TRANSPLANT-
Transplant Int (1992) 5:231-233
International
9 Springer-Verlag 1992
Endoscopic treatment of vesicoureteral reflux prior to renal transplantation M. Salas Sironvalle, A. Gelet, X. Martin, S. Gabriele, J. M. Clavel and J. M. Dubernard Department of Urology and Transplantation Surgery, Hopital Edouard Herriot Pavilion V, F-69437 Lyon Cedex 03, France Received October 11, 1990/Received after revision December 30, 1991/Accepted April 7, 1992
Abstract. E n d o s c o p i c subureteral injection of Teflon was d o n e in 34 potential renal transplant recipients to correct vesicoureteral reflux. Follow-up r a n g e d f r o m 6 to 24 mouths. A f t e r one injection reflux was corrected in 53.7 % of the patients; this increased to 64.8 % after a second injection. T h e p r o c e d u r e is simple, effective, without m a j o r morbidity, and avoids the risk of n e p h r o u r e t e r e c tomy. H o w e v e r , efforts must be m a d e to find an ideal substance with a higher biocompatibility and w i t h o u t risk of migration.
Key words: Reflux, native kidney - Kidney transplantation, reflux, native k i d n e y - E n d o s c o p i c treatment, ureter reflux
Surgical m a n a g e m e n t of vesicoureteral reflux ( V U R ) in the transplant recipient is indicated in massive or symptomatic V U R . T h e treatments c o m m o n l y described are n e p h r o u r e t e r e c t o m y or ureteral reimplantation [15]. However, these o p e n interventions have some potential morbidity. T h e endoscopic technique used to cure reflux is valuable prior to renal transplantation [5, 7]. We r e p o r t our experience with this technique in 34 patients presenting with 54 refluxing ureters.
tient had recurrent urinary infection. Twenty-two patients had chronic pyelonephritis and/or a urinary infection at the first consultation. The ureteral orifice morphology, according to Lyon classification [9], is shown in Fig. 2. We used the technique described by O'Donnel and Puri [12, 14]. The procedure was performed under general anaesthesia, with the patient in lithotomy position. A 6 Fr ureteral catheter was placed in the ureter prior to the injection. The Teflon paste was inserted in a 1ml syringe with a metallic piston. A 23.5 Fr cystoscope with an A1barran bridge and a 30-degree telescope was used. A 7 Fr disposable catheter (Angiomed) was rinsed with glycerine and then charged with Teflon_ Then 0.754 ml of Teflon was injected under the ureteral orifice, at the 6 o'clock position, 10 mm into the submucosa. The paste was injected slowly under direct vision until the orifice acquired the nearly normal or volcan aspect. The ureteral catheter was removed and cystography was performed after injection to confirm the efficacy of the treatment. No indwelling catheters were used and the patients left the hospital the next day, after treatment. Kidney transplantation with cadaveric donorse was performed on 13 patients. An extravesical ureteroneocystostomy (Campos Freire) was performed and triple immunosupressive therapy was employed in each case.
