- Email: [email protected]
Multi-Institutional Review of Outcomes of Robot-Assisted Laparoscopic Extravesical Ureteral Reimplantation
Reconstruction
Multi-Institutional Review of Outcomes of Robot-Assisted Laparoscopic Extravesical Ureteral Reimplantation Gwen M. Grimsby, Moira E. Dwyer, Micah A. Jacobs,* Michael C. Ost, Francis X. Schneck, Glenn M. Cannon and Patricio C. Gargollo† From the Division of Pediatric Urology, Department of Urology, University of Texas Southwestern Medical Center and Children’s Medical Center, Dallas (GMG, MAJ) and Texas Children’s Hospital-Baylor College of Medicine (PCG), Houston, Texas, and Department of Urology, Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center (MED, MCO, FXS, GMC), Pittsburgh, Pennsylvania
Purpose: We performed a multi-institutional assessment of the outcomes and complications of robot-assisted laparoscopic extravesical ureteral reimplantation for vesicoureteral reflux in children. Materials and Methods: We retrospectively reviewed the records of patients who underwent robot-assisted laparoscopic extravesical ureteral reimplantation as done by 1 of 5 surgeons at Children’s Medical Center, Dallas, Texas, or Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, from 2010 to 2013. Procedure failure was defined as persistent vesicoureteral reflux on postoperative voiding cystourethrogram or radionuclide cystogram and/or the need for reoperation. Multivariate logistic regression was done to identify possible risk factors for failure using STATAÒ, version 11. Results: A total of 61 patients (93 ureters) with a mean age of 6.7 years (range 0.6 to 18.0) underwent a procedure, of which 32 (52%) were bilateral. Ten patients (16%) underwent previous subureteral injection for vesicoureteral reflux. At a mean followup of 11.7 months the procedure was successful in 44 of 61 patients (72%). There were 14 cases of persistent vesicoureteral reflux (23%), 6 complications (10%) and 9 reoperations (11%). Multivariate logistic regression identified no factor that increased the risk of failure (p ¼ 0.737). Conclusions: Compared to the literature we found a notably lower success rate for robot-assisted laparoscopic extravesical ureteral reimplantation in the hands of 5 fellowship trained, robotically experienced pediatric urologists. More than 10% of patients required at least 1 reoperation for persistent vesicoureteral reflux or a surgical complication. Our experience suggests a higher complication rate and a lower success rate for robot-assisted laparoscopic ureteral reimplantation compared to the gold standard of open reimplantation.
Abbreviations and Acronyms RALUR ¼ robot-assisted laparoscopic ureteral reimplantation RNC ¼ radionuclide cystogram UTI ¼ urinary tract infection VCUG ¼ voiding cystourethrogram VUR ¼ vesicoureteral reflux Accepted for publication July 25, 2014. Study received institutional review board approval. * Financial interest and/or other relationship with Terumo. † Correspondence: Texas Children’s HospitalBaylor College of Medicine, 6701 Fannin St., CCC Suite 620, Houston, Texas 77030 (telephone: 832-822-3160; FAX: 832-825-3159; e-mail: [email protected]).
Key Words: ureter, vesico-ureteral reflux, robotic, laparoscopy, replantation
VESICOURETERAL reflux, which is present in 1% of children, is commonly encountered by the pediatric urologist.1 The goal of VUR management is to prevent ascending infection and, thus, decrease the risk of pyelonephritis and
renal injury.2 Treatment options include observation with or without antibiotic prophylaxis, or surgical repair via endoscopic injection of a periureteral bulking agent or ureteroneocystostomy in patients with renal
0022-5347/15/1935-1791/0 THE JOURNAL OF UROLOGY® © 2015 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2014.07.128 Vol. 193, 1791-1795, May 2015 Printed in U.S.A.
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scarring, breakthrough infection and worsening, persistent or high grade VUR.1,3 Although open ureteral reimplantation remains the gold standard surgical procedure, RALUR has become increasingly popular. Advantages of a robotic approach include the potential for shorter hospitalization, faster recovery, ease of surgery over pure laparoscopic techniques and possibly better cosmesis.4e6 Disadvantages include longer operative time and increased cost.4 The extravesical approach for ureteroneocystostomy has become the favored robotic technique with the reported advantage of potentially decreased postoperative urinary retention compared to extravesical open procedures.7 The largest studies in the literature show an excellent success rate of 98% to 99% with zero complications.7,8 Others describe a lower 88% VUR resolution rate with a 10% complication rate.9 At this time the most critical questions to be answered before widespread adoption of this new technology include whether the rate of VUR resolution is the same or better than that of standard open approaches and how the complication rates compare for the 2 techniques. We hypothesized that our VUR resolution rate after RALUR was inferior and our complication rate was higher than in the literature. Thus, in this study we share the outcomes of a multi-institutional assessment of the success and complications of RALUR for VUR in children.
MATERIALS AND METHODS After receiving institutional review board approval we retrospectively reviewed the records of all patients who underwent RALUR as done by any 1 of 5 pediatric urologists at Children’s Medical Center, Dallas, Texas, or Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, from February 2010 to September 2013. Patients treated with intravesical RALUR or RALUR for a diagnosis other than VUR were excluded from analysis. Procedure failure was defined as persistent VUR on postoperative VCUG or RNC and/or the need for reoperation. Multivariate logistic regression to identify any preoperative or intraoperative factor that placed a patient at risk for failure was done with STATA, version 11. To perform RALUR an 8.5 mm umbilical camera port was placed with 2, 8.5 mm working ports on either side. The ureter was circumscribed below the pelvic brim and dissected to the bladder. A 3 to 4 cm trough was created in the detrusor from a posterosuperior position down to the orifice of the refluxing ureter. The ureter was laid in the trough and the detrusor was closed over the ureter along the entire length of the trough. Closure was started at the ureteral orifice and carried proximal with running or interrupted polyglactin or polydioxanone barbed suture depending on surgeon preference. No ureteral tapering was done.
