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hyaluronic acid copolymer injection for treatment of secondary vesicoureteral reflux after renal transplantation
CASE REPORT
URETERAL OBSTRUCTION AFTER DEXTRANOMER/HYALURONIC ACID COPOLYMER INJECTION FOR TREATMENT OF SECONDARY VESICOURETERAL REFLUX AFTER RENAL TRANSPLANTATION HANS-HELGE SEIFERT, BRUNELLO MAZZOLA, TOBIAS ZELLWEGER, ROBIN RUSZAT, ALEXANDER MULLER, FELIX BURKHALTER, JÖRG STEIGER, TULLIO SULSER, AND ALEXANDER BACHMANN
ABSTRACT Ureteral obstruction after transurethral injection therapy for primary vesicoureteral reflux is known to occur in less than 1% of cases. We report the first case of a ureteral obstruction after transurethral injection of dextranomer/hyaluronic acid copolymer (Deflux) for the treatment of secondary vesicoureteral reflux after renal transplantation. Loss of transplant function made reimplantation of the ureter necessary. A periureteral phlebitis and moderate foreign body reaction was found histologically, although the patient had received immunosuppressive therapy. Endoscopic therapy of secondary vesicoureteral reflux in patients after renal transplantation is a reasonable minimally invasive treatment option; however, severe complications may occur. UROLOGY 68: 203.e17–203.e19, 2006. © 2006 Elsevier Inc.
O
nly a few reports have been published regarding endoscopic therapy for secondary vesicoureteral reflux (VUR) after renal transplantation. We report the first case of ureteral obstruction and foreign body reaction after transurethral injection of dextranomer/hyaluronic acid copolymer for the treatment of secondary VUR after renal transplantation. CASE REPORT In June 2000, a 48-year-old woman underwent cadaveric renal transplantation because of terminal renal insufficiency with Lich-Gregoir implantation of the transplant ureter. After the transplantation, the patient developed recurrent urinary tract infections, and a significant increase of the serum creatinine level was observed. In November From the Departments of Urology and Nephrology, University Hospital Basel, Basel, Switzerland Address for correspondence: Hans-Helge Seifert, M.D., Department of Urology, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Moorenstrasse 5, Düsseldorf D-40225, Germany. E-mail: [email protected] Submitted: November 15, 2005, accepted (with revisions): January 30, 2006 © 2006 ELSEVIER INC. ALL RIGHTS RESERVED
2003, secondary VUR was identified and treated endoscopically by subureteral injection of 3 mL dextranomer/hyaluronic acid copolymer (Deflux, Q-Med Scandinavia, Uppsala, Sweden). After an initially uneventful course, cystography performed 6 weeks after treatment demonstrated persisting VUR (Fig. 1A). Therefore, a second injection was required in February 2004 using another 3 mL of the substrate. Investigations 6 weeks and 3 and 5 months postoperatively yielded no evidence of VUR (Fig. 1B). No urinary tract infections occurred, and the patient did not report any complaints. Six months after the second injection, dilation of the transplant ureter and the pylon was observed, and the patient had renal insufficiency. Micturition cystography did not show any VUR. Retrograde ureteropyelography was impossible because of stenosis of the ureteral orifice; insertion of a double-J stent also failed. Therefore, percutaneous nephrostomy was required, and antegrade pyeloureterography demonstrated a filiform stenosis of the distal ureter (Fig. 1C). Open revision was performed. Intraoperatively, a 3-cm-long stenotic segment of the distal ureter was found that was obstructed by a periureteral bulky mass (Fig. 2A). After resection of the complete transplant ureter, a 0090-4295/06/$32.00 doi:10.1016/j.urology.2006.01.071 203.e17
FIGURE 1. (A) Persistent VUR detected after first treatment with dextranomer/hyaluronic acid copolymer. (B) Micturition cystography after second transurethral injection did not show any VUR. (C) Six months after second treatment, antegrade pyeloureterography demonstrated filiform stenosis (arrow) of prevesical transplant ureter.
FIGURE 2. (A) Intraoperatively, 3-cm-long stenotic segment of distal ureter found (bracket) with periureteral bulky mass. (B) Histopathologic examination demonstrated unspecific chronic lymphoplasmacellular infection and moderate foreign body reaction (bracket) near deposits of dextranomer/hyaluronic acid copolymer (arrows).
