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Treatment of Vesicoureteral Reflux in Children by Kirsch Endoscopic Injection of Deflux: a 7 Years Experience

Baher Louka, Thierry Merrot, Mamadou Diakite, Pierre Alessandrini
Department of Pediatric Surgery, Hôpital Nord, Université de la Méditerranée, Marseille, France.

 

 

Correspondence

Thierry Merrot
Department of Pediatric Surgery
Hôpital Nord, Université de la Méditerranée, Marseille, France
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Abstract

Objective: The main aim of management of vesicoureteral reflux (VUR) is to prevent or limit the occurrence of renal scars; the procedures for prevention are variable. We evaluate the effectiveness of endoscopic injection of dextranomer/ hyaluronic acid copolymer (Deflux) in the treatment of VUR in children.

Matherial and Method: Between 2001 and 2008 a total of 19 boys and 84 girls with a mean age of 4.6 years (range 11 months to 12.3 years) underwent endoscopic correction of VUR with Deflux. Reflux was unilateral in 61 cases and bilateral in 42, affecting 145 ureters. VUR occurred in a single system in 135 ureters and in renal duplication in the remaining 10. Reflux was grade 1 in 9 ureters (6.6%), grade 2 in 68 ureters (50.37%), grade 3 in 45 ureters (33.33%), grade 4 in 12 ureters (8.89%) and grade 5 in one ureter (0.74%). The intervention performed was endoscopic injection of bulking agent (Deflux°) according to Kirsch procedure. At the follow-up at 3 months after a single injection, the reflux was evaluated on the clinical evolution and the voiding cystourethrography.

Results: After a mean follow-up of 28 months, the reflux was corrected in 108 (74.5%) of the 145 ureters. According to the grade of reflux, the success rate was 100%, 81%, 69% and 67% for grades 1 to 4 respectively and VUR persisted in one ureter with grade 5 reflux. The success rate was 57% for refluxing lower pole ureters. There were limitations of this study because this was a single center, retrospective and no randomization therapy.

Conclusions: Although less effective than surgery in high grade reflux, endoscopic injection of Deflux remains a simple and safe procedure that is successful to eliminate reflux in a great majority of patients with low grade VUR.

Key words: vesicoureteral reflux, endoscopic treatment, Deflux, Kirsch

 

 

Introduction

Vesicoureteral reflux (VUR) is the most common urological anomaly in children and has been reported in 1% of a population of children with a systematic voiding cystourethrography (VCUG) [1] and in 31.3% of children presenting with urinary tract infection (UTI) according to a published meta-analysis of 250 articles [2]. Natural history and management of VUR have been considerably modified in the past 20 years. Although UTI have been always the principal cause of detection of VUR, the systematic practice of obstetric ultra-sonography permits the detection of reflux before the appearance of infectious complications [3].

Regardless of the mode of detection of VUR, the aim of management is always to prevent the degradation of renal parenchyma which can lead to reflux nephropathy as well as renal insufficiency. There has been no consensus regarding when medical or surgical therapy should be used [4]. Multiple studies revealed that conservative therapy carry an ongoing risk of renal scarring [5, 6]. Although open ureteral reimplantation is the standard treatment for VUR when indicated, this operation is not free of complications [7].

Endoscopic correction of VUR has become an established alternative to long-term antibiotic prophylaxis and open surgical treatment since the introduction of the subureteral injection of Teflon by Puri and O’Donnell in the years 1980 [8, 9]. Recently, a number of other tissue augmenting substances have been used endoscopically for subureteral injection [10]. Deflux is a recent substance which consists of dextranomer microspheres in hyaluronic acid solution. The size of microspheres (80-200 μm) is sufficient to prevent their migration [11], it has also been reported that dextranomer/ hyaluronic acid copolymer is biodegradable, has no immunogenic properties and has no potential for malignant transformation [12]. The aim of our study is to evaluate the effectiveness of dextranomer/ hyaluronic acid copolymer for endoscopic correction of VUR.

Material and Methods 

Our study included 103 children with VUR who underwent endoscopic treatment with Deflux in the period between January 2001 and October 2008 at our tertiary center of pediatric surgery.

Eighty four girls and nineteen boys between 11 months and 12 years old (mean age 4.6 years) underwent endoscopic treatment with Deflux. Reflux was unilateral in 61 cases and bilateral in 42, affecting 145 ureters. Vesicoureteral reflux occurred in a single system in 135 ureters and in renal duplication in the remaining 10. According to the International Reflux Classification, reflux was grades 1 to 5 in 9 (6.6%) cases, 68 (50.37%), 45 (33.33%), 12 (8.89%) and 1 (0.74%) case respectively. The indications for endoscopic treatment were the persistence of VUR after the age of continence (about 36 months, 91 patients: 8 VUR grade 1, 68 VUR grade 2, 43 VUR grade 3 and 6 VUR grade 4), the occurrence of recurrent UTI during chemoprophylaxis (5 patients: 1 VUR grade 1, 1 VUR grade 3, 2 VUR grade 4), the intolerance to antibiotics (1 patient with VUR grade 3) and the degradation of renal function on radionuclide scans (4 VUR grade 4 and 1 VUR grade 5 in 5 boys and 1 girl with VUR grade4).

