Int Urol Nephrol DOI 10.1007/s11255-013-0632-7
UROLOGY - ORIGINAL PAPER
A feasibility study of peritoneum preservation in radical cystectomy with extraperitonealization of orthotopic neobladder for invasive high-grade bladder cancer: a preliminary analysis Dong Soo Park • In Hyuck Gong • Don Kyung Choi Jin Ho Hwang • Moon Hyung Kang • Jong Jin Oh
•
Received: 7 October 2013 / Accepted: 11 December 2013 Ó Springer Science+Business Media Dordrecht 2013
Abstract Objective To describe a technique for radical cystectomy with extraperitonealization of orthotopic neobladder (RCEN) that reduces bowel-related complications by preservation of the peritoneum. Materials and methods Fifteen patients with non-metastatic bladder cancer underwent RCEN by a peritoneum preserving technique. The study included 13 patients with T1 high-grade bladder cancer and 2 with T2a bladder cancer. To compare perioperative outcomes including bowel-related complications, we also reviewed 15 patients who underwent traditional cystectomy with ileal Studer neobladder who were matched for age, sex, body mass index, American Society of Anesthesiologists (ASA) score, tumor stage, tumor grade, tumor size, and location. Female genital organs were preserved in five female patients who underwent the RCEN technique. Results There was no significant difference between the two cohorts (RECN vs. traditional technique) with respect to age, body mass index, ASA score, or tumor characteristics. The mean operative time was similar between the two groups. The patients who underwent RECN exhibited earlier recovery of normal gas pattern on plain abdominal X-ray during the postoperative period and an earlier resumption of normal diet. The mean hospital stay was shorter in the RECN group than the traditional group. D. S. Park I. H. Gong D. K. Choi J. H. Hwang M. H. Kang J. J. Oh (&) Department of Urology, CHA Bundang Medical Center, CHA University, 351 Yatap-dong, Bundang-gu, Songnam 463-712, Korea e-mail: [email protected] J. J. Oh CHA Cancer Research Institute, Seoul, Korea
Conclusions The RECN technique preserving the whole peritoneum is a feasible approach that significantly reduces bowel-related complications in selected patients. Keywords Bladder Bladder cancer Radical cystectomy Neobladder Bowel-related complication
Introduction Radical cystectomy is the standard therapy for muscleinvasive bladder cancer and the most powerful means of primary local control [1]. However, radical cystectomy and urinary diversion are major operative procedures with the potential for serious complications [2–4]. In particular, an intestinal obstruction may occur either early or late after surgery as a serious complication that is associated with relatively high mortality rates [1, 3]. There is a 10 % incidence rate of postoperative bowel obstruction requiring treatment in patients who have had gastric or ileal segments removed for urinary diversion [5]. Furthermore, a 10.5 % incidence rate of postoperative bowel obstruction requiring abdominal re-exploration was reported in a large series of patients who underwent radical cystectomy [6]. To reduce bowel-related complications, several studies have focused on early recovery of bowel function [7]. A Cochrane review of the effect of prokinetic agents on bowel-related complications found that certain medications reduce time to flatus and duration of hospital stay [8]. Reyblat et al. [9] showed that extraperitoneal augmentation enterocystoplasty had excellent results in reducing bowel-related complications compared with an intraperitoneal procedure for neurogenic bladder in spinal cord injury. Moreover, an extraperitoneal technique could easily preserve the female genital organs during radical cystectomy, and new data
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indicate that preserving the urethra and gynecological organs is oncologically and clinically acceptable in appropriately selected female patients [10, 11]. Here, we present a feasible technique of radical cystectomy with extraperitonealization of orthotopic neobladder (RCEN) that preserves the entire peritoneum to reduce bowel-related complications with preservation of female genital organs in selected patients.