Patients received cefazolin intravenously at surgery and prophylactic antibiotics were continued perioperatively. Ureteral stents were not routinely placed. Patients were seen 3 months postoperatively, when renal ultrasound was done. Two surgeons also routinely obtained VCUG or RNC 3 months postoperatively. The remaining surgeons obtained VCUG if a febrile UTI developed.
RESULTS A total of 61 RALURs were performed on 93 ureters, including 35 at Children’s Medical Center and 26 at Children’s Hospital of Pittsburgh. Mean VUR grade was 3.3 (range 1 to 5). The indication for surgery was cortical defects on dimercaptosuccinic acid scan performed more than 3 months after the last UTI in 35 cases, breakthrough UTI in 13, VUR nonresolution in 12 and noncompliance with antibiotics in 1. Mean age at surgery was 6.7 years (range 0.4 to 18) and the female-to-male ratio was 4:1. Bilateral RALUR was performed in 32 patients (52%), 10 (16%) underwent prior subureteral injection of a bulking agent, 43 (70%) had constipation requiring medical therapy and high grade VUR (4 or 5) was present in 46%. There was no conversion to an open procedure and no episode of postoperative urinary retention requiring discharge with a catheter. VUR persisted in 14 patients (23%) on postoperative VCUG/RNC performed a mean of 3.9 months postoperatively (table 1). Mean persistent VUR grade was 2.5 (range 1 to 4). Four patients had bilateral persistent VUR. A febrile UTI developed in 11 patients (18%) within 1 year of surgery, of whom 5 had persistent VUR, 4 had no VCUG/RNC performed after UTI, 1 had a negative VCUG and 1 had a dimercaptosuccinic acid scan that showed no new scarring. The 6 complications (10%) included ureteral obstruction in 3 cases, urine leak in 2 and rehospitalization for nausea and vomiting in 1. These complications required a total of 5 immediate reoperations, including 4 bilateral ureteral stents and Table 1. Failures, reoperations and complications No. Pts (%) Persistent VUR Febrile UTI Reoperation: Ureteral stent* Bulking agent subureteral injection Open ureteral reimplantation† Ureteral stricture balloon dilation Complication: Bilat stents for obstruction Urine leak Readmission for nausea þ vomiting * Obstruction in 3 patients and urine leak in 1. † Urine leak and persistent VUR in 1 patient each.
14 11 9 4 2 2 1 6 3 2 1
(23) (18) (7) (3) (3) (2) (10) (5) (3) (2)
ROBOT-ASSISTED EXTRAVESICAL URETERAL REIMPLANTATION
1 open reimplantation. An additional 4 delayed reoperations included 1 balloon dilation for ureterovesical stricture, 2 subureteral injections of a bulking agent and 1 open ureteral reimplantation (table 1). All except 1 of these patients with complications/ reoperations underwent bilateral RALUR and had high grade VUR in at least 1 ureter. One patient experienced mucosal perforation intraoperatively and in 2 a drain was placed at the end of the case based on provider preference. No complication developed in these patients. At a mean 12-month followup (range 1.2 to 32.3) success as defined by VUR resolution and no need for reoperation was achieved in 44 of 61 patients (72%). Multivariate logistic regression identified no factor that increased the patient risk of failure (p ¼ 0.737, table 2).
DISCUSSION Before deciding on an approach to surgical treatment of VUR the pros and cons of the various options should be evaluated based on efficacy, general availability, the known benefits of a minimally invasive approach and cost-effectiveness.2 Open ureteral reimplantation remains the gold standard with an excellent success rate.4 A review of 86 reports of open ureteroneocystostomy in a total of 6,472 patients (8,563 ureters) showed overall surgical success rates of 95.1% per patient and 95.9% per ureter.10 Thus, it is intuitive to compare all new procedures to open surgery. In fact, laparoscopic ureteral reimplantation was not widely adopted because it was technically challenging, required longer operative time and failed to show decreased morbidity despite reported success rates greater than 95%.4,11 Since 2005 when it was first described,12 robotic management of VUR has been increasing because the robotic platform provides improved visualization and suturing techniques over pure laparoscopic methods. It was also reported that improved visualization of the neurovascular bundles allows for bilateral extravesical procedures with a minimal
risk of urinary retention.7 However, a recent study of this purported advantage showed that despite the ability to visualize the nerves stimulating the plexus failed to reproducibly demonstrate any visible response in the bladder.13 Also, notably significant complications after RALUR such as urine leak and ureteral obstruction were reported in approximately 10% of patients, similar to our experience.9,14,15 This is a greater proportion than that of open surgery and it is clinically significant because these complications may require a secondary procedure.4 Complications after RALUR also have higher Clavien classifications than in open cohorts.16 At this time only 3 direct comparisons of robotic to open extravesical approaches exist in a total of 64 patients.15e17 One series showed significantly decreased length of stay in the robotic cohort but the mean hospital stay in the open cohort was 53 hours,15e17 which is surprisingly long. Previous reports exist of extravesical ureteral reimplantation performed on an outpatient basis.18 Two studies mentioned reduced pain medication requirements in the robotic cohort while the third did not.15e17 All 3 studies revealed a significant difference in operative time, which was up to 110 minutes longer in the robotic cohort. In addition, as mentioned, the identified complications were more severe in the robotic cases.16 Thus, at this point it has not been clearly proved that the robotic approach decreases the morbidity associated with extravesical ureteral reimplantation.4 Moreover, there is insufficient evidence to argue that the robotic technique has equal or improved success compared to open approaches. We reviewed the current published literature on RALUR and found a wide 66.7% to 100% range of VUR resolution rates (table 3).3,7e9,14e17,19e21 Many of these studies had a small sample size, may have reflected provider initial experience with the techniques and used various followup imaging methods to confirm Table 3. Pediatric RALUR literature to date References
Table 2. Multivariate logistic regression of risk factors for surgical failure
Hospital Age Gender Grade IV or V VUR Bilat surgery Previous bulking agent subureteral injection Suture: Running vs interrupted Barbed vs polyglactin Constipation
p Value
95% CI
0.352 0.319 0.428 0.792 0.441 0.685
2.3e0.8 0.3e0.1 1.1e2.7 1.3e1.7 0.8e1.9 1.5e2.3
0.829 0.247 0.907
1.9e2.4 4.4e1.1 1.4e1.7
1793
7
Casale et al Chan et al19 Lee et al14 Marchini et al15 Smith et al17 Chalmers et al20 Kasturi et al8 Callewaert et al21 Gundeti et al3 Schomburg et al16 Akhavan et al9 Present series Totals
No. Pts
Mean Age at Surgery (yrs)
