A consensus process to identify research priorities in paediatric urology in the United Kingdom.

INTRODUCTION: Paediatric urologists manage a spectrum of conditions, much of the evidence for relevant treatment pathways is of low quality. For many conditions treatment varies according to location and surgeon; children with the same condition might have surgery in one unit but watchful waiting in another. Underlying this variation are differences in opinion, and insufficient high-level evidence with few prospective randomized studies. Such studies may be challenging to design, fund and recruit into, and are more likely to succeed if there is a collaborative approach. Research prioritization is a tool to identify the research of most value. Delphi methodology is an interpretive technique aiming to gain the consensus view of interested parties. The British Association of Paediatric Urologists (BAPU) set out to ascertain consensus on what paediatric urologists, working in the UK, consider to be areas of priority for research. This paper describes the process used, and the resulting list of research questions. METHODS: A scoping survey of paediatric urologists in the UK was undertaken to identify an initial set of research questions. These were refined by the BAPU research committee (BAPU RC), then prioritized using a modified Delphi process. During Stage 1a multiple new research questions were submitted leading to Stage 1b, an interim process. All UK paediatric urologists were invited to take part in Stage 2 of the prioritization process. RESULTS: Sixty-five questions were submitted to the scoping survey by 24 paediatric urologists. The BAPU RC refined these to 60 questions, which were submitted to Stage 1a of the modified Delphi process. Sixty-seven people completed Stage 1a, at the same time submitting 224 additional research questions. The BAPU RC revised the entire question set, ensuring the key subject of the original question was not altered and novel questions were retained. The BAPU RC undertook interim scoring of the resultant 79 questions, the top scoring 25 questions plus 5 lower scoring 'wild card' questions (to ensure the breadth of the specialty was represented) were put forward to Stage 2. A total of 65 people completed Stage 2, including a lay representative. A list of 30 priority research questions was generated; the top 10 includes management of neuropathic bladder, posterior urethral valves, antibiotic prophylaxis, DSD & CAH, continence, male external genitalia, VUR and transition care (Table). CONCLUSION: This process has provided BAPU, paediatric urologists in the UK, and funders with areas of research considered a priority in the specialty.

"Urinary tract dilatation and vesicoureteral reflux - Adult outcomes, who should be followed, and how to follow them".

Long-term adult outcomes of children diagnosed with urinary tract dilatation (UTD) and vesicoureteral reflux (VUR) are not clearly documented in the literature. Likewise, follow-up protocols for these patients as they transition through adolescence and into adulthood vary with institution and cultures. Several studies have shown that individuals diagnosed with VUR in childhood are at higher risk of urinary tract infection (UTI) throughout their lives, even in the setting of prior VUR resolution or surgical correction. This is particularly relevant in patients with renal scarring, who are at higher risk of UTIs, hypertension and renal function deterioration in pregnancy. The risk of adverse maternal and fetal outcomes in pregnancy are higher for women with significant chronic kidney disease (CKD). Patients who underwent endoscopic injection or reimplantation should be counselled on the long-term particular risks associated with each intervention, including calcification of ureteric injection mounds, and the potential challenges of future endoscopic procedures following reimplantation. Although there is no evidence for the direct correlation between conservatively managed UTD in childhood, and symptomatic UTD diagnosed in adulthood, all patients should be aware of the long-term risks of persistent upper tract dilatation. Lastly, bladder-bowel dysfunction (BBD) management in adolescence can be more challenging and may contribute to symptomatic recurrence in this age group.

Postnatal outcome of prenatally-detected "simple" renal cysts: Are they really simple?

