- Email: [email protected]
hyaluronic acid copolymer (Deflux)
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Journal of Pediatric Urology (2013) xx, 1e6
Outcomes of vesicoureteral reflux in children with non-neurogenic lower urinary tract dysfunction treated with dextranomer/ hyaluronic acid copolymer (Deflux) Jason P. Van Batavia, Shannon N. Nees, Angela M. Fast, Andrew J. Combs, Kenneth I. Glassberg* Division of Pediatric Urology, Morgan Stanley Children’s Hospital of New York-Presbyterian, Department of Urology, Columbia University, College of Physicians and Surgeons, New York, NY, USA Received 30 June 2013; accepted 16 October 2013
KEYWORDS Vesicoureteral reflux; Lower urinary tract conditions; Deflux; Dysfunctional voiding; Pediatrics
Abstract Objective: There has been hesitancy to use dextranomer/hyaluronic acid copolymer (DHXA, Deflux for vesicoureteral reflux (VUR) in the setting of lower urinary tract (LUT) dysfunction because of the limited number of published studies, the possibility of less success, and the manufacturer’s recommendations contraindicating its use in patients with active LUT dysfunction. We report on our experience using DXHA in this subset of patients whose VUR persisted despite targeted therapy for their LUT condition. Materials and methods: We reviewed patients diagnosed with both a LUT condition and VUR who underwent subureteric DXHA while still undergoing treatment for their LUT dysfunction. Persistence of VUR was confirmed by videourodynamic studies (VUDS)/VCUG (voiding cystourethrogram) and all patients were on targeted treatment (TT) and antibiotic prophylaxis prior to and during DXHA injection. VUR was reassessed post-injection. Results: Fifteen patients (22 ureters; 21F,1M) met inclusion criteria (mean age 6.1 years, range 4e12). Following one to three DXHA injections, VUR resolved in 17 ureters (77%) including eight of nine ureters in dysfunctional voiding (DV) patients, five of nine in idiopathic detrusor overactivity disorder (IDOD), and four of four in detrusor underutilization disorder (DUD) patients. Conclusions: DXHA is safe and effective in resolving VUR in children with associated LUT dysfunction, even before their LUT condition has fully resolved. Highest resolution rates were noted in patients with either DV or DUD or who were least symptomatic prior to injection. ª 2013 Published by Elsevier Ltd on behalf of Journal of Pediatric Urology Company.
* Corresponding author. Tel.: þ1 212 305 9918; fax: þ1 212 342 1065. E-mail addresses: [email protected] (J.P. Van Batavia), [email protected] (K.I. Glassberg). 1477-5131/$36 ª 2013 Published by Elsevier Ltd on behalf of Journal of Pediatric Urology Company. http://dx.doi.org/10.1016/j.jpurol.2013.10.017
Please cite this article in press as: Van Batavia JP, et al., Outcomes of vesicoureteral reflux in children with non-neurogenic lower urinary tract dysfunction treated with dextranomer/hyaluronic acid copolymer (Deflux), Journal of Pediatric Urology (2013), http://dx.doi.org/ 10.1016/j.jpurol.2013.10.017
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Introduction Both vesicoureteral reflux (VUR) and lower urinary tract (LUT) dysfunction are common reasons for referral to pediatric urologists and both conditions often appear together [1e3]. According to the 2010 AUA (american urologic association) Guideline on Primary Vesicoureteral Reflux, children with VUR and LUT dysfunction are less likely to have spontaneous resolution of VUR than are those with VUR and no LUT dysfunction (31% vs. 61% in children without LUT dysfunction) [4]. Although it is still not clear if LUT dysfunction causes or even contributes to VUR, it does seem clear that treatment of LUT dysfunction can lead to higher rates of VUR resolution [5,6]. Subureteric dextranomer/hyaluronic acid copolymer (DXHA/Deflux) injection has emerged over the past two decades as an acceptable first-line minimally invasive option for treating persistent VUR in children [7e9]. Despite its high overall success rates, concern exists regarding use of DXHA injection in children with LUT dysfunction, as some reports have shown a decreased rate of cure in these children [4,10,11], In fact, according to manufacturer recommendations, endoscopic treatment with DXHA is contraindicated in patients with active LUT dysfunction. This recommendation may be consistent with some of the earlier articles cited in the 2010 AUA guideline report for primary VUR and its metaanalysis findings that endoscopic bulking agents were only successful in resolving VUR in 50% of children with LUT dysfunction compared with 83% of children without LUT dysfunction [4]. More recent studies in children with LUT dysfunction, however, report higher success rates and question this blanket statement regarding DXHA injection in LUT dysfunction patients [12,13]. We wanted to further add to the literature and report our VUR resolution rate in children actively being treated for LUT dysfunction who underwent treatment with subureteric DXHA. Additionally, we hypothesized that children whose LUTS (lower urinary tract symptoms) subsided while on targeted treatment (TT) would have higher VUR resolution rates following DXHA injection than those children on TT still symptomatic prior to injection.
Materials and methods Using our IRB (internal review board)-approved pediatric urology database, we identified patients diagnosed with both a non-neurogenic LUT condition and VUR from January 2003 to December 2012. Each child was diagnosed with one of four LUT conditions based on the goodness of fit between history, physical exam, voiding diary, noninvasive uroflow/ electromyography (EMG) and VUDS when indicated [14,15]: (1) dysfunctional voiding (DV) Z LUTS with an active EMG during voiding associated detrusor overactivity (DO); treated with biofeedback antimuscarinics. (2) idiopathic detrusor overactivity disorder (IDOD) Z idiopathic (primary) detrusor overactivity with a quiet EMG during voiding with DO established either by urodynamic studies (UDS) or urinary urgency combined with a shortened EMG lag time (<2 s) on uroflow/EMG; treated with antimuscarinics.
