Charles Van Praet

Sacral Neuromodulation with an Implantable Pulse Generator in Children with Lower Urinary Tract Symptoms: 15-Year Experience

PURPOSE Sacral nerve modulation with an implantable pulse generator is not an established treatment in children. This therapy has been described for dysfunctional elimination syndrome and neurogenic bladder. We report 2 new indications for this approach in children, ie bladder overactivity and Fowler syndrome. The aim of this study was to improve the results of future treatment for sacral neuromodulation in children by describing factors favorable for good outcomes with this method. MATERIALS AND METHODS A total of 18 children 9 to 17 years old were studied. Mean ± SD followup was 28.8 ± 43.8 months. Of the patients 16 underwent S3 sacral neuromodulation and 7 underwent pudendal stimulation (5 as a revision, 2 from the beginning). RESULTS Initial full response was achieved in 9 of 18 patients (50%) and partial response in 5 (28%). In patients presenting with incontinence mean ± SD number of incontinence episodes weekly improved significantly from 23.2 ± 12.4 to 1.3 ± 2.63 (p <0.05). In patients requiring clean intermittent catheterization there was a significant decrease in mean ± SD daily frequency of catheterization from 5.2 ± 1.6 to 2.0 ± 1.9 (p <0.05). At the end of the study 6 of 15 patients (40%) had a full response and 5 (33%) had a partial response, while 4 implantable pulse generator devices (27%) were explanted because of failure. CONCLUSIONS Sacral neuromodulation is feasible in the pediatric population, with good short-term (78% full or partial response) and satisfactory long-term results (73%). Sacral neuromodulation can offer good results for overactive bladder, dysfunctional elimination syndrome and Fowler syndrome. Pudendal nerve stimulation is a feasible salvage treatment that can be useful in cases when S3 implantation is impossible or unsuccessful.

Hypofractionated intensity-modulated arc therapy for lymph node metastasized prostate cancer: Early late toxicity and 3-year clinical outcome

BACKGROUND AND PURPOSE For patients with N1 prostate cancer (PCa) aggressive local therapies can be advocated. We evaluated clinical outcome, gastro-intestinal (GI) and genito-urinary (GU) toxicity after intensity modulated arc radiotherapy (IMAT)+androgen deprivation (AD) for N1 PCa. MATERIAL AND METHODS Eighty patients with T1-4N1M0 PCa were treated with IMAT and 2-3years of AD. A median dose of 69.3Gy (normalized isoeffective dose at 2Gy per fraction: 80Gy [α/β=3]) was prescribed in 25 fractions to the prostate. The pelvic lymph nodes received a minimal dose of 45Gy. A simultaneous integrated boost to 72Gy and 65Gy was delivered to the intraprostatic lesion and/or pathologically enlarged lymph nodes, respectively. GI and GU toxicity was scored using the RTOG/RILIT and RTOG-SOMA/LENT-CTC toxicity scoring system respectively. Three-year actuarial risk of grade 2 and 3/4 GI-GU toxicity and biochemical and clinical relapse free survival (bRFS and cRFS) were calculated with Kaplan-Meier statistics. RESULTS Median follow-up was 36months. Three-year actuarial risk for late grade 3 and 2 GI toxicity is 8% and 20%, respectively. Three-year actuarial risk for late grade 3-4 and 2 GU toxicity was 6% and 34%, respectively. Actuarial 3-year bRFS and cRFS was 81% and 89%, respectively. Actuarial 3-year bRFS and cRFS was, respectively 26% and 32% lower for patients with cN1 disease when compared to patients with cN0 disease. CONCLUSION IMAT for N1 PCa offers good clinical outcome with moderate toxicity. Patients with cN1 disease have poorer outcome.

Battling resistance mechanisms in antihormonal prostate cancer treatment: Novel agents and combinations

Prostate cancer (PCa) is a hormone-sensitive disease. Androgen deprivation therapy lowers serum testosterone levels (castration) or blocks the androgen receptor (AR) ligand-binding domain. Especially in metastatic disease, hormonal therapy has been able to delay disease progression, reduce symptoms, and improve overall survival. Despite subsequent disease progression and development of castration resistance, PCa remains AR driven. Secondary hormonal treatments such as abiraterone acetate or enzalutamide have demonstrated increased overall survival. However, new resistance mechanisms to these agents have been identified, and systemic chemotherapy is still needed especially in fast-progressing castration-resistant PCa. Several promising androgen synthesis inhibitors (orteronel and galeterone), AR inhibitors (ARN-509, EPI-001, AZD3514, and ODM-201), and heat shock protein modulators (AT11387, 17-DMAG, STA-9090, and OGX-427) are currently under investigation. The wide variety in upcoming systemic agents underlines the molecular heterogeneity of castration-resistant PCa. This article reviews antihormonal therapy in PCa and resistance mechanisms and focuses on novel and upcoming agents currently in clinical testing.

