KIDNEY TRANSPLANTATION Long-Term Results of Posterolateral Extravesical Ureteroneocystostomy and its Comparison with the Conventional Anterior Extravesical Ureteroneocystostomy Method in the Management of Urologic Complications in Kidney Transplant Patients Farid Dadkhah1, Hooshmand Sofimajidpour2, Majid Aliaskari1, Amirhesam Alirezaei2, Saed Taleghani1, Mohammad Aziz Rasouli3, Heshmatollah Sofimajidpour4* Purpose: Urological complications are common and serious in kidney transplant patients. Correct diagnosis of urological complications and rapid intervention are very important to maintain the transplanted organ. Using en- doscopic methods and rapid access to ureteral orifice can be effective in treatment and management of urological complications in transplant patients. Materials and Methods: In this retrospective cohort study, 934 medical records of kidney transplant patients who underwent surgery through Posterolateral Extravesical Ureteroneocystostomy (PLEVUNC) and anterior extravesi- cal ureteroneocystostomy (AEVUNC) techniques from 2011 to 2018 were evaluated. The outcomes of PLEVUNC and AEVUNC techniques were evaluated in 461 and 473 transplant patients, respectively. The patients were fol- lowed up for 60 months. Immediate and delayed complications, urological complications requiring endoscopic in- tervention, duration of access to ureteral orifice, as well as ureteroscopic and endoscopic outcomes were evaluated. Results: The mean and ± SD (standard deviation) age of patients in PLEVUNC and AEVUNC groups were 46.2 7± 2.7 years and 47.3 ± 3.6 years, respectively. Urinary leakage and UTI were the most common immediate (7% and 6.2%) and delayed (5.5% and 5.5%) complications in both groups, respectively. The time to find ureteral ori- fice in patients requiring endoscopic intervention was significantly shorter in PLEVUNC group 3.5±1.2 compared with the AEVUNC group 10 ± 4.5 (P <.001). In 100% of PLEVUNC group and 62.6% of AEVUNC group, ure- teral orifice of transplanted kidney was observed (P <.001). Ureteroscopy was reported successful in 94.5% and 37.4% of patients in PLEVUNC and AEVUNC groups, respectively. Conclusion: Easy and safe access to the ureteral orifice and to the upper urinary tract in transplant recipients can be achieved with the PLEVUNC technique. In case of urological complications this method facilitates endoscopy. Keywords: kidney transplantation; ureteroneocystostomy; urological complications; urologic surgical procedures INTRODUCTION The number of chronic renal failure patients need-ing alternative treatment is increasing annually. The treatments put a great economic and social bur- den on the health system.(1) There are three treatment methods for patients with End-Stage Renal Disease (ESRD): hemodialysis, peritoneal dialysis and kidney transplantation.(2) The most appropriate and effective treatment for patients with ESRD is kidney transplan- tation.(3,4) In fact the goal of kidney replacement therapy is to increase the patients’ survival rate and quality of life.(1) The incidence of urological renal complications after transplantation has been reported in 3.8% of all recipients.(5,6) Although there has been a significant im- provement in the incidence of such complications in the last decade, urological complications are still common. Anterior Extravesical Ureteroneocystostomy in kidney transplantation has become popular because it is an easy technique to perform(7-10). Modern endoscopic in- 1Department of Urology, Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2Department of Nephrology, Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3Clinical Research Development Unit, Kowsar Hospital, Kurdistan University of Medical Sciences, Sanandaj, Iran. 4Department of Urology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran. *Correspondence: Department of Urology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Pasdaran Ave, Tel: +98-8733611250, E-mail: Hsmajidpour@gmail.com Received September 2020 & Accepted January 2022 struments have made it possible to use endoscopic pro- cedures in kidney and urinary tract.(11,12) Anterior Extravesical Ureteroneocystostomy (Lich- Gregoire) is usually an easy and fast method for ure- teral reimplantation. However, this procedure has been severely criticized due to difficult endoscopic access to the reimplanted ureter and the transplanted kidney. In the AEVUNC method, reimplantation is usually per- formed on bladder dome in a filled bladder, and the angle between the orifice of the reimplanted ureter and the ureteroscopic device is about 90 degrees. In the last two decades, endourology interventions have been in- troduced as acceptable methods for the management of urological complications following kidney transplanta- tion.