J.P. Van Batavia et al. (3) detrusor underutilization disorder (DUD) Z large bladder capacity with voided volume in excess of expected bladder capacity (i.e. >125%) as a result of willful deferred voiding but with otherwise quiet EMG during voiding and normal uroflow pattern; treated with timed voiding. (4) primary bladder neck dysfunction (PBND) Z delayed or incomplete bladder neck opening resulting in impaired urine flow; most commonly associated with hesitancy and characterized by a prolonged EMG lag time (>6 s) and quiet EMG during voiding; treated with alphablocker. VUR was diagnosed with VUDS or VCUG, and graded according to the International Classification grading system [16]. All children underwent TT based on their specific LUT condition as described above with the addition of timed voiding and bowel regimen as needed. Any patient with associated bowel dysfunction was treated with appropriate bowel therapy e dietary fiber supplement, laxatives, adequate hydration, stool softeners, and enemas as indicated for constipation and encopresis [17]. During TT, all patients had a follow-up VUDS to determine the status of bladder function and VUR, as well as periodic uroflow/EMG evaluations to objectively determine the status of the LUT dysfunction. There was no specific protocol followed or set interval between VUDS evaluation with the intent of longer intervals when possible in order to give more time for VUR to resolve. If we were not sure why symptoms were persisting or there were breakthrough urinary tract infections (UTI), the intervals in between VUDS evaluations were shorter. Subjective improvement in urinary symptoms following TT was also evaluated at each follow-up visit by voiding diary review and patient/parent interviews. Children with a history of VUR were excluded if they had previous operative intervention to correct VUR or VUR had resolved on medical management prior to diagnosis of the LUT condition. For inclusion in this study, children had to have persistent VUR on repeat imaging after initiation of TT, have undergone subsequent subureteric DXHA (single hydrodistension implantation technique [HIT] prior to 2008 and double HIT after 2008) and have follow-up imaging post procedure (most often VUDS in those with persistent LUTS and VCUG in those with resolution of LUTS). The indications for intervention with DXHA are listed in the results. The patients in this report represent a subset of children from a larger group in a recent report of ours on the results of VUR resolution in children with LUTS treated with TT [5]. Fisher’s exact tests were used to compare categorical variables. All tests were two-tailed and a p value less than 0.05 was considered significant. Statistical analysis was performed using SPSS version 18.0 (Chicago, IL, USA).
Results Overall, 41 patients (36F, 5M) were identified with VUR (58 ureters) and a LUT condition treated with TT. As we previously reported, VUR resolved completely in 19 of 41 (46%) patients (26 of 58 [45%] ureters) on TT alone [5]. Of the remaining 22 patients with persistent VUR despite TT, 17
Please cite this article in press as: Van Batavia JP, et al., Outcomes of vesicoureteral reflux in children with non-neurogenic lower urinary tract dysfunction treated with dextranomer/hyaluronic acid copolymer (Deflux), Journal of Pediatric Urology (2013), http://dx.doi.org/ 10.1016/j.jpurol.2013.10.017
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Outcomes of vesicoureteral reflux in children with non-neurogenic lower urinary tract dysfunction patients (41%; 16 girls, 1 boy; mean age 6.1 years, range 4e12; mean time on TT Z 3.7 years, range 1.0e8.1 years) required intervention. The primary reasons for intervention were recurrent UTI despite continuous antibiotic prophylaxis and TT, especially if febrile (n Z 8), renal scarring on imaging (n Z 1) and/or failure to significantly improve symptomatically despite maximum appropriate TT (n Z 8). One girl with persistent bilateral grade 5 VUR after resolution of LUT symptoms underwent bilateral ureteral reimplantation and the remaining 16 (23 ureters; 13 left, 10 right) underwent subureteral DXHA injection. The girl who underwent reimplantation was not included in our analyses of DXHA treated patients as was one DXHA patient (with one refluxing ureter) who did not return for follow-up imaging post-injection. Follow-up imaging studies (mean follow-up time after DXHA injection Z 12.9 months, range 3.6e35.6) were available in all of the 15 remaining patients of whom six had DV, six had IDOD and three had DUD; none had PBND. After a single DXHA injection, VUR resolved in 13 of 22 ureters (59%) and one ureter improved from grade IV to I. Three children (four ureters) underwent a second DXHA injection, after which VUR resolved in two ureters and improved from grade III to grade I in the remaining two ureters. One patient with bilateral reflux required three DXHA injections before VUR resolved. The overall response rate was 91% including complete resolution in 17 of 22 ureters (77%) and a decrease of 2 grades in three ureters (14%) after treatment with one to three DXHA injections (Table 1). In terms of overall response rate by patients, 11 of the 15 patients (73%) had complete resolution of VUR after one to three DXHA injections. The breakdown of resolution by VUR grade and LUT condition is listed in Table 2. Seven patients had complete resolution of LUTS while on TT prior to undergoing DXHA injection. Of these, all seven (100%) had resolution of VUR including six patients with unilateral VUR following a single DXHA injection and one with bilateral VUR after three DXHA injections. Of the eight patients who had persistent voiding symptoms despite TT at the time of DXHA injection, four (50%) had VUR resolution after DXHA injection. This difference in resolution rates between patients with successful treatment of LUTS and those without successful treatment was not statistically significant (p Z 0.07). Interestingly, in the eight children with significant LUTS prior to injection, including two with persistent VUR post-injection, five (63%) had resolution of LUTS following DXHA. No patients developed obstruction and no ureter developed worsening reflux following DXHA injection. Overall, 11 of the 15 (73%) children had no further UTI after DXHA injection. The overall breakdown of patients who had a positive response to targeted therapy and/or DXHA by grade of VUR and associated underlying LUT condition is shown in Table 3.
Discussion Despite a clear association between VUR and each LUT condition, the specific nature of this interaction is unknown, although the presence of LUT dysfunction is likely to impact VUR resolution [18,19]. Interestingly, some
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Table 1 Resolution and improvement of vesicoureteral reflux (VUR) in patients treated with subureteral dextranomer/hyaluronic acid copolymer (DXHA) injection (15 children; 22 ureters) by A. VUR grade and B. condition. A. Reflux grade
No. ureters treated with DXHA
No. ureters with resolved VURa (%)
No. ureters decreased by 2 grades (%)
Ib IIb III IV V Total B. Diagnosis
1 3 9 7 2 22
1 2 6 6 2 17
0 0 2 1 0 3
No. ureters
No. ureters with resolved VUR (%)
No. ureters decreased by 2 grades (%)
9 9 4 22
8 5 4 17
1 2 0 3
DV IDOD DUD Total
(100) (67) (67) (86) (100) (77)
(89) (56) (100) (77)
(0) (0) (22) (14) (0) (14)
(11) (22) (0) (14)
DUD, detrusor underutilization disorder; DV, dysfunctional voiding; IDOD, idiopathic detrusor overactivity disorder. a Two patients with unilateral grade 3 reflux required two DXHA injections for resolution and another patient with bilateral (right grade 4, left grade 2) reflux required three DXHA injections for resolution. b All patients with grade IeII VUR had contralateral VUR of higher grade (IIIeV). As these children were undergoing cystoscopy with DXHA injection for the high grade VUR, the contralateral side with low grade VUR was also injected with DXHA.
