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Efficiency and Safety of the Sting Operation on Kidney Transplanted Patients with Symptomatic Vesicoureteral Reflux and Neurogenic Bladder Dysfunction
Efficiency and Safety of the Sting Operation on Kidney Transplanted Patients with Symptomatic Vesicoureteral Reflux and Neurogenic Bladder Dysfunction Muhsin Balabana and Orkunt Özkaptanb,* a Biruni University Shool of Medicine Urology Department, Topkapi, Istanbul-Turkey; and bUrology Department Lütfi Kirdar Training and Research Hospital, Kartal, Istanbul,Turkey
ABSTRACT Purpose. The study aimed to evaluate the feasibility and effectiveness of the endoscopic treatment in transplanted patients with neurogenic bladder who complained of symptomatic vesicoureteral reflux (VUR). Material and Methods. Fifteen patients with VUR who were previously diagnosed with a neurogenic bladder were included in the study. The Lich-Gregoire technique was used for ureterovesical anastomosis during transplantation, and a double J stent was inserted routinely in the ureter to protect the anastomosis. The sting operation was performed under general anesthesia in the lithotomy position. A 4.8 Fr double J stent (Boston Scientific, Boston, MA) was inserted to prevent the risk of ureteral obstruction. Successful treatment was defined as absent acute glomerulopyelonephritis (AGPN) during follow-up and as absent VUR on radiological evaluation. Results. Clinical success was achieved in 6 of 10 patients (60%) who presented with recurrent febrile urinary tract infection (UTI) and in 4 of 6 (66%) patients who presented with gradually graft function deterioration. In 3 patients, the ureteral neo-orifice could not be localized during the operation owing to severe trabeculation of the bladder wall. The other 2 patients with a previous history of augmented bladder procedures had a hypotension attack during bladder filling; hence, the operation was stopped to prevent further complications. Two patients, whose clinical symptoms did not resolve after the sting procedure, accepted open ureteral reimplantation surgery. Conclusion. Endoscopic management of the VUR in the transplant patients with neurogenic bladder function is safe and effective in at least half of the patients in a midterm follow-up period.
V
ESICOURETERAL reflux (VUR) is a common ureteric complication of kidney transplantation; its prevalence varies between 2% and 50% of the cases in different studies in the literature [1e2]. Although most cases do not have any symptoms and can be followed up without any intervention, in some cases this complication can cause pyelonephritis attacks and finally can deteriorate the graft function with a decrease in the patient’s life quality. Therefore, symptomatic VUR in transplant patients should be managed carefully and adequately to protect the graft function. ª 2019 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, XX, 1e5 (2019)
The treatment of VUR can be performed by open surgery with ureteral reimplantation with a success rate of 83% to 100% [3e4]. However, the complication rate of open surgery is reported to be around 16% to 53%. Therefore, minimally invasive treatment may be preferred to open procedures. This
*Address correspondence to Orkunt Özkaptan, Lütfi Kirdar Training and Research Hospital,Cevizli mh S¸emsi Denizer cad E-5 Karayolu Cevizli Mevkiii, 34890 Kartal, Turkey. Tel: 00905058296107. E-mail: [email protected] 0041-1345/19 https://doi.org/10.1016/j.transproceed.2019.10.021
1
2
led surgeons to seek less invasive treatment modalities. Endoscopic treatment with submucosal Teflon injection has a morbidity rate of less than 10% and a success rate of 60% to 80% [5e6]. However, studies about the treatment of VUR in patients with neurogenic bladder dysfunction are very limited in the literature. There are only a few reports of pediatric age patients with neurogenic bladder dysfunction [7e9]. This study aimed to evaluate the feasibility and effectiveness of the endoscopic treatment in transplant patients with neurogenic bladder who complained of symptomatic VUR. To our knowledge, this is the first report about this subgroup of patients with transplanted kidneys. MATERIAL AND METHODS A total of 121 patients with symptomatic VUR were diagnosed among 3560 renal transplant cases during the routine 3-month follow-up periods in a tertiary kidney transplantation center between March 2014 and December 2018. Fifteen of the 121 patients were previously diagnosed with neurogenic bladder and were under a clean intermittent catheterization (CIC) protocol. All patients had undergone a urodynamic evaluation before the transplantation. Patients with neurogenic bladder and patients with contracted bladder capacity who had undergone an augmentation cystoplasty procedure were under long-term follow-up by nephrologists. The Lich-Gregoire technique was used for ureterovesical anastomosis during transplantation, and a double J stent was inserted routinely in the ureter to protect the anastomosis. The ureterovesical anastomosis was principally performed on the midlateral wall of the bladder instead of the dome. The stent was removed on the posto-operative tenth day. In patients with acute glomerulopyelonephritis (AGPN) or patients with deterioration of the graft function, a voiding cystourethrography (VCUG) was performed. The grade of VUR was classified according to the international classification [10]. All patients underwent renal function tests, a urine culture, and urinary system ultrasonography, preoperatively. In patients with a sterile urine culture, an endoscopic intervention was planned.
