Ureteric-urethral engraftment as a new surgical technique for management of incontinence in bladder exstrophy complex: A retrospective cohort

Accepted Manuscript Ureteric-urethral engraftment as a new surgical technique for management of incontinence in bladder exstrophy complex: A retrospective cohort Abdol-Mohammad Kajbafzadeh, Shabnam Sabetkish, Nastaran Sabetish PII:

S1743-9191(17)31241-4

DOI:

10.1016/j.ijsu.2017.08.581

Reference:

IJSU 4119

To appear in:

International Journal of Surgery

Received Date: 28 June 2017 Revised Date:

8 August 2017

Accepted Date: 21 August 2017

Please cite this article as: Kajbafzadeh A-M, Sabetkish S, Sabetish N, Ureteric-urethral engraftment as a new surgical technique for management of incontinence in bladder exstrophy complex: A retrospective cohort, International Journal of Surgery (2017), doi: 10.1016/j.ijsu.2017.08.581. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Ureteric-urethral Engraftment as a New Surgical Technique for Management of Incontinence in Bladder Exstrophy Complex: a Retrospective Cohort

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Abdol-Mohammad Kajbafzadeh* 1, Shabnam Sabetkish, Nastaran Sabetish

Affiliations:

Pediatric Urology and Regenerative Medicine Research Center, Section of Tissue

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1

Engineering and Stem Cells Therapy, Children’s Hospital Medical Center, Tehran

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University of Medical Sciences, Tehran, Iran (IRI)

Correspondence to:

Dr. Abdol-Mohammad Kajbafzadeh

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Postal address: No. 62, Dr. Qarib’s Street, Keshavarz Boulevard Tehran, Iran (IRI)

Postal Code: 1419433151

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Tel/ Fax: +98-21-66565400

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E-mail: [email protected]

Short running title: Ureteric-urethral Engraftment in Bladder Exstrophy Complex

Acknowledgement We highly appreciate Mrs. M. Khalifehʼ assistance for her artistic illustrations.

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Abstract Objectives: To report the results of a novel surgical technique for achieving urinary

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continence in patients with bladder exstrophy complex (BEC) by ureteric-urethral engraftment (UUE) technique.

Patients and methods: Sixteen female patients with BEC and a mean ± SD age of 3.48 ± 1.75 years were referred for primary exstrophy repair from 2009 to 2012. From

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these, 9 patients were operated by single-stage bladder closure (group I); while 7

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patients underwent the novel technique of UUE to compare the continence achievement (group II). In UUE technique, distal ureter was applied for total urethral replacement while the lower part of engraft was fixed in external genitalia. No osteotomy was performed in none of the groups. Continence and upper urinary tract evaluation were performed in the follow-ups with 3 months intervals for the first year and biannually

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thereafter. The patients were followed-up for a mean ± SD duration of 72 ± 6 months. Results: All patients in both groups experienced an uneventful postoperative period. In group II, 5 patients were continent day and night and voided per urethra without need

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for augmentation or intermittent catheterization technique (71.42%); while 55.55% of

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patients in group I achieved total continence (n=5). Partial continence was achieved in 4 (44.44%) and 2 (28.57%) patients in group I and II, respectively. However, 3 patients in UUE group had postoperative vesicoureteral reflux that was successfully managed by Deflux injection.

Conclusion: The eventual clinical outcomes of BEC children undergoing the UUE technique were promising. This practicable, safe, and reproducible option will add one complementary stage to the previously used reconstruction techniques. These patients 2

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would necessitate further surveillance with upper urinary tract evaluations during the adult life.