BACKGROUND: The majority of simple renal cysts diagnosed postnatally are asymptomatic and rarely require treatment unless they become symptomatic or complex. We hypothesised that prenatally-detected simple renal cysts would have a similar harmless outcome. AIMS: To establish the natural history and postnatal outcome of prenatally-diagnosed simple renal cysts. STUDY DESIGN: Single-centre retrospective case-series review (12-year period). SUBJECTS: All patients with prenatally-diagnosed simple renal cysts (defined as a solitary, non-septated, non-communicating cyst in an otherwise normal kidney). OUTCOME MEASURES: Prenatal and postnatal changes to cyst size, persistence, resolution or modification of diagnosis. Data is presented as the proportion of patients or median (range). RESULTS: 30 cysts were detected (2 bilateral, 26 unilateral) in 28 fetuses (median gestational age of 23 [20-36] weeks). Median maximum diameter was 15 (4-35) mm at initial diagnosis and 17.5 (4-100) mm across all prenatal scans. On follow-up scans diagnosis was modified in 16 (53%) to: multicystic dysplastic kidney (MCDK), dilated duplex kidney, hydronephrosis, urinoma, renal agenesis and adrenal mass. 12 (40%) cysts resolved. 2 (7%) asymptomatic cysts persisted at one year postnatally. Cyst maximum diameter in the modified diagnosis group (21.5 [10-100] mm) was significantly larger than the simple cyst group (12 [4-20] mm) (P = 0.03). CONCLUSIONS: Our study revealed the challenges of prenatal ultrasound imaging, with modified diagnoses in over half the cases. Kidneys with solitary cysts could evolve into multicystic kidneys or involute completely, which suggests a true alteration in morphology rather than sonographic error. Persistent simple cysts in an otherwise normal kidney, however, resolved spontaneously or remained asymptomatic. Prenatally-detected simple cysts should be monitored with serial imaging.

Hydronephrosis Classifications: Has UTD Overtaken APD and SFU? A Worldwide Survey.

Objective: To collect baseline information on the ultrasonographic reporting preferences. Method: A 13-multiple choice questionnaire was designed and distributed worldwide among pediatric urologists, pediatric surgeons, and urologists. The statistical analysis of the survey data consisted of 3 steps: a univariate analysis, a bivariate and a multivariate analysis. Results: Three hundred eighty participants responded from all the continents. The bivariate analysis showed the significant differences in the geographical area, the years of experience and the volume of cases. Most of the physicians prefer the SFU and APD systems because of familiarity and simplicity (37 and 34%, respectively). Respondents noted that their imaging providers most often report findings utilizing the mild-moderate-severe system or the APD measurements (28 and 39%, respectively) except for North America (SFU in 50%). Multivariate analysis did not provide significant differences. Conclusion: Our study evaluates the opinions regarding the various pediatric hydronephrosis classification systems from a large number of specialists and demonstrates that there is no single preferred grading system. The greatest reported shortcoming of all the systems was the lack of universal utilization. The observations taken from this study may serve as basis for the construction of a common worldwide system. As APD and SFU are the preferred systems and the UTD a newer combination of both, it is possible that with time, UTD may become the universal language for reporting hydronephrosis. This time, based on the result of this survey, seems not arrived yet.

Therapeutic intervention for fetal lower urinary tract obstruction: Current evidence and future strategies.

In-utero vesica-amniotic shunting for fetal lower urinary obstruction (LUTO) is known to improve perinatal survival. More recently, studies including centres performing fetal cystoscopy, have suggested benefit on longer-term survival and renal outcome - within the limitations of small numbers and limited follow-up. These interventions carry significant risk, and therefore patient selection, and optimal timing, are key. The aim of this article is to explore ways of improving the accuracy of prenatal diagnosis, and of identifying risk factors for fetal and postnatal renal failure. The next step is that of using established staging and classification systems to select the patient group that may benefit from intervention, based on published outcomes. Several factors come into play when selecting the timing of intervention, especially if the aim is that of renal, and not only pulmonary, preservation. Lastly, current technologies and their shortfalls are discussed.

Fetal bladder outflow obstruction: Interventions, outcomes and management uncertainties.