Endoscopic Technique The sting operation was performed under general anesthesia in the lithotomy position. All operations were performed by a senior urologist (MB) who is experienced in the treatment of renal transplant complications. Before the injection of the bulking material into the affected ureteral orifice, we inserted a 4.8 Fr double J stent to prevent the risk of ureteral obstruction and to adjust the angle of the injection needle and ureteral orifice alignment axis parallel to obtain a more successful outcome (see Fig 1). Cystoscopy was performed to identify the location of the neo-ureteral orifice with a 30-degree lens endoscope; in some cases, the orifice could not be located, suprapubic pressure was applied, or the bladder was evaluated at different levels of fullness with a 70-degree lens to obtain more visual area with a higher angle. In cases in which the guide wire could not be inserted into the neo-ureteral orifice owing to difficulty in the angling of the wire or the localization of the neo-orifice, a 5 Fr urology torque catheter (0.038 in/65 cm) (Boston Scientific, Natick, MA) was used to redirect the guide wire. Fluoroscopy was used routinely during the insertion of the guide wire. Afterwards, a 16 cm 4.8 Fr double J stent was advanced over the guide wire with the assistance of a cystoscope as we described in our previous study
BALABAN AND ÖZKAPTAN [11]. In cases where the ureteral orifice could not be localized in the bladder owing to abnormal localization and severe trabeculation, an antegrade double J stent was inserted with the guidance of ultrasonography and fluoroscopic images. After the double J catheter was inserted, the injection of the bulky agent was applied with a metal beveled needle and intraureteral submucosal injection until the ureteral orifice was obliterated. Dextranomer-hyaluronic acid (DX-HA) (Dexel) was used for all cases. After the operation, a ureteral catheter was inserted and removed 12 hours later. Serum creatinine levels were measured routinely, and a urinary ultrasound was performed before the discharge of the patients. The double J stent was removed after ten days postoperatively. In patients where the procedure was unsuccessful, open surgery for ureteral reimplantation was offered to the patients. Further follow-up was done in the first month with serum creatinine measurement, ultrasonography, and urine culture, followed by cystography in the third month. Successful treatment was defined as absent AGPN during follow-up and as absent VUR on radiological evaluation.
RESULTS
The outcome of 15 renal transplant patients, with symptomatic VUR and neurogenic bladder dysfunction, who were treated endoscopically was evaluated. The median time between kidney transplantation and endoscopic management was 24 (6-58) months, and the median time of follow-up was 14 (6-48) months. Five of 15 patients had a history of augmentation cystoplasty in their childhood before chronic renal insufficiency was diagnosed. Further, 2 of 5 patients with augmented cystoplasties had a Mitronoff cystoplasty and performed clean intermittent catheterization (CIC) through an orifice in the abdomen near the umbilicus. Overall, all patients had neurogenic bladder dysfunction, and CIC 6 times per day was performed by all patients for emptying the bladder. Two of the patients had secondary renal transplants. Thirteen of the transplants were performed from live donors. The clinical characteristics of the patients with VUR disease were as follows; 8 patients had at least 2 febrile UTI attacks in 6 months, 1 patient had urosepsis, 4 patients had gradual deterioration of graft function, and 2 patients had simultaneous febrile UTI and deterioration of graft function. Clinical success was achieved in 6 of 10 patients (60%) who presented with recurrent febrile UTI and in 4 of 6 (66%) patients who presented with gradual graft function deterioration. In 3 patients, the ureteral neo-orifice could not be localized during the operation owing to severe trabeculation of the bladder wall. In one of these patients, the neo-orifice was localized after double J stent insertion was performed anterogradely with the guidance of ultrasonography and fluoroscopy. However, the other 2 patients had a hypotension attack during bladder filling; hence, the operation was stopped to prevent further complications. These 2 cases were patients with a previous history of augmented bladder procedures.
STING OPERATION AND NEUROGENIC BLADDER
3
Fig 1. (A) Visualization of the neo-ureteral orifice with 30-degree cystoscope at the midlateral wall of the bladder. (B) Upper right: Insertion of a guidewire through a 5 Fr torque catheter into the ureter. (C) Control of proximal part of the JJ stent under fluoroscopic view after insertion over the guide wire. (D) Mid right: Insertion of 4.8 Fr JJ stent over the guidewire. (E) Bottom left: Injection of the bulking agent into the ureter and around the ureter neo-orifice. (F) Bottom right: Image of the refluxing ureter orifice after the injection procedure.