Results S t a n d a r d micturation c y s t o u r e t h r o g r a p h y was p e r f o r m e d post-injection at 1 m o n t h (54 ureteral units), 3 m o n t h s (39 ureteral units), 6 m o n t h s (25 ureteral units), 1 y e a r
Patients and methods 30
Since January 1986, 34 patients with end-stage renal failure and VUR have been treated by endoscopic injection of polytetrafluoroethylene (Teflon) prior to renal transplantation. The study group consisted of 15 females and 19 males between 19 and 58 years of age (mean 35 years). These cases represent 54 refluxhlg ureters; 14 patients had unilateral VUR and 20 had bilateral VUR. Grading of VUR was established according to the International Classification System [3] (Fig. 1). The ureters with low grades were injected in cases of contralateral high-grade VUR or when the pa-
20
:~
10
0 I
Correspondence to."M. Salas Sironvalle
II
III IV G R A D E S OF VUR
Fig. 1. Classification of reflux
232 30
20
10
o Normal
Stadium
Horseshoe
Golfhole
Fig.2. Orifice morphology
(17 ureteral units), and 2 years (8 ureteral units). Complete disappearance of V U R was observed in 53.7 % of the cases (29/54) after one injection of Teflon paste (Figs. 3, 4). There was an improvement in seven cases after treatment; the refluxing ureteral units of various grades were converted to grade I and they were followed by urinary cultures. A second injection was performed in 12 cases, resulting in six successes (35/54 total correction). All patients treated successfully or who experienced a decrease in V U R to grade I were without urinary infection at follow-up. One patient presented with a severe hematuria in the early postoperative period and was treated by urethral catheter and blood transfusion. Three recurrences were detected at 3 months and i year. Repeated injection of Teflon in two cases resulted in the disappearance of VUR. In 12 cases the endoscopic treatment did not decrease the grade of V U R and the indication of nephroureterectomy was maintained. In the transplanted group (13 patients, 20 ureteral units) there were seven grade II ureters, eight grade III ureters, and 5 grade IV ureters. V U R was successfully treated in nine patients. In two patients a decrease in V U R to an asymptomatic grade I V U R was observed, and two patients required nephroureterectomy. After transplantation no recurrence of V U R was observed at follow-up and only one lower urinary tract infection was detected in a patient with partially corrected VUR.
Discussion Renal transplantation is the best treatment for the majority of patients with end-stage renal disease. The goal for urologists is to optimize the conditions of the urinary tract prior to renal transplantation. A high grade of V U R is a risk factor in transplant recipients and nephroureterectomy is commonly advocated. However, preservation of the native kidney avoids morbidity and mortality and maintains fluid balance, erythropoietin and vitamine D3 production [4]. Low-grade VUR, without a history of urinary infection, in general does not require treatment and commonly disappears spontaneously. It is our policy to treat symptomatic or high-degree V U R only. Ureteral reimplantation of the native ureter is not recommended since this procedure can disturb the transplant. Endoscopic correction should be attempted in infected grade I-II V U R and in high degrees of VUR. In grade V VUR, the endoscopic correction was a
Hg.3. Male patient with symptomatic VUR (renal failure secondary to chronic pyelonephritis) Fig.4. Two years after treatment: no urinary infection and absence of VUR
c I
II
Ill
IV
V
Fig.5. Results of treatment according to grade of VUR. 9 Failure, []SUCCESS
failure in our two patients. Nephroureterectomy seems to be indicated in massive and complex grade V V U R and when endoscopic treatment fails. Laryngologists have been injecting Teflon for many years to treat vocal cord diseases [1, 6] and urologists to treat urinary incontinence [13, 17]. In these applications no untoward side effects have been described. The endoscopic treatment of V U R with Teflon was first described by Matouschek in 1981 [11]. Thereafter, O'Donnel and Puri reported their experimental and clinical series in children [12, 14]. The particles of tetrafluorethylene are suspended in polyethylene-glycol and, after subureteral injection, a granulomatous reaction occurs and the particles are encapsulated with minimal inflammatory reaction. The success rate reported in children has ranged from 70 % to 95 % [2, 8, 16] and in adults the success rate has ranged from 73 % to 83 % [5, 18]. No major complications or intolerance have been reported in these series. The overall success rate of 64.8 % in our files can be explained by the fact that the intramural traject of the ureter
233 was short, all of the ureteral orifices were ectopic, and the detrusors were sclerotic and atrophic. O n l y three recurrences were seen and these were treated successfully in two cases. Transplantation was p e r f o r m e d on 13 patients without incidence and no complications had b e e n detected at the time of writing. Distant migration of p o l y t e t r a f l u o r o e t h y l e n e particles after periurethral injection of Teflon has b e e n well doc u m e n t e d in primates [10]. Migration of Teflon in regional lymph nodes has b e e n described in h u m a n s - in one patient after t r e a t m e n t of urinary incontinence [17] and in two cases after endoscopic correction of V U R in children [16]. H o w e v e r , m o r e than 1000 patients have b e e n treated by endoscopic injection of Teflon in the t r e a t m e n t of V U R without m a j o r complications, embolization, or carcinogenic effects. T h e endoscopic correction of V U R seems a rational alternative to o p e n surgery. H o w e v e r , Teflon paste is not the best material to use in endoscopic injection. T h e risk of distant migration is n o t acceptable in clinical use. Future research will have to be directed towards finding an innocuous and inert material w i t h o u t risk of migration.