Materials and methods Study population From January 2012 to February 2013, 15 patients with nonmetastatic bladder cancer underwent RCEN by a peritoneum preserving technique after obtaining institutional review approval and written informed consent for participation. Thirteen patients had T1 high-grade bladder cancer and 2 had T2a bladder cancer confirmed before radical cystectomy. This study was approved by the Institutional Review Board of CHA Bundang Medical Center. The RCEN group (n = 15) was matched with 15 patients who underwent orthotopic ileal neobladder substitution by traditional cystectomy (traditional group) and were similar in age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, and tumor characteristics from chart review. We excluded patients with previous abdominal surgery, abdominal radiotherapy, or a history of inflammatory bowel disease. Surgical procedure The peritoneum was mobilized from the external iliac vessels laterally up to the common iliac vessels and swept anterolaterally. Pelvic lymphadenectomy included the external, internal, obturator, and common iliac lymph nodes up to the aortic bifurcation. In some cases, the presacral lymph nodes and preaortic and/or precaval lymph nodes below the inferior mesenteric artery were also removed. The right and left ureters were carefully mobilized distally to preserve the periureteral blood supply to approximately 5 cm below the level of the superior vesical artery, after which they were ligated and divided. The distal segments of the ureters were sent for frozen section analysis if distal ureteral margin confirmation was needed. After confirmation of ureteral margin was negative for malignancy, ureteroileal anastomosis was conducted. The peritoneum overlying the bladder was delicately mobilized to the culde-sac and possible perivesical tissue was included in the specimen. A plane between the posterior wall of the bladder and the rectum was created, and the dissection proceeded to Denonvillier’s fascia. Denonvillier’s fascia was incised, and
123
the space was dissected to separate the bladder and prostate from the rectum. In female patients, the peritoneum overlying the bladder was mobilized to the vesicocervical space, and a plane between the posterior wall of the bladder and the anterior wall of the vagina was created. The dissection then proceeded along the vesicovaginal space. The bladder was lifted off the anterior vaginal wall and uterus without injuring the vagina and paravaginal tissues. The superior and inferior vesical arteries and veins were ligated and transected at the origin from the internal iliac vessels. The more distal vessels that entered the paravaginal tissue and pelvic plexus were left intact. The lateral vascular bundles were incised close to the bladder to preserve the pelvic nerves located lateral to the vagina. The dorsal vein complex was ligated and divided after incision into the endopelvic fascia. A right-angled clamp was placed around the smooth muscle of the urethra close to the bladder neck to protect the rhabdosphincter. Care must be taken during dissection of the bladder neck and proximal urethra to protect autonomic nerve fibers innervating the remnant urethral segment. The urethra was divided 1 cm below the bladder neck, and the urethral cut margin was sent for examination by frozen section. A portion of the terminal ileum approximately 54 cm long was isolated approximately 15 cm proximal to the ileocecal valve. Bowel continuity was restored using a two-layer suture anastomosis. Both ends of the isolated segment were closed with single-layer 3-0 chromic seromuscular running sutures. The 40-cm distal portion of the isolated segment was opened along its antimesenteric border and placed in a U shape. The two medial borders of the opened U-shaped isolated segment were oversewn with a single layer of 3-0 chromic seromuscular running sutures. The bottom of the U was folded over between the two ends, resulting in a spherical reservoir. A small window was made in the right side of the peritoneum overlying the pelvic floor. The tailored spherical reservoir was pulled out through the window into the pelvic cavity for extraperitonealization (Figs. 1, 2). The space between the window and the mesentery of the reservoir was closed with interrupted 3-0 silk sutures. The ureters were anastomosed to the 14-cm proximal afferent tubular portion of the reservoir with interrupted 5-0 polyglactin sutures using the Bricker ureterointestinal anastomosis. The ureters were stented with 7 Fr catheters and the ureteral stents were moved anteriorly through separate stab wounds. An 8- to 10-mm-diameter hole was cut from the most caudal part of the reservoir away from the suture line, and urethral anastomosis was then performed. Analysis of outcomes We reviewed perioperative outcomes of operative time, estimated blood loss, transfusion rate, and complications
Int Urol Nephrol Fig. 1 Schematic illustration of the surgical technique. a Dissection plane showing preservation of the peritoneum in males. b Construction of Studer type ileal neobladder. c Extraperitonealization of the neobladder and ureter anastomosis. d Dissection plane showing preservation of the peritoneum and genital tract in females. e Extraperitonealization of the neobladder and urethral anastomosis in females
between the two cohorts. The distribution of clinicopathologic parameters was tested using chi-square and Student t tests. Complications were reviewed for any adverse events that occurred following RCEN or traditional cystectomy, and postoperative surgical complications were defined according to the Clavien classification system [12].