Urinary prostate protein glycosylation profiling as a diagnostic biomarker for prostate cancer

Serum prostate‐specific antigen (sPSA) measurement is widely used as opportunistic screening tool for prostate cancer (PCa). sPSA suffers from considerable sensitivity and specificity problems, particularly in the diagnostic gray zone (sPSA 4–10 µg/L). Furthermore, sPSA is not able to discriminate between poorly‐, moderately‐, and well‐differentiated PCa. We investigated prostatic protein glycosylation profiles as a potential PCa biomarker.

Capillary electrophoresis of urinary prostate glycoproteins assists in the diagnosis of prostate cancer.

Prostate marker assays are widely used for detection of prostate cancer (PCa) but are associated with considerable sensitivity and specificity problems. Therefore, we investigated prostatic protein glycosylation profiles as a potential biomarker. We determined the urinary asparagine‐linked glycan (N‐glycan) profile of prostatic proteins of healthy volunteers (n = 25), patients with benign prostate hyperplasia (BPH; n = 62) and newly diagnosed PCa patients (n = 42) using DNA‐sequencer‐assisted fluorophore‐assisted carbohydrate electrophoresis. Through squeezing of the prostate, a sufficient amount of prostatic proteins was obtained for direct structural analyses of N‐glycan structures. N‐glycans of PCa compared to BPH were characterized by a significant decrease in triantennary structures (p = 0.047) and overall fucosylation (p = 0.026). Prostate‐specific antigen (PSA) and the urinary glycoprofile marker showed comparable overall receiver operating characteristic curve analysis as well as in the diagnostic gray zone with serum PSA values between 4 and 10 μg/L. However, when combining PSA and the urinary glycoprofile marker, the latter gave an additive diagnostic value to serum PSA (p ≤ 0.001). In conclusion, N‐glycosylation profiling demonstrated differences between BPH and PCa. These changes could lead to the discovery of a new biomarker for PCa.

Grade of hypospadias is the only factor predicting for re-intervention after primary hypospadias repair: A multivariate analysis from a cohort of 474 patients

BACKGROUND There is an ongoing quest on how to minimize complications in hypospadias surgery. There is however a lack of high-quality data on the following parameters that might influence the outcome of primary hypospadias repair: age at initial surgery, the type of suture material, the initial technique, and the type of hypospadias. OBJECTIVES The objective of this study was to identify independent predictors for re-intervention in primary hypospadias repair. STUDY DESIGN We retrospectively analyzed our database of 474 children undergoing primary hypospadias surgery. Univariate and multivariate logistic regression was performed to identify variables associated with re-intervention. A p-value <0.05 was considered statistically significant and therefore considered as a prognostic factor for re-intervention. RESULTS Distal penile hypospadias was reported in 77.2% (n = 366), midpenile in 11.4% (n = 54) and proximal in 11.4% (n = 54) of children. Initial repair was based on an incised plate technique in 39.9% (n = 189), meatal advancement in 36.0% (n = 171), an onlay flap in 17.3% (n = 82) and other or combined techniques in 5.3% (n = 25). In 114 patients (24.1%) re-intervention was required (n = 114) of which 54 re-interventions (47.4%) were performed within the first year post-surgery, 17 (14.9%) in the second year and 43 (37.7%) later than 2 years after initial surgery. The reason for the first re-intervention was fistula in 52 patients (46.4%), meatal stenosis in 32 (28.6%), cosmesis in 35 (31.3%) and other in 14 (12.5%). The median time for re-intervention was 14 months after surgery [range 0-114]. Significant predictors for re-intervention on univariate logistic regression (polyglactin suture material versus poliglecaprone, proximal hypospadias, lower age at operation and other than meatal advancement repair) were put in a multivariate logistic regression model. Of all significant variables, only proximal hypospadias remained an independent predictor for re-intervention (OR 3.27; p = 0.012). DISCUSSION The grade of hypospadias remains according to our retrospective analysis the only objective independent predicting factor for re-intervention in hypospadias surgery. This finding is rather obvious for everyone operating hypospadias. Curiously midpenile hypospadias cases were doing slightly better than distal hypospadias in terms of re-intervention rates. Our study however has also some shortcomings. First of all, data was gathered retrospectively and follow-up time was ill-balanced for several variables. We tried to correct this by applying sensitivity analysis, but possible associations between some variables and re-intervention might still be obscured by this. Standard questionnaires to analyze surgical outcome were not available. Therefore, we focused our analysis on re-intervention rate as this is a hard and clinically relevant end point. CONCLUSIONS This retrospective analysis of a large hypospadias database with long-term follow-up indicates that the long-lasting debate about factors influencing the reoperation rate in hypospadias surgery might be futile: in experienced hands, the only variable that independently predicts for re-intervention is the severity of hypospadias, the only factor we cannot modify. This retrospective multivariate analysis of a large hypospadias database with long-term follow-up suggests that the only significant independent predictive factor for re-intervention is proximal hypospadias. In our series, technique did not influence the re-intervention rate.