periureteral deposit of dextranomer/hyaluronic acid was detected. Histopathologic examination demonstrated an unspecific chronic lymphoplasmacellular infection with moderate periphlebitis and a foreign body reaction (Fig. 2B). Anderson-Hynes ureteropyeloplasty using the native right ureter was performed. The postoperative outcome was uneventful. After removal of the double-J stent, no signs of obstruction were noted, and her renal function was within the normal range. COMMENT Only two reports of endoscopic subureteral injection therapy for secondary VUR after renal transplantation have been published. Cloix et al.1 treated 21 patients with endoscopic subureteral injection of Polytef paste. They reported a success rate of only 30% (6 patients) without any signifi203.e18
cant complications. Another small series of 15 patients treated with transurethral Teflon injections was published by Mallet et al.2 They reported a failure rate of 33.3% (5 patients), and a single renal colic due to a temporal meatal stenosis of the ureter was the only complication described. More reports have described endoscopic treatment of primary reflux in adult and pediatric patients, but obstruction has rarely been reported. A multicenter survey that included 41 centers with 12,521 ureters treated found an obstruction rate requiring reimplantation of the ureter of 0.33%.3 Four series of primary reflux in children, comprising 607 ureters treated in total, did not describe any obstruction after subureteral injection of dextranomer/hyaluronic acid copolymer.4 –7 The only case of obstruction after dextranomer/hyaluronic acid injection was reported by Snodgrass8 in a child with a dysmorphic UROLOGY 68 (1), 2006
ureter. That case of obstruction after initial treatment with 0.8 mL substrate later required open surgery and reimplantation of the ureter. In this report, we describe the first case of obstruction after treatment with dextranomer/hyaluronic acid copolymer for secondary reflux after kidney transplantation and the second case ever reported after treatment of VUR with this substrate. VUR is a common phenomenon after renal transplantation, occurring in up to 86% of cases, although ureteral obstruction has occurred in only 3.6% of transplants in large series.9,10 It is considered a main risk factor for recurrent urinary tract infections and may induce reflux nephropathy, resulting in a loss of renal function.9 As mentioned, only a few reports have described endoscopic repair of secondary VUR. For these cases, failure rates of up to 33% have been reported.3 The reasons for failure were not specified in these reports, but could have been technical and/or specific, such as the implantation technique of the ureter, location and anatomy of the neo-orifice, and foreign body reaction. In our case, periureteral phlebitis and a moderate foreign body reaction was found histologically, although the patient had received immunosuppressive therapy with mycophenolate and cyclosporine. However, endoscopic therapy of secondary VUR in patients after kidney transplantation is recommended because of its minimal invasive character. One should be aware that the reported success rates might be lower than for primary reflux. Severe complications such as obstruction resulting in loss of transplant function and the need for reimplantation may occur. Ureteropyelostomy using
UROLOGY 68 (1), 2006
the naive ureter seems to be a valid treatment option in the case of endoscopic treatment failure. REFERENCES 1. Cloix P, Gelet A, Desmettre O, et al: Endoscopic treatment of vesicoureteric reflux in transplanted kidneys. Br J Urol 72: 20 –22, 1993. 2. Mallet R, Game X, Mouzin M, et al: Symptomatic vesicoureteral reflux in kidney transplantation: results of endoscopic injections of Teflon and predictive factors for success. Prog Urol 13: 598 – 601, 2003. 3. Puri P, and Granata C: Multicenter survey of endoscopic treatment of vesicoureteral reflux using polytetrafluoroethylene. J Urol 160: 1007–1011, 1998. 4. Oswald J, Riccabona M, Lusuardi L, et al: Prospective comparison and 1-year follow-up of a single endoscopic subureteral polydimethylsiloxane versus dextranomer/hyaluronic acid copolymer injection for treatment of vesicoureteral reflux in children. Urology 60: 894 – 897, 2002. 5. Puri P, Chertin B, Velayudham M, et al: Treatment of vesicoureteral reflux by endoscopic injection of dextranomer/ hyaluronic acid copolymer: preliminary results. J Urol 170: 1541–1544, 2003. 6. Kirsch AJ, Perez-Brayfield MR, and Scherz HC: Minimally invasive treatment of vesicoureteral reflux with endoscopic injection of dextranomer/hyaluronic acid copolymer: the Children’s Hospitals of Atlanta experiences. J Urol 170: 211–215, 2003. 7. Perez-Brayfield M, Kirsch AJ, Hensle TW, et al: Endoscopic treatment with dextranomer/hyaluronic acid for complex cases of vesicoureteral reflux. J Urol 172: 1614 –1616, 2004. 8. Snodgrass WT: Obstruction of a dysmorphic ureter following dextranomer/hyaluronic acid copolymer. J Urol 171: 395–396, 2004. 9. Mastrosimone S, Pignata G, Maresca MC, et al: Clinical significance of vesicoureteral reflux after kidney transplantation. Clin Nephrol 40: 38 – 45, 1993. 10. Shoskes DA, Hanbury D, Cranston D, et al: Urological complications in 1,000 consecutive renal transplant recipients. J Urol 153: 18 –21, 1995.
