Meeting the challenges of reconstructive urology - Where are we now?

This is based on the 2018 Storz Urology Lecture at the BAPS Conference and is a personal review of three reconstructive paediatric urological conditions: hypospadias, congenital adrenal hyperplasia, and bladder exstrophy from the perspective of changing expectations and outcomes. LEVEL OF EVIDENCE: V (Expert Opinion).

Ureterocystoplasty: long-term functional results.

PURPOSE: Many institutions have reported varied levels of success with ureterocystoplasty. Recently, there have been concerns regarding the efficacy of ureterocystoplasty as a form of bladder augmentation. We report our long-term functional outcomes with the procedure based on the experience of a single surgeon. MATERIALS AND METHODS: A total of 17 procedures were performed during a 12-year period. Of the patients 10 had posterior urethral valves, 3 had bladder exstrophy, 2 had a neuropathic bladder, 1 had a cloacal anomaly and 1 had a left ectopic ureter. Mean patient age at operation was 5.9 years (range 0.3 to 14.2). All patients underwent preoperative ultrasound, urodynamic studies and radionuclide scanning. Postoperative urodynamics were performed at 6 months. RESULTS: Followup ranged from 0.5 to 11.5 years (mean 4.5). Nine patients underwent ureterocystoplasty with preservation of the ipsilateral kidney, and 1 underwent ureterocystoplasty alone and had a solitary right kidney. The remaining 7 patients underwent ureterocystoplasty with ipsilateral nephrectomy. Postoperatively, the mean bladder capacity improved from 125 to 292 ml, while the mean end filling pressure decreased from 72 to 22 cm H(2)O. Mean preoperative system compliance was 2.1 ml/cm H(2)O, which increased to 16.2 ml/cm H(2)O postoperatively. A total of 13 patients did not require further augmentation surgery. The remaining 4 patients had high pressure and poorly compliant bladders, and underwent ileocystoplasty. Subsequent postoperative nucleotide scans in these 4 patients demonstrated stable upper tracts with good drainage. CONCLUSIONS: Based on our results, ureterocystoplasty provides durable functional urodynamic improvement in patients with a megaureter.

Changes to the contractile function of ureter smooth muscle after partial infravesical obstruction in fetal sheep.

OBJECTIVE: To measure spontaneous contractile activity, and the responses to agonists using in vitro preparations of sheep ureter after a period of bladder outlet obstruction (BOO) initiated at mid-gestation. MATERIAL AND METHODS: Date-mated Romney Marsh ewes, bearing fetuses of 70-75 days of gestation (term in this breed is 145 days) were used. Five fetuses underwent urachal obstruction and partial urethral constriction for 30 days. Six fetuses at the same gestational time underwent a sham operation (control group). Small strips of mid-ureter were cut in the longitudinal axis, and in the cross-sectional (transverse) plane of the ureter. Spontaneous contractile activity and the response to carbachol, high-K(+) (120 mM) solution and alpha,beta-methylene ATP (ABMA) were characterized by measuring the magnitude of evoked responses and the magnitude and frequency of spontaneous activity. RESULTS: The ureters from fetuses with BOO were significantly larger in diameter and had expanded lumens. The proportion of smooth muscle was not significantly different between the BOO and control groups. Spontaneous contractile activity in all preparations was resistant to atropine and the neurotoxin, tetrodotoxin. With transverse sections, the magnitude of spontaneous contractions was smaller in the BOO group, but the frequency was greater. The response to carbachol was also smaller in the BOO group, but the response to high-K(+) solution was similar to that of the control group. ABMA did not generate a response in any preparation. With longitudinal ureteric preparations, spontaneous or agonist-induced activity was negligible in the control group, while preparations from the BOO sheep had spontaneous activity and responded to carbachol and high-K(+) solutions. CONCLUSION: These results show that in fetuses with BOO and dilated ureters absolute ureteric contractile activity is diminished. However, there is functional reorganization of the muscle layers that generates more force in the longitudinal rather than the transverse axis. This would contribute to a reduced ability of the ureter to propel urine and contribute to the development of raised upper tract pressures.

Renal transplantation or bladder augmentation first? A comparison of complications and outcomes in children.