Radionuclide scan (DMSA) was practiced in all patients with VUR grades 3 to 5. The same operative protocol was used for all patients. General anesthesia was administered and the patient was placed in lithotomy position. A 10 to 14 Fr cystoscope, according to the age and sex of the child, was used and the bladder is filled half to three-quarters volume in order to permit visualization of the ureter. The technique of hydro distension by submucosal implantation within the intramural ureter which was published afterwards by Kirsch in 2004 [13] was used for all patients. The needle is inserted approximately 4 mm in the submucosa of the distal ureteral tunnel at the 6 o’clock position.

Between 0.2 and 1.5 ml (mean amount was 0,7 ml) of dextranomer/ hyaluronic acid copolymer (Deflux) per ureter was injected depending on patient age and size of the ureteral orifice and ureter until the ureteral orifice appear completely coapted. Attempts at ureteral hydrodistention following injection serve to ensure proper technique as the ureter will remain coapted with irrigation. Antibiotic prophylaxis was maintained for one month after the procedure. Renal and bladder ultra-sonography was performed the next day before discharge and 3, 12 and 24 months following treatment. Voiding cystourethrography was performed for all patients 3 months after the procedure until the year 2007 and then it was prescribed only in case of recurrent UTI.

Results

Results after a single injection of Deflux were evaluated according to the clinical evolution and to the voiding cystourethrography which was performed 3 months after the intervention for 86 patients (83.5% of cases). The results of endoscopic treatment are the following: Disappearance of VUR in 108 ureters (74.48%), in 72 patients (69.90% of cases) Attenuation of VUR in 17 ureters (11.72%), in 14 patients (13.59% of cases) Persistence of VUR in 20 ureters (13.79%), in 17 patients (16.51% of cases).

According to the grade of VUR: reflux was corrected in 9 ureters from 9 (100%) for grade 1, 55 ureters from 68 (80.88%) for grade 2, 31 ureters from 45 (68.89%) for grade 3, and 8 ureters from 12 (66.67%) for grade 4. VUR persisted in one ureter with grade 5 reflux and was corrected in 4 refluxing lower pole ureters from 7 (57.14%) and in one refluxing ureter from 3 with incomplete duplication (33.33%). Within our series, we noted the disappearance of VUR in 13 patients from 15 with associated vesical instability (86.67%) after the submucosal injection of Deflux. VUR was equally corrected in 2 patients with associated paraureteral diverticulum and one patient with associated non obstructing ureterocele. No operative complications were observed with the exception of one patient who developed UTI 2 days after the intervention. Follow up ultrasound showed transient ureteral dilatation in 3 patients which disappeared spontaneously in 3 months.

No distal ureteral obstruction on ultrasound or degradation of renal function on radionuclide scan was observed on follow-up. We performed a second injection of Deflux in 10 patients with grade 3 and 4 VUR, who presented with recurrent UTI after the first injection and with persistent reflux on VCUG. The persistent VUR was successful corrected in 7 patients and was followed by open ureteral reimplantation (Cohen) in 3 patients. For the same indications, eleven patients underwent open ureteral reimplantation after failure of a single injection of Deflux. Two patients with respectively a VUR grade 4 and grade 5 underwent nephrectomy for non functioning kidney after failure of endoscopic treatment to correct VUR. All patients were followed for 3 months to 7 years (mean follow-up 28 months).

Discussion

The main objective of management of VUR is to prevent or limit the occurrence of renal scars. The procedures for prevention are variable. The study of Birming ham and the international study of reflux in children, two randomized prospective studies to assess the benefits and risks of surgical or medical treatment in children with severe reflux, could not demonstrate the superiority of one treatment compared with the other [14,15]. No significant difference was observed after a follow-up of five years between the two treatments on the occurrence of new renal scars, the progression of existing lesions, renal growth, impaired renal function or the overall incidence of urinary tract infections. However, many children with VUR have a prolonged medical treatment (prophylactic antibiotics) for several years with repeated radiological follow-ups while keeping the possibility of surgery later on.