References 1. Arnold GE (1963) Alleviation of aphonia of dysphonia through intrachordal injection of teflon paste. Ann Otol Rhinol Laryngol 70:384-395 2. Brown S (1989) Open versus endoscopic surgery in the treatment of vesicoureteral reflux. J Uro1142: 499-500 3. Faure G, Dechelette E, Rambeaud JJ (1986) Reflux v6sicourdt6ral. Encycl Mdd Chir Rein-organes gdnito-urinaires. Edition Techniques, Paris, France, 18069 F10, 7:7 10
4. Freier DT, Konnak JW, Niederhuber JE, Turcotte JG (1984) Renal transplantation. In: Kendall AR, Karafin L (eds) Urology, vol 2. Harper & Row, Philadelphia, pp 1-37 5. Gelet A, Salas M, Martin X, Faure JL, Dubernard JM (1987) Traitement endoscopique du reflux v6sico-urdtdral. J Urol (Paris) 93:263-268 6. Harris HE, Hawk WA (1969) Laryngeal injection of Teflon paste. Arch Otolaryngo190:194-197 7. Jackson CL, Kay R, Bretan R Novick AC, Steinmuler D (1989) Endoscopic correction of vesicoureteral reflux in the renal transplant candidate. J Uro1142: 710-711 8. Kaplan WE, Dalton DR Firlit CF (1987) The endoscopic correction of reflux by polytetrafluoroethylene injection. J Urol 138: 953-958 9. Lyon RR Marshall S, Tanagho EA (1969) The ureteral orifice: its configuration and competency. J Uro1102: 504-509 10. Malizia AA, Reiman HM, Myers RP, Sanders JR, Barham SS, Benson RC, Dewanjet MK, Utz WJ (1984) Migration and granulomatous reaction after periurethral injection of polytef (Teflon). JAMA 251:3277-3281 11. Matouschek E (1981) Die Behandlung des vesicorenalen Refluxes durch transurethralen Einspritzung yon Teflonpaste. Urologe (A) 20:263-266 12. O'Donnel E, Purl P (1986) Endoscopic correction of primary vesicoureteric reflux. Br J Uro158:601~504 13. Politano VA (1982) Periurethral polytetrafluoroethylene injection for urinary incontinence. J Uro1137:43%441 14. Puri R O'Donnel B (1984) Correction of experimentally produced vesicoureteric reflux in the piglet by intravesicat injection of Teflon. BMJ 289:5-7 15. Reinberg Y, Bumgardner GL, Aliabadi H (1990) Urological aspects of renal transplantation. J Uro1143:1087-1092 16. Valla JS, Aubert D, Dodat H, Chavrier Y, Limonne B, Galifer RB, Montupet R Pamart D, Schulman CC (1989) Traitement endoscopique du reflux v~sico-urdtdral par injection sous muqueuse de pfite de Tdflon chez l'enfant. Chir Pediatr 30: 37-42 17. Vorstman B, Lockhart J, Kaufman KR, Politano VA (1985) Polytetrafluoroethylene injection for urinary incontinence in children. J Uro1133: 248-250 18. Yachia D (1989) Submeatal injection of polytetrafluoroethylene paste for the endoscopic treatment of vesicoureteric reflux in adults. Br J Uro164:552-555
Transplant Int (1992) 5:231-233
International
9 Springer-Verlag 1992
Endoscopic treatment of vesicoureteral reflux prior to renal transplantation M. Salas Sironvalle, A. Gelet, X. Martin, S. Gabriele, J. M. Clavel and J. M. Dubernard Department of Urology and Transplantation Surgery, Hopital Edouard Herriot Pavilion V, F-69437 Lyon Cedex 03, France Received October 11, 1990/Received after revision December 30, 1991/Accepted April 7, 1992
Abstract. E n d o s c o p i c subureteral injection of Teflon was d o n e in 34 potential renal transplant recipients to correct vesicoureteral reflux. Follow-up r a n g e d f r o m 6 to 24 mouths. A f t e r one injection reflux was corrected in 53.7 % of the patients; this increased to 64.8 % after a second injection. T h e p r o c e d u r e is simple, effective, without m a j o r morbidity, and avoids the risk of n e p h r o u r e t e r e c tomy. H o w e v e r , efforts must be m a d e to find an ideal substance with a higher biocompatibility and w i t h o u t risk of migration.
