Filip Poelaert

Hypospadias Repair at a Tertiary Care Center: Long-Term Followup is Mandatory to Determine the Real Complication Rate

PURPOSE The field of reconstructive surgery for hypospadias is lacking standard techniques and followup. Most published series include complication rates after a short followup. We report and analyze the long-term outcome of primary hypospadias repair at a single tertiary care center. MATERIALS AND METHODS We reviewed 1,061 operations performed at our institution between 1997 and 2010 and registered as hypospadias repair. The operations were performed in 543 patients born between June 1997 and June 2005. A retrospective database was created with information about hypospadias characteristics, surgery and followup. RESULTS A total of 474 primary repairs were selected, excluding incomplete/incorrect files. Distal penile hypospadias was reported in 366 patients (77.2%), mid penile hypospadias in 54 (11.4%) and proximal hypospadias in 54 (11.4%). Initial repair technique was based on incised plate in 189 patients (39.9%), meatal advancement in 171 (36%), onlay flap in 82 (17.3%) and other or combined techniques in 25 (5.3%). Insufficient information was reported for 7 patients (1.5%). Mean age at first operation was 22.6 months (range 4 to 134) and mean followup after first operation was 34.0 months (0 to 145). Of the children 360 (75.9%) had a good long-term outcome and required only 1 procedure. Reoperation was needed in 114 patients (24.1%), of whom 54 (47.4%) underwent reoperation in the first year of followup. CONCLUSIONS Overall a good long-term outcome without further complication was achieved in 75.9% of our cases. Of the 24.1% of patients who needed reoperation only 47.4% presented within the first year postoperatively, indicating the need for long-term followup when reporting outcomes of hypospadias repair.

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.

The Role of Androgen Receptor Expression in the Curative Treatment of Prostate Cancer with Radiotherapy: A Pilot Study

The androgen receptor (AR) and its signaling pathway play an important role in the development and progression of prostate cancer (PCa). In the setting of primary treatment of PCa with radiotherapy (RT), where the AR can be expected to be of more importance, studies evaluating the AR expression are lacking. The goal of this research is to evaluate AR protein expression in hormone-naive PCa patients treated by RT and investigate its possible prognostic role. Primary biopsy samples of 18 patients treated with primary RT were analyzed including the corresponding clinical information. AR protein expression of the tumor epithelium (with highest Gleason pattern) and the surrounding stroma was quantified using the Quick score for steroid receptors. The differential expression between epithelium and stroma, respectively, between tumor and normal tissue (ΔTumor − ΔBenign >2 versus ≤2), was predictive for clinical progression-free survival in the biopsy samples (P = 0.014). Preliminary results of this research show already a promising role of differential AR expression in predicting clinical relapse after PCa treatment with primary EBRT. Further research is needed to validate these findings. Hopefully this can lead to a better understanding of PCa evolution and eventually lead to better therapy strategies.

Cytoreductive Prostatectomy for Metastatic Prostate Cancer: First Lessons Learned From the Multicentric Prospective Local Treatment of Metastatic Prostate Cancer (LoMP) Trial

OBJECTIVE To prospectively evaluate patients with newly diagnosed metastatic prostate cancer in the context of the LoMP trial (which investigates the role of cytoreductive radical prostatectomy [cRP] in addition to standard of care [SoC]) and to provide a preliminary analysis of patients characteristics, safety of cRP, and early local symptoms. PATIENTS AND METHODS cRP was performed in asymptomatic patients with a resectable tumor and who were fit to undergo surgery (group A, n = 17). Only SoC was administered to patients with metastatic prostate cancer ineligible or unwilling to undergo cRP (group B, n = 29). At 3 months, surgical complications related to cRP and local symptoms for both groups were evaluated. RESULTS Median operation time, blood loss, and hospital stay for cRP were 215 minutes (150-290), 250 mL (100-900), and 4 days (2-7), respectively. Respectively 5 (29.4%) and 2 (11.8%) patients suffered grades 1 and 2 complications within 3 months postoperatively. When compared with Group B, patients in group A were younger (64 vs 72 years, P = .005), had lower initial prostate-specific antigen (15.9 vs 156 µg/L, P = .002), and less high-volume metastatic disease (5.9% vs 69%, P <.001). At 3 months, 5 (29.4%) patients in group A reported stress urinary incontinence without any further local symptoms. In group B, respectively 2 (6.8%), 11 (37.9%), and 2 (6.8%) patients suffered urge incontinence, obstructive voiding needing medical intervention, and ureteric obstruction. CONCLUSION In a group of well-selected patients, cRP is safe. These patients have more favorable characteristics compared with patients treated with only SoC. If only SoC can be offered, patients are at risk to suffer from local symptoms.

