- Email: [email protected]
Risk Assessment of Stone Formation in Stapled Orthotopic Ileal Neobladder
Risk Assessment of Stone Formation in Stapled Orthotopic Ileal Neobladder Mariaconsiglia Ferriero,* Salvatore Guaglianone, Rocco Papalia, Gian Luca Muto, Michele Gallucci and Giuseppe Simone From the Department of Urology, Regina Elena National Cancer Institute of Rome (MF, SG, RP, MG, GS) and Campus Bio-Medico University of Rome (GLM), Rome, and Department of Urology, San Giovanni Bosco Hospital, Turin (GS), Italy
Purpose: The increasing trend of performing radical cystectomy with a minimally invasive approach has made stapled neobladders an attractive alternative to hand-sewn pouches. To date, data on the incidence and clinical impact of stone formation in long surviving neobladder cases are scarce. We report a long-term, single-center experience of stapled orthotopic ileal neobladder and identify predictors of stone formation. Materials and Methods: From May 2001 to October 2012, 445 consecutive patients (388 male, 57 female) underwent radical cystectomy and stapled orthotopic ileal neobladder. Univariable and multivariable analyses were performed to identify independent predictors of an increased risk of stone formation. Results: At a median followup of 41 months (IQR 16e58) neobladder stone formation occurred in 41 patients (9.2%). All of these patients successfully underwent endoscopic stone lithotripsy with 34 as outpatient procedures. On univariable Cox analysis only female gender (p ¼ 0.001, HR 3.29, 95% CI 1.59e6.83) and intermittent self-catheterization (p <0.001, HR 15.2, 95% CI 5.87e39.5) were associated with an increased risk of stone formation. On multivariable analysis the only independent predictor of stone formation was intermittent self-catheterization (p ¼ 0.001, HR 8.98, 95% CI 2.59e31.1). Conclusions: In our series of stapled orthotopic ileal neobladders the rate of stone formation was comparable to that reported in the literature for completely hand-sewn ileal reservoirs. The only variable independently predictive of stone formation was intermittent self-catheterization.
Abbreviations and Acronyms CT ¼ computerized tomography OIN ¼ orthotopic ileal neobladder RC ¼ radical cystectomy UD ¼ urinary diversion UTI ¼ urinary tract infection Accepted for publication September 5, 2014. Nothing to disclose. * Correspondence: Department of Urology, Regina Elena National Cancer Institute of Rome, Rome, Italy (telephone: þ390652665005; FAX: þ390652666983; e-mail: marilia.ferriero@ gmail.com).
Editor’s Note: This article is the third of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 1072 and 1073.
Key Words: urinary diversion, urinary calculi, surgical staplers, risk, cystectomy
A stapler is used in surgery to simplify the technique by avoiding hand sutures and, thus, reducing operative time. This issue has recently generated interest, especially among surgeons facing minimally invasive procedures with complex reconstructive steps such as intracorporeal
urinary diversion after radical cystectomy. The leakproof closure and the usefulness of staplers in performing anastomosis after bowel resection and reconstruction were demonstrated by general surgeons, and were used routinely for bowel management
0022-5347/15/1933-0891/0 THE JOURNAL OF UROLOGY® © 2015 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2014.09.008 Vol. 193, 891-896, March 2015 Printed in U.S.A.
www.jurology.com
j
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RISK OF STONES IN STAPLED ORTHOTOPIC ILEAL NEOBLADDER
during open and minimally invasive procedures.1e3 The safety of stapler use in managing the urinary tract was first reported in 1993 for a laparoscopic bladder closure.4 Since then, more authors have described the feasibility and safety of stapler use in other urological procedures such as ureterectomy, nephroureterectomy and ileal neobladder reconstruction.5e11 Despite extensive literature supporting excellent fluid and tissue biocompatibility, and the corrosion resistant nature and the low toxicity of titanium staples,4,6,7 the primary challenge to the widespread use of nonabsorbable materials in the urinary tract remains the increased risk of stone formation.11 Several authors have reported an increased risk of lithiasis in the upper tract or in the reservoir after RC and OIN.12e14 The highest incidence of stones in the reservoir was reported in patients with a Kock pouch (43.1%) due to exposed nonabsorbable staples or other foreign materials in the reconstructed urinary tract.14 A lower stone rate was found in a series of Indiana pouch cases (12.9%) but the incidence seemed to increase with longer followup.14 In addition to the exposure of nonabsorbable surgical materials to urine in the neobladder, established risk factors for stone formation include bacterial colonization, diversion associated urinary metabolic derangements, urinary stasis and mucus production.15 To date, few studies with adequate followup have reported the incidence of stone formation in stapled OIN.8e11 Therefore, in this study we report a long-term, single-center experience of stapled OIN and identify the predictors of stone formation.
MATERIALS AND METHODS From May 2001 to October 2012, 445 consecutive patients (388 male, 57 female) underwent open RC and OIN for muscle invasive bladder cancer.
Surgical Technique Padua orthotopic ileal bladder was performed using the technique described by Pagano et al,16 with the only difference that titanium staplers were used to create the neobladder neck and the posterior neobladder wall. The membranous urethra was incised as close as possible to the prostatic apex to preserve the distal urethral sphincter. A 40 cm ileal segment was isolated about 15 to 20 cm proximal to the ileocecal valve. The distal loop (about 20 cm in length) was lowered in a U shape, and tunneled posteriorly and anteriorly using an Endo GIAÔ stapler (TLC75) to configure a neobladder neck (fig. 1). This left an 8 cm right horn (distal loop) and a 24 cm left horn (proximal loop) (fig. 2, a). These nontunneled ileal segments were then split open along the antimesenteric border (fig. 2, b). The first 16 cm of the proximal loop (left horn) were folded over medially in a reverse U shape (fig. 2, c),
Figure 1. a, neobladder neck was configured as U-shaped loop, leaving 8 cm distal segment (right horn) and 24 cm proximal segment (left horn). b, loop was tunneled posteriorly and anteriorly using Endo GIA stapler.
leaving 8 cm unfolded, and the inner opposite borders were stapled together (first posterior wall folding) (fig. 2, d ). A second folding of this U-shaped segment was performed by approaching the cranial point of the folded segment to the distal point of the right horn. Subsequently the posterior neobladder wall was stapled by approaching the medial borders of the unfolded right and left horns to the lower boundary of the double folded proximal loop (fig. 2, e). Le Duc uretero-ileal anastomoses were performed bilaterally. The upper cup was hand sewn to the edge of the lower ileal cup to obtain an oval refashioned reservoir (fig. 2, f ).