(13,14) Previously and traditionally, ureteral obstruction was managed by open surgery, which was associated with significant morbidity and mortality. Nowadays, en- dourological techniques such as intra-luminal ureteral Urology Journal/Vol 19 No. 2/ March-April 2022/ pp. 120-125. [DOI: 10.22037/uj.v18i.6449] Vol 19 No 2 March-April 2022 100 balloon dilatation and ureterotomy are associated with a high success rate.(1) Catheterization and passage of en- dourological equipment as well as subsequent endouro- logical procedures in AEVUNC technique are difficult, time consuming, and sometimes impossible.(4) Inability to manage complications with endoscopic procedures can lead to open surgery.(4,6) The need for an alternative method of ureteroneocystostomy has become apparent because it results in better access to ureter and facil- itates endourological interventions.(1,5,6) Based on this, Therefore, it is claimed that by performing the alterna- tive method of ureteroneocystostomy, the ureter orifice is more accessible and endoscopic interventions are more possible. This study was an attempt to compare and evaluate the long-term outcomes of PLEVUNC and AEVNUC ureteral reimplantation techniques to facili- tate the endoscopic management of urologic complica- tions in kidney transplant patients. Also we compared the abovementioned reimplantation techniques in terms of access to orifice of reimplanted ureter. MATERIALS AND METHODS Study Population In this retrospective cohort study, medical records of 934 kidney transplant patients who underwent ureteral reimplantation with AVUNC and PLVUNC techniques were evaluated. All the patients were referred to Sha- hid Modarres Hospital, affiliated to Shahid Beheshti University of Medical Sciences, from 2011 to 2018. According to clinical conditions, the patients were as- signed to one of the AVUNC and PLVUNC surgical techniques groups by the surgeon. The number of pa- tients in PLEVUNC and AEVUNC groups were 461 and 473, respectively. Demographic characteristics of all 934 patients were recorded in a checklist. All donors were live unrelated. Immunosuppressive treatment pro- tocols included induction with globulin antithymocytes and maintenance therapy with prednisolone, tacrolimus or cyclosporine, and mycophenolate mofetil. Procedures The basic technical principles of the PLEVUNC that we have utilized are described briefly: The bladder was filled with saline solution and a 1-cm full-thickness in- cision was done in the posterolateral wall of the bladder to expose bladder mucosa while applying medial re- traction on anterior bladder wall. An ellipse of mucosa was excised from the distal apex. At the distal segment of the ureter, a 1- cm lateral ureteral spatulation is per- formed and the edges were trimmed. Stent (7-Fr silastic urologic J-J stent) was left in the ureter and apical stitch was placed in spatulated ureter and passed inside out through most caudal portion of mucosal opening. The anastomosis of the mucosa of the bladder to the spatu- lated lower ureter was made using interrupted 4-0 Vic- ryl sutures. Detrusor muscle was subsequently closed over the anastomosis using 4-0 Vicryl in interrupted fashion to create the antireflux mechanism. A distal fullthickness anchoring suture was used to keep the ureter from sliding cephalad in a submucosal tunnel.(13) After surgery, all patients were visited every month in the first year and then every 6 months for 5 years (60 months). They underwent physical and biochemical examination. At each visit, patients were evaluated by careful ultrasound and tests for urinary tract infections or signs of transplant rejection attacks and obstructive complications. Evaluations When a urological complication was suspected, various interventions such as IVP, DTPATC99M and CT scan were used. For all patients with persistent leakage in the surgical field, fluid analysis was performed. Hydrone- phrosis on ultrasound, obstructive uropathy on DTPA scanning, and increased creatinine were considered as ureteral obstruction. A month after the surgery, all pa- Posterolateral Extravesical Ureteroneocystostomy versus Conventional–Dadkhah et al. Table 1. Determination and comparison of demographic variables in the two groups. Variable a PLEVUNC (N= 461) AEVUNC (N=473) P-value Gender, N Male 316 (68.5) 319 (67.4) .71 Female 145 (31.5) 154 (32.6) Age (year); mean ± SD, (range) 47.3 ± 3.6 (17-62) 46.2 ± 2.7 (19-59) .12 Duration of dialysis before transplantation (year) 3.5 ± 0.8 (1-9) 2.5 ± 0.6 (1-8) < 0.001 Duration of transplant surgery (minutes) 125 ± 21 (110-140) 120 ± 17 (107-139) < 0.001 Preoperative creatinine 8.2 ± 1.2 (6.5-11) 8.3 ± 1.1 (7-11) .18 Preoperative BUN 90.4 ± 14.1 (80-115) 95.7 ± 16.2 (80-120) < 0.001 Abbreviations: PLEVUNC, Posterolateral Extravesical Ureteroneocystostomy; AEVUNC, anterior extravesical ureteroneocystostomy; SD, standard deviation a Continuous variables were compared by independent samples t-test Variables PLEVUNC (N= 461) AEVUNC (N=473) P-value Nephrotic syndrome 10 (2.17) 9 (1.90) .95 Pyelonephritis 27 (5.86) 33 (6.98) V.U.R 6 (1.30) 3 (1.06) Glomerulonephritis 45 (9.76) 41 (8.67) Hypertension 133 (25.88) 136 (28.76) Diabetes mellitus 100 (21.70) 108 (22.83) Polycystic kidney 37 (8.03) 32 (6.77) kidney stone 29 (6.29) 31 (6.55) Amyloidosis 1 (0.22) 0 (0) Lupus 3 (0.65) 2 (0.42) Unknown 70 (15.18) 78 (16.4) Abbreviations: PLEVUNC, Posterolateral Extravesical Ureteroneocystostomy; AEVUNC, anterior extravesical ureteroneocystostomy Table 2. Causes of renal failure in the two study groups. Vol 19 No 2 March-April 2022 121 Kidney Transplantation 122 tients underwent cystoscopy and the ureteral orifice was observed. In patients who needed endourological surgery inter- vention due to complications, we initially attempted to access to the urinary system with endoscopic devices. Transplant results in the two groups were compared in terms of ureteral and non-ureteral urological complica- tions. In both groups, a total of 145 patients required endoscopic intervention. Patients in the two groups were also compared based on successful ureteroscopy and manipulation Normal ureteroscopy was defined as success in reaching the pelvis of transplanted kidney. Main outcomes of this study were time to find ureteral orifice, ureteral orifice of transplanted kidney, and rate of successful ureteroscopy. Moreover, immediate and delayed complications and urological complications were primary and secondary outcomes. In order to com- ply with research ethics, all patients participating in the study were informed of the study. Ethical considerations This study was approved by the ethics committee of Sha- hid Beheshti University of Medical Sciences and regis- tered with the code IR.SBMU.MSP.REC.1399.221. Statistical Analysis Categorical variables are expressed as frequency (per- centage) and continuous variables are reported as Mean ± SD. T-test was used for comparison of continuous data. Categorical data was compared by using Chi- square test and Fisher exact test. All statistical analysis was performed by STATA software version 16. P < .05 was considered as statistically significant. RESULTS The results of this study showed that in PLEVUNC group, 316 patients were male (68.5%) and 145 were female (31.5%) while in AEVUNC group, 319 patients were male (67.4%) and 154 were female (32.6%). The mean ± SD age in duration PLEVUNC group was 47.3 ± 3.6 and in AEVUNC group was 46.2 ± 2.7. There was no significant difference between the two groups of the patients in terms of sex and preoperative creatinine (P > .05) (Table 1). The mean ± SD of transplant surgery in PLEVUNC group was 125 ± 21 minutes and in AE- VUNC group was 120 ± 17 minutes. There was no significant difference between the two groups in terms of causes of renal failure (P = .95). The most common causes of renal failure in two groups were hypertension (25.88% and 28.76%) and diabetes mellitus (21.70% and 22.83%) (Table 2). In more than 88.9% of patients in PLEVUNC group and 87.2% patients in AEVUNC groups, no immediate and delayed complications were reported. There was no significant difference between the two groups in terms of immediate and delayed complications (P >.05). The most common delayed complication was UTI (5.5% in both groups). Vesicourerteral reflux as a urinary com- plication in AEVUNC method was four times more than PLEVUNC (1.7% Vs 0.4 %,). In both PLEVUNC and AEVUNC groups, urinary leakage was the most common immediate complication (7% and 6.2%, re- spectively) (Table 3). The most common urological complication requiring endoscopic intervention in the two study groups was urinary leakage. The PLEVUNC group had a urological complication Variables PLEVUNC (N= 461) AEVUNC (N=473) P-value Immediate complications Urinary Leakage 32 (7) 29 (6.2) .92 Urosepsis 0 (0) 1 (0.2) Significant hematuria 2 (0.4) 2 (0.4) Ureteral necrosis 0 (0) 0 (0) Hydronephrosis after stent removal 17 (3.7) 19 (4) Hematoma around the transplanted kidney 4 (0.8) 5 (1) No Complication 406 (88) 417 (88.2) Delayed complications lymphocele 4 (0.8) 5 (1) .61 Vesicoureteral