Release of urinary extracellular vesicles in prostate cancer is associated with altered urinary N-glycosylation profile

Aim Nowadays, extracellular vesicles are of great interest in prostate cancer (PCa) research. Asparagine (N)-linked glycosylation could play a significant role in the pathological mechanism of these vesicles. We investigated if prostatic protein N-glycosylation profiles were related to urinary vesicle-associated prostate-specific antigen (PSA) extractability and if this parameter showed diagnostic potential for PCa. Methods Urinary extracellular vesicles were visualised using transmission electron microscopy. Urinary extracellular vesicles extraction by means of n-butanol allowed determination of urinary vesicle-associated PSA extractability. Diagnostic value was assessed between benign prostate hyperplasia (BPH; n=122) and patients with PCa (n=85). Additionally, correlation with urine N-glycosylation was assessed. Results Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). Next, vesicle-associated PSA extraction ratio was correlated to biantennary core-fucosylation (p=0.003). Finally, vesicle-associated PSA extraction ratio proved beneficial in PCa diagnosis, next to serum PSA and the urinary glycosylation marker (p=0.021). Conclusions The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. The urinary vesicle-associated PSA extraction ratio was associated with changes in N-glycoforms and showed diagnostic potential. Further research is warranted to unravel the pathological link between N-glycosylation and extracellular vesicles in cancer, as well as to assess the prognostic value of this biomarker.

Diagnostic accuracy of urinary prostate protein glycosylation profiling in prostatitis diagnosis.

Introduction Although prostatitis is a common male urinary tract infection, clinical diagnosis of prostatitis is difficult. The developmental mechanism of prostatitis is not yet unraveled which led to the elaboration of various biomarkers. As changes in asparagine-linked-(N-)-glycosylation were observed between healthy volunteers (HV), patients with benign prostate hyperplasia and prostate cancer patients, a difference could exist in biochemical parameters and urinary N-glycosylation between HV and prostatitis patients. We therefore investigated if prostatic protein glycosylation could improve the diagnosis of prostatitis. Materials and methods Differences in serum and urine biochemical markers and in total urine N-glycosylation profile of prostatic proteins were determined between HV (N = 66) and prostatitis patients (N = 36). Additionally, diagnostic accuracy of significant biochemical markers and changes in N-glycosylation was assessed. Results Urinary white blood cell (WBC) count enabled discrimination of HV from prostatitis patients (P < 0.001). Urinary bacteria count allowed for discriminating prostatitis patients from HV (P < 0.001). Total amount of biantennary structures (urinary 2A/MA marker) was significantly lower in prostatitis patients compared to HV (P < 0.001). Combining the urinary 2A/MA marker and urinary WBC count resulted in an AUC of 0.79, 95% confidence interval (CI) = (0.70–0.89) which was significantly better than urinary WBC count (AUC = 0.70, 95% CI = [0.59–0.82], P = 0.042) as isolated test. Conclusions We have demonstrated the diagnostic value of urinary N-glycosylation profiling, which shows great potential as biomarker for prostatitis. Further research is required to unravel the developmental course of prostatic inflammation.

Validated uroflowmetry‐based predictive model for the primary diagnosis of urethral stricture disease in men

To define a uroflowmetry‐based non‐invasive predictive tool for the primary diagnosis of urethral stricture disease.

Androgen Receptor Gene Copy Number and Protein Expression in Treatment-Naïve Prostate Cancer.

