Bilateral Obturator Osteotomy: A Novel Osteotomy for Bladder Exstrophy Closure.

BACKGROUND: Abdominal and pelvic closure remains a challenge during bladder exstrophy initial repair. We aimed to report on the feasibility and results of a novel technique of bilateral obturator osteotomy. METHODS: Retrospective study of prospective collected data of children who underwent single-stage delayed bladder exstrophy closure combined with RSTM (Radical Soft Tissue Mobilization) for BEEC (Bladder Exstrophy Epispadias Complex) by the same team at different institutions between December 2017 and May 2021. When pubic approximation was not feasible at the end of the procedure, bilateral obturator osteotomy was performed through the same approach, consisting in bilateral divisions of the ilio-pubic rami, ischio-pubic rami, obturator membrane, and detachment of the internal obturator muscle. Pubic bone fragments were approximated together on the midline. Immobilization in a thermoformed posterior splint was indicated for 3 weeks. The main outcome criterion was the bladder dehiscence rate at 6 months, assessed by physical inspection. Secondary outcome criteria included neurovascular obturator pedicle injury, analyzed during orthopedic physical examination, wound or bone infections, gait acquisition, reported by parents and evaluated during medical examination, and vascular penile impairment, judged by penile and glans coloration. RESULTS: 17 children (11 males, 6 females) were included, at a median age of 2 months [1-33]; and representing 29% (17/58) of the children with bladder exstrophy who underwent the same surgical approach during the time of study. There was no postoperative bladder dehiscence with a median follow-up of 34 months [6-47]. No complication was observed. Pelvic X-rays showed bilateral normal ossification process. Neither gait abnormality, nor clinical indication of obturator nerve deficiency was observed during follow-up. CONCLUSION: When pubic bones approximation is not possible, bilateral obturator osteotomy is a useful adjunct in bladder exstrophy closure, feasible by the pediatric urologist through the same approach, and not requiring external fixator. LEVEL OF EVIDENCE: IV.

Assessment of Anorectal Function and Related Quality of Life of 27 Patients with Bladder Exstrophy or Epispadias After Kelly Radical Soft Tissue Mobilisation.

INTRODUCTION: The Radical soft-tissue mobilisation (RSTM) described by J.H. Kelly for bladder exstrophy repair implies a detachment of levator ani muscle insertions from the pelvic wall. The aim of this controlled study was to evaluate the impact of this procedure on subsequent anorectal function. METHODS: Monocentric controlled study of prospectively collected data of children who underwent RSTM for BEEC from 2010 to 2017. Patients born after 2017 were not included, as they were below the theoretical age of continence acquisition at the time of the study. Anorectal function was assessed using the Childhood Bladder and Bowel Dysfunction Questionnaire, and quality of life (QoL) related to fecal continence using the CINCY FIS questionnaire. The control group was paired on age and sex with a 1:3 patient/control ratio. Answers to questionnaires were collected from September 2021 to January 2022. Univariate statistical analysis comparing two groups and subgroup analysis following age were also performed. RESULTS: During the period of study, 55 children with BEEC underwent Kelly RSTM. Twenty-seven (49%) were included and paired with 81 healthy children on age and sex. Median age at surgery was 15 months [0.5-93] and median follow-up was 10 years [4-13]. Patient's group median age at evaluation was 11 years [5-19]. There was no difference between patients and control group in anorectal function for both incontinence and constipation items. No significant difference was found in QoL related to fecal incontinence assessment. Subgroup analysis did not show difference. CONCLUSION: This study suggests that the levator ani detachment during Kelly procedure, realised in a paediatric population under the age of 8, did not impact anorectal function with a mid-term follow-up. LEVEL OF EVIDENCE: III.

Hypospadias preputial flap onlay technique - Step by step.

PURPOSE: To present one way of performing onlay preputial flap for hypospadias. PATIENTS AND METHODS: This procedure was performed following the methodology used in one hypospadias expert center to correct hypospadias in boys who are not elective for Koff procedure and in whom Koyanagi procedure is not needed. Operative details were described, and post-operative management were given as example. RESULTS: Long-term results of this technique showed a 10% complication rate (dehiscence, strictures or urethral fistulas) 2 years after surgery. CONCLUSIONS: This video is a step by step description of the onlay preputial flap technique giving the general methodology and also the details resulting from years of practice in one hypospadias expert center.