Key words: Reflux, native kidney - Kidney transplantation, reflux, native k i d n e y - E n d o s c o p i c treatment, ureter reflux
Surgical m a n a g e m e n t of vesicoureteral reflux ( V U R ) in the transplant recipient is indicated in massive or symptomatic V U R . T h e treatments c o m m o n l y described are n e p h r o u r e t e r e c t o m y or ureteral reimplantation [15]. However, these o p e n interventions have some potential morbidity. T h e endoscopic technique used to cure reflux is valuable prior to renal transplantation [5, 7]. We r e p o r t our experience with this technique in 34 patients presenting with 54 refluxing ureters.
tient had recurrent urinary infection. Twenty-two patients had chronic pyelonephritis and/or a urinary infection at the first consultation. The ureteral orifice morphology, according to Lyon classification [9], is shown in Fig. 2. We used the technique described by O'Donnel and Puri [12, 14]. The procedure was performed under general anaesthesia, with the patient in lithotomy position. A 6 Fr ureteral catheter was placed in the ureter prior to the injection. The Teflon paste was inserted in a 1ml syringe with a metallic piston. A 23.5 Fr cystoscope with an A1barran bridge and a 30-degree telescope was used. A 7 Fr disposable catheter (Angiomed) was rinsed with glycerine and then charged with Teflon_ Then 0.754 ml of Teflon was injected under the ureteral orifice, at the 6 o'clock position, 10 mm into the submucosa. The paste was injected slowly under direct vision until the orifice acquired the nearly normal or volcan aspect. The ureteral catheter was removed and cystography was performed after injection to confirm the efficacy of the treatment. No indwelling catheters were used and the patients left the hospital the next day, after treatment. Kidney transplantation with cadaveric donorse was performed on 13 patients. An extravesical ureteroneocystostomy (Campos Freire) was performed and triple immunosupressive therapy was employed in each case.