reflux 2 (0.4) 8 (1.7) Urinary fistula 0 (0) 0 (0) UVJ Obstraction 9 (2) 11 (2.3) Urinary system stones 9 (2) 8 (1.7) UTI 25 (5.5) 26 (5.5) Miss JJ stent 2 (0.4) 3 (0.6) No Complication 410 (88.9) 412 (87.2) Table 3. Immediate and delayed complications in the two study groups. Abbreviations: PLEVUNC, Posterolateral Extravesical Ureteroneocystostomy; AEVUNC, anterior extravesical ureteroneocystostomy Variables PLEVUNC (N=461) AEVUNC (N= 473) P-value Urinary Leakage 32 (6.9) 29 (6.1) .99 Hydronephrosis after stent removal 17 (3.7) 19 (4) lymphocele 4 (0.8) 5 (1) Delayed UVJ Obstraction 9 (1.9) 11 (2.3) Urinary system stones 9 (1.9) 8 (1.7) Miss JJ stent 2 (0.4) 3 (0.6) No Urologic Complications 388 (84.2) 398 (84.1) Abbreviations: PLEVUNC, Posterolateral Extravesical Ureteroneocystostomy; AEVUNC, anterior extravesical ureteroneocystostomy Table 4. Urological complications requiring endoscopic intervention in the two study groups Posterolateral Extravesical Ureteroneocystostomy versus Conventional–Dadkhah et al. Vol 19 No 2 March-April 2022 100 requiring endoscopic intervention rate of 15.8%, which did not significantly differ from those in AEVUNC group (15.9%) (P = .99). Urinary leakage was encoun- tered in 32 (6.9%) patients in PLEVUNC group and 29 (6.1%) in AEVUNC group (Table 4). The results showed that the time to find ureteral orifice in patients requiring endoscopic intervention was sig- nificantly shorter in PLEVUNC group compared with that of the AEVUNC group (3.5 ± 1.2 minutes vs. 10 ± 4.5 minutes) (P < .001) (Table 5). In 73 (100%) of PLEVUNC group and 47 (62.6%) of AEVUNC group, ureteral orifice of transplanted kidney was observed (P < .001). The results showed that the success rate of ure- teroscopy in PLEVUNC group was significantly higher than that of the AEVUNC group. The success rate of ureteroscopy in PLEVANC and AEVUNC groups were 69 (94.5%) and 28 (37.4%), respectively (P < .001) (Table 5). The results of this study showed that 407 patients (88.2%) in PLEVUNC group and 420 patients (88.8%) in AEVUNC group did not have chronic graft nephrop- athy. The mean creatinine one year after the surgery was 1.34 in the PLEVUNC group and 1.37 in the AEVUNC group, there was no significant difference between the two groups (P = .19). DISCUSSION One of the major concerns in ureteroneocystostomy is endurological access to the ureter after transplantation. In this study, the success rate and ease of access to the ureter and endoscopic interventions in two methods PLEVUNC and AEVUNC were evaluated. The most common causes of renal failure in two groups were hy- pertension (25.88% and 28.76%) and diabetes mellitus (21.70% and 22.83%), respectively. In more than 88% of the patients, no immediate and delayed complica- tions were reported. In both PLEVUNC and AEVUNC groups, urinary leakage was the most common immedi- ate complication (7% and 6.2%, respectively). There was no significant difference between the two groups in terms of immediate and delayed complica- tions (P > .05). The most common delayed complica- tion was UTI (5.5% in both groups). Vesicourerteral reflux as a urinary complication in AEVUNC method was four times more than that of PLEVUNC (1.7% Vs 0.4 %,). In the PLEVUNC method, the angle created by the spatula helps to prevent vesicourerteral reflux. The inner part of the ureter is surrounded by the muscles of the posterior bladder wall, which inverts the uretera mucosa inside the bladder lumen.(13) In a study by Sanei et al., which evaluated urological complications in two Full-Thickness Single Layer Anastomosis and Lich- Gregoir methods, vesicouvertral reflux was reported as 7.4% in the Lich-Gregoir group(14) which was higher than the results of our study. In a study by Balaban et al. they concluded that endoscopic treatment of sympto- matic VUR in transplanted kidney is a safe and feasible procedure.(15) There were no urological complications, requiring en- doscopic intervention, in 84% of the patients in both groups. There was also no significant difference be- tween the two groups in terms of urological complica- tions requiring endoscopic intervention (P > .05). In our study urinary leakage was the most common urological complication. In the previous studies, urinary leakage has been reported as one of the most common urologi- cal complication after transplantation.