Postoperative JJ stent is not necessary after balloon high-pressure endoscopic dilatation of primary obstructive megaureter.

INTRODUCTION: A wide range of surgical interventions have been described for the management of primary obstructive megaureter (POM). Endoscopic balloon dilatation has been developed through last decades as a minimally invasive alternative to classic surgery. OBJECTIVE: To assess the need for placement of a double J stent after endoscopic balloon dilatation procedure, by comparing the post-operative related outcomes with and without double J placement. Secondary outcome was the success rate, considering the need for further procedure after endoscopic balloon dilatation and the improvement of the ureteral diameter in the two groups. STUDY DESIGN: Historical retrospective comparison of children treated by endoscopic dilatation for POM, with post-operative JJ stent left in place (2012-2014) or without ureteral JJ stent (since 2015). Post-operative complications were reported following Clavien-Dindo grading system and compared between the two groups. Success rate was defined as absence of need for further surgical reimplantation. Ureteral diameters on preoperative and postoperative renal ultrasounds were compared. RESULTS: Endoscopic dilatations were performed in 42 patients for 46 renal units during the study period. There was a significantly higher rate of post-operative complications in the group with JJ stenting compared to the group without double J stenting regarding all Clavien-Dindo grades (56% vs 15%, p = 0.014) and Clavien-Dindo grade III only (31% vs 0%, p = 0,0051) (Figure). The success rate was similar in the JJ group (75%, F-up: 70 months [13-101]) and the no JJ group (81%, F-up: 26 months [12-95]). There was a significant improvement of US renal pelvis and ureter dilatation in both groups, with a median follow-up of 35.5 months [12-101]. DISCUSSION: The overall rate of complications was slightly higher than in other reports and higher in the JJ group regarding Clavien-Dindo grade III complications. The success rate was comparable to previous studies reviewing endoscopic dilatations and equivalent in the two groups. CONCLUSION: In our study, the omission of postoperative ureteral drainage by a JJ stent after endoscopic balloon dilatation of POM did not increase post-operative complications rate without demonstrable impact on the success rate.

Adults with previous hypospadias surgery during childhood: Beware of bulbar strictures.

BACKGROUND: Urethral strictures represent the most frequent long-term complication in men after history of hypospadias surgery. OBJECTIVES: To better define the spectrum of men previously treated for hypospadias during childhood, presenting at an adult urology clinic with persistent urethral complications. STUDY DESIGN: Retrospective review of the records of 42 consecutive adult patients with a personal history of hypospadias repair during childhood referred at one adult tertiary urology center between 2004 and 2017. Those with persistent urethral strictures were included: 28 patients (median age 28yr [17-81]). Residual chordee, aesthetic concerns, isolated fistulas, and motives of consultation unrelated to hypospadias were excluded. Early initial success rate and location of urethral stricture were studied. Statistical Analysis was done by non-parametric tests. RESULTS: On the 42 consecutive adults eligible, a total of 28 patients had a persistent urethral stricture. During childhood, 13/28 boys had required multiple surgical revision procedures, including six of them for postoperative urethral strictures. During adulthood, initial urethral assessment revealed 29 urethral strictures in 28 patients (penile urethra 23/29, bulbar urethra 8/29). The early initial success rate of stricture treatment was 50% (median follow-up: 4 years [1-7]). Additional surgical procedures were needed and performed in 11 patients. Eight patients were eventually diagnosed with a bulbar stricture, either isolated (n = 5) or combined with a distal stricture (n = 3), without significant relationship with initial position of meatus. DISCUSSION: Predictive factors for bulbar strictures locations could not be identified. It was however observed that symptomatic bulbar strictures do exist in adults, in the long term after penile hypospadias repair during childhood, independently of the initial site of hypospadias, initial success of primary repair, and the type of surgical reconstructions performed during childhood. CONCLUSION: Bulbar strictures represent more than 25% of the overall strictures diagnosed in adult patients treated for hypospadias during childhood, independently of the original site of urethral reconstruction.

What we learned from the Covid-19 first wave: a survey from Young Pediatric Urology Committee (YPUC) from ESPU.