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Key words: Bladder Exstrophy Complex; urinary incontinence; pediatrics Abbreviations: Bladder Exstrophy Complex (BEC); Bladder Neck Reconstruction

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(BNR); ureteric-urethral engraftment (UUE)

Introduction

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The surgical management of bladder exstrophy complex (BEC) has extremely developed in the course of time. Several techniques have been applied to address the challenges of BEC reconstruction. Trendelenberg has first described his technique with initial success and early failure in 1906 [1]. Sufficient bladder capacity and eventual

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development of continence can be obtained by successful initial bladder closure [2]. Successful reconstruction at the first attempt is extremely associated with spontaneous voiding. Relatively, 75% of children with successful primary closure and 30% of children

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with failed initial repair will gain eventual urinary continence [3]. Another study showed that only 18% of children with failed primary closure were eventually continent and

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voiding per urethra [4]. So, it is of great importance to apply the best surgical technique in the first attempt in order to obtain satisfactory results in terms of eventual continence. Urethral replacement with ureter was first described by Mitchell et al. in 1988 in which proximal or total urethral replacement was executed in 7 patients with classical/cloacal bladder exstrophy and 1 patient with imperforated anus and hypoplasia of the bladder neck and urethra [5]. In the study of Feng et al., the double tunnel ureteral pedicle was

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applied as an option in the urological armamentarium in order to construct a catheterizable stoma (ureteral Mitrofanoff) [6]. In another pilot study, ureteral grafts were applied as tube and patch segments in urethral reconstruction in order to form a

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continent catheterizable stoma [7]. In spite of promising results achieved in terms of continence grade in our earlier studies [8-14], the hopeful outcomes of ureteric-urethral engraftment (UUE) in previous investigations [6, 7, 15] encouraged us to evaluate the

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continence outcomes of this surgical technique in females with BEC with more longterm follow-ups.

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The objective of this study is to describe a new surgical technique for obtaining eventual urinary continence at a urology center of excellence with over 20 years of experience in the reconstruction of BEC. Specific focus was placed on comparing the incontinence grade in patients undergoing single-stage bladder closure with female patients in whom

Patients and methods

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UUE technique was applied.

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All female patients with BEC referring to our institution between June 2009 and October 2012 for primary exstrophy repair formed the cohort of the present study after obtaining

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institutional approval and informed consent from the parents. To obtain medical, surgical, and radiologic data, retrospective chart review was applied. Premature patients or children with failed primary reconstruction performed at other institutions were excluded from the study. The mean ± SD follow-up period was 72 ± 6 months (range 52-93 months).

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A total of 16 female patients with BEC were referred for further management. Patients were randomly divided in 2 groups. Patients of group I (N=9, aged 3.15 ± 1.25 years) were operated by single-stage bladder closure without osteotomy. Individuals of group II

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(N=7, aged 3.68 ± 1.5 years) underwent the novel technique of UUE to compare the continence achievement. Osteotomy was not performed in this group, neither.

In patients undergoing the UUE technique (group II), distal left ureter accompanied with

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the vascular pedicle and a part of detrusor muscles was applied as a flap for total urethral replacement. We performed this technique by the application of distal part of

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the left ureter in all patients as the ureteral orifice was more near to the bladder neck. The ureteral segment was based solely on a vascular pedicle arising from the internal iliac artery. After opening the bladder, distal ureter (approximate length of 2 – 2.5 cm). We performed this technique by the application of distal part of the left ureter in all

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patients as the ureteral orifice was more near to the bladder neck. The flap was reimplanted transtrigonally on the lower edge of the trigone, and the lower part of the ureteral segment was fixed in external genitalia. Reimplantation was performed in a

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submucosal tunnel in urethral plate and the edge of the flap was sutured to the rim of the urethral plate. The proximal portion of the flap was sutured to the edge of trigone by

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a fish mouth appearance in order to avoid funneling. The end part of proximal portion of the ureteral segment was sutured to the ureteral orifice. Dissected distal ureter was supposed to be reimplanted from the bladder neck down to the external genitalia and not just the distal part of the urethra. The length was adjusted in order to avoid the creation of bladder outlet obstruction. If the segment is too long, the bladder was wrapped around the segment proximally at the level of the bladder neck. A single-stage

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complete functional reconstruction of the whole length of the urethra, bladder neck, and external genitalia was performed. Figure 1 & 2 depicts different stages of UUE technique.

