated with worse prognosis than pN0 in pT2-4 upper tract urothelial cancer only. CONCLUSIONS Nodal status is a significant predictor of cancer specific survival in upper tract urothelial cancer. pNx is significantly associated with a worse prognosis than pN0 in pT2-4 tumors. Patients expected to have pT2-4 disease should undergo lymphadenectomy to improve staging and thereby help guide decision making regarding adjuvant chemotherapy.

HIGH INTENSITY FOCUSED ULTRASOUND AS NONINVASIVE THERAPY FOR MULTILOCAL RENAL CELL CARCINOMA: CASE STUDY AND REVIEW OF THE LITERATURE

PURPOSE Noninvasive tumor ablation can be achieved by extracorporeally induced high intensity focused ultrasound. Clinical high intensity focused ultrasound performed to date for renal tumors have only been experimental in nature. We present specific details on a patient with renal cell carcinoma who underwent high intensity focused ultrasound with curative intent and long-term followup examinations. MATERIALS AND METHODS Ultrasound waves were generated by a cylindrical piezoelectric element focused by a paraboloid reflector. High intensity focused ultrasound was applied to 3 tumors in 3 sessions with the patient under general anesthesia or sedation analgesia, followed by magnetic resonance imaging for 6 months. RESULTS After treatment magnetic resonance imaging showed necrosis in the 2 tumors in the lower kidney pole within 17 and 48 days, respectively. The necrotic tumor area shrank thereafter within 6 months. The tumor in the upper pole was not affected by treatment due to absorption of the ultrasound energy by the interposed ribs. General anesthesia was required to apply high energy levels of focused ultrasound. Absorption of high intensity focused ultrasound in the tissue induced sharply demarcated thermonecrosis. For 50 years patients have been treated with high intensity focused ultrasound for different indications, focusing on the brain, eyes, prostate, liver and bladder. For the kidney experimental but only few clinical studies indicate sufficient tissue ablation. CONCLUSIONS In our case contactless noninvasive application of high intensity focused ultrasound to 2 renal carcinomas achieved thermal ablation. When high intensity focused ultrasound energy was coupled correctly, no lesions occurred outside of the target area. Successful high intensity focused ultrasound application depended on optimum energy coupling, a sufficiently high ultrasound energy level and general anesthesia.

Increase of AKT/PKB expression correlates with gleason pattern in human prostate cancer

AKT/PKB is a central signaling molecule related to stimulation of cell proliferation and inhibition of apoptosis. Perturbations of AKT expression and function play an important role in tumor development and progression. We wanted to determine (a) whether AKT is overexpressed in human prostatic tumors, (b) whether AKT expression is correlated with tumor grade, and (c) whether AKT expression correlates with clinicopathological parameters. AKT expression was investigated by immunohistochemistry in sections from 56 paraffin‐embedded prostate specimens displaying benign prostatic tissue (BPT), prostatic intraepithelial neoplasia (PIN), and primary tumors graded 2–5 according to Gleason. The staining intensity for AKT was significantly more pronounced in tumors compared to BPT, with PIN ranging between BPT and carcinomas. Similarly, the fraction of AKT‐positive cells was higher in tumors than in BPT. A score of AKT expression (calculated as product from intensity and fraction of positive cells) ranging from 0–6 was also significantly higher in tumors than in BPT. Furthermore, the intensity of AKT expression in tumors showed a positive correlation with high preoperative serum levels of prostate specific antigen (PSA ≥ 10 ng/ml, p = 0.0325). These data show that AKT is upregulated in prostate cancer and that expression is correlated with tumor progression.

Cystinuria in childhood and adolescence: recommendations for diagnosis, treatment, and follow-up

Cystinuria, an autosomal-recessive disorder of a renal tubular amino acid transporter, is the cause of about 10% of all kidney stones observed in children. Different genetic characteristics are not represented by different phenotypes. The stones are formed of cystine, which is relatively insoluble at the physiological pH of urine. Without any preventive measures, the patients will suffer from recurrent stone formation throughout their life. Even with medical management, long-term outcome is poor due to insufficient efficacy and low patient compliance. Many patients suffer from renal insufficiency as a result of recurrent stone formation and repeated interventions. However, regular follow-up and optimal pharmacotherapy significantly increase stone-free intervals. Medical management is mainly based on hyperhydration and urine alkalinization. Sulfhydryl agents such as tiopronin can be added. Recurrent stone formation necessitates repeated urological interventions. These mostly minimally invasive procedures carry the risk of impairment of renal function. In adults, extracorporeal shockwave lithotripsy (SWL) as well as intracorporeal lithotripsy is often unsuccessful. However, in children SWL shows excellent results for cystine stones. In cases with large stone burden, percutaneous nephrolithotripsy (PNL) or even open surgical nephrolithotomy are preferred. This review discusses the underlying pathogenetic mechanisms and provides guidance for the diagnosis, therapy, and management of cystinuria following the recommendations of the International Cystinuria Consortium and the European Association of Urology.