Only 2 patients whose clinical symptoms did not resolve after the sting procedure accepted open ureteral reimplantation surgery. The other patients, whose endoscopic treatment failed and whose symptoms did not resolve after
the endoscopic approach, were followed-up with suppressive antibiotic treatment and CIC. Ureteral J stent insertion succeeded in 12 patients (in 11 with a retrograde approach and in 1 with an antegrade
4
approach). However, in 1 patient, the angle of the neoorifice did allow insertion of the guidewire through the ureter, so the injection was performed carefully without the guidance of a double J stent. Some complications occurred during or after endoscopic management. In the first case that was performed, the sting material was applied without double J stent insertion, and anuria developed after that. After 24 hours, the patient underwent a second operation. The neo-orifical area was resected, and a double J catheter was inserted. In 3 cases, macroscopic hematuria developed after the intervention but resolved without any need for intervention. In 1 patient, a febrile UTI developed 1 week postoperatively. DISCUSSION
VUR is a common ureteric complication after renal transplant; however, asymptomatic VUR does not compromise long-term function or survival of the transplant [12]. Whang et al reported the VUR rate in their series with more than 2500 renal transplants as 3%. Similarly, Akiki et al reported the VUR rate in 897 renal transplant patients as 5.8% in their recently published article [13,14]. In our series, this rate was 3.4% (n ¼ 121) in 3460 renal transplants. According to the literature, the VUR rate is related to the experience of the surgeon, the ureteral reimplantation technique, the submucosal tunnel length, the use of stents, and the quality of the vesical wall [15]. In our series, 2 experienced surgical teams performed the transplants using the Lich-Gregoire technique for ureteral re-implantation. All urological complications were managed by a urologist who is experienced in the management of transplant complications. Neurogenic bladder is a challenging condition that can affect graft survival and decrease the patient’s quality of life. The aim for patients with neurogenic bladders is to decrease the vesical pressure and thus to protect renal function. In our study group, 5 patients underwent augmented cystoplasty operation in their childhood, and all of them were under a CIC protocol. Renal transplant is an effective treatment modality for renal insufficiency, and in cases where symptomatic VUR develops, the first-line treatment with an endoscopic approach is possible. Misra et al reported a study of 51 children with neurogenic bladder who were managed with endoscopic Teflon injection (sting) into the refluxing ureters with a success rate of 82% (8). In the other study, Granata et al reported the success rate of the sting operation in 40 refluxing ureters in children with neuropathic bladder as 72.5%. However, there is no report for VUR in patients with renal transplantat and neurogenic bladder dysfunction in the literature. In the current study group, the sting operation was performed for VUR in transplant patients with recurrent febrile UTI attacks or progressive deterioration of the graft function. Wang et al reported, on 16 renal transplant patients with normal bladder function, a success rate of 75% after endoscopic treatment in a mean follow-up time of 18.9
BALABAN AND ÖZKAPTAN
months. Similarly, Aikikai et al reported a clinical success rate of 56.1% in transplant patients with symptomatic clinical VUR in a follow-up period of 30.5 months [14]. In our series, the success rate in preventing infection and protecting graft function after the first DX-HA (Dexel) injection in a mean follow-up period of 14 months was 60% and 66%, respectively. Clinical success was used to define the overall success rate of the procedure. VCUG for evaluating the radiological success rate was not applied, because transplanted patients were under immunosuppression, and we aimed to avoid invasive investigations, as possible, to prevent infections. Further, we think that the regression of clinical symptoms and the preservation of graft function should be the primary aim of this procedure. Our success rate was less than the study of Whang et al [6]. The reason for this is the lower quality of the bladder wall in neurogenic bladders. Our success rate is slightly better than the success rate of the study from Akiki et al [14]. The follow-up period is more extended than in our study, and the patient number is larger than it is in our study. Pichler et al used DX-HA in 19 renal transplant recipients, with a technique of intraureteral submucosal injection after hydrodistension [15]. This technique was first described by Kirsch et al in children. However, early ureteral obstruction with hydronephrosis and increased serum creatinine level was observed in 10.5% of patients. In our series, we performed intraureteral submucosal injection without double J stent placement in the first case with VUR. In this case, obstruction developed, and the serum creatinine level increased; therefore, the patient had to be reoperated. The obstructed neo-orifice had to be resected, and after that, a double J stent was inserted. After that case, we routinely inserted a double J stent when possible before the injection material to prevent obstruction in the ureteral neo-orifice. There are various injection materials for endoscopic treatment of VUR secondary to the renal transplantation, such as collagen, polytetrafluoroethylene, and carbon-coated beads (Durasphere). In this study, DX-HA (Dexel) was used as injection material in all cases because a recent study reported a higher success rate with DX-HA (Dexel) than with polydimethylsiloxane [14]. In our study, 2 cases had severe hypotension attacks during the bladder hydrodilatation for localizing the ureteral orifice. Therefore, endoscopic surgery was canceled. Both of the cases were patients with previous bladder augmentation surgery, and we think that hydrodilatation of the ileal segment led to a hypotension attack owing to parasympathetic nerve stimulation. These patients refused further operative treatment; therefore, suppressive antibiotics were applied to prevent further urinary tract infection. There were 3 patients in whom febrile UTI attacks continued after the procedure, and in 1 of the patients, deterioration of graft function occurred. Two of these patients underwent ureteral reimplantation surgery. One of them did not accept further intervention.