infants with congenital or primary VUR have been found to have abnormal urodynamic patterns, including DO during filling and increased external sphincter activity during voiding, suggesting that interactions between VUR and LUT function may even pre-date toilet training in some children [2,20]. The significance of that, however, is unclear given that those very same abnormal urodynamic patterns are often seen in normal infants without reflux and usually normalize during the first year of life without sequelae. According to the 2010 AUA guideline on primary VUR, children with a LUT dysfunction and VUR have been reported to have a lower rate of spontaneous resolution of VUR and a lower cure rate following endoscopic treatment (50% success rate with endoscopic bulking agents in children with LUT dysfunction vs. 83% success rate in children without LUT dysfunction) [4]. Thus, an underlying LUT dysfunction can be a significant cause of surgical failure if it is not diagnosed and treated beforehand [21e23]. If a patient is not responding to TT and is having breakthrough infections, our preference has been to at least give subureteric DXHA a chance rather than risk ureteral reimplantation failure in this scenario. Capozza et al. reported their findings on repeat DXHA injection in 50 children [10]. Of this cohort, 27 children were found to have implant displacement at the time of re-
Please cite this article in press as: Van Batavia JP, et al., Outcomes of vesicoureteral reflux in children with non-neurogenic lower urinary tract dysfunction treated with dextranomer/hyaluronic acid copolymer (Deflux), Journal of Pediatric Urology (2013), http://dx.doi.org/ 10.1016/j.jpurol.2013.10.017
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J.P. Van Batavia et al. dropped to only 50% in children with “voiding dysfunction” [24]. In accordance with these findings, the manufacturer of DXHA has contraindicated its use for the endoscopic treatment of VUR in patients with active LUT dysfunction. However, other studies have shown that treatment of VUR in these children with DXHA to be equally effective to those without a LUT condition, particularly if they had undergone prior treatment for their LUT condition, regardless of the outcome of that treatment [12,13,25]. Kraft et al. recently published data on the use of endoscopic DXHA treatment of VUR in patients with overactive bladder (OAB) [12]. They found that 83% of patients had resolution of VUR on VCUG as well as no further UTI after a single treatment. Our VUR resolution rate was 64% overall (86% for children asymptomatic on TT vs. 50% for children still symptomatic on TT at the time of injection) after a single treatment in a group of patients with three different LUT conditions, DV, IDOD and DUD, and increased to 82% after multiple treatments. Interestingly, no patient in the present series with LUT dysfunction and VUR was identified with PBND, an infrequent association that we have reported before [14]. Although Kraft et al. did not notice a difference in terms of subureteric DXHA success between children with wellcontrolled vs. poorly controlled OAB (77% vs. 86%, respectively), our results differed in that successful resolution of VUR was more likely to occur depending on whether they were or were not symptomatic at the time of injection (50% vs. 86%). Although this difference did not achieve statistical significance (p Z 0.07), these numbers are strikingly similar to those reported in the 2010 AUA guideline for primary VUR for success of endoscopic bulking agents in children with and without LUT dysfunction (50% and 83%, respectively) [4]. This suggests that successful treatment of LUT dysfunction can improve the odds of success to the same
Table 2 Resolution and improvement of vesicoureteral reflux (VUR) by condition and grade in patients treated with periureteral Deflux injection (15 children, 22 ureters). Diagnosis
Grade
No. ureters
No. ureters w/resolved VUR (%)
No. ureters with improveda VUR (%)
II III IV V
1 2 4 2
1 2 3 2
(100) (100) (75) (100)
0 0 1 0
(0) (0) (25) (0)
I II III IV
1 1 5 2
1 0 2 2
(100) (0) (40) (100)
0 0 2 0
(0) (0) (40) (0)
II III IV
1 2 1
1 (100) 2 (100) 1 (100)
DV
IDOD
DUD 0 (0) 0 (0) 0 (0)
DUD, detrusor underutilization disorder; DV, dysfunctional voiding; IDOD, idiopathic detrusor overactivity disorder. a Improvement defined as decreased by 2 grades.
injection and 25 of these 27 children had active LUTS. Given this finding, Capozza et al. suggested that high intravesical pressure associated with LUT dysfunction may have caused or contributed to the DXHA migration and they recommended treating active LUT dysfunction for a minimum of 6 months prior to considering subureteric DXHA injection [10]. Likewise, Aboutaleb et al. noted an overall 91.6% cure rate of VUR with subureteral injection but this success
Table 3 Overall resolution of reflux with targeted treatment (TT) dextranomer/hyaluronic acid copolymer (DXHA) by A. vesicoureteral reflux (VUR) grade and B. lower urinary tract (LUT) condition. A. Grade
No. ureters
Ureters resolved with targeted treatment alone (%)a
Ureters resolved with DXHA (%)
Ureters resolved with reimplant (%)
Overall no. ureters resolved (%)
I II III IV V Total B. Condition
4 13 21 11 9 58
2 8 10 4 2 26
1 2 6 6 2 17
e e e e 2 (22) 2 (4)
3 10 16 9 6 45
No. ureters
Ureters resolved with targeted treatment alone (%)a
Ureters resolved with DXHA (%)
Ureters resolved with reimplant (%)
Overall no. ureters resolved (%)
30 23 5 58
17 8 1 26
8 5 4 17
e 2 (9) e 2 (4)
25 15 5 45
DV IDOD DUD Total
(50) (62) (48) (36) (22) (45)
(57) (35) (20) (45)
(25) (15) (29) (55) (22) (29)
(27) (22) (80) (29)
(75) (77) (76) (82) (67) (78)
(83) (65) (100) (78)
DUD, detrusor underutilization disorder; DV, dysfunctional voiding; IDOD, idiopathic detrusor overactivity disorder. a Data from Ref. [5].