Fetal lower urinary tract obstruction (LUTO) is classically based on prenatal ultrasound identification of a dilated/ thick-walled bladder, bilateral hydronephrosis, dilated ureters and a dilated posterior urethra (also known as the "keyhole sign") in a male fetus. Although the most common underlying diagnosis is posterior urethral valves, the prenatal appearance may be similar with urethral atresia or stenosis, the Prune-Belly Syndrome, or even a cloacal anomaly in a female. These conditions form part of the Congenital Anomalies of Kidney and Urinary Tract (CAKUT) spectrum, which is the commonest cause of end-stage renal disease in children. Although it is difficult to predict postnatal renal function from the prenatal appearance, studies have recently identified predictive features (based on ultrasound findings and fetal biochemistry), and established staging systems to assist with counselling, and, where indicated, patient selection for in-utero intervention. Current in-utero therapy includes amnio-infusion, vesico-amniotic shunting, and fetal cystoscopy with valve ablation or urethral stenting. Postnatal survival and renal functional outcomes, complications and management uncertainties are described, highlighting areas of future development.

Renal scarring is the most significant predictor of breakthrough febrile urinary tract infection in patients with simplex and duplex primary vesico-ureteral reflux.

INTRODUCTION: The association of high-grade vesico-ureteral reflux (VUR) with renal dysplasia and/or scarring is well-established, and the combination of these factors has been shown to decrease the likelihood of VUR resolution. Other VUR parameters have similarly been shown to be associated with VUR non-resolution, including VUR grade and timing at cystography, associated urinary tract anatomical abnormalities, and bladder dysfunction. OBJECTIVE: To establish independent risk factors that can predict symptomatic persistence of VUR. DESIGN: This was a single-centre study (2011-2017) including consecutive prospectively collected patients with primary VUR on voiding cystourethrogram (VCUG). Patients with dilating VUR also underwent renography (dimercaptosuccinic acid [DMSA] or 99m-technetium mercaptoacetyltriglycine [99mTc-MAG3]). All patients were initially managed medically with antibiotic prophylaxis. Primary outcome was febrile culture-positive breakthrough urinary tract infection (BT-UTI). Demographic parameters, as well as VUR grade, VUR timing at cystography, presence of ureteral anomaly, VUR index (VURx), and differential renal function (DRF) or scarring were analysed to determine independent predictors. RESULTS: A total of 61 patients (41 male, of whom 7 circumcised at presentation) were studied. VUR was diagnosed following investigation of prenatal hydronephrosis in 37 patients (62%) and following a febrile UTI in 22 (37%). Median [range] follow-up period was 38 [12-84] months. Data from a total of 77 refluxing renal units (RUs) were used for analysis. Analysis of VCUG data demonstrated that high VURx might be a potential significant predictor of breakthrough UTI (RR: 1.7, 95% CI: 1.1-2.7, p < 0.05 vs low VURx) but this was not the case for individual VURx components. Renography data showed increased risk of breakthrough UTI in patients with renal scarring (relative risk (RR): 5.1, 95% confidence interval (CI: 2.0-10.7, p < 0.0001 vs no renal scarring), but not in patients with reduced DRF. Multivariate regression analysis revealed that renal scarring was the only significant risk factor for breakthrough UTI. VUR patients with renal scarring were three times more likely to develop breakthrough UTI (odds ratio (OR): 3.3, 95% CI: 1.4-7.4, p < 0.01). DISCUSSION: Multiple factors have been shown to be significant predictors of radiological VUR resolution. Univariate analysis of these factors suggests that only scarring on DMSA and VURx are significant predictors of symptomatic non-resolution. On multivariate analysis, scarring on DMSA was the only significant predictive variable. This information will be useful in targeting investigation and treatment in susceptible patients and when counselling families. CONCLUSION: Renal scarring is the most significant risk factor for breakthrough UTI in primary VUR patients and could be used to determine those at risk of symptomatic VUR persistence.

Fetal bladder outlet obstruction: Embryopathology, in utero intervention and outcome.