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The patients were discharged after 35 ±3 days. No ureteric stent was used in any of the patients. However, urethral catheter was used for drainage of the urine which was approximately used for 10 days. Antibiotics were continued for 2 weeks after surgery

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and then the patinas were placed on prophylactic antibiotics for 6 months after the surgery.

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All the patients were followed up with 3 months intervals for the first year and biannually thereafter for evaluation of continence and upper urinary tract performance. If needed, endoscopic

injection

of

dextranomer/hyaluronic

acid

(Dx/HA)

copolymer

(Deflux, Q-Med, Uppsala, Sweden) in periureteral or subtrigonal region was conducted

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for treatment of vesicoureteral reflux.

As described in our previous study [16], if the patient was dry at night and continent for a minimum of 6 hours throughout the day, it was considered as a total continent patient

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(Grade 0, socially continent). However, occasional nighttime leakage and dryness of at least 3 hours during the day was defined as grade I of continence (occasionally wet).

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Children with dry intervals of lasting less than 3 hours during day were considered as grade II of continence (frequently wet). Those patients with urinary bothers that needed further reconstruction were defined as incontinent (Grade III). The bladder outlet patency was examined before discharge. An ultrasound study was performed to rule out hydronephrosis after removal of urethral catheter. Residual urines were then measured during few days after clamping the suprapubic tube. The

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suprapubic tube removal was performed if the residual urines were low. Before the removal of the suprapubic tube, a urine culture was sent to ensure the sterility of the bladder urine. Cystoscopy was performed in the case of high residual urines. Urine

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cultures accompanied with renal and bladder ultrasounds were performed for monthly monitoring.

Statistical Package for Social Sciences (SPSS for Windows 18.0 Chicago, USA)

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program was used for data analysis. Results were presented as frequency and mean ± standard deviation. Pearson’s chi-squared test was used for the analysis of categorical

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data. A p value < 0.05 was considered to be significant.

Results

All operative reconstructive procedures were undertaken by one pediatric urologist in

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our institution (AMK). All patients underwent bladder closure at a mean ± SD age of 3.48 ± 1.75 years (range 18-65 months) with no significant difference among groups (p=0.08). Reasons for delayed closure included a poor prenatal diagnosis of BEC,

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coexistent neonatal problems, and low socioeconomic status of some patients. Complete primary closure was successful in all children of both groups in which the

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bladder and posterior urethra were safely placed in a closed bony pelvis without any major complication including anastomotic stricture, obstruction, wound dehiscence and chronic renal failure. Even though, an isolated distal segment of ureter was applied in each individual of group II, all segments remained viable with no difficulty in catheterization.

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In order to decrease any bias and regarding the wide range of ages, the bladder capacities were adjusted for patient weight. Bladder capacity improved in the majority of patients in this cohort with a significant higher mean ± SD bladder capacity (p=0.04) of

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patients undergoing the UUE technique (185.5 ± 22.1 ml). However, the mean bladder capacity was 123.8 ± 19.1 ml in those children having reconstruction with simple bladder closure technique. None of the patients were noted with reduction in bladder

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capacity over time.

With this long-term follow-up of 52 to 93 months, continence grade was significantly

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higher in group II compared to group I (p= 0.03). Continence with normal voiding has been achieved in 5 of the 7 patients in UUE group (71.42%). However, 5 cases (55.55%) in simple closure group were finally able to void per urethra, with dry periods of at least 6 hours during the daytime and complete dryness at night without any need

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for bladder augmentation or intermittent catheterization. Partial continence with episodes of nocturnal enuresis was achieved in 4 (44.44%) and 2 (28.57%) patients in group I and II, respectively. In this regards, 3 (33.3%) and 1 (11.1%) patients were

undergoing

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occasionally and frequently wet in group I, respectively. However, none of the patients UUE

technique

suffered

from

being

frequently

wet.

Intermittent

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catheterization was required for complete bladder emptying in patients with partial continence. None of the patients remained incontinent neither in group I nor in patients undergoing the new UUE surgical technique. Patients undergoing standard closure did not complain from vesicoureteral reflux (VUR) during the postoperative period; while 3 out of 7 patients in UUE group (42.85%) were referred with postoperative unilateral VUR in the side from which the ureteral segment

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was dissected for reimplantation. VUR was successfully managed by Deflux injection and none of the patients suffered from upper urinary tract deterioration (Figure 3).