203.e19
URETERAL OBSTRUCTION AFTER DEXTRANOMER/HYALURONIC ACID COPOLYMER INJECTION FOR TREATMENT OF SECONDARY VESICOURETERAL REFLUX AFTER RENAL TRANSPLANTATION HANS-HELGE SEIFERT, BRUNELLO MAZZOLA, TOBIAS ZELLWEGER, ROBIN RUSZAT, ALEXANDER MULLER, FELIX BURKHALTER, JÖRG STEIGER, TULLIO SULSER, AND ALEXANDER BACHMANN
ABSTRACT Ureteral obstruction after transurethral injection therapy for primary vesicoureteral reflux is known to occur in less than 1% of cases. We report the first case of a ureteral obstruction after transurethral injection of dextranomer/hyaluronic acid copolymer (Deflux) for the treatment of secondary vesicoureteral reflux after renal transplantation. Loss of transplant function made reimplantation of the ureter necessary. A periureteral phlebitis and moderate foreign body reaction was found histologically, although the patient had received immunosuppressive therapy. Endoscopic therapy of secondary vesicoureteral reflux in patients after renal transplantation is a reasonable minimally invasive treatment option; however, severe complications may occur. UROLOGY 68: 203.e17–203.e19, 2006. © 2006 Elsevier Inc.
O
nly a few reports have been published regarding endoscopic therapy for secondary vesicoureteral reflux (VUR) after renal transplantation. We report the first case of ureteral obstruction and foreign body reaction after transurethral injection of dextranomer/hyaluronic acid copolymer for the treatment of secondary VUR after renal transplantation. CASE REPORT In June 2000, a 48-year-old woman underwent cadaveric renal transplantation because of terminal renal insufficiency with Lich-Gregoir implantation of the transplant ureter. After the transplantation, the patient developed recurrent urinary tract infections, and a significant increase of the serum creatinine level was observed. In November From the Departments of Urology and Nephrology, University Hospital Basel, Basel, Switzerland Address for correspondence: Hans-Helge Seifert, M.D., Department of Urology, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Moorenstrasse 5, Düsseldorf D-40225, Germany. E-mail: [email protected] Submitted: November 15, 2005, accepted (with revisions): January 30, 2006 © 2006 ELSEVIER INC. ALL RIGHTS RESERVED
2003, secondary VUR was identified and treated endoscopically by subureteral injection of 3 mL dextranomer/hyaluronic acid copolymer (Deflux, Q-Med Scandinavia, Uppsala, Sweden). After an initially uneventful course, cystography performed 6 weeks after treatment demonstrated persisting VUR (Fig. 1A). Therefore, a second injection was required in February 2004 using another 3 mL of the substrate. Investigations 6 weeks and 3 and 5 months postoperatively yielded no evidence of VUR (Fig. 1B). No urinary tract infections occurred, and the patient did not report any complaints. Six months after the second injection, dilation of the transplant ureter and the pylon was observed, and the patient had renal insufficiency. Micturition cystography did not show any VUR. Retrograde ureteropyelography was impossible because of stenosis of the ureteral orifice; insertion of a double-J stent also failed. Therefore, percutaneous nephrostomy was required, and antegrade pyeloureterography demonstrated a filiform stenosis of the distal ureter (Fig. 1C). Open revision was performed. Intraoperatively, a 3-cm-long stenotic segment of the distal ureter was found that was obstructed by a periureteral bulky mass (Fig. 2A). After resection of the complete transplant ureter, a 0090-4295/06/$32.00 doi:10.1016/j.urology.2006.01.071 203.e17
FIGURE 1. (A) Persistent VUR detected after first treatment with dextranomer/hyaluronic acid copolymer. (B) Micturition cystography after second transurethral injection did not show any VUR. (C) Six months after second treatment, antegrade pyeloureterography demonstrated filiform stenosis (arrow) of prevesical transplant ureter.
FIGURE 2. (A) Intraoperatively, 3-cm-long stenotic segment of distal ureter found (bracket) with periureteral bulky mass. (B) Histopathologic examination demonstrated unspecific chronic lymphoplasmacellular infection and moderate foreign body reaction (bracket) near deposits of dextranomer/hyaluronic acid copolymer (arrows).