STING OPERATION AND NEUROGENIC BLADDER
We had 3 cases with mild hematuria and febrile UTI after the endoscopic treatment. Mild hematuria resolved within 12 hours, and the UTI was treated with antibiotics. Surgery is the first-line treatment with a higher success rate for VUR after transplantation. However, it has a higher complication rate [16]. This is why some groups advocated antibiotic prophylaxis and surveillance only [17]. There is some limitation in this study. First of all, our mean follow-up period was 14 months, and our success rate may decrease with a longer follow-up period. This study presents our midterm results. Further, the transplantations were performed by 2 different surgeons who created ureteral anastomosis with different localizations in the bladder; thus, we don not know the impact of the neo-orifice localization on VUR incidence and the success rate of the sting operation. Third, our study groups were small. However, this study is the first report in the Literature, so we compared our results with the outcome of transplanted patients with VUR who have normal bladder function. CONCLUSION
Endoscopic management of the VUR in transplant patients with neurogenic bladder function is safe and effective in at least half of the patients in a midterm follow-up period. Although neurogenic bladder can compromise the location of the ureteral neo-orifice, a ureteral double J stent can be inserted retrogradely in most cases. In the augmented bladder with ileum segment, severe hypotension attacks can occur; therefore, this clinical situation should be kept in mind during the operation. REFERENCES [1] Ostrowski M, Wlodarczyk Z, Wesolowsky T, et al. Influence of ureterovesical anastomosis technique on the incidence of vesicoureteral reflux in renal transplant recipients. Ann Transplant 1999;4:54e8. [2] Karam G, Maillet F, Braud G, et al. Surgical complications in kidney transplantation. Ann Urol 2007;41:261e75.
5 [3] Hau HM, Tautenhahn HM, Schmelzle M, et al. Management of urologic complications in renal transplantation: a single-center experience. Transplant Proc 2014;46:1332. [4] Lehmann K, MVuller MK, Schiesser M, et al. Treatment of ureteral complications after kidney transplantation with native ureteropyelostomy reduces the risk of pyelonephritis. Clin Transplant 2011;25:201. [5] Seifert HH, Mazzola B, Ruszat R, et al. Transurethral injection therapy with dextranomer/hyaluronic acid copolymer (Deflux) for treatment of secondary vesicoureteral reflux after renal transplantation. J Endourol 2007;21:1357e60. [6] Wang HH, Ding WF, Chu SH, Chiang YJ, Liu KL, Lin KJ, et al. Endoscopic treatment of post-transplant vesicoureteral reflux. Transplant Proc 2019;51(5):1420e3. [7] Engel JD, Palmer LS, Cheng EY, et al. Surgical versus endoscopic correction of vesicoureteral reflux in children with neurogenic bladder dysfunction. J Urol 1997;157:2291e4. [8] Misra D, Potts SR, Brown S, et al. Endoscopic treatment of vesico-ureteric reflux in neurogenic bladder: 8 years experience. J Pediatr Surg 1996;31:1262e4. [9] Morioka A, Miyano T, Ando K, et al. Management of vesicoureteral reflux secondary to neurogenic bladder. Pediatr Surg Int 1998;13:584e6. [10] Lebowitz RL, Olbing H, Parkkulainen KV, et al. International system of radiographic grading of vesicoureteric reflux. International Reflux Study in Children. Pediatr Radiol 1985;15:105. [11] Sevinc C, Balaban M, Ozkaptan O, Karadeniz T. Flexible ureterorenoscopy and laser lithotripsy for the treatment of allograft kidney lithiasis. Transplant Proc 2015;47(6):1766e71. [12] Farr A, GyVori G, MVuhlbacher F, et al. Gender has no influence on VUR rates after renal transplantation. Transpl Int 2014;27:1152. [13] Granata C, Buffa P, Di Rovasenda E, Mattioli G, Scarsi PL, Podesta E, et al. Treatment of vesico-ureteric reflux in children with neuropathic bladder: a comparison of surgical and endoscopic correction. J Ped Surg 1999;34(12):1836e8. [14] Akiki A, Boissier R, Delaporte V, Maurin C, Gaillet S, et al. Endoscopic treatment of symptomatic vesicoureteral reflux after renal transplantation. J Urol 2015;193:225e9. [15] Pichler R, Buttazzoni A, Rehder P, et al. Endoscopic application of dextranomer/hyaluronic acid copolymer in the treatment of vesicoureteric reflux after renal transplantation. BJU Int 2011;107:1967. [16] Krishnan A, Swana H, Mathias R, et al. Redo ureteroneocystostomy using an extravesical approach in pediatric renal transplant patients with reflux: a retrospective analysis and description of technique. J Urol 2006;176:1582. [17] Ranchin B, Chapuis F, Dawhara M, et al. Vesicoureteral reflux after kidney transplantation in children. Nephrol Dial Transplant 2000;15:1852.