Please cite this article in press as: Van Batavia JP, et al., Outcomes of vesicoureteral reflux in children with non-neurogenic lower urinary tract dysfunction treated with dextranomer/hyaluronic acid copolymer (Deflux), Journal of Pediatric Urology (2013), http://dx.doi.org/ 10.1016/j.jpurol.2013.10.017
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Outcomes of vesicoureteral reflux in children with non-neurogenic lower urinary tract dysfunction rates noted for children without any LUT dysfunction. We still consider this group of children with resolution of LUTS on TT as having active LUT dysfunction, however, as they are only asymptomatic while on treatment and if treatment is stopped their LUT dysfunction would re-emerge. These results are also similar to those reported by Lackgren et al. in 54 children with “bladder dysfunction” who underwent subureteric DXHA injection [13]. Lackgren et al. defined “bladder dysfunction” as urge incontinence or frequency, dysfunctional voiding, or infrequent voiding and they noted that 45 of 54 children (83%) had resolution of VUR after one to three DXHA injections [13]. Although our success rate was similar to that of Lackgren, we prefer to separate LUT dysfunction into specific LUT conditions instead of grouping all children with LUT dysfunction into one umbrella category. We feel this approach allows for greater diagnostic accuracy, enhances interpretation of the data, and allows for better comparisons with other investigators [15]. Our data support the position that for patients with LUT dysfunction who continue to have VUR despite receiving TT for their particular LUT condition, subureteric DXHA injection is a safe and effective option, even when the LUT dysfunction has not fully resolved. Following resolution of VUR after DXHA injection(s), episodes of UTI greatly decrease. Interestingly, the majority of children with significant LUTS despite TT at the time of DXHA injection had resolution of LUTS following injection. Almost three-quarters of children, regardless of response to TT and DXHA injection, had no further UTI after DXHA injection. In fact, our 27% incidence of recurrent UTI after DXHA injection in children with LUT dysfunction is similar to the incidence of febrile UTI noted in other studies [26,27]. Sedberry-Ross et al. also noted a 27% incidence of post-DXHA febrile UTI, although this was in all patients treated not just those with LUT dysfunction [26]. They did, however, note that “dysfunctional elimination” was a risk factor for post-DXHA febrile UTI [26]. Lastly, our data suggest that the persistence of LUTS on TT may well be related to the VUR as evidenced by the majority becoming asymptomatic following successful treatment of the reflux. In summary, on the basis of studies in the literature, the AUA meta-analysis, and our own experience, it can be concluded that DXHA is most effective in correcting VUR when active LUT dysfunction is not present. However, although we and others have found DXHA to be less effective in the presence of active LUT dysfunction, its use in that circumstance should not be avoided, as at least 50% of children will have resolution of VUR after one injection and that number can approach non-LUT dysfunction levels with careful patient selection and additional injections. Whether VUR is resolved or improved after DXHA, it still decreases the incidence of both recurrent infections and persistent LUT symptoms. In addition, DXHA seems to be most successful in patients with either DV or DUD. As a minimally invasive procedure, DXHA injection appears to be more advantageous than reimplantation surgery, especially in this scenario, as the latter has been shown to have higher complication and failure rates when performed in children with active LUT dysfunction than when performed in those without, particularly DV [21,22]. It should be noted,
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however, that approximately 25% of these children will require more than one DXHA injection for VUR resolution and thus will require repeat procedures and anesthesia. There are several limitations to our study. First, this is a retrospective study and children were not randomized to treatment. Second, all children were treated at a tertiary referral center by a single pediatric urologist and therefore these findings may not be generalizable to the entire pediatric population with VUR and LUT dysfunction as often the more complex or refractory patients were referred to us. Third, although we tried to adhere to the ICCS terminology for non-neurogenic LUT dysfunction whenever possible, we found it necessary to use alternative terminology when current ICCS terminology was inadequate for the precise categorization of the patients’ underlying LUT condition. In those instances, urodynamic criteria to support the diagnosis were used, as previously described [5,15]. Fourth, by dividing patients into one of four LUT conditions, the number of patients in each group was small making statistical comparisons difficult and underscoring the need for corroboration by other investigators.
Conclusions Subureteric DXHA injection is an effective and safe option for the treatment of VUR in children with associated LUT dysfunction particularly when treatment progress is hampered by recurrent breakthrough infections and/or persistent symptoms despite appropriate TT and antibiotic prophylaxis. VUR is more likely to resolve when associated with DV compared with IDOD and in patients who became asymptomatic on TT compared with those who remained symptomatic on TT. Use of subureteric DXHA in patients with VUR should not be contraindicated in patients with active LUT dysfunction as stated by the current manufacturer insert.
Conflict of interest None.
Funding Shannon Nees and Angela Fast were funded by the Doris Duke Charitable Foundation.
Ethical approval This study was approved by the Internal Review Board at Columbia University Medical Center (IRB-AAAC1100).
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Please cite this article in press as: Van Batavia JP, et al., Outcomes of vesicoureteral reflux in children with non-neurogenic lower urinary tract dysfunction treated with dextranomer/hyaluronic acid copolymer (Deflux), Journal of Pediatric Urology (2013), http://dx.doi.org/ 10.1016/j.jpurol.2013.10.017
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6 [3] Koff SA, Wagner TT, Jayanthi VR. The relationship among dysfunctional elimination syndromes, primary vesicoureteral reflux and urinary tract infections in children. J Urol 1998;160: 1019. [4] Peters CA, Skoog SJ, Arant Jr BS, Copp HL, Elder JS, Hudson RG, et al. Summary of the AUA guideline on management of primary vesicoureteral reflux in children. J Urol 2010; 184:1134. [5] Fast AM, Nees SN, Van Batavia JP, Combs AJ, Glassberg KI. Outcomes of vesicoureteral reflux in children with nonneurogenic lower urinary tract dysfunction. J Urol 2013; 190(3):1028e32. [6] Ural Z, Ulman I, Avanoglu A. Bladder dynamics and vesicoureteral reflux: factors associated with idiopathic lower urinary tract dysfunction in children. J Urol 2008;179(4): 1564e7. [7] Holmadhl G, Brandstrom P, Lackgren G, Sillen U, Stokland E, Jodal U, et al. The Swedish reflux trial in children: II. Vesicoureteral reflux outcome. J Urol 2010;184(1):280e5. [8] Hacker FM, Frech-Dorfler M, von Rotz M, Rudin C. Endoscopic hyaluronic acid/dextranomer gel implantation is effective as first-line treatment of vesicoureteral reflux in children: a single center experience. Eur J Pediatr Surg 2011;21(5): 299e303. [9] Scarpa AA, Del Rossi C, Casolari E, Gatti C, Scarpa AG. Endoscopic treatment of vesicoureteric reflux in pediatric patient: results of a long-term study. Acta Biomed 2011;82(2):137e45. [10] Capozza N, Lais A, Matarazzo E, Nappo S, Patricolo M, Caione P. Influence of voiding dysfunction on the outcome of endoscopic treatment for vesicoureteral reflux. J Urol 2002; 168:1695. [11] Capozza N, Patricolo M, Lais A, Matarazzo E, Caione P. Endoscopic treatment of vesico-ureteral reflux: twelve years’ experience. Urol Int 2001;67:228e31. [12] Kraft KH, Molitierno Jr JA, Dewhurst L, Geers C, Gunderson K, Scherz HC, et al. Is endoscopic injection therapy a reasonable treatment option for low-grade vesicoureteral reflux in association with overactive bladder? Urology 2011;78(3):675e8. [13] Lackgren G, Skoldenberg E, Stenberg A. Endoscopic treatment with stabilized nonanimal hyaluronic acid/dextranomer gel is effective in vesicoureteral reflux associated with bladder dysfunction. J Urol 2007;177:1124e8. [14] Glassberg KI, Combs AJ, Horowitz M. Nonneurogenic voiding disorders in children and adolescents: clinical and videourodynamic findings in 4 specific conditions. J Urol 2010; 184(5):2123e7.