Followup The followup schedule included a baseline visit 1 month after surgery, subsequent visits at 3, 6, 12, 18 and 24 months postoperatively, and yearly visits thereafter. Physical examination, serum creatinine and electrolyte determination, urinalysis and urine culture were performed at each visit. Patients underwent abdominal ultrasonography and chest x-ray at the 3, 12 and 24-month visits and yearly visits thereafter. CT was performed at the 6, 18 and 30-month visits and yearly thereafter. Cystoscopy, urine cytology and positron emission tomography-CT were performed at physician discretion.
Statistical Analysis The chi-square test and Student t-test were used to evaluate differences between the neobladder stone and stone-free groups for categorical and continuous variables, respectively. Univariable and multivariable Cox analyses were performed to identify variables predictive of an increased risk of stone formation. Statistical analysis was performed with SPSSÒ v.19.0.
RESULTS Clinical, perioperative and functional data are reported in the supplementary table (http://jurology. com/). At a median followup of 41 months (IQR 16e58) neobladder stones occurred in 41 patients (9.2%, 11 female and 30 male). All stones found were
RISK OF STONES IN STAPLED ORTHOTOPIC ILEAL NEOBLADDER
893
Figure 2. a, neobladder neck was configured leaving left and right horns. b, nontunneled ileal segments were detubularized along antimesenteric border. c, first 16 cm of proximal loop (left horn) was folded on itself. Inner opposite borders were stapled together side to side. d, aspect of stapled ileal mucosa. e, folded segment was subsequently folded again, approaching right and left horns, to close posterior neobladder. Posterior neobladder wall was stapled, accosting medial borders of unfolded right and left horns, to lower boundary of double folded proximal loop, and borders were stapled. f, upper cup was hand-sewn to edge of lower ileal cup to obtain globular reservoir.
matrix/mucous like and median size was 1 cm (IQR 0.6e2.1). Of these 41 patients 35 experienced recurrent stones. Endoscopic laser lithotripsy was performed successfully via the urethra in 37 of 41 cases and 34 of these 37 cases were performed as outpatient procedures without the use of general anesthesia. At cystoscopic evaluation the staple lines were usually covered by ileal mucosa. In 15 cases (36.6%) the stones were anchored to titanium staples. The remaining 4 patients experienced spontaneous stone expulsion. The incidence of UTIs excluding asymptomatic bacteriuria, neobladder urethral anastomosis stricture and intermittent selfcatheterization (those with post-void volume greater than 100 ml) in the cohort of patients who experienced stone formation was significantly higher than in those observed in the cohort of stonefree patients (19.5% vs 7.6%, p ¼ 0.01; 17.1% vs 2.2%, p <0.001 and 9.75% vs 0%, p <0.001, respectively, table 1). Stone rates at 3, 5 and 7-year followup were 8%, 19.5% and 24.9%, respectively (fig. 3).
On univariable Cox analysis including age, gender, daytime and nighttime continence, UTI, intermittent self-catheterization and urethral anastomosis strictures, only female gender (p ¼ 0.001, HR 3.29, 95% CI 1.59e6.83) and intermittent self-catheterization (p <0.001, HR 15.2, 95% CI 5.87e39.5) were associated with an increased risk of stone formation. On multivariable analysis the only independent predictor of stone formation Table 1. Demographic and functional features of cohorts
Mean age (SD) Mean kg/m2 body mass index (SD) No. gender (%): M F No. UTIs (%) No. neobladder-urethral anastomosis stricture (%) No. intermittent self-catheterization (%)
Cohort with Stones
Stone-Free Cohort
p Value
59.6 (14.1) 25.8 (3.4)
63.7 (9.9) 26.1 (2.3)
0.017 0.55
31 10 8 7
(75.6) (24.4) (19.5) (17.1)
356 48 31 9
(88.1) (11.9) (7.6) (2.2)
0.023 0.01 <0.001
4
(9.75)
0
(0)
<0.001
RISK OF STONES IN STAPLED ORTHOTOPIC ILEAL NEOBLADDER
894
Figure 3. Kaplan-Meier curve showing stone-free survival rate after RC.
was intermittent self-catheterization (p ¼ 0.001, HR 8.98, 95% CI 2.59e31.1, table 2).