Objectives: To evaluate the androgen receptor (AR) gene copy number in androgen deprivation therapy (ADT) treatment-naïve prostate cancer (PCa) patients and to evaluate the corresponding AR protein expression and assess the association between these features and prognostic factors. Materials and Methods: Chromosome X and AR gene copy number, using fluorescence-in-situ-hybridization, and epithelial-stromal AR expression, using AR immunohistochemistry, were analyzed in 62 ADT treatment-naïve PCa patients and 8 castration-refractory patients. Results: In ADT treatment-naïve PCa patients, the AR expression was higher in tumor epithelial cells versus surrounding stromal cells (p < 0.001) and versus normal epithelium in the same patient (p = 0.043). The difference between tumoral AR expression and expression in normal epithelium was higher in patients with ≥15% of tumor cells with increased AR copy number (p = 0.019). Peritumoral stroma had lower AR expression in patients with lymph-node or distant metastases compared to those without metastases (p = 0.038). Conclusions: This research evaluates the link between AR gene status, expression profile, and possible prognostic factors. Furthermore, it highlights the importance of the peritumoral environment in PCa. Additional research is needed to further clarify the role of stromal AR in PCa dissemination and identify possible therapeutic strategies to target this mechanism.

Duration of urethral catheterization after urethroplasty: how long is enough?

BACKGROUND To report the impact of duration of urethral catheterization (DUC) on the rate of extravasation on voiding cysto-urethrography (VCUG) and the subsequent need of catheter replacement in urethroplasty. METHODS Two hundred nineteen consecutive patients undergoing urethroplasty between October 2010 and November 2014 were evaluated for the impact of DUC. Patients were divided into 2 groups, based on the scheduled DUC≤10 days (group 1, N.=86) or >10 days (group 2, N.=133). RESULTS Fourteen patients (6.4%) had extravasation on VCUG with an additional period of catheter usage. In 10 of the 14 patients (71.4%) clinical signs of impaired wound healing were present. In group 1 (median DUC 8 days) 3 patients (3.5%) needed an additional period of urethral catheterization, compared to 11 patients (8.3%) in group 2 (median DUC 14 days). Strictures in group 2 were longer (4 vs. 2 cm, P<0.001) and more complex. Redo urethroplasty was needed in 9 of the 14 patients with extravasation. CONCLUSIONS In uncomplicated cases of urethroplasty, the urethral catheter can be safely removed after 8 to 10 days postoperatively. Extravasation on VCUG occurs in around 6% of urethroplasties and is a prognostic factor for stricture recurrence and reoperation.

Prospective Randomized Controlled Trial Exploring the Effect of TachoSil on Lymphocele Formation After Extended Pelvic Lymph Node Dissection in Prostate Cancer

OBJECTIVE To explore whether TachoSil, a hemostatic patch, can reduce the incidence of lymphocele formation. Development of a lymphocele is a frequent complication after pelvic lymph node dissection (PLND) for nodal staging in prostate cancer. MATERIALS AND METHODS From 2013 to 2017, 100 patients with prostate cancer who were set to undergo a staging PLND before external beam radiotherapy (n = 50) or PLND concomitant with radical prostatectomy (RP) (n = 50) were prospectively randomized 1:1 between bilateral TachoSil placement or nonplacement. Primary end points were radiographic lymphocele development, lymphocele volume (1 week and 1 month postoperatively), and the duration and volume of postoperative catheter drainage. RESULTS Patient, tumor, and surgical characteristics of the TachoSil and the control groups did not differ significantly. In total, 65 patients (65%) experienced a radiographic lymphocele up to 3 months after surgery: 29 (58%) in the TachoSil group and 36 (72%) in the control group (P = .34). Significantly less radiographic lymphoceles were observed 1 week postoperatively for patients who underwent sole PLND and 1 month postoperatively for patients who underwent PLND with RP in the TachoSil group compared with the control group (16% vs 48%, P = .024, and 24% vs 52%, P = .047, respectively). The other postoperative characteristics presented no significant differences between the 2 groups, neither for patients undergoing sole PLND nor for patients undergoing PLND with RP. CONCLUSION Patients undergoing bilateral TachoSil placement after PLND seem less likely to develop a radiographic lymphocele early postoperatively. Nevertheless, the clinical relevance of the use of TachoSil remains highly debatable.