J.P. Van Batavia et al. [15] Van Batavia JP, Combs AJ, Hyun G, Bayer A, MedinaKreppein D, Schlussel RN, et al. Simplifying the diagnosis of 4 common voiding conditions using uroflow/electromyography, electromyography lag time and voiding history. J Urol 2011; 186(4):1721e6. [16] Lebowitz RL, Olbing H, Parkhulainen KV, Smellie JM, Tamminen-Mobius TE. International system of radiographic grading of vesicoureteric reflux. Pediatr Radiol 1985;15:105e9. [17] Combs AJ, Van Batavia JP, Chan J, Glassberg KI. Dysfunctional elimination syndromes: How closely linked are constipation and encopresis with specific lower urinary tract conditions? J Urol 2013;190(3):1015e20. [18] Demirbag S, Atabek C, Caliskan B, Guven A, Sakarya MT, Surer I, et al. Bladder dysfunction in infants with primary vesicoureteric reflux. J Int Med Res 2009;37:1877e81. [19] Koff SA, Lapides J, Piazza DH. Association of urinary tract infection and reflux with uninhibited bladder contractions and voluntary sphincteric obstruction. J Urol 1979;122(2):373e6. [20] Yeung CK, Godley ML, Dhillon HK, Duffy PG, Ransley PG. Urodynamic patterns in infants with normal lower urinary tracts or primary vesico-ureteric reflux. Br J Urol 1998;81(3):461e7. [21] Noe HN. The role of dysfunctional voiding in failure or complication of ureteral reimplantation for primary reflux. J Urol 1985;134(6):1172e5. [22] Hinman Jr F, Baumann FW. Complications of vesicoureteral operations from incoordination of micturition. J Urol 1976; 116:638e43. [23] Sillen U, Brandstrom P, Jodal U, Homdahl G, Sandin A, Sjoberg I, et al. The Swedish reflux trial in children: v. Bladder dysfunction. J Urol 2010;184(1):298e304. [24] Aboutaleb H, Bolduc S, Upadhyay J, Farhat W, Bagli DJ, Khoury AE. Subureteral polydimethylsiloxane injection versus extravesical reimplantation for primary low grade vesicoureteral reflux in children: a comparative study. J Urol 2003;169: 313e6. [25] Lavelle MT, Conlin MJ, Skoog SJ. Subureteral injection of Deflux for correction of reflux: analysis of factors predicting success. Urology 2005;65(3):564e7. [26] Sedberry-Ross S, Rice DC, Pohl HG, Belman AB, Majd M, Rushton HG. Febrile urinary tract infections in children with an early negative voiding cystourethrogram after treatment of vesicoureteral reflux with dextranomer/hyaluronic acid. J Urol 2008;180:1605e10. [27] Traxel E, DeFoor W, Reddy P, Sheldon C, Minevich E. Risk factors for urinary tract infection after dextranomer/hyaluronic acid endoscopic injection. J Urol 2009;182(4):1708e12.
Please cite this article in press as: Van Batavia JP, et al., Outcomes of vesicoureteral reflux in children with non-neurogenic lower urinary tract dysfunction treated with dextranomer/hyaluronic acid copolymer (Deflux), Journal of Pediatric Urology (2013), http://dx.doi.org/ 10.1016/j.jpurol.2013.10.017
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Journal of Pediatric Urology (2013) xx, 1e6
Outcomes of vesicoureteral reflux in children with non-neurogenic lower urinary tract dysfunction treated with dextranomer/ hyaluronic acid copolymer (Deflux) Jason P. Van Batavia, Shannon N. Nees, Angela M. Fast, Andrew J. Combs, Kenneth I. Glassberg* Division of Pediatric Urology, Morgan Stanley Children’s Hospital of New York-Presbyterian, Department of Urology, Columbia University, College of Physicians and Surgeons, New York, NY, USA Received 30 June 2013; accepted 16 October 2013
KEYWORDS Vesicoureteral reflux; Lower urinary tract conditions; Deflux; Dysfunctional voiding; Pediatrics
Abstract Objective: There has been hesitancy to use dextranomer/hyaluronic acid copolymer (DHXA, Deflux for vesicoureteral reflux (VUR) in the setting of lower urinary tract (LUT) dysfunction because of the limited number of published studies, the possibility of less success, and the manufacturer’s recommendations contraindicating its use in patients with active LUT dysfunction. We report on our experience using DXHA in this subset of patients whose VUR persisted despite targeted therapy for their LUT condition. Materials and methods: We reviewed patients diagnosed with both a LUT condition and VUR who underwent subureteric DXHA while still undergoing treatment for their LUT dysfunction. Persistence of VUR was confirmed by videourodynamic studies (VUDS)/VCUG (voiding cystourethrogram) and all patients were on targeted treatment (TT) and antibiotic prophylaxis prior to and during DXHA injection. VUR was reassessed post-injection. Results: Fifteen patients (22 ureters; 21F,1M) met inclusion criteria (mean age 6.1 years, range 4e12). Following one to three DXHA injections, VUR resolved in 17 ureters (77%) including eight of nine ureters in dysfunctional voiding (DV) patients, five of nine in idiopathic detrusor overactivity disorder (IDOD), and four of four in detrusor underutilization disorder (DUD) patients. Conclusions: DXHA is safe and effective in resolving VUR in children with associated LUT dysfunction, even before their LUT condition has fully resolved. Highest resolution rates were noted in patients with either DV or DUD or who were least symptomatic prior to injection. ª 2013 Published by Elsevier Ltd on behalf of Journal of Pediatric Urology Company.