DISCUSSION The ideal features of UD are globular shape, reconfiguration through a double folding and small pelvis allocation. We have already reported adequate and stable urodynamic assessment together with a good urinary continence profile and excellent health related quality of life in a series of Padua ileal bladder during a 48-month followup.17 Urolithiasis is an established long-term complication of UD.13e15 Hyperchloremic metabolic acidosis results in increased renal calcium and hydrogen excretion, and is often associated with hypocitraturia. The presence of fat malabsorption can induce hyperoxaluria. Hypocitraturia and Table 2. Univariable and multivariable analyses to identify predictors of neobladder stone formation Univariable HR (95% CI) Female 3.29 UTI 1.92 Neobladder-urethral 1.84 anastomosis stricture Intermittent 15.24 self-catheterization
(1.59e6.83) (0.88e4.2) (1.06e2.38)
p Value
Multivariable HR (95% CI)
0.001 2.16 (0.82e5.65) 0.101 e 0.168 e
p Value 0.118 e e
(5.87e39.5) <0.001 8.98 (2.59e31.1) <0.001
hyperoxaluria may induce calcium phosphate and/ or calcium oxalate stone formation. The tendency toward dehydration in patients with UD may further increase susceptibility to stone formation. Chronic colonization and infection of the reservoir, especially with urease producing bacteria, may result in struvite and/or carbonate apatite stones. Consequently the incidence of urinary stone formation increases in patients with UD.12 In the bowel reservoir these previously mentioned metabolic changes, as well as the presence of foreign materials (eg sutures, staples), mucus production and chronic infection, act as a nidus for struvite stone formation. Moreover the presence of residual urine after catheterization or micturition is an additional risk factor for lithiasis and infection. Urolithiasis in continent UD has a multifactorial origin.12 In our series of patients with OIN, the incidence of UTI, neobladder-urethral anastomosis strictures and intermittent self-catheterization (due to ineffective abdominal straining or to posterior prolapse of the pouch) was significantly associated with neobladder stone occurrence (p ¼ 0.01, p <0.001 and p <0.001, respectively). Nevertheless, on univariable Cox analysis only female gender (p ¼ 0.001) and intermittent self-catheterization (p <0.001) were significant predictors of neobladder stone formation. Possible explanations of these results could be the low number of events in the analyzed cohort or the efficient followup and education of patients with voiding dysfunction to ensure complete neobladder emptying. Interestingly we found female gender was a significant predictor of neobladder stone formation on univariable analysis. This finding is consistent with the available literature reporting a higher incidence of retention and intermittent self-catheterization in female patients with OIN, ranging from 11% to 70%.18 Such conditions often appear late, after a year or more of good neobladder function and voiding patterns. The etiology has been debated but most believe it is due to a kink in the urethral pouch anastomosis related to posterior prolapse of the neobladder during the Valsalva maneuver.19,20 Some attempts to fill the posterior pelvis (peritoneal or omental flap) and restore anterior and superior fixation of the reservoir were applied to prevent prolapse.21 In a recent report Bartsch et al highlighted how the rate of retention increased steadily with time.22 In a series of 56 women who received OIN, at a mean followup of 62.9 months the intermittent selfcatheterization rate was 62.5%. The authors did not identify any predictor of this outcome, likely due to the small sample size.22 In the present series we found that only self-catheterization was an independent predictor of stone formation in OIN. Many
RISK OF STONES IN STAPLED ORTHOTOPIC ILEAL NEOBLADDER
patients in whom stones developed were women, most of whom routinely used intermittent selfcatheterization to empty the neobladder. These findings supported the theory that stones occurred more often in women with urinary retention due to a posterior prolapse of the reservoir. Titanium staples are well tolerated in the urinary tract due to their resistance to corrosion, low toxicity, and excellent tissue and fluid biocompatibility. Shalhav et al reported a 0% stone rate in 25 patients treated with laparoscopic nephroureterectomy in whom titanium staples were used to secure the bladder cuff just caudal to the ureter.6 Even if staples were visible during cystoscopy 3.5 years postoperatively, no signs of encrustation or infection were found at the staple line. No stones developed in patients in the 11-year experience reported by Shalhav et al with stapling the bladder cuff 6 or in the series reported by Grubb et al in which titanium staples were used for reductive pelvioplasty.7 The incidence of neobladder stones in our series of stapled Padua ileal bladder was 9.2% without impairing renal function. Recorded at a median followup of 41 months, this rate is slightly higher than similar reports of hand-sewn UD, ranging from 3% to 8.1% (table 3).23e27 Nevertheless, our study highlighted a linear correlation between neobladder stone formation rate and followup length, an issue not yet addressed in the literature. In fact, this rate increased from 2.4% at the 1-year followup to 24.9% at the 7-year followup (fig. 3). Detractors of staple use in neobladders could argue that such a high rate of stones (24.9%) could be the result of staples. However, after adjusting the data for followup duration, the incidence of neobladder stone formation was comparable to that reported by other authors. In a series by Fontana et al on a novel stapled OIN, the stone formation rate was 6% at a median followup of 20 months.10 This finding is in line with the incidence of neobladder stone formation reported in the present series, with a 94.3% 2-year Table 3. Reports of stone rate in stapled or hand-sewn orthotopic reservoirs
References 10
Fontana et al Steven and Poulsen11 Abol-Enein and Ghoneim23 Stein et al24 Hautmann et al25 Gamal et al26 Zhong et al27 Present series
Diversion
No. Pts
Mos Followup
Stapled
No. Pts with Stones
Y-shaped Kock
50 166
20 (median) 60
Yes Yes
3 58
6 35
W-shaped
344
38
(mean)
No
10
3
T-pouch W-shaped
209 363
33 (median) 57 (mean)
No No
17 2
8.1 0.5
N-shaped U-shaped Padua
42 50 445
25 (median) 26.3 (median) 41 (median)
No No Yes
2 2 41
4.8 4 9.2
Stone Rate (%)
895
stone-free rate. Similarly, in a series of T pouches by Stein et al the rate of stone formation in the ileal reservoir was 8.1% at a median 33-month followup.24 In our series the 3-year neobladder stone rate was 8% (table 3). Other series in the literature with a shorter median followup (range 20 to 26 months) reported lower rates of stones ranging from 0.5% to 4.8% (table 3).23,25e27 The reader may argue that the reported incidence of stones in some series of handsewn pouch approached 0%. However, lithiasis of the reservoir is not always symptomatic so that small stones may be under detected on telephone interviews. Our study highlights the need for strict imaging based followup, including ultrasound and CT alternatively for the early detection of neobladder stones. In a review by Barbalat et al the analysis of costs showed that the use of staples to construct a neobladder saves approximately 1 hour of operating time in an open case and can save approximately $2,997 per case.28 These data recently generated interest, especially at centers performing laparoscopic and robotic RC with totally intracorporeal OIN. The main limitations of this study are the retrospective nature and the lack of a control group (hand-sewn OIN). Consequently, despite the comparable incidence of neobladder stone formation between our series and other series of hand-sewn OIN, the question of whether staple use in OIN would increase neobladder stone formation risk remains to be answered by prospective studies comparing stapled and hand-sewn OIN. We highlighted the independent role of intermittent self-catheterization as a predictor of increased neobladder stone formation risk as well as the potential roles of UTI and neobladder urethral anastomosis stricture. The latter 2 variables, although not predictive of increased risk on univariable Cox analysis, were significantly associated with neobladder stones using the chi-square test. These data should be verified by larger series with more events. The key point of our counseling is to inform patients about the need for hydration and adequate voiding function. Finally, a strict imaging based followup, aimed not only to detect oncologic events but also to evaluate functional assessment, remains mandatory to identify and promptly treat neobladder stones.