Results S t a n d a r d micturation c y s t o u r e t h r o g r a p h y was p e r f o r m e d post-injection at 1 m o n t h (54 ureteral units), 3 m o n t h s (39 ureteral units), 6 m o n t h s (25 ureteral units), 1 y e a r
Patients and methods 30
Since January 1986, 34 patients with end-stage renal failure and VUR have been treated by endoscopic injection of polytetrafluoroethylene (Teflon) prior to renal transplantation. The study group consisted of 15 females and 19 males between 19 and 58 years of age (mean 35 years). These cases represent 54 refluxhlg ureters; 14 patients had unilateral VUR and 20 had bilateral VUR. Grading of VUR was established according to the International Classification System [3] (Fig. 1). The ureters with low grades were injected in cases of contralateral high-grade VUR or when the pa-
20
:~
10
0 I
Correspondence to."M. Salas Sironvalle
II
III IV G R A D E S OF VUR
Fig. 1. Classification of reflux
232 30
20
10
o Normal
Stadium
Horseshoe
Golfhole
Fig.2. Orifice morphology
(17 ureteral units), and 2 years (8 ureteral units). Complete disappearance of V U R was observed in 53.7 % of the cases (29/54) after one injection of Teflon paste (Figs. 3, 4). There was an improvement in seven cases after treatment; the refluxing ureteral units of various grades were converted to grade I and they were followed by urinary cultures. A second injection was performed in 12 cases, resulting in six successes (35/54 total correction). All patients treated successfully or who experienced a decrease in V U R to grade I were without urinary infection at follow-up. One patient presented with a severe hematuria in the early postoperative period and was treated by urethral catheter and blood transfusion. Three recurrences were detected at 3 months and i year. Repeated injection of Teflon in two cases resulted in the disappearance of VUR. In 12 cases the endoscopic treatment did not decrease the grade of V U R and the indication of nephroureterectomy was maintained. In the transplanted group (13 patients, 20 ureteral units) there were seven grade II ureters, eight grade III ureters, and 5 grade IV ureters. V U R was successfully treated in nine patients. In two patients a decrease in V U R to an asymptomatic grade I V U R was observed, and two patients required nephroureterectomy. After transplantation no recurrence of V U R was observed at follow-up and only one lower urinary tract infection was detected in a patient with partially corrected VUR.
Discussion Renal transplantation is the best treatment for the majority of patients with end-stage renal disease. The goal for urologists is to optimize the conditions of the urinary tract prior to renal transplantation. A high grade of V U R is a risk factor in transplant recipients and nephroureterectomy is commonly advocated. However, preservation of the native kidney avoids morbidity and mortality and maintains fluid balance, erythropoietin and vitamine D3 production [4]. Low-grade VUR, without a history of urinary infection, in general does not require treatment and commonly disappears spontaneously. It is our policy to treat symptomatic or high-degree V U R only. Ureteral reimplantation of the native ureter is not recommended since this procedure can disturb the transplant. Endoscopic correction should be attempted in infected grade I-II V U R and in high degrees of VUR. In grade V VUR, the endoscopic correction was a
Hg.3. Male patient with symptomatic VUR (renal failure secondary to chronic pyelonephritis) Fig.4. Two years after treatment: no urinary infection and absence of VUR
c I
II
Ill
IV
V
Fig.5. Results of treatment according to grade of VUR. 9 Failure, []SUCCESS
failure in our two patients. Nephroureterectomy seems to be indicated in massive and complex grade V V U R and when endoscopic treatment fails. Laryngologists have been injecting Teflon for many years to treat vocal cord diseases [1, 6] and urologists to treat urinary incontinence [13, 17]. In these applications no untoward side effects have been described. The endoscopic treatment of V U R with Teflon was first described by Matouschek in 1981 [11]. Thereafter, O'Donnel and Puri reported their experimental and clinical series in children [12, 14]. The particles of tetrafluorethylene are suspended in polyethylene-glycol and, after subureteral injection, a granulomatous reaction occurs and the particles are encapsulated with minimal inflammatory reaction. The success rate reported in children has ranged from 70 % to 95 % [2, 8, 16] and in adults the success rate has ranged from 73 % to 83 % [5, 18]. No major complications or intolerance have been reported in these series. The overall success rate of 64.8 % in our files can be explained by the fact that the intramural traject of the ureter
233 was short, all of the ureteral orifices were ectopic, and the detrusors were sclerotic and atrophic. O n l y three recurrences were seen and these were treated successfully in two cases. Transplantation was p e r f o r m e d on 13 patients without incidence and no complications had b e e n detected at the time of writing. Distant migration of p o l y t e t r a f l u o r o e t h y l e n e particles after periurethral injection of Teflon has b e e n well doc u m e n t e d in primates [10]. Migration of Teflon in regional lymph nodes has b e e n described in h u m a n s - in one patient after t r e a t m e n t of urinary incontinence [17] and in two cases after endoscopic correction of V U R in children [16]. H o w e v e r , m o r e than 1000 patients have b e e n treated by endoscopic injection of Teflon in the t r e a t m e n t of V U R without m a j o r complications, embolization, or carcinogenic effects. T h e endoscopic correction of V U R seems a rational alternative to o p e n surgery. H o w e v e r , Teflon paste is not the best material to use in endoscopic injection. T h e risk of distant migration is n o t acceptable in clinical use. Future research will have to be directed towards finding an innocuous and inert material w i t h o u t risk of migration.