Postoperative high-dose pelvic radiotherapy for N+ prostate cancer: Toxicity and matched case comparison with postoperative prostate bed-only radiotherapy

PURPOSE To report on toxicity of postoperative high-dose whole-pelvis radiotherapy (WPRT) with androgen deprivation therapy for lymph node metastasized (N1) prostate cancer (PC). To perform a matched-case analysis to compare this toxicity profile to postoperative prostate bed-only radiotherapy (PBRT). MATERIALS AND METHODS Forty-eight N1-PC patients were referred for WPRT and 239 node-negative patients for PBRT. Patients were matched 1:1 according to pre-treatment demographics, symptoms, treatment and tumor characteristics. Mean dose to the prostate bed was 75Gy (WPRT-PBRT) and 54Gy to the elective nodes (WPRT) in 36 or 37 fractions. End points are genito-urinary (GU) and gastro-intestinal (GI) toxicity. RESULTS After WPRT, 35% developed grade 2 (G2) and 4% G3 acute GU toxicity. Acute GI toxicity developed in 42% (G2). Late GU toxicity developed in 36% (G2) and 7% (G3). One patient had G4 incontinence. Recuperation occurred in 59%. Late GI toxicity developed in 25% (G2) with 100% recuperation. Incidence of acute and late GI toxicity was higher following WPRT compared to PBRT (p⩽0.041). GU toxicity was similar. With WPRT mean dose to bladder and rectosigmoid were higher. CONCLUSIONS Postoperative high-dose WPRT comes at the cost of a temporary increase in G2. GI toxicity compared to PBRT because larger volumes of rectosigmoid are irradiated.

Agreement of Gleason Score on Prostate Biopsy and Radical Prostatectomy Specimen: Is There Improvement With Increased Number of Biopsy Cylinders and the 2005 Revised Gleason Scoring?

INTRODUCTION The objectives of this study were to assess the agreement of GS on biopsy compared with RP specimens and to assess whether an increased number of biopsy cylinders and the 2005 International Society of Urological Pathology (ISUP) GS modification improved this agreement. MATERIALS AND METHODS Pathological data of biopsy and RP specimens were analyzed in 328 consecutive patients, before (group 1; n = 135) and after (group 2; n = 193) implementation of the 2005 ISUP modification. Additionally, patients had more biopsy cylinders taken in group 2 (mean 10 vs. 6.9). The agreement of GS between biopsy and RP specimens was evaluated using the kappa coefficient. GS was pooled into 3 grades: low- (GS ≤ 6), intermediate- (GS = 7), and high-grade (GS ≥ 8) prostate cancer. RESULTS Kappa coefficient for GS in group 1 and 2 was 0.261 and 0.341, respectively. For tumor grade, this was 0.308 and 0.359 for group 1 and 2, respectively. For RP specimens, there was more agreement between biopsy and RP GS in group 2 compared with group 1 (53.9% vs. 37.8%). Upgrading was almost exclusively (89.5%) seen in patients with biopsy GS ≤ 6 and was lower in group 2 (25.4% vs. 48.1%) because of classification of more intermediate- and high-grade tumors using the 2005 ISUP modification. Taking > 6 biopsy cylinders was associated with better GS and tumor grade agreement. CONCLUSION Extended biopsy template and the 2005 ISUP modification resulted in an improved agreement between biopsy GS and RP GS and a shift toward more aggressive tumors.

Contemporary minimally-invasive extended pelvic lymph node dissection for prostate cancer before curative radiotherapy: Prospective standardized analysis of complications

To prospectively assess contemporary complication rates of minimally‐invasive staging pelvic lymph node dissection before curative radiotherapy for prostate cancer using a standardized classification.

Prostate magnetic resonance spectroscopic imaging at 1.5 tesla with endorectal coil versus 3.0 tesla without endorectal coil: comparison of spectral quality

OBJECTIVES To compare the spectral quality of prostate magnetic resonance spectroscopic imaging (MRSI) at 1.5Tesla with endorectal coil (ER-1.5T) to MRSI at 3.0Tesla without coil (3.0T). METHODS In 30 patients, the spectral quality of 6107 voxels at ER-1.5T and that of 5667 at 3.0T were visually evaluated by three radiologists. RESULTS There were 57.6% good quality voxels at ER-1.5T versus 64.3% at 3.0T (P=.121). The posterior two rows showed better quality at ER-1.5T (P=.047). CONCLUSION There is no significant difference in overall spectral quality between ER-1.5T and 3.0T, although ER-1.5T shows better quality close to the endorectal coil.