CONCLUSIONS Stapled OIN seems to compare favorably with other series of hand-sewn pouches. Strict followup has a key role in the early diagnosis of neobladder stones and in minimizing the clinical impact of lithotripsy.
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RISK OF STONES IN STAPLED ORTHOTOPIC ILEAL NEOBLADDER
REFERENCES 1. Kracht M, Hay JM, Fagniez PL et al: Ileocolonic anastomosis after right hemicolectomy for carcinoma: stapled or hand-sewn? A prospective, multicenter, randomized trial. Int J Colorectal Dis 1993; 8: 29. 2. Gustavsson K, Gunnarsson U and Jestin P: Postoperative complications after closure of a diverting ileostomaedifferences according to closure technique. Int J Colorectal Dis 2012; 27: 55. 3. Leung TT, MacLean AR, Buie WD et al: Comparison of stapled versus handsewn loop ileostomy closure: a meta-analysis. J Gastrointest Surg 2008; 12: 939. 4. Kerbl K, Chandhoke P, McDougall E et al: Laparoscopic stapled bladder closure: laboratory and clinical experience. J Urol 1993; 149: 1437. 5. Chandhoke PS, Clayman RV, Kerbl K et al: Laparoscopic ureterectomy: initial clinical experience. J Urol 1993; 149: 992. 6. Shalhav AL, Dunn MD, Portis AJ et al: Laparoscopic nephroureterectomy for upper tract transitional cell cancer: the Washington University experience. J Urol 2000; 163: 1100. 7. Grubb RL 3rd, Sundaram CP, Yan Y et al: Use of titanium staples during upper tract laparoscopic reconstructive surgery: initial experience. J Urol 2002; 168: 1366. 8. Abreu SC, Messias FI, Argollo RS et al: Laparoscopic assisted radical cystoprostatectomy with Y-shaped orthotopic ileal neobladder constructed with non-absorbable titanium staples through a 5 cm Pfannensteil incision. Int Braz J Urol 2005; 31: 362. 9. Abreu SC, Araujo MB, Silveira RA et al: Laparoscopic-assisted radical cystectomy with U-shaped orthotopic ileal neobladder
constructed using nonabsorbable titanium staples. Urology 2006; 68: 193.
cystectomy and orthotopic neobladders in women. J Urol 2008; 180: 206.
10. Fontana D, Bellina M, Fasolis G et al: Y-neobladder: an easy, fast, and reliable procedure. Urology 2004; 63: 699.
20. Hautmann RE, Abol-Enein H, Davidsson T et al: ICUD-EAU International Consultation on Bladder Cancer 2012: Urinary diversion. Eur Urol 2013; 63: 67.
11. Steven K and Poulsen AL: The orthotopic Kock ileal neobladder: functional results, urodynamic features, complications and survival in 166 men. J Urol 2000; 164: 288. 12. Van der Aa F, De Ridder D and Van Poppel H: When the bowel becomes the bladder: changes in metabolism after urinary diversion. Pract Gastroenterol 2012; 36: 15. 13. Turk TM, Koleski FC and Albala DM: Incidence of urolithiasis in cystectomy patients after intestinal conduit or continent urinary diversion. World J Urol 1999; 17: 305. 14. Terai A, Ueda T, Kakehi Y et al: Urinary calculi as a late complication of the Indiana continent urinary diversion: comparison with the Kock pouch procedure. J Urol 1996; 155: 66. 15. Okhunov Z, Duty B, Smith AD et al: Management of urolithiasis in patients after urinary diversions. BJU Int 2011; 108: 330. 16. Pagano F, Artibani W, Ligato P et al: Vescica Ileale Padovana: a technique for total bladder replacement. Eur Urol 1990; 17: 149. 17. Ferriero M, Simone G, Rocchegiani A et al: Early and late assessment of Padua ileal bladder. Urology 2009; 73: 1357. 18. Lee KR, Abol-Enein H, Artibani W et al: Urinary diversion after radical cystectomy for bladder cancer: options, patient selection, and outcomes. BJU Int 2014; 113: 11. 19. Ali-el-Dein B, Shaaban AA, Abu-Eideh RH et al: Surgical complications following radical
21. Ali-El-Dein B, Gomha M and Ghoneim MA: Critical evaluation of the problem of chronic urinary retention after orthotopic bladder substitution in women. J Urol 2002; 168: 587. 22. Bartsch G, Daneshmand S, Skinner EC et al: Urinary functional outcomes in female neobladder patients. World J Urol 2014; 32: 221. 23. Abol-Enein H and Ghoneim MA: Functional results of orthotopic ileal neobladder with serous-lined extramural ureteral reimplantation: experience with 450 patients. J Urol 2001; 165: 1427. 24. Stein JP, Dunn MD, Quek ML et al: The orthotopic T pouch ileal neobladder: experience with 209 patients. J Urol 2004; 172: 584. 25. Hautmann RE, de Petriconi R, Gottfried HW et al: The ileal neobladder: complications and functional results in 363 patients after 11 years of followup. J Urol 1999; 161: 422. 26. Gamal WM, Osman MM, Hammady A et al: Modified N-shaped ileal neobladder after radical cystectomy. Urol Oncol 2011; 29: 366. 27. Zhong S, Zhu Z, Wang X et al: Modified U shaped ileal neobladder after radical cystectomy: assessment of functional outcomes and complications in Chinese patients. Urol Oncol 2013; 31: 1683. 28. Barbalat Y, Morales D and Weiss RE: Contemporary use of titanium staples for orthotopic urinary diversion. Urology 2012; 80: 1176.