* Corresponding author. Tel.: þ1 212 305 9918; fax: þ1 212 342 1065. E-mail addresses: [email protected] (J.P. Van Batavia), [email protected] (K.I. Glassberg). 1477-5131/$36 ª 2013 Published by Elsevier Ltd on behalf of Journal of Pediatric Urology Company. http://dx.doi.org/10.1016/j.jpurol.2013.10.017
Please cite this article in press as: Van Batavia JP, et al., Outcomes of vesicoureteral reflux in children with non-neurogenic lower urinary tract dysfunction treated with dextranomer/hyaluronic acid copolymer (Deflux), Journal of Pediatric Urology (2013), http://dx.doi.org/ 10.1016/j.jpurol.2013.10.017
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Introduction Both vesicoureteral reflux (VUR) and lower urinary tract (LUT) dysfunction are common reasons for referral to pediatric urologists and both conditions often appear together [1e3]. According to the 2010 AUA (american urologic association) Guideline on Primary Vesicoureteral Reflux, children with VUR and LUT dysfunction are less likely to have spontaneous resolution of VUR than are those with VUR and no LUT dysfunction (31% vs. 61% in children without LUT dysfunction) [4]. Although it is still not clear if LUT dysfunction causes or even contributes to VUR, it does seem clear that treatment of LUT dysfunction can lead to higher rates of VUR resolution [5,6]. Subureteric dextranomer/hyaluronic acid copolymer (DXHA/Deflux) injection has emerged over the past two decades as an acceptable first-line minimally invasive option for treating persistent VUR in children [7e9]. Despite its high overall success rates, concern exists regarding use of DXHA injection in children with LUT dysfunction, as some reports have shown a decreased rate of cure in these children [4,10,11], In fact, according to manufacturer recommendations, endoscopic treatment with DXHA is contraindicated in patients with active LUT dysfunction. This recommendation may be consistent with some of the earlier articles cited in the 2010 AUA guideline report for primary VUR and its metaanalysis findings that endoscopic bulking agents were only successful in resolving VUR in 50% of children with LUT dysfunction compared with 83% of children without LUT dysfunction [4]. More recent studies in children with LUT dysfunction, however, report higher success rates and question this blanket statement regarding DXHA injection in LUT dysfunction patients [12,13]. We wanted to further add to the literature and report our VUR resolution rate in children actively being treated for LUT dysfunction who underwent treatment with subureteric DXHA. Additionally, we hypothesized that children whose LUTS (lower urinary tract symptoms) subsided while on targeted treatment (TT) would have higher VUR resolution rates following DXHA injection than those children on TT still symptomatic prior to injection.
Materials and methods Using our IRB (internal review board)-approved pediatric urology database, we identified patients diagnosed with both a non-neurogenic LUT condition and VUR from January 2003 to December 2012. Each child was diagnosed with one of four LUT conditions based on the goodness of fit between history, physical exam, voiding diary, noninvasive uroflow/ electromyography (EMG) and VUDS when indicated [14,15]: (1) dysfunctional voiding (DV) Z LUTS with an active EMG during voiding associated detrusor overactivity (DO); treated with biofeedback antimuscarinics. (2) idiopathic detrusor overactivity disorder (IDOD) Z idiopathic (primary) detrusor overactivity with a quiet EMG during voiding with DO established either by urodynamic studies (UDS) or urinary urgency combined with a shortened EMG lag time (<2 s) on uroflow/EMG; treated with antimuscarinics.
J.P. Van Batavia et al. (3) detrusor underutilization disorder (DUD) Z large bladder capacity with voided volume in excess of expected bladder capacity (i.e. >125%) as a result of willful deferred voiding but with otherwise quiet EMG during voiding and normal uroflow pattern; treated with timed voiding. (4) primary bladder neck dysfunction (PBND) Z delayed or incomplete bladder neck opening resulting in impaired urine flow; most commonly associated with hesitancy and characterized by a prolonged EMG lag time (>6 s) and quiet EMG during voiding; treated with alphablocker. VUR was diagnosed with VUDS or VCUG, and graded according to the International Classification grading system [16]. All children underwent TT based on their specific LUT condition as described above with the addition of timed voiding and bowel regimen as needed. Any patient with associated bowel dysfunction was treated with appropriate bowel therapy e dietary fiber supplement, laxatives, adequate hydration, stool softeners, and enemas as indicated for constipation and encopresis [17]. During TT, all patients had a follow-up VUDS to determine the status of bladder function and VUR, as well as periodic uroflow/EMG evaluations to objectively determine the status of the LUT dysfunction. There was no specific protocol followed or set interval between VUDS evaluation with the intent of longer intervals when possible in order to give more time for VUR to resolve. If we were not sure why symptoms were persisting or there were breakthrough urinary tract infections (UTI), the intervals in between VUDS evaluations were shorter. Subjective improvement in urinary symptoms following TT was also evaluated at each follow-up visit by voiding diary review and patient/parent interviews. Children with a history of VUR were excluded if they had previous operative intervention to correct VUR or VUR had resolved on medical management prior to diagnosis of the LUT condition. For inclusion in this study, children had to have persistent VUR on repeat imaging after initiation of TT, have undergone subsequent subureteric DXHA (single hydrodistension implantation technique [HIT] prior to 2008 and double HIT after 2008) and have follow-up imaging post procedure (most often VUDS in those with persistent LUTS and VCUG in those with resolution of LUTS). The indications for intervention with DXHA are listed in the results. The patients in this report represent a subset of children from a larger group in a recent report of ours on the results of VUR resolution in children with LUTS treated with TT [5]. Fisher’s exact tests were used to compare categorical variables. All tests were two-tailed and a p value less than 0.05 was considered significant. Statistical analysis was performed using SPSS version 18.0 (Chicago, IL, USA).
Results Overall, 41 patients (36F, 5M) were identified with VUR (58 ureters) and a LUT condition treated with TT. As we previously reported, VUR resolved completely in 19 of 41 (46%) patients (26 of 58 [45%] ureters) on TT alone [5]. Of the remaining 22 patients with persistent VUR despite TT, 17
Please cite this article in press as: Van Batavia JP, et al., Outcomes of vesicoureteral reflux in children with non-neurogenic lower urinary tract dysfunction treated with dextranomer/hyaluronic acid copolymer (Deflux), Journal of Pediatric Urology (2013), http://dx.doi.org/ 10.1016/j.jpurol.2013.10.017
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Outcomes of vesicoureteral reflux in children with non-neurogenic lower urinary tract dysfunction patients (41%; 16 girls, 1 boy; mean age 6.1 years, range 4e12; mean time on TT Z 3.7 years, range 1.0e8.1 years) required intervention. The primary reasons for intervention were recurrent UTI despite continuous antibiotic prophylaxis and TT, especially if febrile (n Z 8), renal scarring on imaging (n Z 1) and/or failure to significantly improve symptomatically despite maximum appropriate TT (n Z 8). One girl with persistent bilateral grade 5 VUR after resolution of LUT symptoms underwent bilateral ureteral reimplantation and the remaining 16 (23 ureters; 13 left, 10 right) underwent subureteral DXHA injection. The girl who underwent reimplantation was not included in our analyses of DXHA treated patients as was one DXHA patient (with one refluxing ureter) who did not return for follow-up imaging post-injection. Follow-up imaging studies (mean follow-up time after DXHA injection Z 12.9 months, range 3.6e35.6) were available in all of the 15 remaining patients of whom six had DV, six had IDOD and three had DUD; none had PBND. After a single DXHA injection, VUR resolved in 13 of 22 ureters (59%) and one ureter improved from grade IV to I. Three children (four ureters) underwent a second DXHA injection, after which VUR resolved in two ureters and improved from grade III to grade I in the remaining two ureters. One patient with bilateral reflux required three DXHA injections before VUR resolved. The overall response rate was 91% including complete resolution in 17 of 22 ureters (77%) and a decrease of 2 grades in three ureters (14%) after treatment with one to three DXHA injections (Table 1). In terms of overall response rate by patients, 11 of the 15 patients (73%) had complete resolution of VUR after one to three DXHA injections. The breakdown of resolution by VUR grade and LUT condition is listed in Table 2. Seven patients had complete resolution of LUTS while on TT prior to undergoing DXHA injection. Of these, all seven (100%) had resolution of VUR including six patients with unilateral VUR following a single DXHA injection and one with bilateral VUR after three DXHA injections. Of the eight patients who had persistent voiding symptoms despite TT at the time of DXHA injection, four (50%) had VUR resolution after DXHA injection. This difference in resolution rates between patients with successful treatment of LUTS and those without successful treatment was not statistically significant (p Z 0.07). Interestingly, in the eight children with significant LUTS prior to injection, including two with persistent VUR post-injection, five (63%) had resolution of LUTS following DXHA. No patients developed obstruction and no ureter developed worsening reflux following DXHA injection. Overall, 11 of the 15 (73%) children had no further UTI after DXHA injection. The overall breakdown of patients who had a positive response to targeted therapy and/or DXHA by grade of VUR and associated underlying LUT condition is shown in Table 3.