BACKGROUND: The Corona virus still has a big impact on medical work. All medical specialties have been called to confront this unexpected event, even pediatric surgery. The objective of this study is to highlight the effect of pandemic on daily work of young pediatric surgeons during the Covid-19 first wave. METHODS: An online survey was sent via email by the Scientific Committee of YPUC in April 2020. The impact of Covid-19 was invested, by analyzing the results of answers received. The difference between young consultants and trainees (C and T) were examined to assess the effect of pandemic in 2 different categories. RESULTS: A total of 88 participants filled out the questionnaire. Guidelines around surgeries were well arranged: clear for 98% concerning triage with no difference between T and C; clear for 84% concerning pre-operative screening and for 81% concerning surgical dressing with a significance difference between T and C in understanding (p=0.07 and p=0.06). Forty-two respondents (48%) tested all surgical patients and the 20% operated patients positive for COVID-19. Thirteen (15%) were relocated to work in other divisions on different tasks, 12 were C. 86% of T did not participate in surgeries as much as before. CONCLUSIONS: The impact of the pandemic has been very significant for pediatric urologists and the difference between C and T confirm that the training could be impacted. After the first wave we should be careful on PPE, on pre-operative screening of surgical patients and we should protect the trainee learning curve.

Impairing temozolomide resistance driven by glioma stem-like cells with adjuvant immunotherapy targeting O-acetyl GD2 ganglioside.

Stem cell chemoresistance remains challenging the efficacy of the front-line temozolomide against glioblastoma. Novel therapies are urgently needed to fight those cells in order to control tumor relapse. Here, we report that anti-O-acetyl-GD2 adjuvant immunotherapy controls glioma stem-like cell-driven chemoresistance. Using patient-derived glioblastoma cells, we found that glioma stem-like cells overexpressed O-acetyl-GD2. As a result, monoclonal antibody 8B6 immunotherapy significantly increased temozolomide genotoxicity and tumor cell death in vitro by enhancing temozolomide tumor uptake. Furthermore, the combination therapy decreased the expression of the glioma stem-like cell markers CD133 and Nestin and compromised glioma stem-like cell self-renewal capabilities. When tested in vivo, adjuvant 8B6 immunotherapy prevented the extension of the temozolomide-resistant glioma stem-like cell pool within the tumor bulk in vivo and was more effective than the single agent therapies. This is the first report demonstrating that anti-O-acetyl-GD2 monoclonal antibody 8B6 targets glioblastoma in a manner that control temozolomide-resistance driven by glioma stem-like cells. Together our results offer a proof of concept for using anti-O-acetyl GD2 reagents in glioblastoma to develop more efficient combination therapies for malignant gliomas.

Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation.

Potentiation of hostile monoclonal antibodies (mAb) by chemotherapeutic agents constitutes a valuable strategy for designing effective and safer therapy against cancer. Here we provide a protocol to identify a rational combination at the preclinical step. First, we describe a cell-based assay to assess the synergism between anticancer mAb and cytotoxic drugs, that uses the combination index equation of Chou and Talalay1. This includes the measurement of tumor cell drug- and antibody-sensitivity using an MTT assay, followed by an automated computer analysis to calculate the combination index (CI) values. CI values of <1 indicate synergism between tested mAbs and cytotoxic agents1. To corroborate the in vitro findings in vivo, we further describe a method to assess the combination regimen efficacy in a xenograft tumor model. In this model, the combined regimen significantly delays tumor growth, which results in a significant extended survival in comparison to single-agent controls. Importantly, the in vivo experimentation reveals that the combination regimen is well tolerated. This protocol allows the effective evaluation of anticancer drug combinations in preclinical models and the identification of rational combination to evaluate in clinical trials.

Primary female epispadias: Perineal approach or Kelly repair?