Purpose: The increasing trend of performing radical cystectomy with a minimally invasive approach has made stapled neobladders an attractive alternative to hand-sewn pouches. To date, data on the incidence and clinical impact of stone formation in long surviving neobladder cases are scarce. We report a long-term, single-center experience of stapled orthotopic ileal neobladder and identify predictors of stone formation. Materials and Methods: From May 2001 to October 2012, 445 consecutive patients (388 male, 57 female) underwent radical cystectomy and stapled orthotopic ileal neobladder. Univariable and multivariable analyses were performed to identify independent predictors of an increased risk of stone formation. Results: At a median followup of 41 months (IQR 16e58) neobladder stone formation occurred in 41 patients (9.2%). All of these patients successfully underwent endoscopic stone lithotripsy with 34 as outpatient procedures. On univariable Cox analysis only female gender (p ¼ 0.001, HR 3.29, 95% CI 1.59e6.83) and intermittent self-catheterization (p <0.001, HR 15.2, 95% CI 5.87e39.5) were associated with an increased risk of stone formation. On multivariable analysis the only independent predictor of stone formation was intermittent self-catheterization (p ¼ 0.001, HR 8.98, 95% CI 2.59e31.1). Conclusions: In our series of stapled orthotopic ileal neobladders the rate of stone formation was comparable to that reported in the literature for completely hand-sewn ileal reservoirs. The only variable independently predictive of stone formation was intermittent self-catheterization.
Abbreviations and Acronyms CT ¼ computerized tomography OIN ¼ orthotopic ileal neobladder RC ¼ radical cystectomy UD ¼ urinary diversion UTI ¼ urinary tract infection Accepted for publication September 5, 2014. Nothing to disclose. * Correspondence: Department of Urology, Regina Elena National Cancer Institute of Rome, Rome, Italy (telephone: þ390652665005; FAX: þ390652666983; e-mail: marilia.ferriero@ gmail.com).
Editor’s Note: This article is the third of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 1072 and 1073.
Key Words: urinary diversion, urinary calculi, surgical staplers, risk, cystectomy
A stapler is used in surgery to simplify the technique by avoiding hand sutures and, thus, reducing operative time. This issue has recently generated interest, especially among surgeons facing minimally invasive procedures with complex reconstructive steps such as intracorporeal
urinary diversion after radical cystectomy. The leakproof closure and the usefulness of staplers in performing anastomosis after bowel resection and reconstruction were demonstrated by general surgeons, and were used routinely for bowel management
0022-5347/15/1933-0891/0 THE JOURNAL OF UROLOGY® © 2015 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2014.09.008 Vol. 193, 891-896, March 2015 Printed in U.S.A.
www.jurology.com
j
891
892
RISK OF STONES IN STAPLED ORTHOTOPIC ILEAL NEOBLADDER
during open and minimally invasive procedures.1e3 The safety of stapler use in managing the urinary tract was first reported in 1993 for a laparoscopic bladder closure.4 Since then, more authors have described the feasibility and safety of stapler use in other urological procedures such as ureterectomy, nephroureterectomy and ileal neobladder reconstruction.5e11 Despite extensive literature supporting excellent fluid and tissue biocompatibility, and the corrosion resistant nature and the low toxicity of titanium staples,4,6,7 the primary challenge to the widespread use of nonabsorbable materials in the urinary tract remains the increased risk of stone formation.11 Several authors have reported an increased risk of lithiasis in the upper tract or in the reservoir after RC and OIN.12e14 The highest incidence of stones in the reservoir was reported in patients with a Kock pouch (43.1%) due to exposed nonabsorbable staples or other foreign materials in the reconstructed urinary tract.14 A lower stone rate was found in a series of Indiana pouch cases (12.9%) but the incidence seemed to increase with longer followup.14 In addition to the exposure of nonabsorbable surgical materials to urine in the neobladder, established risk factors for stone formation include bacterial colonization, diversion associated urinary metabolic derangements, urinary stasis and mucus production.15 To date, few studies with adequate followup have reported the incidence of stone formation in stapled OIN.8e11 Therefore, in this study we report a long-term, single-center experience of stapled OIN and identify the predictors of stone formation.
MATERIALS AND METHODS From May 2001 to October 2012, 445 consecutive patients (388 male, 57 female) underwent open RC and OIN for muscle invasive bladder cancer.
Surgical Technique Padua orthotopic ileal bladder was performed using the technique described by Pagano et al,16 with the only difference that titanium staplers were used to create the neobladder neck and the posterior neobladder wall. The membranous urethra was incised as close as possible to the prostatic apex to preserve the distal urethral sphincter. A 40 cm ileal segment was isolated about 15 to 20 cm proximal to the ileocecal valve. The distal loop (about 20 cm in length) was lowered in a U shape, and tunneled posteriorly and anteriorly using an Endo GIAÔ stapler (TLC75) to configure a neobladder neck (fig. 1). This left an 8 cm right horn (distal loop) and a 24 cm left horn (proximal loop) (fig. 2, a). These nontunneled ileal segments were then split open along the antimesenteric border (fig. 2, b). The first 16 cm of the proximal loop (left horn) were folded over medially in a reverse U shape (fig. 2, c),
Figure 1. a, neobladder neck was configured as U-shaped loop, leaving 8 cm distal segment (right horn) and 24 cm proximal segment (left horn). b, loop was tunneled posteriorly and anteriorly using Endo GIA stapler.
leaving 8 cm unfolded, and the inner opposite borders were stapled together (first posterior wall folding) (fig. 2, d ). A second folding of this U-shaped segment was performed by approaching the cranial point of the folded segment to the distal point of the right horn. Subsequently the posterior neobladder wall was stapled by approaching the medial borders of the unfolded right and left horns to the lower boundary of the double folded proximal loop (fig. 2, e). Le Duc uretero-ileal anastomoses were performed bilaterally. The upper cup was hand sewn to the edge of the lower ileal cup to obtain an oval refashioned reservoir (fig. 2, f ).