Results A total of 15 patients who underwent RCEN were reviewed and matched to a contemporary cohort of 15 patients who
underwent traditional cystectomy with orthotopic ileal neobladder substitution by the same surgeon. Demographic data are summarized in Table 1. There was no significant difference between the two cohorts with respect to age, sex, BMI, ASA score, or tumor characteristics. The operative time was not significantly different between the two cohorts (RCEN vs. traditional technique = 387.6 vs. 370.1 min) (Table 2). The estimated blood loss and transfusion rate was similar between the cohorts. There were no differences of ureteral size and length between two cohorts. Postoperative complications occurred in seven cases in the traditional group including
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Int Urol Nephrol Fig. 2 Preservation of the peritoneum and gynecological organs in a female patient. a The bladder was dissected from the overlying peritoneum, uterus, and anterior vaginal wall in sequence. The urethra was divided 1 cm below the bladder neck. b Intact entire peritoneum, uterus, and vagina. c A small window is made in the right side of the peritoneum for neobladder extraperitonealization. d The neobladder is pulled out into the pelvic cavity through the window
Table 1 Baseline characteristics
Characteristics
RCEN
Traditional technique
N
15
15
Mean age (years) ± SD
64.5 ± 7.3
63.2 ± 3.4
Male (%)
10 (66.7)
10 (66.7)
Female (%)
5 (33.3)
5 (33.3)
Mean BMI (kg/m ) ± SD
25.48 ± 3.47
25.14 ± 2.73
Mean ASA score
1.5
1.6
p value
0.870
Gender
2
Preoperative tumor stage RCEN radical cystectomy with extraperitonealization of orthotopic neobladder, BMI body mass index, ASA American society of Anesthesiologist
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0.280 0.981
T1
13
13
T2a
2
2
Low grade
1
2
High grade
14
13
Preoperative tumor grade
four bowel-related complications. There were no bowelrelated complications in the RCEN group. Resumption of a normal diet occurred earlier in the RCEN group than the traditional group (6.3 vs. 9.8 days, p = 0.010). The time
0.161
0.748
until return of normal gas pattern was also shorter in the RCEN group (3.8 vs. 6.7 days, p = 0.015). None of the patients in the RCEN group suffered any delay in resuming an oral diet or any abdominal pain. The time for Levin tube
Int Urol Nephrol Table 2 Perioperative outcomes compared RCEN and traditional technique for bladder cancer
Variables
RCEN
Traditional technique
p value
N
15
15
Operative time (min) ± SD
387.6 ± 34.1
370.1 ± 12.8
0.178
Estimated blood loss (cc) ± SD
277.5 ± 197.4
314.9 ± 241.1
0.444
Transfusion (%)
2 (13.3)
3 (20)
0.281
Complications
1
7
Clavien-Dindo classification 1
1 (wound problem)
3 (wound problem)
2
0
3 (ileus)
3
0
1 (bowel obstruction)
Bowel-related complication (mean ± SD)
RCEN radical cystectomy with extraperitonealization of orthotopic neobladder
Resumption of normal diet (days)
6.3 ± 1.7
9.8 ± 2.1
0.010
Time for Levin tube indwelling (days)
2.1 ± 0.8
4.5 ± 2.7
0.021
3.8 ± 1.0
6.7 ± 3.4
0.015
9.9 ± 1.4
12.5 ± 5.4
0.014
Time for return of normal gas pattern (days) Mean hospital stay (days) ± SD
indwelling time was significantly shorter in RCEN group than traditional group (2.1 vs. 4.5 days, p = 0.021), and mean hospital stay of the RCEN group was 9.9 days, which was shorter than that of the traditional group (12.5 days). The pathological findings confirmed clear surgical margins, and none of the patients developed local recurrence or metastasis during the follow-up period. Mean 15.5 lymph nodes were removed in RCEN group; however, mean 20.1 lymph nodes were removed in traditional technique group. Only one patient had positive lymph node in RCEN group and two patients in traditional technique group. The neobladder functions were similar between the two cohorts in male patients. However, among female patients, maximal flow rate and residual urine volume significantly improved in the RCEN group compared with the traditional group (data not shown). All patients remained continent during the day without catheterization for residual urine but had varying degrees of night incontinence requiring no more than one pad.