ABSTRACT Purpose. The study aimed to evaluate the feasibility and effectiveness of the endoscopic treatment in transplanted patients with neurogenic bladder who complained of symptomatic vesicoureteral reflux (VUR). Material and Methods. Fifteen patients with VUR who were previously diagnosed with a neurogenic bladder were included in the study. The Lich-Gregoire technique was used for ureterovesical anastomosis during transplantation, and a double J stent was inserted routinely in the ureter to protect the anastomosis. The sting operation was performed under general anesthesia in the lithotomy position. A 4.8 Fr double J stent (Boston Scientific, Boston, MA) was inserted to prevent the risk of ureteral obstruction. Successful treatment was defined as absent acute glomerulopyelonephritis (AGPN) during follow-up and as absent VUR on radiological evaluation. Results. Clinical success was achieved in 6 of 10 patients (60%) who presented with recurrent febrile urinary tract infection (UTI) and in 4 of 6 (66%) patients who presented with gradually graft function deterioration. In 3 patients, the ureteral neo-orifice could not be localized during the operation owing to severe trabeculation of the bladder wall. The other 2 patients with a previous history of augmented bladder procedures had a hypotension attack during bladder filling; hence, the operation was stopped to prevent further complications. Two patients, whose clinical symptoms did not resolve after the sting procedure, accepted open ureteral reimplantation surgery. Conclusion. Endoscopic management of the VUR in the transplant patients with neurogenic bladder function is safe and effective in at least half of the patients in a midterm follow-up period.
V
ESICOURETERAL reflux (VUR) is a common ureteric complication of kidney transplantation; its prevalence varies between 2% and 50% of the cases in different studies in the literature [1e2]. Although most cases do not have any symptoms and can be followed up without any intervention, in some cases this complication can cause pyelonephritis attacks and finally can deteriorate the graft function with a decrease in the patient’s life quality. Therefore, symptomatic VUR in transplant patients should be managed carefully and adequately to protect the graft function. ª 2019 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, XX, 1e5 (2019)
The treatment of VUR can be performed by open surgery with ureteral reimplantation with a success rate of 83% to 100% [3e4]. However, the complication rate of open surgery is reported to be around 16% to 53%. Therefore, minimally invasive treatment may be preferred to open procedures. This
*Address correspondence to Orkunt Özkaptan, Lütfi Kirdar Training and Research Hospital,Cevizli mh S¸emsi Denizer cad E-5 Karayolu Cevizli Mevkiii, 34890 Kartal, Turkey. Tel: 00905058296107. E-mail: [email protected] 0041-1345/19 https://doi.org/10.1016/j.transproceed.2019.10.021
1
2
led surgeons to seek less invasive treatment modalities. Endoscopic treatment with submucosal Teflon injection has a morbidity rate of less than 10% and a success rate of 60% to 80% [5e6]. However, studies about the treatment of VUR in patients with neurogenic bladder dysfunction are very limited in the literature. There are only a few reports of pediatric age patients with neurogenic bladder dysfunction [7e9]. This study aimed to evaluate the feasibility and effectiveness of the endoscopic treatment in transplant patients with neurogenic bladder who complained of symptomatic VUR. To our knowledge, this is the first report about this subgroup of patients with transplanted kidneys. MATERIAL AND METHODS A total of 121 patients with symptomatic VUR were diagnosed among 3560 renal transplant cases during the routine 3-month follow-up periods in a tertiary kidney transplantation center between March 2014 and December 2018. Fifteen of the 121 patients were previously diagnosed with neurogenic bladder and were under a clean intermittent catheterization (CIC) protocol. All patients had undergone a urodynamic evaluation before the transplantation. Patients with neurogenic bladder and patients with contracted bladder capacity who had undergone an augmentation cystoplasty procedure were under long-term follow-up by nephrologists. The Lich-Gregoire technique was used for ureterovesical anastomosis during transplantation, and a double J stent was inserted routinely in the ureter to protect the anastomosis. The ureterovesical anastomosis was principally performed on the midlateral wall of the bladder instead of the dome. The stent was removed on the posto-operative tenth day. In patients with acute glomerulopyelonephritis (AGPN) or patients with deterioration of the graft function, a voiding cystourethrography (VCUG) was performed. The grade of VUR was classified according to the international classification [10]. All patients underwent renal function tests, a urine culture, and urinary system ultrasonography, preoperatively. In patients with a sterile urine culture, an endoscopic intervention was planned.