OBJECTIVE: To identify whether the order of performing transplant and bladder reconstruction operations in children who need both operations affects outcome of either operation. PATIENTS AND METHODS: A retrospective case note review was performed of children identified from our database, who had undergone both renal transplantation and bladder augmentation between 1990 and 2005. RESULTS: In all, 18 renal transplants (eight live-related) were performed in 16 children with 10 transplants done after bladder augmentation and eight transplants done before augmentation. The median age at transplantation was 7.5 years and at augmentation was 7.0 years. The median interval between the operations was 33.5 months and the median follow-up was 58.4 months after transplantation. Outcomes were compared between the two groups of patients: those who received their transplantation before bladder augmentation, and those who were transplanted after bladder augmentation. There was no difference between these groups in: the pre- transplant estimated glomerular filtration rate, inpatient stay after transplantation or after augmentation, and incidence of urinary tract infection in the 3 months after renal transplantation or after bladder augmentation. There was no statistical difference in renal allograft loss with one graft failure in the group who were augmented first, and four graft failures in the group who were transplanted first. However, it is of note that the single graft failure in the patient augmented first was due to renal artery thrombosis on the first day related to a double arterial anastomosis, whilst in the other group, three of the graft failures were in transplants that had initially been drained by ureterostomy. Three patients in the group transplanted first developed significant ureteric pathology, of which one developed graft failure. CONCLUSION: Bladder reconstruction can be performed safely before transplantation; it does not increase complications and might better protect the renal graft and specifically the transplant ureter.

Spiral rotational flap for the creation of a new umbilicus in bladder exstrophy.

OBJECTIVE: A range of surgical techniques have been described to create a new umbilicus in children with bladder exstrophy. We present a detailed video demonstrating our technique for the creation of a new umbilicus. METHOD: The position of the planned umbilicus and flap were marked on the abdomen. Incisions were made using monopolar diathermy. The flap was raised and excess fat thinned. Subcutaneous tissues were apposed, and the flap rotated and sutured in spiral fashion with interrupted 6/0 monocryl forming a cone which was subsequently inverted. RESULTS: Between May 1999 and August 2014, we used this technique for the creation of a new umbilicus in 47 bladder exstrophy patients (31 boys and 16 girls). No complications occurred. All were followed up as part of our bladder exstrophy programme. CONCLUSION: The technique allows reproducible excellent cosmetic results. Aesthetic results are durable and it should be considered as an alternative to existing reported techniques.

A Case of Embryonal Rhabdomyosarcoma Presenting as a Lobulated Protrusion From the Urethral Meatus at Birth.

This is the first reported case of rhabdomyosarcoma presenting as a mass protruding from the urethral meatus present at birth. A male neonate was transferred to a tertiary pediatric urology center on day 4 of life where the mass was surgically excised. Histology confirmed an embryonal rhabdomyosarcoma and chemotherapy commenced. The patient completed chemotherapy at the age of 8 months. The child is now 3.5 years old and well with no recurrence of disease.

The predictive value of a repeat micturating cystourethrogram for remnant leaflets after primary endoscopic ablation of posterior urethral valves.

OBJECTIVE: We routinely perform a cystourethroscopy 3 months after initial ablation of posterior urethral valves. The aim of this study was to determine the predictive value of the urethral appearance on preoperative micturating cystourethrogram (MCUG) for further valve resection at check cystoscopy. PATIENTS AND METHODS: We retrospectively reviewed 31 consecutive boys (aged 4-18 months) who underwent check cystoscopy and repeat MCUG between 2006 and 2008. RESULTS: Repeat MCUG suggested remnant valves in 10, but no residual leaflets were identified cystoscopically in 4. In 20 boys, the valves appeared completely ablated on MCUG but valve leaflets received further resection in 10. One study was undiagnostic. Residual valves were resected in 83% (5/6) where valves and urethral dilatation were noted on MCUG. Where MCUG suggested either valves or persistent dilatation alone, further resection occurred in 40% (4/10). Remnant leaflets were also present in half of those (7/14) in whom the repeat MCUG had shown complete ablation and resolved/reduced posterior urethral dilatation. CONCLUSIONS: The positive predictive value of valve leaflets and/or posterior urethral dilatation on repeat MCUG for subsequent resection of valve remnants was 56%; the negative predictive value was 50%. We found repeat MCUG alone imprecise in excluding residual valve tissue and recommend check cystoscopy in all.

An initial experience of 100 paediatric laparoscopic nephrectomies with transperitoneal or posterior prone retroperitoneoscopic approach.

The objective of this study was to evaluate the outcome of the initial 100 consecutive laparoscopic nephrectomies using a transperitoneal or a posterior prone retroperitoneoscopic approach. The medical records of 97 consecutive children who underwent laparoscopic nephrectomy between January 2000 and December 2003 were reviewed. Children having concomitant operative procedures were excluded from the study. Laparoscopy was performed by a transperitoneal (TP) or a posterior prone retroperitoneoscopic (PPR) approach based on the preference of the operating surgeon. A total of 100 procedures were successfully completed laparoscopically. Two children required conversion to open surgery. The median operating time was 112 min for the TP approach and 96 min for the PPR approach (P = 0.002). There was no significant difference in the analgesic requirements between the two groups. The rate of complications was similar, as was the length of hospital stay. This was despite the fact that the children in the TP group were somewhat older in age. In children having bilateral native kidney nephrectomy, peritoneal dialysis was successfully established within 48 h after surgery in the PPR group. Taking into account the heterogeneous nature of our group of patients, a reliable conclusion in regard to the difference in operative time, analgesic requirement or approach could not be ascertained. There is the suggestion however, that both the TP and PPR approaches for nephrectomy are equally applicable in children. The posterior prone retroperitoneoscopic approach may have an advantage in children who require peritoneal dialysis.