Fetal bladder outlet obstruction (BOO), most commonly caused by posterior urethral valves (PUV), remains a challenging and multi-faceted condition. Evolving techniques, and refinement in ultrasound, optics and instrumentation, have increased our rate of prenatal diagnosis, and enabled valve ablation not only in smaller newborns, but also in fetuses. Long-term outcome studies have raised our awareness of the silent damage caused by bladder dysfunction and polyuria and encouraged their proactive management. In spite of our best efforts, the proportion of boys with PUV who progress to chronic and end-stage renal disease (ESRD) has not changed in the last 25 years. Evidence suggests a reduction in perinatal mortality following prenatal intervention, probably resulting from amelioration of oligohydramnios at the crucial time of lung development between 16 and 28 weeks' gestation, but no improvement in postnatal renal outcome. There are no bladder functional outcome studies in patients who have undergone prenatal intervention and hence the long-term effect of in utero defunctionalisation of the bladder is not known. This aim of this review is to revisit the embryopathology of fetal BOO, in particular the renal and bladder structural and functional changes that occur with in utero obstruction. The effect of earlier prenatal diagnosis, and therapy, on postnatal outcome is also explored and compared with outcomes published for traditional postnatal treatment.

The value of contrast studies in the evaluation of bowel strictures after necrotising enterocolitis.

PURPOSE: Strictures of the bowel are a frequent complication post-necrotising enterocolitis (NEC). Contrast studies are routinely performed prior to stoma closure following NEC. The aim of this study was to evaluate the ability of these studies to detect strictures and also directly compare them to operative and histological findings. METHODS: Two hundred and fourteen neonates who had a diagnosis of NEC (Bell stage 2 or greater) in a single unit (2007-2011) were analysed. Their case notes, radiology, and histology were reviewed. RESULTS: One hundred and sixteen neonates underwent an emergency laparotomy and 77 had stomas fashioned. Sixty-six patients had a contrast study prior to stoma closure (distal loopogram 18, contrast enema 37, both studies 11). Colonic strictures were reported in 18 patients and small bowel strictures were reported in two patients. Fourteen of these colonic strictures were confirmed at operation and on histology but three colonic strictures were missed on contrast studies; one patient had had both contrast studies and the other two only a distal loopogram. Two small bowel strictures reported were confirmed and an additional small bowel stricture missed on distal loopogram was also detected at the time of operation. The incidence of post-op strictures was 19 out of 68 patients (27.9 %) and 16 (84.2 %) of these strictures were found in the colon. Contrast enemas had a much higher sensitivity for detecting post-NEC colonic strictures than distal loopograms; 93 versus 50 %, respectively; however, they are more likely to give a false positive result and therefore their specificity is lower; 88 versus 95 %, respectively. CONCLUSION: Colon is the commonest site for post-NEC stricture and contrast enema is the study of choice for detecting these strictures prior to stoma closure.

Laparoscopic management of obstructed partial duplex with Y ureteric configuration.

An 11-year-old girl underwent a laparoscopic upper-to-lower moiety ureteropyelostomy for lower moiety pelviureteric junction obstruction associated with Y ureteric duplication. She presented with left flank pain and was noted to be hypertensive with microscopic haematuria on admission. An abdominal ultrasound scan revealed a duplex left kidney with gross lower moiety pelvicalyceal dilatation. A subsequent MAG-3 scan demonstrated reduced differential function in the left lower moiety. A laparoscopic transmesocolic approach confirmed a dilated lower moiety pelvis and revealed the Y ureteric duplication. An upper to lower moiety ureteropyelostomy and insertion of a JJ stent is described in the accompanying video. The child was discharged home on the second day post operation. Postoperative imaging showed good decompression and improved differential function. The child has been completely well and normotensive at 2 years' follow-up.

British Association of Paediatric Urologists consensus statement on the management of the primary obstructive megaureter.