Endoscopic Technique The sting operation was performed under general anesthesia in the lithotomy position. All operations were performed by a senior urologist (MB) who is experienced in the treatment of renal transplant complications. Before the injection of the bulking material into the affected ureteral orifice, we inserted a 4.8 Fr double J stent to prevent the risk of ureteral obstruction and to adjust the angle of the injection needle and ureteral orifice alignment axis parallel to obtain a more successful outcome (see Fig 1). Cystoscopy was performed to identify the location of the neo-ureteral orifice with a 30-degree lens endoscope; in some cases, the orifice could not be located, suprapubic pressure was applied, or the bladder was evaluated at different levels of fullness with a 70-degree lens to obtain more visual area with a higher angle. In cases in which the guide wire could not be inserted into the neo-ureteral orifice owing to difficulty in the angling of the wire or the localization of the neo-orifice, a 5 Fr urology torque catheter (0.038 in/65 cm) (Boston Scientific, Natick, MA) was used to redirect the guide wire. Fluoroscopy was used routinely during the insertion of the guide wire. Afterwards, a 16 cm 4.8 Fr double J stent was advanced over the guide wire with the assistance of a cystoscope as we described in our previous study
BALABAN AND ÖZKAPTAN [11]. In cases where the ureteral orifice could not be localized in the bladder owing to abnormal localization and severe trabeculation, an antegrade double J stent was inserted with the guidance of ultrasonography and fluoroscopic images. After the double J catheter was inserted, the injection of the bulky agent was applied with a metal beveled needle and intraureteral submucosal injection until the ureteral orifice was obliterated. Dextranomer-hyaluronic acid (DX-HA) (Dexel) was used for all cases. After the operation, a ureteral catheter was inserted and removed 12 hours later. Serum creatinine levels were measured routinely, and a urinary ultrasound was performed before the discharge of the patients. The double J stent was removed after ten days postoperatively. In patients where the procedure was unsuccessful, open surgery for ureteral reimplantation was offered to the patients. Further follow-up was done in the first month with serum creatinine measurement, ultrasonography, and urine culture, followed by cystography in the third month. Successful treatment was defined as absent AGPN during follow-up and as absent VUR on radiological evaluation.
RESULTS
The outcome of 15 renal transplant patients, with symptomatic VUR and neurogenic bladder dysfunction, who were treated endoscopically was evaluated. The median time between kidney transplantation and endoscopic management was 24 (6-58) months, and the median time of follow-up was 14 (6-48) months. Five of 15 patients had a history of augmentation cystoplasty in their childhood before chronic renal insufficiency was diagnosed. Further, 2 of 5 patients with augmented cystoplasties had a Mitronoff cystoplasty and performed clean intermittent catheterization (CIC) through an orifice in the abdomen near the umbilicus. Overall, all patients had neurogenic bladder dysfunction, and CIC 6 times per day was performed by all patients for emptying the bladder. Two of the patients had secondary renal transplants. Thirteen of the transplants were performed from live donors. The clinical characteristics of the patients with VUR disease were as follows; 8 patients had at least 2 febrile UTI attacks in 6 months, 1 patient had urosepsis, 4 patients had gradual deterioration of graft function, and 2 patients had simultaneous febrile UTI and deterioration of graft function. Clinical success was achieved in 6 of 10 patients (60%) who presented with recurrent febrile UTI and in 4 of 6 (66%) patients who presented with gradual graft function deterioration. In 3 patients, the ureteral neo-orifice could not be localized during the operation owing to severe trabeculation of the bladder wall. In one of these patients, the neo-orifice was localized after double J stent insertion was performed anterogradely with the guidance of ultrasonography and fluoroscopy. However, the other 2 patients had a hypotension attack during bladder filling; hence, the operation was stopped to prevent further complications. These 2 cases were patients with a previous history of augmented bladder procedures.
STING OPERATION AND NEUROGENIC BLADDER
3
Fig 1. (A) Visualization of the neo-ureteral orifice with 30-degree cystoscope at the midlateral wall of the bladder. (B) Upper right: Insertion of a guidewire through a 5 Fr torque catheter into the ureter. (C) Control of proximal part of the JJ stent under fluoroscopic view after insertion over the guide wire. (D) Mid right: Insertion of 4.8 Fr JJ stent over the guidewire. (E) Bottom left: Injection of the bulking agent into the ureter and around the ureter neo-orifice. (F) Bottom right: Image of the refluxing ureter orifice after the injection procedure.
