A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy.

Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility.

Ultra-mini-PCNL using the urological Dyna-CT in small infants: a single-center experience.

PURPOSE: To analyze and share our experience with ultra-mini-PCNL using the urological Dyna-CT in small infants. METHODS: A retrospective analysis was performed on all infants younger than 3 years of age who underwent ultra-mini-PCNL at our institution since 2016. Operating time, fluoroscopy time, dose area product (DAP), stone-free status, intra- and postoperative complications and the duration of hospital stay were analyzed. RESULTS: A total of nine interventions conducted on eight children were evaluated. The mean age of infants was 22.8 ± 11.9 months. The mean operation time and the mean fluoroscopy time were 119.2 ± 51.8 min, and 190.4 ± 93.8 s, respectively. The mean DAP was 11.4 ± 6.9 µGym2 and the stone clearance at 3 months was 87.5%. No major postoperative complications were assessed, and no transfusion was given. The mean hospital stay was 4 (IQR 3-6) days. CONCLUSION: Ultra-mini-PCNL utilizing the urological Dyna-CT can safely and effectively be performed in small infants with kidney stones. In this setting, the urological Dyna-CT allows for a very low radiation exposure.

Bladder cancer in patients with neurogenic bladder disorder: a comparative study of different etiologies.

PURPOSE: The objective of this study was to conduct a comparative study of different etiologies of neurogenic bladder disorders (NBDs) in patients with bladder cancer (BC) regarding patient- and tumor-related parameters and their oncological outcome. METHODS: Out of 98 patients with bladder tumors and neurogenic disease, 23 patients with BC and NBDs from Jan 1, 2010, to Dec 31, 2020, were included. The different etiologies of NBDs were merged in three groups based on the level of the nervous system (NS)-lesion: (i) central (n = 6), (ii) spinal cord (n = 10), and (iii) peripheral lesions (n = 7). RESULTS: Patients with lesions at the spinal cord level were younger at the time of BC diagnosis compared to patients with central or peripheral NS lesions (54 vs. 68 vs. 78 years, p = 0.0219). However, the latency to malignant transformation was more than twice as long (33 vs. 15 years, p = 0.0108). Most tumors were muscle-invasive or locally advanced BCs (62%) and presented lymph node metastases (55%), resulting in a poor mean overall survival of 30.9 ± 3.6 months. No significant differences regarding histopathology, tumor stage, and oncological outcome could be observed between the groups. CONCLUSION: Patients with NBDs have a poor prognosis regardless of their etiology or the level of NS lesion. Patients with spinal cord lesions, including congenital NBDs, appear to develop BC at a young age, but compared to other etiologies latency from NBD to BC is longer.

Postnatal Management in Congenital Lower Urinary Tract Obstruction With and Without Prenatal Vesicoamniotic Shunt.

Purpose: Congenital lower urinary tract obstruction (cLUTO) includes a heterogeneous group of conditions caused by a functional or mechanical outlet obstruction. Early vesicoamniotic shunting (VAS) possibly reduces the burden of renal impairment. Postpartum, pediatric urologists are confronted with neonates who have a shunt in place and a potentially impassable urethra with a narrow caliber. Early management of these patients can be challenging. Here, we would like to share the approach we have developed over time. Materials and Methods: We conducted a single-center retrospective analysis from 2016 to 2020 and included all patients diagnosed with cLUTO. Data focusing on time point and type of intervention was collected. Furthermore, patients with temporary diversion via a percutaneous VAS were selected for a more detailed review. Results: In total, 71 cases of cLUTO were identified during the study period. Within this group, 31 neonates received postnatal management and surgical intervention in our center. VAS was performed in 55% of these cases (N = 17). The postnatal treatment varied between transurethral or suprapubic catheterization and early Blocksom vesicostomy. In five infants with VAS, the urinary drainage was secured through the existing VAS by inserting a gastric tube (N = 1) or a 4.8 Fr JJ-stent (N = 4). To our knowledge, this is the first report of a stent-in-stent scheme, which can remain indwelling until the definite treatment. Conclusion: Having a secure urine drainage through a VAS allows the often premature infant to grow until definite surgery can be performed. This avoids placing a vesicostomy, which requires anesthesia.

Single- vs multiple-layer wound closure for flank incisions: results of a prospective, randomised, double-blinded multicentre study.

OBJECTIVE: To compare the incidence of postoperative flank bulges between patients with multiple-layer closure and single superficial-layer closure after retroperitoneal surgery via open flank incision in the SIngle versus MUltiple-LAyer wound Closure for flank incision (SIMULAC) trial. PATIENTS AND METHODS: The study was a randomised controlled, patient- and assessor-blinded, multicentre trial. Between May 2015 and February 2017, 225 patients undergoing flank incisions were randomised 1:1 to a multiple-layer closure (SIMULAC-I) or a single superficial-layer closure (SIMULAC-II) group. The primary outcome was the occurrence of a flank bulge 6 months after surgery. RESULTS: Overall, 177 patients (90 in SIMULAC-I, 87 in SIMULAC-II) were eligible for final assessment. The cumulative incidence of a flank bulge was significantly higher in the SIMULAC-II group (51.7%) compared to the SIMULAC-I group [34.4%; odds ratio (OR) 2.04, 95% confidence interval (CI) 1.11-3.73; P = 0.02]. Rate of severe postoperative complications (4.4% SIMULAC-I vs 10.3% SIMULAC-II; P = 0.21) or hernia (6.7% SIMULAC-I vs 10.3% SIMULAC-II; P = 0.59) was similar between the groups. There was no difference in pain (visual analogue scale) and the requirement for pain medication at 6 months postoperatively. Quality of life assessed with the European Quality of Life 5 Dimensions Questionnaire was higher in the SIMULAC-I group compared to the SIMULAC-II group at 6 months postoperatively, with a (median range) score of 80 (30-100) vs 75 (5-100) (P = 0.012). CONCLUSION: The overall risk of a flank bulge after flank incision is high. Multiple-layer closure after flank incision should be performed as a standard procedure.