References 1. Arnold GE (1963) Alleviation of aphonia of dysphonia through intrachordal injection of teflon paste. Ann Otol Rhinol Laryngol 70:384-395 2. Brown S (1989) Open versus endoscopic surgery in the treatment of vesicoureteral reflux. J Uro1142: 499-500 3. Faure G, Dechelette E, Rambeaud JJ (1986) Reflux v6sicourdt6ral. Encycl Mdd Chir Rein-organes gdnito-urinaires. Edition Techniques, Paris, France, 18069 F10, 7:7 10
4. Freier DT, Konnak JW, Niederhuber JE, Turcotte JG (1984) Renal transplantation. In: Kendall AR, Karafin L (eds) Urology, vol 2. Harper & Row, Philadelphia, pp 1-37 5. Gelet A, Salas M, Martin X, Faure JL, Dubernard JM (1987) Traitement endoscopique du reflux v6sico-urdtdral. J Urol (Paris) 93:263-268 6. Harris HE, Hawk WA (1969) Laryngeal injection of Teflon paste. Arch Otolaryngo190:194-197 7. Jackson CL, Kay R, Bretan R Novick AC, Steinmuler D (1989) Endoscopic correction of vesicoureteral reflux in the renal transplant candidate. J Uro1142: 710-711 8. Kaplan WE, Dalton DR Firlit CF (1987) The endoscopic correction of reflux by polytetrafluoroethylene injection. J Urol 138: 953-958 9. Lyon RR Marshall S, Tanagho EA (1969) The ureteral orifice: its configuration and competency. J Uro1102: 504-509 10. Malizia AA, Reiman HM, Myers RP, Sanders JR, Barham SS, Benson RC, Dewanjet MK, Utz WJ (1984) Migration and granulomatous reaction after periurethral injection of polytef (Teflon). JAMA 251:3277-3281 11. Matouschek E (1981) Die Behandlung des vesicorenalen Refluxes durch transurethralen Einspritzung yon Teflonpaste. Urologe (A) 20:263-266 12. O'Donnel E, Purl P (1986) Endoscopic correction of primary vesicoureteric reflux. Br J Uro158:601~504 13. Politano VA (1982) Periurethral polytetrafluoroethylene injection for urinary incontinence. J Uro1137:43%441 14. Puri R O'Donnel B (1984) Correction of experimentally produced vesicoureteric reflux in the piglet by intravesicat injection of Teflon. BMJ 289:5-7 15. Reinberg Y, Bumgardner GL, Aliabadi H (1990) Urological aspects of renal transplantation. J Uro1143:1087-1092 16. Valla JS, Aubert D, Dodat H, Chavrier Y, Limonne B, Galifer RB, Montupet R Pamart D, Schulman CC (1989) Traitement endoscopique du reflux v~sico-urdtdral par injection sous muqueuse de pfite de Tdflon chez l'enfant. Chir Pediatr 30: 37-42 17. Vorstman B, Lockhart J, Kaufman KR, Politano VA (1985) Polytetrafluoroethylene injection for urinary incontinence in children. J Uro1133: 248-250 18. Yachia D (1989) Submeatal injection of polytetrafluoroethylene paste for the endoscopic treatment of vesicoureteric reflux in adults. Br J Uro164:552-555