41 3 4 20 24 17 150 5 74 20 50 61
3.2 5.0 2.3 8.6 5.8 6.2 3.6 6.8 5.4 6.2 6.2 6.7
40 2 4 20 23 14 149 4 60 20 44 47
(97.6) (66.7) (100.0) (100.0) (95.8) (82.4) (99.3) (80.0) (81.1) (100.0) (88.0) (77.0)
469
e
427
(91)
No. VUR Resolution (%)
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ROBOT-ASSISTED EXTRAVESICAL URETERAL REIMPLANTATION
VUR resolution.14,19e21 Our cohort falls on the lower end of the success spectrum with a VUR resolution rate of only 77%. To elucidate the variables responsible for the differences in persistent VUR in our series compared to others we performed multivariate logistic regression to determine whether any specific demographic or intraoperative factor was responsible. Unfortunately no such cause stood out, possibly secondary to small sample size. However, although it was not significant on logistic regression, in 3 of the 4 cases of ureteral obstruction a detrusor tunnel had been created with barbed suture. Our practice has consequently changed in that we now use polyglactin suture exclusively. Other possibilities may explain our increased rate of persistent VUR. Publication bias exists and studies with favorable results are more likely to be submitted and published compared to those with negative findings.22 Also, practicing pediatric urologists report surgical outcomes that are significantly different than those published in the literature.23 Our experience may be similar to that of others who have not reported seemingly suboptimal data. In addition, journals may not accept unfavorable studies that may have been submitted. Another possibility is that our surgeons are still in the learning curve for this procedure. However, most of each case was performed by an experienced surgeon who had been in practice a mean of 7.4 years and had completed a number of these procedures during fellowship training. Unfortunately the number of cases needed to complete this learning curve is unknown and likely differs by the cases and parameters measured.24 Depending on the study the operative time of robotic pyeloplasty performed by fellows decreased to the median time of an experienced attending surgeon after 15 to 37 cases.24,25 For robotic ureteral reimplantation specifically Gundeti et al reported an improved success rate with evolution of the robotic extravesical technique through maneuvers such as lengthening the detrusor tunnel.3 It is also conceivable that our definition of failure was too strict or routine postoperative VCUGS/RNC in asymptomatic patients over diagnosed persistent VUR. We disagree with these arguments because any new procedure should be rigorously evaluated with the highest level of scrutiny before it is deemed equivalent to the gold standard. In other large RALUR series VCUG was routinely done postoperatively in all patients.8,9 On the other hand, series in which postoperative VCUG was not obtained in all patients may under diagnose persistent VUR. This may have occurred in our series since VCUG or RNC was performed postoperatively in only 37 of our 61 patients (61%).
Another possibility is that our cases were more complex than those in other studies. High grade VUR was present in 46% of patients and 57% had persistent VUR. Unfortunately it is difficult to compare the VUR grade in our cohort to that in other large series that provide only the mean or median, or group grade III VUR with grades IV and V.7e9 Other providers may have used an open approach with ureteral tapering in high grade cases while in our cohort no tapering was done despite a large percent of high grade VUR. In addition, although we could not reliably capture dysfunctional voiding in this retrospective cohort, 70% of patients were treated for constipation. Because dysfunctional elimination of urine and stool often coexist, the high constipation rate may serve as a surrogate for a high rate of bladder dysfunction, which also may have placed our patients at increased risk for failure. In regard to the potential advantages of a robotic approach we maintain that the 2 to 4 abdominal scars associated with a robotic technique provide a potentially inferior cosmetic result compared to an open Pfannenstiel incision, which is concealed below the underwear or bathing suit line. Validated scar surveys revealed that parents and patients prefer incisions that are hidden at the Pfannenstiel line vs traditional open or laparoscopic pyeloplasty incisions.26 A study using a nonvalidated survey showed that most patients and parents preferred robotic scars on the abdomen vs an open Pfannenstiel incision but they would ultimately base the choice of surgery on the clinical outcome.6 Furthermore, we assume that the cost of the robotic approach is significantly higher than that of the open technique not only due to the cost of robot maintenance but also secondary to prolonged operative time. While to our knowledge no cost comparison has been reported for ureteral reimplantation, pyeloplasty studies showed that robotic approaches were significantly more costly than open and pure laparoscopic techniques, largely due to prolonged operative time and robotic supplies.27 Moreover, these prolonged operative times raise concern regarding the neurotoxic effects of anesthesia. Previous studies demonstrated an increased risk of learning disabilities and attention deficit disorder in children after multiple exposures to general anesthesia and it was suggested that the duration of general anesthesia be minimized.28 Our experience suggests a higher complication rate and a lower success rate for RALUR compared to the gold standard of open reimplantation. Based on these findings we disagree with routine application of RALUR in all children. Rather we speculate that the robotic approach may maintain an advantage in bilateral cases as well as in older children
ROBOT-ASSISTED EXTRAVESICAL URETERAL REIMPLANTATION
who would benefit from the potentially improved pain control. Advantages of this study include its multiinstitutional nature and the inclusion of surgeons who trained at various facilities and had extensive robotic experience. Disadvantages include its retrospective nature, which made determining voiding dysfunction difficult since no objective measure was used to capture these data. Other disadvantages are the varied suturing techniques used to create the detrusor tunnel and the lack of postoperative VCUG/RNC in all patients. While it is difficult to pinpoint an exact cause of the higher than expected number of patients with persistent VUR in our cohort, further multi-institutional collaborations should be performed to assess the long-term success and complications of this and other novel robotic applications in pediatric urology. Our findings emphasize the importance for pediatric
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urologists to periodically critically review their outcomes to ensure that in the spirit of evidencebased surgical practice they meet accepted standards and, if not, to facilitate opportunities to identify areas for change and improvement.