Followup The followup schedule included a baseline visit 1 month after surgery, subsequent visits at 3, 6, 12, 18 and 24 months postoperatively, and yearly visits thereafter. Physical examination, serum creatinine and electrolyte determination, urinalysis and urine culture were performed at each visit. Patients underwent abdominal ultrasonography and chest x-ray at the 3, 12 and 24-month visits and yearly visits thereafter. CT was performed at the 6, 18 and 30-month visits and yearly thereafter. Cystoscopy, urine cytology and positron emission tomography-CT were performed at physician discretion.
Statistical Analysis The chi-square test and Student t-test were used to evaluate differences between the neobladder stone and stone-free groups for categorical and continuous variables, respectively. Univariable and multivariable Cox analyses were performed to identify variables predictive of an increased risk of stone formation. Statistical analysis was performed with SPSSÒ v.19.0.
RESULTS Clinical, perioperative and functional data are reported in the supplementary table (http://jurology. com/). At a median followup of 41 months (IQR 16e58) neobladder stones occurred in 41 patients (9.2%, 11 female and 30 male). All stones found were
RISK OF STONES IN STAPLED ORTHOTOPIC ILEAL NEOBLADDER
893
Figure 2. a, neobladder neck was configured leaving left and right horns. b, nontunneled ileal segments were detubularized along antimesenteric border. c, first 16 cm of proximal loop (left horn) was folded on itself. Inner opposite borders were stapled together side to side. d, aspect of stapled ileal mucosa. e, folded segment was subsequently folded again, approaching right and left horns, to close posterior neobladder. Posterior neobladder wall was stapled, accosting medial borders of unfolded right and left horns, to lower boundary of double folded proximal loop, and borders were stapled. f, upper cup was hand-sewn to edge of lower ileal cup to obtain globular reservoir.
matrix/mucous like and median size was 1 cm (IQR 0.6e2.1). Of these 41 patients 35 experienced recurrent stones. Endoscopic laser lithotripsy was performed successfully via the urethra in 37 of 41 cases and 34 of these 37 cases were performed as outpatient procedures without the use of general anesthesia. At cystoscopic evaluation the staple lines were usually covered by ileal mucosa. In 15 cases (36.6%) the stones were anchored to titanium staples. The remaining 4 patients experienced spontaneous stone expulsion. The incidence of UTIs excluding asymptomatic bacteriuria, neobladder urethral anastomosis stricture and intermittent selfcatheterization (those with post-void volume greater than 100 ml) in the cohort of patients who experienced stone formation was significantly higher than in those observed in the cohort of stonefree patients (19.5% vs 7.6%, p ¼ 0.01; 17.1% vs 2.2%, p <0.001 and 9.75% vs 0%, p <0.001, respectively, table 1). Stone rates at 3, 5 and 7-year followup were 8%, 19.5% and 24.9%, respectively (fig. 3).
On univariable Cox analysis including age, gender, daytime and nighttime continence, UTI, intermittent self-catheterization and urethral anastomosis strictures, only female gender (p ¼ 0.001, HR 3.29, 95% CI 1.59e6.83) and intermittent self-catheterization (p <0.001, HR 15.2, 95% CI 5.87e39.5) were associated with an increased risk of stone formation. On multivariable analysis the only independent predictor of stone formation Table 1. Demographic and functional features of cohorts
Mean age (SD) Mean kg/m2 body mass index (SD) No. gender (%): M F No. UTIs (%) No. neobladder-urethral anastomosis stricture (%) No. intermittent self-catheterization (%)
Cohort with Stones
Stone-Free Cohort
p Value
59.6 (14.1) 25.8 (3.4)
63.7 (9.9) 26.1 (2.3)
0.017 0.55
31 10 8 7
(75.6) (24.4) (19.5) (17.1)
356 48 31 9
(88.1) (11.9) (7.6) (2.2)
0.023 0.01 <0.001
4
(9.75)
0
(0)
<0.001
RISK OF STONES IN STAPLED ORTHOTOPIC ILEAL NEOBLADDER
894
Figure 3. Kaplan-Meier curve showing stone-free survival rate after RC.
was intermittent self-catheterization (p ¼ 0.001, HR 8.98, 95% CI 2.59e31.1, table 2).