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Discussion

In the current study, a single-institution, single-surgeon experience of patients with BEC who have been managed with UUE technique and with a minimum of 52 months follow-

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up, have been represented.

Children with BEC can be best treated at pediatric centers with expertise in

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management of these patients. The initial step in a pathway towards reconstruction of the lower urinary tract is closure of the bladder template in patients with BEC. The major milestone in a child with BEC or other lower urinary tract birth defects is the achievement of urinary continence which can be failed with all methods of exstrophy

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repair. This failure will almost result in a great deal of confidence loss and decreased quality of life. The critical point in any adolescent who remains incontinent is a precise preoperative scrutiny to choose the best method in which continence can be reliably

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achieved with the least morbidity and failure occurrence. In cases with failure of continent reconstruction, combinations of surgical techniques are often applied as

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salvage procedures [17]. In the current study, we investigated the long-term safety and efficacy of ureteric-urethral engraftment as a new surgical technique, especially regarding the preservation of postoperative renal function and avoidance of major complications.

Modern techniques of lower urinary tract reconstruction have increased the potentials for urinary continence with controlled urethral voiding in children with BEC [18].

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However, patients with ongoing incontinence in whom repeated surgeries have not been successful, will need urinary diversion which has numerous complications [19]. Emptying of the bladder in normal individuals depends on the balance between

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sphincter relaxation and detrusor contraction. However, expectation of such an action in patients with BEC is doubtable. In these children, it is still uncertain if reconstruction creates a control mechanism that actually works [20]. Increasing of the outlet resistance

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after initial closure and bladder neck reconstruction (BNR), urethral strictures, and vesicoureteral reflux are among the factors that can affect renal function in children with

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BEC [21].

Deterioration of the upper urinary tract is considered to be as one of the most overwhelming complications of BEC reconstruction. Anticholinergics and clean intermittent catheterization are two alternatives for management of neurogenic bladders

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as well as BEC. Bladder augmentation and creation of continent stoma in conjunction with clean intermittent catheterization have been applied for selected exstrophy patients who are suffering from persistent upper urinary tract deteriorations, urinary

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incontinence, and small bladder capacity [22]. However, this procedure is usually delayed in young patients due to perioperative and numerous long-term postoperative

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complications that can significantly decrease the quality of life in these children [23, 24]. In the present study, both the elimination of upper urinary tract changes and urinary continence has been achieved by the application of a novel surgical technique. This method may be beneficial to reduce the incidence of mucus production, metabolic disturbance, urolithiasis, bowel obstruction, malignancy, and perforation as known complications of enterocystoplasty and catheterizable stomas.

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In the study of Baradaran et al., all the patients were finally continent after primary or rediverted incontinent urinary diversion in long-term follow-up [25]. Similar results were obtained in the study of Surer et al. and Barbosa et al. in which 93% and 95.4%

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continence rate was reported, respectively [26, 27]. The critical point is whether these children face an acceptable quality of life and psychological challenges after urinary diversion.

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Bladder capacity at the time of BNR is the single most important predictor factor in continence achievement of BEC patients [18, 28]. Any improvement in bladder capacity

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will have a positive effect on subsequent BNR. Moreover, a better template for later augmentation will be provided by increases in bladder capacity [29]. According to previous reports, a median capacity of 85 cc is highly associated with a higher probability of final voided continence in patients undergoing any type of staged

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reconstruction [18]. Similar results were obtained in the study of Purves et al. in which dryness was mostly achieved in patients with large capacities [30]. Outlet resistance should be adequate to permit bladder growth but it should be also low

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enough for complete bladder emptying and avoidance of upper urinary tract deterioration at the time of initial bladder closure. In the study of Puves et al., immediate