CONCLUSIONS We found a lower success rate for RALUR than that reported in the literature. Of our patients 23% had persistent VUR and more than 10% required at least 1 reoperation for persistent VUR or a surgical complication. Coupled with a debatably inferior cosmetic result as well as the increased operative time and costs associated with a robotic procedure, we encourage pediatric urologists to critically review their results and weigh the advantages of the technique against realistic expectations for outcomes.
REFERENCES 1. Routh JC, Bogaert GA, Kaefer M et al: Vesicoureteral reflux: current trends in diagnosis, screening, and treatment. Eur Urol 2012; 61: 773. 2. Baek M and Kim KD: Current surgical management of vesicoureteral reflux. Korean J Urol 2013; 54: 732. 3. Gundeti MS, Kojima Y, Haga N et al: Roboticassisted laparoscopic reconstructive surgery in the lower urinary tract. Curr Urol Rep 2013; 14: 333. 4. Savio LF and Nguyen HT: Robot-assisted laparoscopic urological surgery in children. Nat Rev Urol 2013; 10: 632.
11. Riquelme M, Lopez M, Landa S et al: Laparoscopic extravesical ureteral reimplantation (LEVUR): a multicenter experience with 95 cases. Eur J Pediatr Surg 2013; 23: 143.
20. Chalmers D, Herbst K and Kim C: Roboticassisted laparoscopic extravesical ureteral reimplantation: an initial experience. J Pediatr Urol 2012; 8: 268.
12. Peters CA and Woo R: Intravesical robotically assisted bilateral ureteral reimplantation. J Endourol 2005; 19: 618.
21. Callewaert PR, Biallosterski BT, Rahnama’i MS et al: Robotic extravesical anti-reflux operations in complex cases: technical considerations and preliminary results. Urol Int 2012; 88: 6.
13. Dangle PP, Razmaria AA, Towle VL et al: Is pelvic plexus nerve documentation feasible during robotic assisted laparoscopic ureteral reimplantation with extravesical approach? J Pediatr Urol 2013; 9: 442.
22. Hopewell S, Loudon K, Clarke MJ et al: Publication bias in clinical trials due to statistical significance or direction of trial results. Cochrane Database Syst Rev 2009; 1: MR000006.
5. Stanasel I, Atala A and Hemal A: Robotic assisted ureteral reimplantation: current status. Curr Urol Rep 2013; 14: 32.
14. Lee RS, Sethi AS, Passerotti CC et al: Robot-assisted laparoscopic nephrectomy and contralateral ureteral reimplantation in children. J Endourol 2010; 24: 123.
6. Barbosa JA, Barayan G, Gridley CM et al: Parent and patient perceptions of robotic vs open urological surgery scars in children. J Urol 2013; 190: 244.
15. Marchini GS, Hong YK, Minnillo BJ et al: Robotic assisted laparoscopic ureteral reimplantation in children: case matched comparative study with open surgical approach. J Urol 2011; 185: 1870.
24. Tasian GE, Wiebe DJ and Casale P: Learning curve of robotic assisted pyeloplasty for pediatric urology fellows. J Urol 2013; 190: 1622.
7. Casale P, Patel RP and Kolon TF: Nerve sparing robotic extravesical ureteral reimplantation. J Urol 2008; 179: 1987.
16. Schomburg JL, Haberman K, Willihnganz-Lawson KH et al: Robot-assisted laparoscopic ureteral reimplantation: a single surgeon comparison to open surgery. J Pediatr Urol 2014; 10: 875.
25. Sorensen MD, Delostrinos C, Johnson MH et al: Comparison of the learning curve and outcomes of robotic assisted pediatric pyeloplasty. J Urol 2011; 185: 2517.
8. Kasturi S, Sehgal SS, Christman MS et al: Prospective long-term analysis of nerve-sparing extravesical robotic-assisted laparoscopic ureteral reimplantation. Urology 2012; 79: 680.
17. Smith RP, Oliver JL and Peters CA: Pediatric robotic extravesical ureteral reimplantation: comparison with open surgery. J Urol 2011; 185: 1876.
26. Gargollo PC: Hidden incision endoscopic surgery: description of technique, parental satisfaction and applications. J Urol 2011; 185: 1425.
9. Akhavan A, Avery D and Lendvay TS: Robot-assisted extravesical ureteral reimplantation: outcomes and conclusions from 78 ureters. J Pediatr Urol 2014; 10: 864.
18. Wicher C, Hadley D, Ludlow D et al: 250 Consecutive unilateral extravesical ureteral reimplantations in an outpatient setting. J Urol 2010; 184: 311.
27. Varda BK, Johnson EK, Clark C et al: National trends of perioperative outcomes and costs for open, laparoscopic and robotic pediatric pyeloplasty. J Urol 2014; 191: 1090.