DISCUSSION The ideal features of UD are globular shape, reconfiguration through a double folding and small pelvis allocation. We have already reported adequate and stable urodynamic assessment together with a good urinary continence profile and excellent health related quality of life in a series of Padua ileal bladder during a 48-month followup.17 Urolithiasis is an established long-term complication of UD.13e15 Hyperchloremic metabolic acidosis results in increased renal calcium and hydrogen excretion, and is often associated with hypocitraturia. The presence of fat malabsorption can induce hyperoxaluria. Hypocitraturia and Table 2. Univariable and multivariable analyses to identify predictors of neobladder stone formation Univariable HR (95% CI) Female 3.29 UTI 1.92 Neobladder-urethral 1.84 anastomosis stricture Intermittent 15.24 self-catheterization
(1.59e6.83) (0.88e4.2) (1.06e2.38)
p Value
Multivariable HR (95% CI)
0.001 2.16 (0.82e5.65) 0.101 e 0.168 e
p Value 0.118 e e
(5.87e39.5) <0.001 8.98 (2.59e31.1) <0.001
hyperoxaluria may induce calcium phosphate and/ or calcium oxalate stone formation. The tendency toward dehydration in patients with UD may further increase susceptibility to stone formation. Chronic colonization and infection of the reservoir, especially with urease producing bacteria, may result in struvite and/or carbonate apatite stones. Consequently the incidence of urinary stone formation increases in patients with UD.12 In the bowel reservoir these previously mentioned metabolic changes, as well as the presence of foreign materials (eg sutures, staples), mucus production and chronic infection, act as a nidus for struvite stone formation. Moreover the presence of residual urine after catheterization or micturition is an additional risk factor for lithiasis and infection. Urolithiasis in continent UD has a multifactorial origin.12 In our series of patients with OIN, the incidence of UTI, neobladder-urethral anastomosis strictures and intermittent self-catheterization (due to ineffective abdominal straining or to posterior prolapse of the pouch) was significantly associated with neobladder stone occurrence (p ¼ 0.01, p <0.001 and p <0.001, respectively). Nevertheless, on univariable Cox analysis only female gender (p ¼ 0.001) and intermittent self-catheterization (p <0.001) were significant predictors of neobladder stone formation. Possible explanations of these results could be the low number of events in the analyzed cohort or the efficient followup and education of patients with voiding dysfunction to ensure complete neobladder emptying. Interestingly we found female gender was a significant predictor of neobladder stone formation on univariable analysis. This finding is consistent with the available literature reporting a higher incidence of retention and intermittent self-catheterization in female patients with OIN, ranging from 11% to 70%.18 Such conditions often appear late, after a year or more of good neobladder function and voiding patterns. The etiology has been debated but most believe it is due to a kink in the urethral pouch anastomosis related to posterior prolapse of the neobladder during the Valsalva maneuver.19,20 Some attempts to fill the posterior pelvis (peritoneal or omental flap) and restore anterior and superior fixation of the reservoir were applied to prevent prolapse.21 In a recent report Bartsch et al highlighted how the rate of retention increased steadily with time.22 In a series of 56 women who received OIN, at a mean followup of 62.9 months the intermittent selfcatheterization rate was 62.5%. The authors did not identify any predictor of this outcome, likely due to the small sample size.22 In the present series we found that only self-catheterization was an independent predictor of stone formation in OIN. Many
RISK OF STONES IN STAPLED ORTHOTOPIC ILEAL NEOBLADDER
patients in whom stones developed were women, most of whom routinely used intermittent selfcatheterization to empty the neobladder. These findings supported the theory that stones occurred more often in women with urinary retention due to a posterior prolapse of the reservoir. Titanium staples are well tolerated in the urinary tract due to their resistance to corrosion, low toxicity, and excellent tissue and fluid biocompatibility. Shalhav et al reported a 0% stone rate in 25 patients treated with laparoscopic nephroureterectomy in whom titanium staples were used to secure the bladder cuff just caudal to the ureter.6 Even if staples were visible during cystoscopy 3.5 years postoperatively, no signs of encrustation or infection were found at the staple line. No stones developed in patients in the 11-year experience reported by Shalhav et al with stapling the bladder cuff 6 or in the series reported by Grubb et al in which titanium staples were used for reductive pelvioplasty.7 The incidence of neobladder stones in our series of stapled Padua ileal bladder was 9.2% without impairing renal function. Recorded at a median followup of 41 months, this rate is slightly higher than similar reports of hand-sewn UD, ranging from 3% to 8.1% (table 3).23e27 Nevertheless, our study highlighted a linear correlation between neobladder stone formation rate and followup length, an issue not yet addressed in the literature. In fact, this rate increased from 2.4% at the 1-year followup to 24.9% at the 7-year followup (fig. 3). Detractors of staple use in neobladders could argue that such a high rate of stones (24.9%) could be the result of staples. However, after adjusting the data for followup duration, the incidence of neobladder stone formation was comparable to that reported by other authors. In a series by Fontana et al on a novel stapled OIN, the stone formation rate was 6% at a median followup of 20 months.10 This finding is in line with the incidence of neobladder stone formation reported in the present series, with a 94.3% 2-year Table 3. Reports of stone rate in stapled or hand-sewn orthotopic reservoirs
References 10
Fontana et al Steven and Poulsen11 Abol-Enein and Ghoneim23 Stein et al24 Hautmann et al25 Gamal et al26 Zhong et al27 Present series
Diversion
No. Pts
Mos Followup
Stapled
No. Pts with Stones
Y-shaped Kock
50 166
20 (median) 60
Yes Yes
3 58
6 35
W-shaped
344
38
(mean)
No
10
3
T-pouch W-shaped
209 363
33 (median) 57 (mean)
No No
17 2
8.1 0.5
N-shaped U-shaped Padua
42 50 445
25 (median) 26.3 (median) 41 (median)
No No Yes
2 2 41
4.8 4 9.2
Stone Rate (%)
895
stone-free rate. Similarly, in a series of T pouches by Stein et al the rate of stone formation in the ileal reservoir was 8.1% at a median 33-month followup.24 In our series the 3-year neobladder stone rate was 8% (table 3). Other series in the literature with a shorter median followup (range 20 to 26 months) reported lower rates of stones ranging from 0.5% to 4.8% (table 3).23,25e27 The reader may argue that the reported incidence of stones in some series of handsewn pouch approached 0%. However, lithiasis of the reservoir is not always symptomatic so that small stones may be under detected on telephone interviews. Our study highlights the need for strict imaging based followup, including ultrasound and CT alternatively for the early detection of neobladder stones. In a review by Barbalat et al the analysis of costs showed that the use of staples to construct a neobladder saves approximately 1 hour of operating time in an open case and can save approximately $2,997 per case.28 These data recently generated interest, especially at centers performing laparoscopic and robotic RC with totally intracorporeal OIN. The main limitations of this study are the retrospective nature and the lack of a control group (hand-sewn OIN). Consequently, despite the comparable incidence of neobladder stone formation between our series and other series of hand-sewn OIN, the question of whether staple use in OIN would increase neobladder stone formation risk remains to be answered by prospective studies comparing stapled and hand-sewn OIN. We highlighted the independent role of intermittent self-catheterization as a predictor of increased neobladder stone formation risk as well as the potential roles of UTI and neobladder urethral anastomosis stricture. The latter 2 variables, although not predictive of increased risk on univariable Cox analysis, were significantly associated with neobladder stones using the chi-square test. These data should be verified by larger series with more events. The key point of our counseling is to inform patients about the need for hydration and adequate voiding function. Finally, a strict imaging based followup, aimed not only to detect oncologic events but also to evaluate functional assessment, remains mandatory to identify and promptly treat neobladder stones.