Bladder cancer in patients with spina bifida: a serious risk.

PURPOSE: After bladder augmentation (BA) using bowel segments, it is known that there is a risk for secondary malignancies. It remains unclear whether this also applies to spina bifida (SB) patients without BA. The aim of this study was to analyze the frequency of bladder cancer (BC) in SB at a single tertiary institution and assess the patients' oncologic outcome. METHODS: Patients with SB and BC treated from January 2016 until March 2020 were included and corresponding data were collected retrospectively. Endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: Among 132 adult patients with SB, four with a median age of 34.5 years (IQR 31.5-36.8, range 31-37) had a BC. None of the patients had undergone BA. Most common symptoms included recurrent urinary tract infections (UTI) (75%) and hydronephrosis (75%). At the time of the diagnosis, tumors were locally advanced (≥ T3) and lymph-node positive in all cases. All patients underwent radical cystectomy with adjuvant chemotherapy in two out of four cases. Histology showed squamous cell carcinomas (SCC) or at least a squamous cell component in all patients. The median PFS was 5.9 months (IQR 5.1-124.5) and the median OS was 8.7 months (IQR 6.3-125.5). CONCLUSIONS: SCC in SB can appear at a young age and is usually diagnosed in an advanced tumor stage with poor prognosis despite radical surgical resection. Patients with SB without BA with clinical symptoms, new onset of hematuria, and/or upper tract dilatation should receive a cystoscopy ± further imaging.

[Testicular tumors in prepubertal boys-organ preservation possible more often than expected]. / Hodentumoren bei präpubertären Jungen ­ Organerhalt häufiger möglich als gedacht.

In prepubertal boys, testicular tumors are rare with an incidence between 2 and 5/million. In contrast to testicular tumors in adolescents and adults, more than 2/3 of these tumors are benign. Unfortunately, in Germany in most cases, only malignant tumors (usually yolk sac tumors) are reported to the study center (MAKEI IV and now V). Therefore, the incidence in Germany is unknown. Since the introduction of polychemotherapy in the 1970s, the prognosis of malignant testicular tumors has improved enormously and has become a curable disease, even in the case of recurrence. Today the orchiectomy, which was usually carried out in the past, appears to be no longer justified in most prepubertal boys due to the high incidence of benign tumors. It has been shown in various studies that organ-sparing surgery in germ cell tumors (epidermoid cysts, teratoma); gonadal stoma tumors (Sertoli, Leydig and granulosa cell tumors) and cystic lesions (intratesticular cysts and tubular ectasia of the rete testis) is reliable and safe. In cases with preoperative significantly increased AFP (caution: norm values not valid in the first year of life) and a clear testicular tumor in the ultrasound (yolk sac tumor) or if no testicular parenchyma is sonographically detectable, orchiectomy can still be carried out. Today orchiectomies in prepubertal boys should be an exception and the reasons for an orchiectomy must be well documented.

[Pelviureteric junction obstruction and crossing vessels: pro "vascular hitch"]. / Subpelvine Stenose & kreuzende Gefäße ­ Pro "vascular hitch".

The vascular hitch procedure for pelviureteric junction obstruction caused by crossing lower-pole vessels is a controversial treatment option. Since this minimally-invasive technique has been introduced in patients with aberrant lower-pole vessels, multiple publications have reported successful short, intermediate and long-term outcomes. Success rates of > 90 % are similar to those of Anderson-Hynes pyeloplasty. In general, an associated intrinsic stenosis seems to be rare. Histological evidence of muscular hypertrophy may simply indicate a compensatory mechanism and may be reversible to a certain degree. To differentiate between those patients who are eligible for a vascular hitch procedure and those who should receive an initial Anderson-Hynes pyeloplasty, an intraoperative diuretic test should be performed (volume bolus plus intravenous administration of furosemide). An associated intrinsic stenosis seems to be unlikely in a funnel-like and otherwise normal-looking pelviureteric junction, decreasing hydronephrosis after mobilisation of renal pelvis and crossing vessels and effective peristalsis of the renal pelvis after intraoperative diuretic testing. The vascular hitch technique is less demanding than laparoscopic Anderson-Hynes pyeloplasty and less time-consuming with regard to the duration of the surgical procedure and anaesthesia. Further advantages are: no risk of urinary leakage or anastomotic stricture and no need for intra-luminal stenting. Therefore, in a selected group of patients with solely extrinsic pelviureteric junction obstruction, the vascular hitch procedure is a valuable alternative to classic Anderson-Hynes pyeloplasty with seemingly long-term efficiency.