Discussion Our RCEN technique that preserved the entire peritoneum and selectively preserved genital organs in female patients had excellent outcomes with respect to recovery of normal bowel function and reduction in bowel-related complications. Moreover, the RCEN technique might be favored for female patients who are sexually active as the gynecologic tract was fully preserved. The reported perioperative morbidity rate after radical cystectomy ranges from 20 to 64 % [13–16]. Among the reported complications, bowel-related complications such as prolonged ileus and bowel obstruction have been a major problem in patients undergoing radical cystectomy
with a prevalence of 20–30 % [17, 18]. Attempts to reduce bowel-related morbidity have mainly been studied in general surgery. In a meta-analysis, Noble et al. [7] showed that postoperative gum chewing significantly decreased the time of ileus. Traut et al. [8] investigated the effect of prokinetic agents on prolonged ileus and found that certain medications reduce time to flatus and duration of hospital stay. In the urological field, a surgical technique to reduce bowel-related complications was introduced by Reyblat et al. [9], who showed that an extraperitoneal technique during augmentation enterocystoplasty facilitated early postoperative recovery. Their results suggested that the incidence of postoperative major intestinal obstruction might be reduced by reconstituting the pelvic floor. During radical cystectomy, there is insufficient sigmoid colon and omentum available to fill the pelvis, which results in small bowel entrapment within the denuded pelvis and subsequent bowel obstruction. Preservation of the peritoneum, which prevents bowel entrapment within the pelvis, might reduce the possibility of major bowel obstruction requiring re-exploratory abdominal surgery. Additionally, Mandhani et al. [19] showed in their report with technique including extraperitonealization during radical cystectomy and orthotopic neobladder that extraperitonealization of orthotopic neobladder offered the advantage of reduction in length of hospitalization, early recovery and less bowelrelated complications. Likewise in our study, patients who underwent the RCEN technique preserving the entire peritoneum experienced earlier recovery of bowel function than those who underwent the traditional technique. A radical cystectomy in women traditionally removes the bladder along with surrounding perivesical soft tissue including the ovaries, fallopian tubes, uterus, cervix, and anterior vagina [20]. However, new data indicate that preserving the gynecological organs and urethra is
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oncologically and clinically acceptable in appropriately selected female patients because urethral tumors occur rarely. The urethral involvement rate is approximately 12 %, even in female patients with high-grade invasive bladder cancer [10], and the incidence of secondary malignant involvement of the gynecological organs from bladder cancer is only 2.6 % [11]. Several studies have reported that radical cystectomy and orthotopic urinary diversion that spares the gynecological organs result in excellent oncological and functional outcomes [20, 21]. Performing RCEN technique in female invasive bladder cancer patients preserved the female genital organ effectively, and it would preserve the sexual function and reproductive function in selected patients. Patient selection is important in order to achieve promising oncological outcomes after organ-sparing techniques. The patient must have no evidence of lymph node metastasis, extravesical spread, or bladder neck invasion on clinical evaluation and imaging studies. Analysis of intraoperative frozen sections of the proximal urethra is an important way to identify candidates for orthotopic urinary diversion. Tumors located in the dome or posterior bladder wall should be carefully evaluated for appropriate invasion depth and should be analyzed by intra-operative frozen sections to achieve a safe margin. Additionally, application of RCEN technique had difficulty to remove lymph node in extended area; therefore, careful patient selection is more important. The main limitations of our preliminary data are the short follow-up duration and small study population. Oncologic outcomes after RCEN could not be investigated due to very short-term follow-up duration, and preliminary data with including only 15 cases were difficult to generalize our results. It should be overcome by validation in a large-scale study over a longer duration. Another variable that was hard to control was previous medical history that might change baseline bowel function. Although all patients received pain control according to the same protocol after surgery, use of postoperative analgesics differed somewhat between patients.
Conclusions The routine resection of the peritoneum overlying the bladder and the female genital tract during radical cystectomy may be unnecessary and undesirable. Our RCEN technique that preserves the peritoneum helps to reduce postoperative bowel-related complications and maintains pelvic support via the peritoneum to improve neobladder function. In selected patients, the RCEN technique could preserve the female genital organs, which should contribute to improved functional outcome with a positive impact on quality of life.
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Conflict of interest The authors have no conflict of interest with any institutions or products.