CONCLUSIONS Stapled OIN seems to compare favorably with other series of hand-sewn pouches. Strict followup has a key role in the early diagnosis of neobladder stones and in minimizing the clinical impact of lithotripsy.
896
RISK OF STONES IN STAPLED ORTHOTOPIC ILEAL NEOBLADDER
REFERENCES 1. Kracht M, Hay JM, Fagniez PL et al: Ileocolonic anastomosis after right hemicolectomy for carcinoma: stapled or hand-sewn? A prospective, multicenter, randomized trial. Int J Colorectal Dis 1993; 8: 29. 2. Gustavsson K, Gunnarsson U and Jestin P: Postoperative complications after closure of a diverting ileostomaedifferences according to closure technique. Int J Colorectal Dis 2012; 27: 55. 3. Leung TT, MacLean AR, Buie WD et al: Comparison of stapled versus handsewn loop ileostomy closure: a meta-analysis. J Gastrointest Surg 2008; 12: 939. 4. Kerbl K, Chandhoke P, McDougall E et al: Laparoscopic stapled bladder closure: laboratory and clinical experience. J Urol 1993; 149: 1437. 5. Chandhoke PS, Clayman RV, Kerbl K et al: Laparoscopic ureterectomy: initial clinical experience. J Urol 1993; 149: 992. 6. Shalhav AL, Dunn MD, Portis AJ et al: Laparoscopic nephroureterectomy for upper tract transitional cell cancer: the Washington University experience. J Urol 2000; 163: 1100. 7. Grubb RL 3rd, Sundaram CP, Yan Y et al: Use of titanium staples during upper tract laparoscopic reconstructive surgery: initial experience. J Urol 2002; 168: 1366. 8. Abreu SC, Messias FI, Argollo RS et al: Laparoscopic assisted radical cystoprostatectomy with Y-shaped orthotopic ileal neobladder constructed with non-absorbable titanium staples through a 5 cm Pfannensteil incision. Int Braz J Urol 2005; 31: 362. 9. Abreu SC, Araujo MB, Silveira RA et al: Laparoscopic-assisted radical cystectomy with U-shaped orthotopic ileal neobladder
constructed using nonabsorbable titanium staples. Urology 2006; 68: 193.
cystectomy and orthotopic neobladders in women. J Urol 2008; 180: 206.
10. Fontana D, Bellina M, Fasolis G et al: Y-neobladder: an easy, fast, and reliable procedure. Urology 2004; 63: 699.
20. Hautmann RE, Abol-Enein H, Davidsson T et al: ICUD-EAU International Consultation on Bladder Cancer 2012: Urinary diversion. Eur Urol 2013; 63: 67.
11. Steven K and Poulsen AL: The orthotopic Kock ileal neobladder: functional results, urodynamic features, complications and survival in 166 men. J Urol 2000; 164: 288. 12. Van der Aa F, De Ridder D and Van Poppel H: When the bowel becomes the bladder: changes in metabolism after urinary diversion. Pract Gastroenterol 2012; 36: 15. 13. Turk TM, Koleski FC and Albala DM: Incidence of urolithiasis in cystectomy patients after intestinal conduit or continent urinary diversion. World J Urol 1999; 17: 305. 14. Terai A, Ueda T, Kakehi Y et al: Urinary calculi as a late complication of the Indiana continent urinary diversion: comparison with the Kock pouch procedure. J Urol 1996; 155: 66. 15. Okhunov Z, Duty B, Smith AD et al: Management of urolithiasis in patients after urinary diversions. BJU Int 2011; 108: 330. 16. Pagano F, Artibani W, Ligato P et al: Vescica Ileale Padovana: a technique for total bladder replacement. Eur Urol 1990; 17: 149. 17. Ferriero M, Simone G, Rocchegiani A et al: Early and late assessment of Padua ileal bladder. Urology 2009; 73: 1357. 18. Lee KR, Abol-Enein H, Artibani W et al: Urinary diversion after radical cystectomy for bladder cancer: options, patient selection, and outcomes. BJU Int 2014; 113: 11. 19. Ali-el-Dein B, Shaaban AA, Abu-Eideh RH et al: Surgical complications following radical
21. Ali-El-Dein B, Gomha M and Ghoneim MA: Critical evaluation of the problem of chronic urinary retention after orthotopic bladder substitution in women. J Urol 2002; 168: 587. 22. Bartsch G, Daneshmand S, Skinner EC et al: Urinary functional outcomes in female neobladder patients. World J Urol 2014; 32: 221. 23. Abol-Enein H and Ghoneim MA: Functional results of orthotopic ileal neobladder with serous-lined extramural ureteral reimplantation: experience with 450 patients. J Urol 2001; 165: 1427. 24. Stein JP, Dunn MD, Quek ML et al: The orthotopic T pouch ileal neobladder: experience with 209 patients. J Urol 2004; 172: 584. 25. Hautmann RE, de Petriconi R, Gottfried HW et al: The ileal neobladder: complications and functional results in 363 patients after 11 years of followup. J Urol 1999; 161: 422. 26. Gamal WM, Osman MM, Hammady A et al: Modified N-shaped ileal neobladder after radical cystectomy. Urol Oncol 2011; 29: 366. 27. Zhong S, Zhu Z, Wang X et al: Modified U shaped ileal neobladder after radical cystectomy: assessment of functional outcomes and complications in Chinese patients. Urol Oncol 2013; 31: 1683. 28. Barbalat Y, Morales D and Weiss RE: Contemporary use of titanium staples for orthotopic urinary diversion. Urology 2012; 80: 1176.