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leakage after suprapubic tube removal was demonstrated 7.3% of patients in postoperative period that was attributed to poor outlet resistance [30]. Moreover, decreased capacity with decreased compliance was observed in the urodynamic study of all the previously mentioned children. According to the study of Novak et al. only 18% of patients with failed primary closure attained the continence per urethra [4]. Enterocystoplasty and a lifetime intermittent

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catheterization are the expense of continence achievement in the majority of these patients. Similarly, only 14% of children with a history of failed primary closure were eventually dry when performing repeat closure in conjunction with bilateral anterior iliac

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osteotomies and spica casting [31]. As a preliminary study in our center, we chose to try this technique in patients with primary closure in a limited number of patients, rather than in a subgroup of secondary closure for failed initial closures in order to compare

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the results with patients undergoing conventional technique of single-stage bladder closure. However, it would be of utmost importance if this could be used for a failed

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procedure as it then might be able to salvage a bladder and avoid resultant need for augmentation. More investigations are required to evaluate the potential benefits of UUE technique in this subgroup of patients in whom achieving the continence is extremely challenging and in patients with complex urethral issues not amenable to

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more conservative measures.

In spite of the fact that the role of ureteral segment in urological reconstruction was previously discussed [5-7], this technique was not previously compared with single-

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stage bladder closure in female patients with BEC in long-terms. By the application of this technique, we can reduce the number of surgeries, minimize further hospitalization,

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and eliminate the quality of the bladder plate deterioration following failed bladder exstrophy surgeries. However, the significant claims of the present study are limited by the restricted number of patients in each group to identify statistical significance. In addition, due to the length of urethra in males, we limited the performance of this surgical technique for females. However, a distal ureteral segment should be considered as a potentially useful section in the reconstruction of the proximal (male)

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urethra in patients with congenital urethral malformations. Continued prospective assessments of the patients can verify whether these data can be replicated. Long-term follow-up of the upper tracts is suggested even in children who have achieved

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satisfactory reconstruction.

Conclusion

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The authors believe that these promising outcomes can be achieved in all excellent centers with precise patient selection. Distal ureter can be a reasonable option for long-

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term urethral reconstruction with preserved renal function in carefully selected BEC patients. While our results were promising, failure may still occur with the abovementioned repair technique. Hence, more clinical studies are in process to focus on

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improving the quality of life in children with BEC.

None

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Figure Legends:

urethral replacement

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Figure 1: Surgical technique of UUE technique: distal ureter was applied for total

Figure 2: Schematic step- by- step surgical process of UUE technique: (A) resecting distal pedicled ureteric segment (B) submucosal ureteric engraftment at urethral plate

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(C) mucosal urothelial coverage of grafted ureter, fish mouth appearance and trigonal

ureter

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widening (D) coverage of the ureter by the remaining muscles (E) closure of the grafted

Figure 3: Different characteristics of one of the patients undergoing UUE technique: (A) Preoperative multislice spiral CT scan of the bony pelvic showing increase in pubic diastasis (B) postoperative appearance of the surgical area (C) vesicoureteral reflux after undergoing UUE technique that was successfully managed with Deflux injection

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(D) ultrasound evaluations showed no abnormal finding after surgical management and

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Deflux injection

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Table 1: characteristics of patients in group I and II undergoing simple closure and UUE technique:

3.15 ± 1.25 123.8 ± 19.1

Occasionally wet (Grade I) Frequently wet (Grade II) VUR

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5 (71.42%)

p= 0.03

3 (33.3%) 1 (11.1%)

2 (28.57%) ---

---

3 (42.85%)

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Partial continence

5 (55.5%)

p value

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Complete continence (grade 0)

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Continence

Age (mean ± SD) Bladder capacity (mL)

Group II (UUE technique) N=7 3.68 ± 1.5 185.5 ± 22.1

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Group I N=9

p=0.08 p=0.04

p= 0.04

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Highlights A novel surgical technique for achieving urinary continence in bladder exstrophy

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Ureteric-urethral engraftment technique in bladder exstrophy

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A practicable, safe, and reproducible option for achieving urinary continence

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SC

RI PT

•