Consequently, the surgical indications of VUR in children typically rely on the existence of febrile urinary tract infections not controlled by medical treatment, the objective deterioration of renal function and/or the persistence of reflux in an age when it cannot disappear [16]. The main indication of endoscopic treatment in our study was the persistence of reflux after the age of continence at 88.35% of patients, decreased renal function at 5.83% of patients, the appearance of new episodes of urinary tract infection despite antibiotic prophylaxis at 4.85% of patients and intolerance to antibiotics in an infant of 8 months. The choice of surgical treatment remains much debated between the traditional ureteral reimplantation and endoscopic injection. The endoscopic treatment of reflux has demonstrated its effectiveness and safety, despite the results of conventional surgical treatment that allows correcting the vesicoureteral reflux in 95% of cases [17].

A comparative study showed a higher complication rate with surgical treatment in the form of contralateral reflux in 4 patients, hydronephrosis in 2 patients and urinary tract infection in 4 patients against a single patient who developed a contralateral reflux after endoscopic treatment, with no hydronephrosis or urinary tract infection [18]. Our series consisted of 84 girls (81.55%) and 19 boys (18.45%), or a sex ratio of 4.5. The mean age at the time of intervention was 4.6 years and the extremes of age were 8 months and 12.3 years. The female preponderance of reflux beginning from the age of two years and the severity of reflux in younger children are well known[19]. In describing the endoscopic treatment of VUR, a number of uncertainties exist related to the local tolerance of the injected product, the risk of migration and the reliability in the medium and long term of this type of treatment which influences the choice of the injected product [20].

The Deflux was introduced in 1995 by Sternberg and Lackgren [11], as a non-animal product, so with no immune response and whose particle size over 80 μm is sufficient to prevent their migration. Several experimental and clinical studies suggest the superior efficacy of dextranomer/ hyaluronic acid copolymer as an alternative to other biological implants [21, 22]. The effectiveness of endoscopic treatment by Deflux (disappearance of reflux) after a first injection in our series is 74.48%; this result is comparable with most published series with a treatment success rate from 68 to 75 % [12, 22, 23]. Regarding other injected products, the success rate after Teflon injection is between 75 and 95% in the literature and increases with the number of re-injections.

Multicenter series of Puri reporting the result of injection of Teflon over 12000 ureters confirms the results of other authors: Seventy-five per cent of reflux disappears after an injection; this treatment can achieve a rate of 95.5% success after several injections [24]. Dodat reported better results with the Macroplastique than with Teflon [25]. However, the results with collagen are clearly lower and degrade over the time [26]. These outcomes depend on the grade of reflux and vesico-ureteral abnormalities associated. Thus, the best results in our series are obtained with grades 1 (9 refluxing ureters out of 145) and 2 that give 100% and 88.9% cure rate, followed by grades 3 and 4 with a cure rate of 68.9 % and 66.7% respectively. The endoscopic treatment was ineffective in a patient with grade 5 reflux in a non functioning kidney probably due to the absence of sub-mucosal ureteral segment.

These results are superior to those of Lackgren [22] who reported 78% cure rate for grade 1 and 2 against 59% for grades 3 and 4, and inferior to the results of Puri [12] who reported a cure rate of 86% of 166 ureters with reflux grades 2 to 5 after a first injection of Deflux. Kirsch has shown a success rate increasing from 76% to 89% with its modification of submucosal implantation of Deflux within the intramural ureter which allows the location of the implant over the entire length of the ureteral intravesical tunnel. In addition, local migration of the implant with Kirsch modification is most likely to occur within the tunnel, maintaining ureteral coaptation, while with the standard procedure, as the implant is only located within the inferior edge of the subureteral space, local migration of the product caudally will likely lead to failure [13]. In our study, the cure rate in total duplications is 57.14%, or disappearance of reflux in 4 lower pole ureters out of 7, in accordance with published series that have a success rate of 51% with reflux in renal duplication [18].

The lower results are explained mainly by the short submucosal tunnel of the lower pole ureter. Among our patients, we did not observe any strictures or post-injection bleeding. One patient developed a urinary tract infection on the 2nd postoperative day. Lackgren reported that the risk of developing a urinary tract infection was 1.9% in these children compared to 25% after ureteral reimplantation [22, 27]. The main criticism that can be done in relation to endoscopic treatment concerns the uncertainties on the long-term outcome of the product used.

Conclusion

The endoscopic treatment of vesicoureteral reflux (Kirsch modification) by Deflux is recognized as a reliable alternative for the treatment of vesicoureteral reflux in children, particularly low grade. Our results, as all data from the literature, tend to confirm the reliability and low morbidity of this treatment in comparison with antibiotic prophylaxis and surgical treatment. However, surgical reimplantation remains the gold standard treatment for grades 4 and 5 because, in these grades of reflux, the shortness or total absence of the submucosal intravesical ureteral tunnel makes the injection of Deflux ineffective.

 

 

 

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