Discussion Despite a clear association between VUR and each LUT condition, the specific nature of this interaction is unknown, although the presence of LUT dysfunction is likely to impact VUR resolution [18,19]. Interestingly, some
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Table 1 Resolution and improvement of vesicoureteral reflux (VUR) in patients treated with subureteral dextranomer/hyaluronic acid copolymer (DXHA) injection (15 children; 22 ureters) by A. VUR grade and B. condition. A. Reflux grade
No. ureters treated with DXHA
No. ureters with resolved VURa (%)
No. ureters decreased by 2 grades (%)
Ib IIb III IV V Total B. Diagnosis
1 3 9 7 2 22
1 2 6 6 2 17
0 0 2 1 0 3
No. ureters
No. ureters with resolved VUR (%)
No. ureters decreased by 2 grades (%)
9 9 4 22
8 5 4 17
1 2 0 3
DV IDOD DUD Total
(100) (67) (67) (86) (100) (77)
(89) (56) (100) (77)
(0) (0) (22) (14) (0) (14)
(11) (22) (0) (14)
DUD, detrusor underutilization disorder; DV, dysfunctional voiding; IDOD, idiopathic detrusor overactivity disorder. a Two patients with unilateral grade 3 reflux required two DXHA injections for resolution and another patient with bilateral (right grade 4, left grade 2) reflux required three DXHA injections for resolution. b All patients with grade IeII VUR had contralateral VUR of higher grade (IIIeV). As these children were undergoing cystoscopy with DXHA injection for the high grade VUR, the contralateral side with low grade VUR was also injected with DXHA.
infants with congenital or primary VUR have been found to have abnormal urodynamic patterns, including DO during filling and increased external sphincter activity during voiding, suggesting that interactions between VUR and LUT function may even pre-date toilet training in some children [2,20]. The significance of that, however, is unclear given that those very same abnormal urodynamic patterns are often seen in normal infants without reflux and usually normalize during the first year of life without sequelae. According to the 2010 AUA guideline on primary VUR, children with a LUT dysfunction and VUR have been reported to have a lower rate of spontaneous resolution of VUR and a lower cure rate following endoscopic treatment (50% success rate with endoscopic bulking agents in children with LUT dysfunction vs. 83% success rate in children without LUT dysfunction) [4]. Thus, an underlying LUT dysfunction can be a significant cause of surgical failure if it is not diagnosed and treated beforehand [21e23]. If a patient is not responding to TT and is having breakthrough infections, our preference has been to at least give subureteric DXHA a chance rather than risk ureteral reimplantation failure in this scenario. Capozza et al. reported their findings on repeat DXHA injection in 50 children [10]. Of this cohort, 27 children were found to have implant displacement at the time of re-
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J.P. Van Batavia et al. dropped to only 50% in children with “voiding dysfunction” [24]. In accordance with these findings, the manufacturer of DXHA has contraindicated its use for the endoscopic treatment of VUR in patients with active LUT dysfunction. However, other studies have shown that treatment of VUR in these children with DXHA to be equally effective to those without a LUT condition, particularly if they had undergone prior treatment for their LUT condition, regardless of the outcome of that treatment [12,13,25]. Kraft et al. recently published data on the use of endoscopic DXHA treatment of VUR in patients with overactive bladder (OAB) [12]. They found that 83% of patients had resolution of VUR on VCUG as well as no further UTI after a single treatment. Our VUR resolution rate was 64% overall (86% for children asymptomatic on TT vs. 50% for children still symptomatic on TT at the time of injection) after a single treatment in a group of patients with three different LUT conditions, DV, IDOD and DUD, and increased to 82% after multiple treatments. Interestingly, no patient in the present series with LUT dysfunction and VUR was identified with PBND, an infrequent association that we have reported before [14]. Although Kraft et al. did not notice a difference in terms of subureteric DXHA success between children with wellcontrolled vs. poorly controlled OAB (77% vs. 86%, respectively), our results differed in that successful resolution of VUR was more likely to occur depending on whether they were or were not symptomatic at the time of injection (50% vs. 86%). Although this difference did not achieve statistical significance (p Z 0.07), these numbers are strikingly similar to those reported in the 2010 AUA guideline for primary VUR for success of endoscopic bulking agents in children with and without LUT dysfunction (50% and 83%, respectively) [4]. This suggests that successful treatment of LUT dysfunction can improve the odds of success to the same
Table 2 Resolution and improvement of vesicoureteral reflux (VUR) by condition and grade in patients treated with periureteral Deflux injection (15 children, 22 ureters). Diagnosis
Grade
No. ureters
No. ureters w/resolved VUR (%)
No. ureters with improveda VUR (%)
II III IV V
1 2 4 2
1 2 3 2
(100) (100) (75) (100)
0 0 1 0
(0) (0) (25) (0)
I II III IV
1 1 5 2
1 0 2 2
(100) (0) (40) (100)
0 0 2 0
(0) (0) (40) (0)
II III IV
1 2 1
1 (100) 2 (100) 1 (100)
DV
IDOD
DUD 0 (0) 0 (0) 0 (0)
DUD, detrusor underutilization disorder; DV, dysfunctional voiding; IDOD, idiopathic detrusor overactivity disorder. a Improvement defined as decreased by 2 grades.