10. Elder JS, Peters CA, Arant BS Jr et al: Pediatric Vesicoureteral Reflux Guidelines Panel summary report on the management of primary vesicoureteral reflux in children. J Urol 1997; 157: 1846.
19. Chan KW, Lee KH, Tam YH et al: Early experience of robotic-assisted reconstructive operations in pediatric urology. J Laparoendosc Adv Surg Tech A 2010; 20: 379.
28. Hays SR and Deshpande JK: Newly postulated neurodevelopmental risks of pediatric anesthesia: theories that could rock our world. J Urol 2013; 189: 1222.
23. Prasad MM, Marks A, Vasquez E et al: Published surgical success rates in pediatric urologydfact or fiction? J Urol 2012; 188: 1643.
Multi-Institutional Review of Outcomes of Robot-Assisted Laparoscopic Extravesical Ureteral Reimplantation Gwen M. Grimsby, Moira E. Dwyer, Micah A. Jacobs,* Michael C. Ost, Francis X. Schneck, Glenn M. Cannon and Patricio C. Gargollo† From the Division of Pediatric Urology, Department of Urology, University of Texas Southwestern Medical Center and Children’s Medical Center, Dallas (GMG, MAJ) and Texas Children’s Hospital-Baylor College of Medicine (PCG), Houston, Texas, and Department of Urology, Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center (MED, MCO, FXS, GMC), Pittsburgh, Pennsylvania
Purpose: We performed a multi-institutional assessment of the outcomes and complications of robot-assisted laparoscopic extravesical ureteral reimplantation for vesicoureteral reflux in children. Materials and Methods: We retrospectively reviewed the records of patients who underwent robot-assisted laparoscopic extravesical ureteral reimplantation as done by 1 of 5 surgeons at Children’s Medical Center, Dallas, Texas, or Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, from 2010 to 2013. Procedure failure was defined as persistent vesicoureteral reflux on postoperative voiding cystourethrogram or radionuclide cystogram and/or the need for reoperation. Multivariate logistic regression was done to identify possible risk factors for failure using STATAÒ, version 11. Results: A total of 61 patients (93 ureters) with a mean age of 6.7 years (range 0.6 to 18.0) underwent a procedure, of which 32 (52%) were bilateral. Ten patients (16%) underwent previous subureteral injection for vesicoureteral reflux. At a mean followup of 11.7 months the procedure was successful in 44 of 61 patients (72%). There were 14 cases of persistent vesicoureteral reflux (23%), 6 complications (10%) and 9 reoperations (11%). Multivariate logistic regression identified no factor that increased the risk of failure (p ¼ 0.737). Conclusions: Compared to the literature we found a notably lower success rate for robot-assisted laparoscopic extravesical ureteral reimplantation in the hands of 5 fellowship trained, robotically experienced pediatric urologists. More than 10% of patients required at least 1 reoperation for persistent vesicoureteral reflux or a surgical complication. Our experience suggests a higher complication rate and a lower success rate for robot-assisted laparoscopic ureteral reimplantation compared to the gold standard of open reimplantation.
Abbreviations and Acronyms RALUR ¼ robot-assisted laparoscopic ureteral reimplantation RNC ¼ radionuclide cystogram UTI ¼ urinary tract infection VCUG ¼ voiding cystourethrogram VUR ¼ vesicoureteral reflux Accepted for publication July 25, 2014. Study received institutional review board approval. * Financial interest and/or other relationship with Terumo. † Correspondence: Texas Children’s HospitalBaylor College of Medicine, 6701 Fannin St., CCC Suite 620, Houston, Texas 77030 (telephone: 832-822-3160; FAX: 832-825-3159; e-mail: [email protected]).
Key Words: ureter, vesico-ureteral reflux, robotic, laparoscopy, replantation
VESICOURETERAL reflux, which is present in 1% of children, is commonly encountered by the pediatric urologist.1 The goal of VUR management is to prevent ascending infection and, thus, decrease the risk of pyelonephritis and
renal injury.2 Treatment options include observation with or without antibiotic prophylaxis, or surgical repair via endoscopic injection of a periureteral bulking agent or ureteroneocystostomy in patients with renal
0022-5347/15/1935-1791/0 THE JOURNAL OF UROLOGY® © 2015 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2014.07.128 Vol. 193, 1791-1795, May 2015 Printed in U.S.A.
www.jurology.com
j
1791
1792
ROBOT-ASSISTED EXTRAVESICAL URETERAL REIMPLANTATION
scarring, breakthrough infection and worsening, persistent or high grade VUR.1,3 Although open ureteral reimplantation remains the gold standard surgical procedure, RALUR has become increasingly popular. Advantages of a robotic approach include the potential for shorter hospitalization, faster recovery, ease of surgery over pure laparoscopic techniques and possibly better cosmesis.4e6 Disadvantages include longer operative time and increased cost.4 The extravesical approach for ureteroneocystostomy has become the favored robotic technique with the reported advantage of potentially decreased postoperative urinary retention compared to extravesical open procedures.7 The largest studies in the literature show an excellent success rate of 98% to 99% with zero complications.7,8 Others describe a lower 88% VUR resolution rate with a 10% complication rate.9 At this time the most critical questions to be answered before widespread adoption of this new technology include whether the rate of VUR resolution is the same or better than that of standard open approaches and how the complication rates compare for the 2 techniques. We hypothesized that our VUR resolution rate after RALUR was inferior and our complication rate was higher than in the literature. Thus, in this study we share the outcomes of a multi-institutional assessment of the success and complications of RALUR for VUR in children.