References 1. Hautmann RE, Abol-Enein H, Davidsson T, Gudjonsson S, Hautmann SH, Holm HV, Lee CT, Liedberg F, Madersbacher S, Manoharan M, Mansson W, Mills RD, Penson DF, Skinner EC, Stein R, Studer UE, Thueroff JW, Turner WH, Volkmer BG, Xu A (2013) ICUD-EAU International Consultation on Bladder Cancer 2012: urinary diversion. Eur Urol 63(1):67–80. doi:10. 1016/j.eururo.2012.08.050 2. Lawrentschuk N, Colombo R, Hakenberg OW, Lerner SP, Mansson W, Sagalowsky A, Wirth MP (2010) Prevention and management of complications following radical cystectomy for bladder cancer. Eur Urol 57(6):983–1001. doi:10.1016/j.eururo. 2010.02.024 3. Nazmy M, Yuh B, Kawachi M, Lau CS, Linehan J, Ruel NH, Torrey RR, Yamzon J, Wilson TG, Chan KG. (2013) Early and late complications of robotic assisted radical cystectomy: a standardized analysis by urinary diversion type. J Urol. doi:10. 1016/j.juro.2013.10.022 4. Hollenbeck BK, Miller DC, Taub D, Dunn RL, Khuri SF, Henderson WG, Montie JE, Underwood W, 3rd, Wei JT (2005) Identifying risk factors for potentially avoidable complications following radical cystectomy. J Urol 174(4 Pt 1):1231–1237; discussion 1237 5. Azzouni F (2013) Current status of minimally invasive radical cystectomy: an outcome-based comparison. Expert Rev Anticancer Ther 13(6):681–695. doi:10.1586/era.13.59 6. Varkarakis IM, Chrisofos M, Antoniou N, Papatsoris A, Deliveliotis C (2007) Evaluation of findings during re-exploration for obstructive ileus after radical cystectomy and ileal-loop urinary diversion: insight into potential technical improvements. BJU Int 99(4):893–897. doi:BJU664410.1111/j.1464-410X.2006. 06644.x 7. Noble EJ, Harris R, Hosie KB, Thomas S, Lewis SJ (2009) Gum chewing reduces postoperative ileus? A systematic review and metaanalysis. Int J Surg 7(2):100–105. doi:10.1016/j.ijsu.2009.01.006 8. Traut U, Brugger L, Kunz R, Pauli-Magnus C, Haug K, Bucher HC, Koller MT (2008) Systemic prokinetic pharmacologic treatment for postoperative adynamic ileus following abdominal surgery in adults. Cochrane Database Syst Rev (1):CD004930. doi:10.1002/14651858.CD004930.pub3 9. Reyblat P, Chan KG, Josephson DY, Stein JP, Freeman JA, Grossfeld GD, Esrig D, Ginsberg DA (2009) Comparison of extraperitoneal and intraperitoneal augmentation enterocystoplasty for neurogenic bladder in spinal cord injury patients. World J Urol 27(1):63–68. doi:10.1007/s00345-008-0351-3 10. Stein JP, Penson DF, Wu SD, Skinner DG (2007) Pathological guidelines for orthotopic urinary diversion in women with bladder cancer: a review of the literature. J Urol 178(3 Pt 1):756–760. doi:10.1016/j.juro.2007.05.013 11. Ali-El-Dein B, Abdel-Latif M, Mosbah A, Eraky I, Shaaban AA, Taha NM, Ghoneim MA (2004) Secondary malignant involvement of gynecologic organs in radical cystectomy specimens in women: is it mandatory to remove these organs routinely? J Urol 172(3):885–887. doi:10.1097/01.ju.0000133986.29257.bf 12. Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240(2):205–213. doi:00000658-200408000-00003 13. Shabsigh A, Korets R, Vora KC, Brooks CM, Cronin AM, Savage C, Raj G, Bochner BH, Dalbagni G, Herr HW, Donat SM
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(2009) Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol 55(1):164–174. doi:10.1016/j.eururo. 2008.07.031 Novara G, De Marco V, Aragona M, Boscolo-Berto R, Cavalleri S, Artibani W, Ficarra V (2009) Complications and mortality after radical cystectomy for bladder transitional cell cancer. J Urol 182(3):914–921. doi:10.1016/j.juro.2009.05.032 Brunocilla E, Pernetti R, Martorana G (2011) The role of pelvic lymph node dissection during radical cystectomy for bladder cancer. Anticancer Res 31(1):271–275. doi:31/1/271 Konety BR, Allareddy V, Herr H (2006) Complications after radical cystectomy: analysis of population-based data. Urology 68(1):58–64. doi:10.1016/j.urology.2006.01.051 Schiavina R, Borghesi M, Guidi M, Vagnoni V, Zukerman Z, Pultrone C, Passaretti G, Romagnoli D, Bianchi L, Morselli-Labate A, Brunocilla E, Garofalo M, Manferrari F, Concetti S, Martorana G (2013) Perioperative complications and mortality after radical cystectomy when using a standardized reporting methodology. Clin Genitourin Cancer. doi:10.1016/j.clgc.2012.12.003