Radiotelemetered urodynamics of obstructed ovine fetal bladders: correlations with ex vivo cystometry and renal histopathology.

OBJECTIVE: To test the hypothesis that fetal bladder outlet obstruction (BOO) in sheep causes abnormal urodynamics correlating with the initiation of renal pathology, as most boys with posterior urethral valves (PUV) have bladder dysfunction when assessed after birth. MATERIALS AND METHODS: Male ovine fetuses at 94 days of gestation were assigned to BOO (four) or sham control (five) groups. In BOO fetuses, radiotelemetry catheters were inserted transurachally and intraperitoneally, and the urethra was partly occluded. In two sham controls catheters were inserted directly through the bladder wall; the remaining three had sham surgery only. Radiotelemetered cystometry was recorded daily where possible. At the end of the experiment (9 days), ex vivo cystometry, bladder contractility studies and renal tract histology were assessed. RESULTS: Ultrasonography showed dilated renal tracts only in BOO fetuses; three of four BOO fetuses had renal cortical cysts. The control fetuses with bladder catheters died in utero, so urodynamics were recorded only in fetuses with BOO. The baseline filling/storage detrusor pressures increased slightly (by a mean of 5 mmHg) during the first 4 days of BOO, thereafter returning to those at the outset. There were marked changes in the patterns of bladder activity from 1 to 9 days. The frequency and duration of 'voiding' increased; as such the higher sustained pressures of emptying activity were progressively extended and the periods of low pressure filling/storage accordingly shortened. The patterns among individual fetuses with BOO were not substantially different, except that the one with the non-cystic kidneys had a more moderate frequency and duration of voiding. Ex vivo compliance and contractility showed no consistent differences in detrusor compliance or contractility between BOO and sham bladders. CONCLUSION: In this fetal model of PUV, there was a progressive increase in the duration and frequency of sustained elevated 'voiding' pressures, with no change in bladder compliance. Fetal kidneys were sensitive to these altered dynamics, with the formation of cortical cysts by 9 days after initiating BOO.

The two-stage repair for severe primary hypospadias.

OBJECTIVES: The repair of severe primary hypospadias represents a major surgical challenge. After initial enthusiasm for single-stage procedures, many paediatric urologists have turned to the alternative two-stage approach after experiencing disappointing results. A single surgeon's experience of the two-stage procedure is reported. METHODS: Between 1998 and 2003, 62 boys underwent a two-stage reconstruction for primary hypospadias. Indications for staged repair included proximal meatus (mid-shaft [18 patients], peno-scrotal [23] or perineal [two]), moderate or severe chordee (38 patients), poor glans groove, and lichen sclerosis. Inner prepuce was the graft of choice. Median age was 27.6 months at completion of surgery and median follow-up was 26 months. RESULTS: All grafts took well and none of the 62 patients needed revision. One patient developed a haematoma. Maturation of the graft for at least six months ensured the best conditions for the second-stage closure. Overall the cosmetic and functional results after the second stage were excellent. The outcomes were determined by the parents' and surgeon's assessment of function and the cosmetic appearance. Complications included partial glans dehiscense (three patients), residual mild curvature (three) and meatal stenosis (three). CONCLUSION: The two-stage repair has proved to be a reliable and reproducible technique with a low complication rate in a difficult cohort of hypospadias patients. Inner preputial skin grafts take very successfully on the ventral surface of the penis, and splitting the glans enables a slit-like meatus to be achieved. Excellent cosmetic results can be anticipated.

The role of unilateral nephrectomy in the treatment of nephrogenic hypertension in children.

OBJECTIVES: To define the efficacy of unilateral nephrectomy in a large series of patients presenting with renal disease and hypertension, as the latter may be a prominent finding in children with nephrourological disease (renal parenchymal disease, renovascular disease, obstruction, renal dysplasia and cancer). PATIENTS AND METHODS: We retrospectively reviewed the hospital and outpatient records of 118 children who presented for evaluation with hypertension, and who had a nephrectomy between 1968 and 2003. Patients included in the study were those who had a unilateral nephrectomy for benign renal hypertension with a normal contralateral kidney; in all, 21 had complete records and follow-up were evaluated. The hypertension was associated with primary renal disease, obstruction and renovascular disease. Blood pressure and medication requirements were compared before and after surgery, the blood pressure values also being compared with published nomograms. RESULTS: Patients were diagnosed with hypertension at a median age of 5 years and had a nephrectomy at a median of 11 months after the diagnosis. The median follow-up after surgery was 39 months. Most patients responded well and became normotensive, or there was a reduction in the need for medication. The median time to normalization was 2, 10 and 11 days in patients with primary renal disease, obstruction and renovascular disease, respectively. CONCLUSION: Nephrectomy is successful in normalizing blood pressure in children with benign renal hypertension and with a normal contralateral kidney.