MATERIALS AND METHODS After receiving institutional review board approval we retrospectively reviewed the records of all patients who underwent RALUR as done by any 1 of 5 pediatric urologists at Children’s Medical Center, Dallas, Texas, or Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, from February 2010 to September 2013. Patients treated with intravesical RALUR or RALUR for a diagnosis other than VUR were excluded from analysis. Procedure failure was defined as persistent VUR on postoperative VCUG or RNC and/or the need for reoperation. Multivariate logistic regression to identify any preoperative or intraoperative factor that placed a patient at risk for failure was done with STATA, version 11. To perform RALUR an 8.5 mm umbilical camera port was placed with 2, 8.5 mm working ports on either side. The ureter was circumscribed below the pelvic brim and dissected to the bladder. A 3 to 4 cm trough was created in the detrusor from a posterosuperior position down to the orifice of the refluxing ureter. The ureter was laid in the trough and the detrusor was closed over the ureter along the entire length of the trough. Closure was started at the ureteral orifice and carried proximal with running or interrupted polyglactin or polydioxanone barbed suture depending on surgeon preference. No ureteral tapering was done.
Patients received cefazolin intravenously at surgery and prophylactic antibiotics were continued perioperatively. Ureteral stents were not routinely placed. Patients were seen 3 months postoperatively, when renal ultrasound was done. Two surgeons also routinely obtained VCUG or RNC 3 months postoperatively. The remaining surgeons obtained VCUG if a febrile UTI developed.
RESULTS A total of 61 RALURs were performed on 93 ureters, including 35 at Children’s Medical Center and 26 at Children’s Hospital of Pittsburgh. Mean VUR grade was 3.3 (range 1 to 5). The indication for surgery was cortical defects on dimercaptosuccinic acid scan performed more than 3 months after the last UTI in 35 cases, breakthrough UTI in 13, VUR nonresolution in 12 and noncompliance with antibiotics in 1. Mean age at surgery was 6.7 years (range 0.4 to 18) and the female-to-male ratio was 4:1. Bilateral RALUR was performed in 32 patients (52%), 10 (16%) underwent prior subureteral injection of a bulking agent, 43 (70%) had constipation requiring medical therapy and high grade VUR (4 or 5) was present in 46%. There was no conversion to an open procedure and no episode of postoperative urinary retention requiring discharge with a catheter. VUR persisted in 14 patients (23%) on postoperative VCUG/RNC performed a mean of 3.9 months postoperatively (table 1). Mean persistent VUR grade was 2.5 (range 1 to 4). Four patients had bilateral persistent VUR. A febrile UTI developed in 11 patients (18%) within 1 year of surgery, of whom 5 had persistent VUR, 4 had no VCUG/RNC performed after UTI, 1 had a negative VCUG and 1 had a dimercaptosuccinic acid scan that showed no new scarring. The 6 complications (10%) included ureteral obstruction in 3 cases, urine leak in 2 and rehospitalization for nausea and vomiting in 1. These complications required a total of 5 immediate reoperations, including 4 bilateral ureteral stents and Table 1. Failures, reoperations and complications No. Pts (%) Persistent VUR Febrile UTI Reoperation: Ureteral stent* Bulking agent subureteral injection Open ureteral reimplantation† Ureteral stricture balloon dilation Complication: Bilat stents for obstruction Urine leak Readmission for nausea þ vomiting * Obstruction in 3 patients and urine leak in 1. † Urine leak and persistent VUR in 1 patient each.
14 11 9 4 2 2 1 6 3 2 1
(23) (18) (7) (3) (3) (2) (10) (5) (3) (2)
ROBOT-ASSISTED EXTRAVESICAL URETERAL REIMPLANTATION
1 open reimplantation. An additional 4 delayed reoperations included 1 balloon dilation for ureterovesical stricture, 2 subureteral injections of a bulking agent and 1 open ureteral reimplantation (table 1). All except 1 of these patients with complications/ reoperations underwent bilateral RALUR and had high grade VUR in at least 1 ureter. One patient experienced mucosal perforation intraoperatively and in 2 a drain was placed at the end of the case based on provider preference. No complication developed in these patients. At a mean 12-month followup (range 1.2 to 32.3) success as defined by VUR resolution and no need for reoperation was achieved in 44 of 61 patients (72%). Multivariate logistic regression identified no factor that increased the patient risk of failure (p ¼ 0.737, table 2).