18. Guillotreau J, Game X, Mouzin M, Doumerc N, Mallet R, Sallusto F, Malavaud B, Rischmann P (2009) Radical cystectomy for bladder cancer: morbidity of laparoscopic versus open surgery. J Urol 181(2):554–559; discussion 559. doi:10.1016/j.juro. 2008.10.011 19. Mandhani A, Dhrarskar A, Kapoor R (2010) Technical steps of open radical cystectomy and orthotopic neobladder to achieve the goals of ‘‘minimally invasive surgery’’? Indian J Urol 26(3): 457–460. doi:10.4103/0970-1591.70596 20. Todenho¨fer T, Stenzl A, Schwentner C (2013) Optimal use and outcomes of orthotopic neobladder reconstruction in men and women. Curr Opin Urol 23(5):479–486. doi:10.1097/MOU. 0b013e328363f6e9 21. Chang SS, Cole E, Cookson MS, Peterson M, Smith JA Jr (2002) Preservation of the anterior vaginal wall during female radical cystectomy with orthotopic urinary diversion: technique and results. J Urol 168(4 Pt 1):1442–1445. doi:10.1097/01.ju.0000030700.53228. aa
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UROLOGY - ORIGINAL PAPER
A feasibility study of peritoneum preservation in radical cystectomy with extraperitonealization of orthotopic neobladder for invasive high-grade bladder cancer: a preliminary analysis Dong Soo Park • In Hyuck Gong • Don Kyung Choi Jin Ho Hwang • Moon Hyung Kang • Jong Jin Oh
•
Received: 7 October 2013 / Accepted: 11 December 2013 Ó Springer Science+Business Media Dordrecht 2013
Abstract Objective To describe a technique for radical cystectomy with extraperitonealization of orthotopic neobladder (RCEN) that reduces bowel-related complications by preservation of the peritoneum. Materials and methods Fifteen patients with non-metastatic bladder cancer underwent RCEN by a peritoneum preserving technique. The study included 13 patients with T1 high-grade bladder cancer and 2 with T2a bladder cancer. To compare perioperative outcomes including bowel-related complications, we also reviewed 15 patients who underwent traditional cystectomy with ileal Studer neobladder who were matched for age, sex, body mass index, American Society of Anesthesiologists (ASA) score, tumor stage, tumor grade, tumor size, and location. Female genital organs were preserved in five female patients who underwent the RCEN technique. Results There was no significant difference between the two cohorts (RECN vs. traditional technique) with respect to age, body mass index, ASA score, or tumor characteristics. The mean operative time was similar between the two groups. The patients who underwent RECN exhibited earlier recovery of normal gas pattern on plain abdominal X-ray during the postoperative period and an earlier resumption of normal diet. The mean hospital stay was shorter in the RECN group than the traditional group. D. S. Park I. H. Gong D. K. Choi J. H. Hwang M. H. Kang J. J. Oh (&) Department of Urology, CHA Bundang Medical Center, CHA University, 351 Yatap-dong, Bundang-gu, Songnam 463-712, Korea e-mail: [email protected] J. J. Oh CHA Cancer Research Institute, Seoul, Korea
Conclusions The RECN technique preserving the whole peritoneum is a feasible approach that significantly reduces bowel-related complications in selected patients. Keywords Bladder Bladder cancer Radical cystectomy Neobladder Bowel-related complication
Introduction Radical cystectomy is the standard therapy for muscleinvasive bladder cancer and the most powerful means of primary local control [1]. However, radical cystectomy and urinary diversion are major operative procedures with the potential for serious complications [2–4]. In particular, an intestinal obstruction may occur either early or late after surgery as a serious complication that is associated with relatively high mortality rates [1, 3]. There is a 10 % incidence rate of postoperative bowel obstruction requiring treatment in patients who have had gastric or ileal segments removed for urinary diversion [5]. Furthermore, a 10.5 % incidence rate of postoperative bowel obstruction requiring abdominal re-exploration was reported in a large series of patients who underwent radical cystectomy [6]. To reduce bowel-related complications, several studies have focused on early recovery of bowel function [7]. A Cochrane review of the effect of prokinetic agents on bowel-related complications found that certain medications reduce time to flatus and duration of hospital stay [8]. Reyblat et al. [9] showed that extraperitoneal augmentation enterocystoplasty had excellent results in reducing bowel-related complications compared with an intraperitoneal procedure for neurogenic bladder in spinal cord injury. Moreover, an extraperitoneal technique could easily preserve the female genital organs during radical cystectomy, and new data
123
Int Urol Nephrol
indicate that preserving the urethra and gynecological organs is oncologically and clinically acceptable in appropriately selected female patients [10, 11]. Here, we present a feasible technique of radical cystectomy with extraperitonealization of orthotopic neobladder (RCEN) that preserves the entire peritoneum to reduce bowel-related complications with preservation of female genital organs in selected patients.