Only 2 patients whose clinical symptoms did not resolve after the sting procedure accepted open ureteral reimplantation surgery. The other patients, whose endoscopic treatment failed and whose symptoms did not resolve after
the endoscopic approach, were followed-up with suppressive antibiotic treatment and CIC. Ureteral J stent insertion succeeded in 12 patients (in 11 with a retrograde approach and in 1 with an antegrade
4
approach). However, in 1 patient, the angle of the neoorifice did allow insertion of the guidewire through the ureter, so the injection was performed carefully without the guidance of a double J stent. Some complications occurred during or after endoscopic management. In the first case that was performed, the sting material was applied without double J stent insertion, and anuria developed after that. After 24 hours, the patient underwent a second operation. The neo-orifical area was resected, and a double J catheter was inserted. In 3 cases, macroscopic hematuria developed after the intervention but resolved without any need for intervention. In 1 patient, a febrile UTI developed 1 week postoperatively. DISCUSSION
VUR is a common ureteric complication after renal transplant; however, asymptomatic VUR does not compromise long-term function or survival of the transplant [12]. Whang et al reported the VUR rate in their series with more than 2500 renal transplants as 3%. Similarly, Akiki et al reported the VUR rate in 897 renal transplant patients as 5.8% in their recently published article [13,14]. In our series, this rate was 3.4% (n ¼ 121) in 3460 renal transplants. According to the literature, the VUR rate is related to the experience of the surgeon, the ureteral reimplantation technique, the submucosal tunnel length, the use of stents, and the quality of the vesical wall [15]. In our series, 2 experienced surgical teams performed the transplants using the Lich-Gregoire technique for ureteral re-implantation. All urological complications were managed by a urologist who is experienced in the management of transplant complications. Neurogenic bladder is a challenging condition that can affect graft survival and decrease the patient’s quality of life. The aim for patients with neurogenic bladders is to decrease the vesical pressure and thus to protect renal function. In our study group, 5 patients underwent augmented cystoplasty operation in their childhood, and all of them were under a CIC protocol. Renal transplant is an effective treatment modality for renal insufficiency, and in cases where symptomatic VUR develops, the first-line treatment with an endoscopic approach is possible. Misra et al reported a study of 51 children with neurogenic bladder who were managed with endoscopic Teflon injection (sting) into the refluxing ureters with a success rate of 82% (8). In the other study, Granata et al reported the success rate of the sting operation in 40 refluxing ureters in children with neuropathic bladder as 72.5%. However, there is no report for VUR in patients with renal transplantat and neurogenic bladder dysfunction in the literature. In the current study group, the sting operation was performed for VUR in transplant patients with recurrent febrile UTI attacks or progressive deterioration of the graft function. Wang et al reported, on 16 renal transplant patients with normal bladder function, a success rate of 75% after endoscopic treatment in a mean follow-up time of 18.9
BALABAN AND ÖZKAPTAN
months. Similarly, Aikikai et al reported a clinical success rate of 56.1% in transplant patients with symptomatic clinical VUR in a follow-up period of 30.5 months [14]. In our series, the success rate in preventing infection and protecting graft function after the first DX-HA (Dexel) injection in a mean follow-up period of 14 months was 60% and 66%, respectively. Clinical success was used to define the overall success rate of the procedure. VCUG for evaluating the radiological success rate was not applied, because transplanted patients were under immunosuppression, and we aimed to avoid invasive investigations, as possible, to prevent infections. Further, we think that the regression of clinical symptoms and the preservation of graft function should be the primary aim of this procedure. Our success rate was less than the study of Whang et al [6]. The reason for this is the lower quality of the bladder wall in neurogenic bladders. Our success rate is slightly better than the success rate of the study from Akiki et al [14]. The follow-up period is more extended than in our study, and the patient number is larger than it is in our study. Pichler et al used DX-HA in 19 renal transplant recipients, with a technique of intraureteral submucosal injection after hydrodistension [15]. This technique was first described by Kirsch et al in children. However, early ureteral obstruction with hydronephrosis and increased serum creatinine level was observed in 10.5% of patients. In our series, we performed intraureteral submucosal injection without double J stent placement in the first case with VUR. In this case, obstruction developed, and the serum creatinine level increased; therefore, the patient had to be reoperated. The obstructed neo-orifice had to be resected, and after that, a double J stent was inserted. After that case, we routinely inserted a double J stent when possible before the injection material to prevent obstruction in the ureteral neo-orifice. There are various injection materials for endoscopic treatment of VUR secondary to the renal transplantation, such as collagen, polytetrafluoroethylene, and carbon-coated beads (Durasphere). In this study, DX-HA (Dexel) was used as injection material in all cases because a recent study reported a higher success rate with DX-HA (Dexel) than with polydimethylsiloxane [14]. In our study, 2 cases had severe hypotension attacks during the bladder hydrodilatation for localizing the ureteral orifice. Therefore, endoscopic surgery was canceled. Both of the cases were patients with previous bladder augmentation surgery, and we think that hydrodilatation of the ileal segment led to a hypotension attack owing to parasympathetic nerve stimulation. These patients refused further operative treatment; therefore, suppressive antibiotics were applied to prevent further urinary tract infection. There were 3 patients in whom febrile UTI attacks continued after the procedure, and in 1 of the patients, deterioration of graft function occurred. Two of these patients underwent ureteral reimplantation surgery. One of them did not accept further intervention.