DISCUSSION Before deciding on an approach to surgical treatment of VUR the pros and cons of the various options should be evaluated based on efficacy, general availability, the known benefits of a minimally invasive approach and cost-effectiveness.2 Open ureteral reimplantation remains the gold standard with an excellent success rate.4 A review of 86 reports of open ureteroneocystostomy in a total of 6,472 patients (8,563 ureters) showed overall surgical success rates of 95.1% per patient and 95.9% per ureter.10 Thus, it is intuitive to compare all new procedures to open surgery. In fact, laparoscopic ureteral reimplantation was not widely adopted because it was technically challenging, required longer operative time and failed to show decreased morbidity despite reported success rates greater than 95%.4,11 Since 2005 when it was first described,12 robotic management of VUR has been increasing because the robotic platform provides improved visualization and suturing techniques over pure laparoscopic methods. It was also reported that improved visualization of the neurovascular bundles allows for bilateral extravesical procedures with a minimal
risk of urinary retention.7 However, a recent study of this purported advantage showed that despite the ability to visualize the nerves stimulating the plexus failed to reproducibly demonstrate any visible response in the bladder.13 Also, notably significant complications after RALUR such as urine leak and ureteral obstruction were reported in approximately 10% of patients, similar to our experience.9,14,15 This is a greater proportion than that of open surgery and it is clinically significant because these complications may require a secondary procedure.4 Complications after RALUR also have higher Clavien classifications than in open cohorts.16 At this time only 3 direct comparisons of robotic to open extravesical approaches exist in a total of 64 patients.15e17 One series showed significantly decreased length of stay in the robotic cohort but the mean hospital stay in the open cohort was 53 hours,15e17 which is surprisingly long. Previous reports exist of extravesical ureteral reimplantation performed on an outpatient basis.18 Two studies mentioned reduced pain medication requirements in the robotic cohort while the third did not.15e17 All 3 studies revealed a significant difference in operative time, which was up to 110 minutes longer in the robotic cohort. In addition, as mentioned, the identified complications were more severe in the robotic cases.16 Thus, at this point it has not been clearly proved that the robotic approach decreases the morbidity associated with extravesical ureteral reimplantation.4 Moreover, there is insufficient evidence to argue that the robotic technique has equal or improved success compared to open approaches. We reviewed the current published literature on RALUR and found a wide 66.7% to 100% range of VUR resolution rates (table 3).3,7e9,14e17,19e21 Many of these studies had a small sample size, may have reflected provider initial experience with the techniques and used various followup imaging methods to confirm Table 3. Pediatric RALUR literature to date References
Table 2. Multivariate logistic regression of risk factors for surgical failure
Hospital Age Gender Grade IV or V VUR Bilat surgery Previous bulking agent subureteral injection Suture: Running vs interrupted Barbed vs polyglactin Constipation
p Value
95% CI
0.352 0.319 0.428 0.792 0.441 0.685
2.3e0.8 0.3e0.1 1.1e2.7 1.3e1.7 0.8e1.9 1.5e2.3
0.829 0.247 0.907
1.9e2.4 4.4e1.1 1.4e1.7
1793
7
Casale et al Chan et al19 Lee et al14 Marchini et al15 Smith et al17 Chalmers et al20 Kasturi et al8 Callewaert et al21 Gundeti et al3 Schomburg et al16 Akhavan et al9 Present series Totals
No. Pts
Mean Age at Surgery (yrs)
41 3 4 20 24 17 150 5 74 20 50 61
3.2 5.0 2.3 8.6 5.8 6.2 3.6 6.8 5.4 6.2 6.2 6.7
40 2 4 20 23 14 149 4 60 20 44 47
(97.6) (66.7) (100.0) (100.0) (95.8) (82.4) (99.3) (80.0) (81.1) (100.0) (88.0) (77.0)
469
e
427
(91)
No. VUR Resolution (%)
1794
ROBOT-ASSISTED EXTRAVESICAL URETERAL REIMPLANTATION
VUR resolution.14,19e21 Our cohort falls on the lower end of the success spectrum with a VUR resolution rate of only 77%. To elucidate the variables responsible for the differences in persistent VUR in our series compared to others we performed multivariate logistic regression to determine whether any specific demographic or intraoperative factor was responsible. Unfortunately no such cause stood out, possibly secondary to small sample size. However, although it was not significant on logistic regression, in 3 of the 4 cases of ureteral obstruction a detrusor tunnel had been created with barbed suture. Our practice has consequently changed in that we now use polyglactin suture exclusively. Other possibilities may explain our increased rate of persistent VUR. Publication bias exists and studies with favorable results are more likely to be submitted and published compared to those with negative findings.22 Also, practicing pediatric urologists report surgical outcomes that are significantly different than those published in the literature.23 Our experience may be similar to that of others who have not reported seemingly suboptimal data. In addition, journals may not accept unfavorable studies that may have been submitted. Another possibility is that our surgeons are still in the learning curve for this procedure. However, most of each case was performed by an experienced surgeon who had been in practice a mean of 7.4 years and had completed a number of these procedures during fellowship training. Unfortunately the number of cases needed to complete this learning curve is unknown and likely differs by the cases and parameters measured.24 Depending on the study the operative time of robotic pyeloplasty performed by fellows decreased to the median time of an experienced attending surgeon after 15 to 37 cases.24,25 For robotic ureteral reimplantation specifically Gundeti et al reported an improved success rate with evolution of the robotic extravesical technique through maneuvers such as lengthening the detrusor tunnel.3 It is also conceivable that our definition of failure was too strict or routine postoperative VCUGS/RNC in asymptomatic patients over diagnosed persistent VUR. We disagree with these arguments because any new procedure should be rigorously evaluated with the highest level of scrutiny before it is deemed equivalent to the gold standard. In other large RALUR series VCUG was routinely done postoperatively in all patients.8,9 On the other hand, series in which postoperative VCUG was not obtained in all patients may under diagnose persistent VUR. This may have occurred in our series since VCUG or RNC was performed postoperatively in only 37 of our 61 patients (61%).