OBJECTIVES: Primary female epispadias encompasses a spectrum of disease, presenting with a variable degree of incontinence. We hypothesized that although perineal urethrocervicoplasty can be a successful first-line procedure in patients with normal bladder, a more radical reconstruction was necessary to achieve continence in cases lying at the most severe end of the spectrum. Our aim was to assess the results of a surgical management using perineal approach in girls with normal bladder capacity, and Kelly radical soft-tissue mobilization (RSTM) in patients with inadequate bladder, based on the assumption that bladder capacity (BC) is a reliable marker of epispadias severity. STUDY DESIGN: Prospective inclusion of incontinent girls with female epispadias referred to a single institution. Patients with normal BC were treated with perineal urethrocervicoplasty (PUCP, group 1). Patients with small bladder underwent RSTM (group 2). Follow-up was at 1, 3, 6, and 12 months postoperatively, then annually, including physical examination, renal ultrasound at each visit, continence status, and estimation of functional/maximal BC. The main study outcome was continence status at the age of 5 years or later, if postoperative follow-up was >12 months. RESULTS: From 2006 to 2017, 16 consecutive children were prospectively included in this study, at a median age of 39 months (5-102 months). Seven girls were included in group 1 and underwent PUCP; at the last follow-up, five out of seven were dry by day (4/5 day and night), although three out of five required bladder-neck injection after perineal reconstruction due to stress incontinence. Two patients with persistent incontinence and absence of BC increase after PUCP subsequently underwent RSTM. Eleven patients with low BC (56% [10-94%] of expected BC) were included in group 2 (9 without prior surgery, 2 after PUCP failure). Among the eight evaluable patients, eight out of eight achieved diurnal continence, and 3/8 were fully continent. One girl with obstructive micturition required clean intermittent catheterization. DISCUSSION: The traditional approach of female epispadias based on staged reconstruction (urethroplasty followed by bladder-neck reconstruction) raised concerns regarding the risk of non-physiological obstructive micturition. The perineal approach was suggested as an alternative, with reported diurnal continence rates of 60-80%, but less than 50% of nocturnal continence, presumably in relation with limited bladder capacity. In cases selected within the most severe end of the epispadias spectrum, the Kelly RSTM seems to offer excellent continence rates. CONCLUSION: A tailored approach to female epispadias, based on perineal reconstruction in favorable cases, and radical soft-tissue mobilization in severe cases, seems to yield good continence outcomes in the long term.

Laparoscopic transposition of lower-pole crossing vessels: Long-term follow-up of 33 patients at puberty.

PURPOSE: Laparoscopic transposition of lower-pole crossing vessels (LPCV) has been described as an effective alternative to dismembered pyeloplasty in selected indications of hydronephrosis, with purely extrinsic vascular PUJ obstruction. We hypothesized that the initial good results of laparoscopic transposition of LPCV in children presenting with pure extrinsic PUJO were sustained at puberty when these children go through statural growth, without inducing significant changes in systemic arterial blood pressure. Hence, we analysed the long-term follow-up of adolescents successfully treated with this technique during childhood, reviewed after they have reached puberty, focusing on the incidence of recurrent symptoms, renal dilatation, and systemic hypertension. PATIENTS AND METHODS: Early 2015, among a cohort of 70 patients prospectively followed-up since they had undergone laparoscopic transposition of LPCV during childhood (2005-2012), we performed systematic clinical assessment of the 33 adolescent patients (16 years; range 12-22) who had reached puberty age. Assessment focused on clinical examination, arterial blood pressure measurements, and renal ultrasonography (Table). RESULTS: The median delay since surgery was 67 months (31-113 months). Arterial blood pressure adjusted for age and height was within normal range in all patients. Three patients had occasional episodes of abdominal pain: two of them had normal US (including during pain episodes), one had persistent extra-renal dilated pelvis with no calyceal dilatation. None of them showed obvious clinical characteristics linking the pain to a renal origin. Renal US showed residual SFU grade 2 pelvicalyceal dilatation in 2/33 asymptomatic patients; SFU grade 1 extra-renal pelvis dilatation in 3, and was normal in the remaining. When Doppler analysis was performed, there was no evidence of lower-pole parenchyma perfusion defect. DISCUSSION: In adolescents successfully treated during childhood with transposition of LPCV, there seemed to be no impact of this procedure on systemic arterial blood pressure in adolescents after puberty, nor any evidence of late recurrence of symptoms or hydronephrosis. The main limitation of the present study relies in its retrospective nature, the limited sample size, and the obvious difficulty in adequate selection of candidate patients to this technique. The present experience however reinforces the hypothesis that a vast majority of children can be definitely cured with transposition of LPCV when they represent the sole aetiology of obstruction. CONCLUSION: In the long-term follow-up, most adolescents successfully treated during childhood by laparoscopic transposition of LCPV for PUJ extrinsic obstruction remain asymptomatic, with normal arterial blood pressure, and normal renal ultrasound when they reach puberty.