periureteral deposit of dextranomer/hyaluronic acid was detected. Histopathologic examination demonstrated an unspecific chronic lymphoplasmacellular infection with moderate periphlebitis and a foreign body reaction (Fig. 2B). Anderson-Hynes ureteropyeloplasty using the native right ureter was performed. The postoperative outcome was uneventful. After removal of the double-J stent, no signs of obstruction were noted, and her renal function was within the normal range. COMMENT Only two reports of endoscopic subureteral injection therapy for secondary VUR after renal transplantation have been published. Cloix et al.1 treated 21 patients with endoscopic subureteral injection of Polytef paste. They reported a success rate of only 30% (6 patients) without any signifi203.e18
cant complications. Another small series of 15 patients treated with transurethral Teflon injections was published by Mallet et al.2 They reported a failure rate of 33.3% (5 patients), and a single renal colic due to a temporal meatal stenosis of the ureter was the only complication described. More reports have described endoscopic treatment of primary reflux in adult and pediatric patients, but obstruction has rarely been reported. A multicenter survey that included 41 centers with 12,521 ureters treated found an obstruction rate requiring reimplantation of the ureter of 0.33%.3 Four series of primary reflux in children, comprising 607 ureters treated in total, did not describe any obstruction after subureteral injection of dextranomer/hyaluronic acid copolymer.4 –7 The only case of obstruction after dextranomer/hyaluronic acid injection was reported by Snodgrass8 in a child with a dysmorphic UROLOGY 68 (1), 2006
ureter. That case of obstruction after initial treatment with 0.8 mL substrate later required open surgery and reimplantation of the ureter. In this report, we describe the first case of obstruction after treatment with dextranomer/hyaluronic acid copolymer for secondary reflux after kidney transplantation and the second case ever reported after treatment of VUR with this substrate. VUR is a common phenomenon after renal transplantation, occurring in up to 86% of cases, although ureteral obstruction has occurred in only 3.6% of transplants in large series.9,10 It is considered a main risk factor for recurrent urinary tract infections and may induce reflux nephropathy, resulting in a loss of renal function.9 As mentioned, only a few reports have described endoscopic repair of secondary VUR. For these cases, failure rates of up to 33% have been reported.3 The reasons for failure were not specified in these reports, but could have been technical and/or specific, such as the implantation technique of the ureter, location and anatomy of the neo-orifice, and foreign body reaction. In our case, periureteral phlebitis and a moderate foreign body reaction was found histologically, although the patient had received immunosuppressive therapy with mycophenolate and cyclosporine. However, endoscopic therapy of secondary VUR in patients after kidney transplantation is recommended because of its minimal invasive character. One should be aware that the reported success rates might be lower than for primary reflux. Severe complications such as obstruction resulting in loss of transplant function and the need for reimplantation may occur. Ureteropyelostomy using
UROLOGY 68 (1), 2006
the naive ureter seems to be a valid treatment option in the case of endoscopic treatment failure. REFERENCES 1. Cloix P, Gelet A, Desmettre O, et al: Endoscopic treatment of vesicoureteric reflux in transplanted kidneys. Br J Urol 72: 20 –22, 1993. 2. Mallet R, Game X, Mouzin M, et al: Symptomatic vesicoureteral reflux in kidney transplantation: results of endoscopic injections of Teflon and predictive factors for success. Prog Urol 13: 598 – 601, 2003. 3. Puri P, and Granata C: Multicenter survey of endoscopic treatment of vesicoureteral reflux using polytetrafluoroethylene. J Urol 160: 1007–1011, 1998. 4. Oswald J, Riccabona M, Lusuardi L, et al: Prospective comparison and 1-year follow-up of a single endoscopic subureteral polydimethylsiloxane versus dextranomer/hyaluronic acid copolymer injection for treatment of vesicoureteral reflux in children. Urology 60: 894 – 897, 2002. 5. Puri P, Chertin B, Velayudham M, et al: Treatment of vesicoureteral reflux by endoscopic injection of dextranomer/ hyaluronic acid copolymer: preliminary results. J Urol 170: 1541–1544, 2003. 6. Kirsch AJ, Perez-Brayfield MR, and Scherz HC: Minimally invasive treatment of vesicoureteral reflux with endoscopic injection of dextranomer/hyaluronic acid copolymer: the Children’s Hospitals of Atlanta experiences. J Urol 170: 211–215, 2003. 7. Perez-Brayfield M, Kirsch AJ, Hensle TW, et al: Endoscopic treatment with dextranomer/hyaluronic acid for complex cases of vesicoureteral reflux. J Urol 172: 1614 –1616, 2004. 8. Snodgrass WT: Obstruction of a dysmorphic ureter following dextranomer/hyaluronic acid copolymer. J Urol 171: 395–396, 2004. 9. Mastrosimone S, Pignata G, Maresca MC, et al: Clinical significance of vesicoureteral reflux after kidney transplantation. Clin Nephrol 40: 38 – 45, 1993. 10. Shoskes DA, Hanbury D, Cranston D, et al: Urological complications in 1,000 consecutive renal transplant recipients. J Urol 153: 18 –21, 1995.
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