Another possibility is that our cases were more complex than those in other studies. High grade VUR was present in 46% of patients and 57% had persistent VUR. Unfortunately it is difficult to compare the VUR grade in our cohort to that in other large series that provide only the mean or median, or group grade III VUR with grades IV and V.7e9 Other providers may have used an open approach with ureteral tapering in high grade cases while in our cohort no tapering was done despite a large percent of high grade VUR. In addition, although we could not reliably capture dysfunctional voiding in this retrospective cohort, 70% of patients were treated for constipation. Because dysfunctional elimination of urine and stool often coexist, the high constipation rate may serve as a surrogate for a high rate of bladder dysfunction, which also may have placed our patients at increased risk for failure. In regard to the potential advantages of a robotic approach we maintain that the 2 to 4 abdominal scars associated with a robotic technique provide a potentially inferior cosmetic result compared to an open Pfannenstiel incision, which is concealed below the underwear or bathing suit line. Validated scar surveys revealed that parents and patients prefer incisions that are hidden at the Pfannenstiel line vs traditional open or laparoscopic pyeloplasty incisions.26 A study using a nonvalidated survey showed that most patients and parents preferred robotic scars on the abdomen vs an open Pfannenstiel incision but they would ultimately base the choice of surgery on the clinical outcome.6 Furthermore, we assume that the cost of the robotic approach is significantly higher than that of the open technique not only due to the cost of robot maintenance but also secondary to prolonged operative time. While to our knowledge no cost comparison has been reported for ureteral reimplantation, pyeloplasty studies showed that robotic approaches were significantly more costly than open and pure laparoscopic techniques, largely due to prolonged operative time and robotic supplies.27 Moreover, these prolonged operative times raise concern regarding the neurotoxic effects of anesthesia. Previous studies demonstrated an increased risk of learning disabilities and attention deficit disorder in children after multiple exposures to general anesthesia and it was suggested that the duration of general anesthesia be minimized.28 Our experience suggests a higher complication rate and a lower success rate for RALUR compared to the gold standard of open reimplantation. Based on these findings we disagree with routine application of RALUR in all children. Rather we speculate that the robotic approach may maintain an advantage in bilateral cases as well as in older children
ROBOT-ASSISTED EXTRAVESICAL URETERAL REIMPLANTATION
who would benefit from the potentially improved pain control. Advantages of this study include its multiinstitutional nature and the inclusion of surgeons who trained at various facilities and had extensive robotic experience. Disadvantages include its retrospective nature, which made determining voiding dysfunction difficult since no objective measure was used to capture these data. Other disadvantages are the varied suturing techniques used to create the detrusor tunnel and the lack of postoperative VCUG/RNC in all patients. While it is difficult to pinpoint an exact cause of the higher than expected number of patients with persistent VUR in our cohort, further multi-institutional collaborations should be performed to assess the long-term success and complications of this and other novel robotic applications in pediatric urology. Our findings emphasize the importance for pediatric
1795
urologists to periodically critically review their outcomes to ensure that in the spirit of evidencebased surgical practice they meet accepted standards and, if not, to facilitate opportunities to identify areas for change and improvement.
CONCLUSIONS We found a lower success rate for RALUR than that reported in the literature. Of our patients 23% had persistent VUR and more than 10% required at least 1 reoperation for persistent VUR or a surgical complication. Coupled with a debatably inferior cosmetic result as well as the increased operative time and costs associated with a robotic procedure, we encourage pediatric urologists to critically review their results and weigh the advantages of the technique against realistic expectations for outcomes.
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11. Riquelme M, Lopez M, Landa S et al: Laparoscopic extravesical ureteral reimplantation (LEVUR): a multicenter experience with 95 cases. Eur J Pediatr Surg 2013; 23: 143.
20. Chalmers D, Herbst K and Kim C: Roboticassisted laparoscopic extravesical ureteral reimplantation: an initial experience. J Pediatr Urol 2012; 8: 268.
12. Peters CA and Woo R: Intravesical robotically assisted bilateral ureteral reimplantation. J Endourol 2005; 19: 618.
21. Callewaert PR, Biallosterski BT, Rahnama’i MS et al: Robotic extravesical anti-reflux operations in complex cases: technical considerations and preliminary results. Urol Int 2012; 88: 6.
13. Dangle PP, Razmaria AA, Towle VL et al: Is pelvic plexus nerve documentation feasible during robotic assisted laparoscopic ureteral reimplantation with extravesical approach? J Pediatr Urol 2013; 9: 442.
22. Hopewell S, Loudon K, Clarke MJ et al: Publication bias in clinical trials due to statistical significance or direction of trial results. Cochrane Database Syst Rev 2009; 1: MR000006.
5. Stanasel I, Atala A and Hemal A: Robotic assisted ureteral reimplantation: current status. Curr Urol Rep 2013; 14: 32.
14. Lee RS, Sethi AS, Passerotti CC et al: Robot-assisted laparoscopic nephrectomy and contralateral ureteral reimplantation in children. J Endourol 2010; 24: 123.
6. Barbosa JA, Barayan G, Gridley CM et al: Parent and patient perceptions of robotic vs open urological surgery scars in children. J Urol 2013; 190: 244.
15. Marchini GS, Hong YK, Minnillo BJ et al: Robotic assisted laparoscopic ureteral reimplantation in children: case matched comparative study with open surgical approach. J Urol 2011; 185: 1870.
24. Tasian GE, Wiebe DJ and Casale P: Learning curve of robotic assisted pyeloplasty for pediatric urology fellows. J Urol 2013; 190: 1622.
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16. Schomburg JL, Haberman K, Willihnganz-Lawson KH et al: Robot-assisted laparoscopic ureteral reimplantation: a single surgeon comparison to open surgery. J Pediatr Urol 2014; 10: 875.
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17. Smith RP, Oliver JL and Peters CA: Pediatric robotic extravesical ureteral reimplantation: comparison with open surgery. J Urol 2011; 185: 1876.
26. Gargollo PC: Hidden incision endoscopic surgery: description of technique, parental satisfaction and applications. J Urol 2011; 185: 1425.
9. Akhavan A, Avery D and Lendvay TS: Robot-assisted extravesical ureteral reimplantation: outcomes and conclusions from 78 ureters. J Pediatr Urol 2014; 10: 864.
18. Wicher C, Hadley D, Ludlow D et al: 250 Consecutive unilateral extravesical ureteral reimplantations in an outpatient setting. J Urol 2010; 184: 311.
27. Varda BK, Johnson EK, Clark C et al: National trends of perioperative outcomes and costs for open, laparoscopic and robotic pediatric pyeloplasty. J Urol 2014; 191: 1090.
10. Elder JS, Peters CA, Arant BS Jr et al: Pediatric Vesicoureteral Reflux Guidelines Panel summary report on the management of primary vesicoureteral reflux in children. J Urol 1997; 157: 1846.
19. Chan KW, Lee KH, Tam YH et al: Early experience of robotic-assisted reconstructive operations in pediatric urology. J Laparoendosc Adv Surg Tech A 2010; 20: 379.
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