INTRODUCTION: It is well-known that the majority of congenital megaureters may be managed conservatively, but the indications and surgical options in patients requiring intervention are less well defined. Hence this topic was selected for discussion at the 2012 consensus meeting of the British Association of Paediatric Urologists (BAPU). Our aim was to establish current UK practice and derive a consensus management strategy. METHODS: An evidence-based literature review on a predefined set of questions on the management of the primary congenital megaureter was presented to a panel of 56 Consultant Surgeon members of the British Association of Paediatric Urologists (BAPU), and current opinion and practice established. Each question was discussed, and a show of hands determined whether the panel reached a consensus (two-thirds majority). RESULTS: The BAPU defined a ureteric diameter over 7 mm as abnormal. The recommendation was for newborns with prenatally diagnosed hydroureteronephrosis to receive antibiotic prophylaxis and be investigated with an ultrasound scan and micturating cystourethrogram, followed by a diuretic renogram once VUR and bladder outlet obstruction had been excluded. Initial management of primary megaureters is conservative. Indications for surgical intervention include symptoms such as febrile UTIs or pain, and in the asymptomatic patient, a DRF below 40% associated with massive or progressive hydronephrosis, or a drop in differential function on serial renograms. The BAPU recommended a ureteral reimplantation in patients over 1 year of age but recognized that the procedure may be challenging in infancy. Proposed alternatives were the insertion of a temporary JJ stent or a refluxing reimplantation. CONCLUSION: A peer-reviewed consensus guideline for the management of the primary megaureter has been established. The guideline is based on current evidence and peer practice and the BAPU recognized that new techniques requiring further studies may have a role in future management.

The utilization of stents in the management of primary obstructive megaureters requiring intervention before 1 year of age.

OBJECTIVE: To analyse the long-term outcome of 16 infants with primary obstructive megaureter managed by (endoscopic or open) stenting over a 10-year period. METHODS: A retrospective case-note and imaging review was performed between 1997 and 2007. Data are presented as medians (range) and were compared using the Mann-Whitney test. RESULTS: Sixteen infants with 19 obstructed megaureters were stented at a median age of 24 weeks, for a median of 6 months. One-third of stents were inserted endoscopically. Complications (stent migration, stone formation or infection) occurred in 31.6%. One infant was excluded due to a co-existent pelviureteric junction obstruction. Drainage improved in 10 ureters (56%) following stent removal. Of the remaining renal units, 6 were reimplanted, and 2 underwent a nephrectomy due to deterioration in renal function following stent removal. Resolution of the vesicoureteric junction obstruction occurred in 4 of 6 infants following endoscopic stent insertion, and in 6 of 12 infants following open stent insertion (P=0.60). There was no difference in the length of time that ureters were stented in the resolved (7.5 (6-15) months) versus the reimplanted (6.0 (1-18) months) group (P=0.13). CONCLUSIONS: Of obstructive megaureters managed by stenting for a median of 6 months, 56% did not require further surgery. However, morbidity occurred in one third of patients, and function deteriorated after removal of stent in two patients who later required a nephrectomy.

Multicystic dysplastic kidney and cystic accessory uterine cavity: a new prenatally diagnosed association.

The co-existence of renal and mullerian anomalies is well-recognised. Multicystic dysplastic kidneys (MCDK) are known to be associated with the presence of genital cysts in both males and females, but this is the first report of a prenatally diagnosed MCDK associated with a non-communicating cystic uterine cavity. The management of these abnormalities in childhood is not well-established.

Educational article: The Mitrofanoff procedure.

The management of urinary incontinence has been revolutionized by the introduction of intermittent catheterization by Lapides in 1972, and later, by the description of the 'trans-appendicular continent cystostomy' by Mitrofanoff in 1980. Mitrofanoff launched a new concept whereby the bladder could be emptied by a route other than the urethra. This concept led to the publication of a plethora of alternatives to the appendix conduit, including the transverse ileal (Yang-Monti) tube, and conduits constructed from ureter, Fallopian tube, tubularized preputial transverse island flap, and longitudinally tubularized ileal and gastric segments. Further experience with the procedure, and the onset of complications such as stomal stenosis and leakage, instigated the description of various stomal options and conduit implantation techniques. More recently, laparoscopic and robotically assisted techniques have also been performed. We present a review of these techniques, and the outcomes reported over the last 30 years since the Mitrofanoff principle was first described.