(12,14,18) In endoscopy procedure, easy and safe access to reim- planted ureter and renal pelvis is important. The results of our study showed that the time to find ureteral orifice in patients requiring endoscopic intervention was sig- nificantly shorter in PLEVUNC group compared with that of AEVUNC group (3.5 minutes vs. 10 minutes), (P < .001). PLEVUNC provides approximate anatomi- cal location for the ureteral orifice, as well as approx- imate normal anatomical alignment for the ureter. In this method, ureteral reimplantation is performed in the posterior side of the bladder, which is closer to the anatomical location of the ureteral orifice, as a result endoscopic procedures and finding the new ureteral or- ifice is easier.(13) Reoperation on transplanted kidneys is associated with a significant increase in morbidity and mortality. The mortality rate for patients who un- derwent open correction of ureteral stenosis has been reported as 8%.(19) Currently, the first treatment for ure- teral obstruction in a transplanted kidney is endoscopy. (20) The first option for treatment of ureteral obstruction, which occurs in 2% to 10% of renal transplant patients postoperatively is interventional radiological methods. If all of these methods are unsuccessful, surgical treat- ment should be applied.(21) In our study in 100% (73 patients) of PLEVUNC group and 37.4% (28 patients) of AEVUNC group, ureteral orifice of transplanted kidney was observed during the procedure (P < .001). Ureteroscopy success rate was 94.5% (69 patients) in PLEVUNC group and 37.4% (28 patients) in AEVUNC group and the difference between two groups was statistically significant (P < .001). There are limited studies related to our study topic. In the previous study by Dadkhah et al, done with a few- er patients, conducted with the aim of easier access to the upper urinary tract in transplanted kidney with the help of endoscopic devices, the results of renal trans- plantation comparing two techniques of AEVUNC and PLEVUNC were evaluated. They also compared ure- teral and nonureteral complications at 36- to 51-month follow-up. The results showed that access to ureter- al orifice and endoscopic interventions were easier in PLEVUNC than AEVUNC methods and the general complications of PLEVUNC technique were not sig- nificantly different from that of the AEVUNC, which is the usual method.(13) Krajewski et al. concluded in Variables a PLEVUNC (N= 461) AEVUNC (N=473) P-value Mean time to find ureteral orifice (min) 3.5 ± 1.2 (2.5-6) 10 ± 4.5 (7-11) < 0.001 Finding of Ureteral orifice of transplanted kidney 73 (100) 47 (62.5) < 0.001 Successful ureteroscopy 69 (94.5) 28 (37.5) < 0.001 Table 5. Data regarding ureteroscopy. Abbreviations: PLEVUNC, Posterolateral Extravesical Ureteroneocystostomy; AEVUNC, anterior extravesical ureteroneocystostomy a Continuous variables were compared by independent samples t-test Posterolateral Extravesical Ureteroneocystostomy versus Conventional–Dadkhah et al. Vol 19 No 2 March-April 2022 123 Kidney Transplantation 124 their study that most urological complications could be successfully treated with endourological procedures and kidney function improved in most patients.(16) In the study by Ooms et al., 50 patients who had ureter stricture following kidney transplantation were treated with antegrade balloon dilatation which was technically successful in 86%.(17) Endoscopic treatment of ureteral stenosis after kidney transplantation is recommended to prevent complications of open surgical treatment.(18) The present study was performed with a higher statisti- cal population and longer follow-up of patients. It con- firmed the success and ease of access of endourology interventions in reimplanted patients with PLEVUNC technique. Limitation of this study is, the study was per- formed as a retrospective group and it could have been done as a clinical trial. The study was also conducted at a center. CONCLUSIONS The study showed that ureteroneocystostomy by PLE- VUNC method provides easy and safe access to the ure- teral orifice and upper urinary tract in kidney transplant recipients. This method facilitates endoscopic intervention in case of urological complications. Therefore, it is recom- mended to use PLEVUNC method instead of AEVUNC method in kidney transplantation. ACKNOWLEDGEMENT The study was sponsored by the deputy of research and technology of Shahid Beheshti University of Medical Scienc¬es, Tehran, Iran. CONFLICT ON INTEREST The authors declare that there is no conflict of interest. REFERENCES 1. Veale JL, Yew J, Gjertson DW, Smith CV, Singer JS, Rosenthal JT, Gritsch HA. Long- term comparative outcomes between 2 common ureteroneocystostomy techniques for renal transplantation. J Urol. 2007 Feb;177:632-6. 2. Wong G, Howard K, Chapman JR, Chadban S, Cross N, Tong A, Webster AC, Craig JC. 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