Contractile properties of the developing fetal sheep bladder.

AIM: To characterise the developmental changes to the normal bladder by examining the in vitro contractile properties of the fetal sheep detrusor smooth muscle bladder at different gestational ages. METHODS: Three groups of normally developing fetal sheep bladders were investigated: (1) 65-70 days gestation (2nd trimester); (2) 105-110 days (3rd trimester); (3) 135-140 days (term). Isometric contractions in isolated detrusor strips were measured during either electrical field stimulation (EFS) or exposure to agonists: carbachol, alpha-beta methylene-ATP (ABMA) and KCl. RESULTS: There was a significant increase of absolute force elicited by EFS with fetal age. Contractures elicited by carbachol, ABMA and KCl increased between Groups 1 and 2, but not thereafter. The proportional increase of contractions elicited by carbachol and ABMA was also greater between Groups 1 and 2, than for EFS and KCl. CONCLUSIONS: Fetal development between 65 and 140 days in the sheep is associated with increased contractile activation. The data are consistent with an increase of muscle development in the earlier stages (65-110 days). In the later stage (110-140 days) muscle development is complete but functional innervation of the tissue continues.

Urinary outflow obstruction increases apoptosis and deregulates Bcl-2 and Bax expression in the fetal ovine bladder.

During organogenesis, net growth of tissues is determined by a balance between proliferation, hypertrophy, and apoptotic death. Human fetal bladder outflow obstruction is a major cause of end-stage renal failure in children and is associated with complex pathology in the kidney and lower urinary tract. Experimental manipulation of the fetal sheep urinary tract has proved informative in understanding the pathobiology of congenital obstructive uropathy. In this study we used an ovine model of fetal bladder outflow obstruction to examine effects on apoptotic cell death in the developing urinary bladder. While 30 days of obstruction in utero between 75 and 105 days gestation resulted in overall growth of the fetal bladder as assessed by weight, protein, and DNA measurements, we found that apoptosis, as assessed by in situ end-labeling, was up-regulated in fetal bladder detrusor muscle and lamina propria cells and that this was accompanied by a down-regulation of the anti-death protein Bcl-2 and an up-regulation of the pro-death protein Bax. Moreover, activated caspase-3, an effector of apoptotic death, was increased in obstructed bladders. This is the first study to define altered death in an experimental fetal model of bladder dysmorphogenesis. We speculate that enhanced apoptosis in detrusor smooth muscle cells is part of a remodeling response during compensatory hyperplasia and hypertrophy. Conversely, in the lamina propria, an imbalance between death and proliferation leads to a relative depletion of cells.

Effects of in utero bladder outflow obstruction on fetal sheep detrusor contractility, compliance and innervation.

PURPOSE: Congenital bladder outflow obstruction caused by posterior urethral valves is a common cause of end stage renal failure in boys. We hypothesized that fetal bladder outflow obstruction perturbs detrusor contractility and innervation and bladder storage volume-pressure relationships. MATERIALS AND METHODS: Severe bladder outflow obstruction was induced in male fetal sheep by placing a urethral ring and urachal ligation midway through gestation at 75 days. Fetuses were examined 30 days after surgery, when urinary tract dilatation, enlarged bladders and histologically abnormal kidneys were documented. Isolated strips of bladder detrusor from sham operated and obstructed fetuses were subjected to electrical field stimulation, carbachol, KCl and alpha-beta methylene-adenosine triphosphate. Whole bladder storage characteristics were determined by filling cystometry and bladder innervation was investigated by immunohistochemistry and Western blot. RESULTS: Tension-frequency contractility studies showed that obstructed fetal bladder strips were significantly hypocontractile versus sham operated controls in response to electrical field stimulation and the specific agonists carbachol, KCl and alpha-beta methylene-adenosine triphosphate. Hypocontractility was greater with nerve mediated stimulation than with carbachol, suggesting relative denervation. Reduced innervation was confirmed by S100 and protein gene product 9.5 immunohistochemistry and by measuring a significant reduction in protein gene product 9.5 protein expression using Western blot. Filling cystometry showed that obstructed fetal bladders appeared more compliant (Delta V/Delta P, where Delta V is the change in volume and Delta P is the change in pressure) with larger capacity, more flaccidity and yet retained stress relaxation. CONCLUSIONS: In response to severe experimental fetal bladder outflow obstruction the bladder becomes large and hypocontractile, and has aberrant innervation.