Do Patients Benefit from Miniaturized Tubeless Percutaneous Nephrolithotomy? A Comparative Prospective Study

BACKGROUND AND PURPOSE A benefit of miniaturized percutaneous nephrolithotomy (MPCNL) compared with conventional percutaneous nephrolithotomy (PCNL) has not been demonstrated as yet. Thus, the aim of this study was to evaluate the outcome of conventional vs MPCNL and to determine if MPCNL offers an advantage for the patient. PATIENTS AND METHODS A prospective, nonrandomized series of 50 consecutive patients with solitary calculi (lower pole or the renal pelvis) were treated either by conventional PCNL (26F) or MPCNL (18F). Ultrasound or holmium laser were used for lithotripsy. Patients were treated tubeless after uncomplicated MPCNL, with thrombin-matrix tract closure and antegrade Double-J catheter placement. After PCNL, all patients received 22F nephrostomies. Demographic data, stone characteristics, perioperative course, and complication rates were assessed. RESULTS Patients characteristics were comparable in both groups, except for stone size, which was 18 +/- 8 mm (MPCNL) and 23 +/- 9 (PCNL; P = 0.042). Operative time was comparable in both groups (48 +/- 17 vs 57 +/- 22 min, not significant [NS]). After MPCNL, 96% were stone free at day 1 vs 92% after PCNL (NS). Significant complications did not occur in both groups. Minor complications were: Fever, 12% (MPCNL) vs 20% (PCNL; NS); bleeding, 4% vs 8%; perforations, 0% vs 4% (all NS). Overall outcome was not influenced by body mass index. Calcium oxalate stones were predominant with 75%. Patients after tubeless MPCNL had less pain (visual analogue score, 3 +/- 3 vs 4 +/- 3; P = 0.048.) and needed slightly less additional pain medication (25 +/- 12 mg/d vs 37 +/- 10 mg/d piritramid; NS). Hospital stay was significantly shorter after MPCNL (3.8 +/- 28 vs 6.9 +/- 3.5 d; P = 0.021.). CONCLUSIONS Both techniques were safe and effective for the management of renal calculi. While stone-free rates were comparable in our series, MPCNL showed advantages in terms of shorter hospital stay and postoperative pain. The lower stone burden and the tubeless fashion of MPCNL, however, might have influenced these results.

Risk stratification of patients with nodal involvement in upper tract urothelial carcinoma: value of lymph-node density

To determine the risk factors associated with clinical outcome in patients with lymph node (LN)‐positive urothelial carcinoma of the upper urinary tract (UTUC) treated with radical nephroureterectomy (RNU) and lymphadenectomy, focusing on the concept of LN density (LND).

Systematic Evaluation of a Recently Introduced 2-μm Continuous-Wave Thulium Laser for Vaporesection of the Prostate

BACKGROUND AND PURPOSE A novel 2-microm continuous wave (CW) thulium laser device for interventional treatment of benign prostatic hyperplasia was recently introduced into clinical practice and is postulated to have several advantages over more established laser devices. A systematic ex-vivo evaluation of the thulium laser was undertaken to compare the results to transurethral resection of the prostate (TURP) and the potassium-titanyl-phosphate (KTP) laser as reference standard methods. MATERIALS AND METHODS The RevoLix CW thulium laser system was evaluated in the well-established model of the isolated blood-perfused porcine kidney to determine its tissue ablation capacity and hemostatic properties at different power settings. Histologic examination of the ablated tissue followed. The results were compared to the reference standards, TURP and 80-W KTP laser. RESULTS At a power setting of 70 W, the CW thulium laser displays a higher tissue ablation rate, reaching 6.56+/-0.69 g after 10 minutes, compared to the 80 W KTP laser (3.99+/-0.48 g; P<0.05). Only 30 seconds were needed to resect tissue with the same surface area using TURP, resulting in 8.28+/-0.38 g of tissue removal. With a bleeding rate of 0.16+/-0.07 g/min, the CW thulium laser offers hemostatic properties equal to those of the KTP laser (0.21+/-0.07 g/min), and a significantly reduced bleeding rate compared to TURP (20.14+/-2.03 g/min; P<0.05). The corresponding depths of the coagulation zones were 264.7+/-41.3 microm for the CW thulium laser, 666.9+/-64.0 microm for the KTP laser (P<0.05), and 287.1+/-27.5 microm for TURP. CONCLUSION In this standardized ex-vivo investigation, the 2-microm CW thulium laser offered a higher tissue ablation capacity and similar hemostatic properties as those of the KTP laser, and in comparison to TURP both tissue ablation and the bleeding rate were significantly reduced.

Reduction of PTEN and p27kip1 expression correlates with tumor grade in prostate cancer. Analysis in radical prostatectomy specimens and needle biopsies

The extreme variability of prostate cancer implies latent disease with missing clinical symptoms in some cases. Tumor suppressors PTEN (phosphatase and tensin homolog deleted on chromosome ten) and p27kip1 are frequently mutated in various human cancers. PTEN negatively influences cell growth and induces apoptosis, while p27kip1 binds to cyclin-E-Cdk2 and counteracts mitosis. This study investigated the expression of PTEN and p27kip1 in prostatectomies and needle biopsies in order to determine whether protein localization or expression levels are correlated with tumor grade and whether PTEN and p27kip1 expression in biopsies are valuable predictive tumor markers. Analysis of PTEN demonstrated that weak expression levels were significantly more prevalent in high-grade tumors. Analysis of p27kip1 revealed that high-grade tumors had a higher percentage of cytoplasmic localization of the protein than low-grade tumors, where nuclear localization was more frequent. Furthermore, this study indicated a positive association between PTEN and p27kip1 levels. An increase of high-grade tumors corresponded to a progressive loss of both tumor suppressors in needle biopsies and prostatectomies. p27kip1 and PTEN did not show a higher predictive accuracy of the tumor grade in the surgical specimen than the Gleason score. However, p27kip1 had the same predictive value as the Gleason score in needle biopsies.

Validation of computer-based training in ureterorenoscopy

To evaluate the outcome of training both urological novices and experts, using the recently developed UroMentor (Simbionix Ltd, Israel) trainer, that provides a realistic simulation of rigid and flexible ureterorenoscopy (URS).