STING OPERATION AND NEUROGENIC BLADDER
We had 3 cases with mild hematuria and febrile UTI after the endoscopic treatment. Mild hematuria resolved within 12 hours, and the UTI was treated with antibiotics. Surgery is the first-line treatment with a higher success rate for VUR after transplantation. However, it has a higher complication rate [16]. This is why some groups advocated antibiotic prophylaxis and surveillance only [17]. There is some limitation in this study. First of all, our mean follow-up period was 14 months, and our success rate may decrease with a longer follow-up period. This study presents our midterm results. Further, the transplantations were performed by 2 different surgeons who created ureteral anastomosis with different localizations in the bladder; thus, we don not know the impact of the neo-orifice localization on VUR incidence and the success rate of the sting operation. Third, our study groups were small. However, this study is the first report in the Literature, so we compared our results with the outcome of transplanted patients with VUR who have normal bladder function. CONCLUSION
Endoscopic management of the VUR in transplant patients with neurogenic bladder function is safe and effective in at least half of the patients in a midterm follow-up period. Although neurogenic bladder can compromise the location of the ureteral neo-orifice, a ureteral double J stent can be inserted retrogradely in most cases. In the augmented bladder with ileum segment, severe hypotension attacks can occur; therefore, this clinical situation should be kept in mind during the operation. REFERENCES [1] Ostrowski M, Wlodarczyk Z, Wesolowsky T, et al. Influence of ureterovesical anastomosis technique on the incidence of vesicoureteral reflux in renal transplant recipients. Ann Transplant 1999;4:54e8. [2] Karam G, Maillet F, Braud G, et al. Surgical complications in kidney transplantation. Ann Urol 2007;41:261e75.
5 [3] Hau HM, Tautenhahn HM, Schmelzle M, et al. Management of urologic complications in renal transplantation: a single-center experience. Transplant Proc 2014;46:1332. [4] Lehmann K, MVuller MK, Schiesser M, et al. Treatment of ureteral complications after kidney transplantation with native ureteropyelostomy reduces the risk of pyelonephritis. Clin Transplant 2011;25:201. [5] Seifert HH, Mazzola B, Ruszat R, et al. Transurethral injection therapy with dextranomer/hyaluronic acid copolymer (Deflux) for treatment of secondary vesicoureteral reflux after renal transplantation. J Endourol 2007;21:1357e60. [6] Wang HH, Ding WF, Chu SH, Chiang YJ, Liu KL, Lin KJ, et al. Endoscopic treatment of post-transplant vesicoureteral reflux. Transplant Proc 2019;51(5):1420e3. [7] Engel JD, Palmer LS, Cheng EY, et al. Surgical versus endoscopic correction of vesicoureteral reflux in children with neurogenic bladder dysfunction. J Urol 1997;157:2291e4. [8] Misra D, Potts SR, Brown S, et al. Endoscopic treatment of vesico-ureteric reflux in neurogenic bladder: 8 years experience. J Pediatr Surg 1996;31:1262e4. [9] Morioka A, Miyano T, Ando K, et al. Management of vesicoureteral reflux secondary to neurogenic bladder. Pediatr Surg Int 1998;13:584e6. [10] Lebowitz RL, Olbing H, Parkkulainen KV, et al. International system of radiographic grading of vesicoureteric reflux. International Reflux Study in Children. Pediatr Radiol 1985;15:105. [11] Sevinc C, Balaban M, Ozkaptan O, Karadeniz T. Flexible ureterorenoscopy and laser lithotripsy for the treatment of allograft kidney lithiasis. Transplant Proc 2015;47(6):1766e71. [12] Farr A, GyVori G, MVuhlbacher F, et al. Gender has no influence on VUR rates after renal transplantation. Transpl Int 2014;27:1152. [13] Granata C, Buffa P, Di Rovasenda E, Mattioli G, Scarsi PL, Podesta E, et al. Treatment of vesico-ureteric reflux in children with neuropathic bladder: a comparison of surgical and endoscopic correction. J Ped Surg 1999;34(12):1836e8. [14] Akiki A, Boissier R, Delaporte V, Maurin C, Gaillet S, et al. Endoscopic treatment of symptomatic vesicoureteral reflux after renal transplantation. J Urol 2015;193:225e9. [15] Pichler R, Buttazzoni A, Rehder P, et al. Endoscopic application of dextranomer/hyaluronic acid copolymer in the treatment of vesicoureteric reflux after renal transplantation. BJU Int 2011;107:1967. [16] Krishnan A, Swana H, Mathias R, et al. Redo ureteroneocystostomy using an extravesical approach in pediatric renal transplant patients with reflux: a retrospective analysis and description of technique. J Urol 2006;176:1582. [17] Ranchin B, Chapuis F, Dawhara M, et al. Vesicoureteral reflux after kidney transplantation in children. Nephrol Dial Transplant 2000;15:1852.