injection and 25 of these 27 children had active LUTS. Given this finding, Capozza et al. suggested that high intravesical pressure associated with LUT dysfunction may have caused or contributed to the DXHA migration and they recommended treating active LUT dysfunction for a minimum of 6 months prior to considering subureteric DXHA injection [10]. Likewise, Aboutaleb et al. noted an overall 91.6% cure rate of VUR with subureteral injection but this success
Table 3 Overall resolution of reflux with targeted treatment (TT) dextranomer/hyaluronic acid copolymer (DXHA) by A. vesicoureteral reflux (VUR) grade and B. lower urinary tract (LUT) condition. A. Grade
No. ureters
Ureters resolved with targeted treatment alone (%)a
Ureters resolved with DXHA (%)
Ureters resolved with reimplant (%)
Overall no. ureters resolved (%)
I II III IV V Total B. Condition
4 13 21 11 9 58
2 8 10 4 2 26
1 2 6 6 2 17
e e e e 2 (22) 2 (4)
3 10 16 9 6 45
No. ureters
Ureters resolved with targeted treatment alone (%)a
Ureters resolved with DXHA (%)
Ureters resolved with reimplant (%)
Overall no. ureters resolved (%)
30 23 5 58
17 8 1 26
8 5 4 17
e 2 (9) e 2 (4)
25 15 5 45
DV IDOD DUD Total
(50) (62) (48) (36) (22) (45)
(57) (35) (20) (45)
(25) (15) (29) (55) (22) (29)
(27) (22) (80) (29)
(75) (77) (76) (82) (67) (78)
(83) (65) (100) (78)
DUD, detrusor underutilization disorder; DV, dysfunctional voiding; IDOD, idiopathic detrusor overactivity disorder. a Data from Ref. [5].
Please cite this article in press as: Van Batavia JP, et al., Outcomes of vesicoureteral reflux in children with non-neurogenic lower urinary tract dysfunction treated with dextranomer/hyaluronic acid copolymer (Deflux), Journal of Pediatric Urology (2013), http://dx.doi.org/ 10.1016/j.jpurol.2013.10.017
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Outcomes of vesicoureteral reflux in children with non-neurogenic lower urinary tract dysfunction rates noted for children without any LUT dysfunction. We still consider this group of children with resolution of LUTS on TT as having active LUT dysfunction, however, as they are only asymptomatic while on treatment and if treatment is stopped their LUT dysfunction would re-emerge. These results are also similar to those reported by Lackgren et al. in 54 children with “bladder dysfunction” who underwent subureteric DXHA injection [13]. Lackgren et al. defined “bladder dysfunction” as urge incontinence or frequency, dysfunctional voiding, or infrequent voiding and they noted that 45 of 54 children (83%) had resolution of VUR after one to three DXHA injections [13]. Although our success rate was similar to that of Lackgren, we prefer to separate LUT dysfunction into specific LUT conditions instead of grouping all children with LUT dysfunction into one umbrella category. We feel this approach allows for greater diagnostic accuracy, enhances interpretation of the data, and allows for better comparisons with other investigators [15]. Our data support the position that for patients with LUT dysfunction who continue to have VUR despite receiving TT for their particular LUT condition, subureteric DXHA injection is a safe and effective option, even when the LUT dysfunction has not fully resolved. Following resolution of VUR after DXHA injection(s), episodes of UTI greatly decrease. Interestingly, the majority of children with significant LUTS despite TT at the time of DXHA injection had resolution of LUTS following injection. Almost three-quarters of children, regardless of response to TT and DXHA injection, had no further UTI after DXHA injection. In fact, our 27% incidence of recurrent UTI after DXHA injection in children with LUT dysfunction is similar to the incidence of febrile UTI noted in other studies [26,27]. Sedberry-Ross et al. also noted a 27% incidence of post-DXHA febrile UTI, although this was in all patients treated not just those with LUT dysfunction [26]. They did, however, note that “dysfunctional elimination” was a risk factor for post-DXHA febrile UTI [26]. Lastly, our data suggest that the persistence of LUTS on TT may well be related to the VUR as evidenced by the majority becoming asymptomatic following successful treatment of the reflux. In summary, on the basis of studies in the literature, the AUA meta-analysis, and our own experience, it can be concluded that DXHA is most effective in correcting VUR when active LUT dysfunction is not present. However, although we and others have found DXHA to be less effective in the presence of active LUT dysfunction, its use in that circumstance should not be avoided, as at least 50% of children will have resolution of VUR after one injection and that number can approach non-LUT dysfunction levels with careful patient selection and additional injections. Whether VUR is resolved or improved after DXHA, it still decreases the incidence of both recurrent infections and persistent LUT symptoms. In addition, DXHA seems to be most successful in patients with either DV or DUD. As a minimally invasive procedure, DXHA injection appears to be more advantageous than reimplantation surgery, especially in this scenario, as the latter has been shown to have higher complication and failure rates when performed in children with active LUT dysfunction than when performed in those without, particularly DV [21,22]. It should be noted,
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however, that approximately 25% of these children will require more than one DXHA injection for VUR resolution and thus will require repeat procedures and anesthesia. There are several limitations to our study. First, this is a retrospective study and children were not randomized to treatment. Second, all children were treated at a tertiary referral center by a single pediatric urologist and therefore these findings may not be generalizable to the entire pediatric population with VUR and LUT dysfunction as often the more complex or refractory patients were referred to us. Third, although we tried to adhere to the ICCS terminology for non-neurogenic LUT dysfunction whenever possible, we found it necessary to use alternative terminology when current ICCS terminology was inadequate for the precise categorization of the patients’ underlying LUT condition. In those instances, urodynamic criteria to support the diagnosis were used, as previously described [5,15]. Fourth, by dividing patients into one of four LUT conditions, the number of patients in each group was small making statistical comparisons difficult and underscoring the need for corroboration by other investigators.
Conclusions Subureteric DXHA injection is an effective and safe option for the treatment of VUR in children with associated LUT dysfunction particularly when treatment progress is hampered by recurrent breakthrough infections and/or persistent symptoms despite appropriate TT and antibiotic prophylaxis. VUR is more likely to resolve when associated with DV compared with IDOD and in patients who became asymptomatic on TT compared with those who remained symptomatic on TT. Use of subureteric DXHA in patients with VUR should not be contraindicated in patients with active LUT dysfunction as stated by the current manufacturer insert.
Conflict of interest None.
Funding Shannon Nees and Angela Fast were funded by the Doris Duke Charitable Foundation.
Ethical approval This study was approved by the Internal Review Board at Columbia University Medical Center (IRB-AAAC1100).
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Please cite this article in press as: Van Batavia JP, et al., Outcomes of vesicoureteral reflux in children with non-neurogenic lower urinary tract dysfunction treated with dextranomer/hyaluronic acid copolymer (Deflux), Journal of Pediatric Urology (2013), http://dx.doi.org/ 10.1016/j.jpurol.2013.10.017