Materials and methods Study population From January 2012 to February 2013, 15 patients with nonmetastatic bladder cancer underwent RCEN by a peritoneum preserving technique after obtaining institutional review approval and written informed consent for participation. Thirteen patients had T1 high-grade bladder cancer and 2 had T2a bladder cancer confirmed before radical cystectomy. This study was approved by the Institutional Review Board of CHA Bundang Medical Center. The RCEN group (n = 15) was matched with 15 patients who underwent orthotopic ileal neobladder substitution by traditional cystectomy (traditional group) and were similar in age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, and tumor characteristics from chart review. We excluded patients with previous abdominal surgery, abdominal radiotherapy, or a history of inflammatory bowel disease. Surgical procedure The peritoneum was mobilized from the external iliac vessels laterally up to the common iliac vessels and swept anterolaterally. Pelvic lymphadenectomy included the external, internal, obturator, and common iliac lymph nodes up to the aortic bifurcation. In some cases, the presacral lymph nodes and preaortic and/or precaval lymph nodes below the inferior mesenteric artery were also removed. The right and left ureters were carefully mobilized distally to preserve the periureteral blood supply to approximately 5 cm below the level of the superior vesical artery, after which they were ligated and divided. The distal segments of the ureters were sent for frozen section analysis if distal ureteral margin confirmation was needed. After confirmation of ureteral margin was negative for malignancy, ureteroileal anastomosis was conducted. The peritoneum overlying the bladder was delicately mobilized to the culde-sac and possible perivesical tissue was included in the specimen. A plane between the posterior wall of the bladder and the rectum was created, and the dissection proceeded to Denonvillier’s fascia. Denonvillier’s fascia was incised, and
123
the space was dissected to separate the bladder and prostate from the rectum. In female patients, the peritoneum overlying the bladder was mobilized to the vesicocervical space, and a plane between the posterior wall of the bladder and the anterior wall of the vagina was created. The dissection then proceeded along the vesicovaginal space. The bladder was lifted off the anterior vaginal wall and uterus without injuring the vagina and paravaginal tissues. The superior and inferior vesical arteries and veins were ligated and transected at the origin from the internal iliac vessels. The more distal vessels that entered the paravaginal tissue and pelvic plexus were left intact. The lateral vascular bundles were incised close to the bladder to preserve the pelvic nerves located lateral to the vagina. The dorsal vein complex was ligated and divided after incision into the endopelvic fascia. A right-angled clamp was placed around the smooth muscle of the urethra close to the bladder neck to protect the rhabdosphincter. Care must be taken during dissection of the bladder neck and proximal urethra to protect autonomic nerve fibers innervating the remnant urethral segment. The urethra was divided 1 cm below the bladder neck, and the urethral cut margin was sent for examination by frozen section. A portion of the terminal ileum approximately 54 cm long was isolated approximately 15 cm proximal to the ileocecal valve. Bowel continuity was restored using a two-layer suture anastomosis. Both ends of the isolated segment were closed with single-layer 3-0 chromic seromuscular running sutures. The 40-cm distal portion of the isolated segment was opened along its antimesenteric border and placed in a U shape. The two medial borders of the opened U-shaped isolated segment were oversewn with a single layer of 3-0 chromic seromuscular running sutures. The bottom of the U was folded over between the two ends, resulting in a spherical reservoir. A small window was made in the right side of the peritoneum overlying the pelvic floor. The tailored spherical reservoir was pulled out through the window into the pelvic cavity for extraperitonealization (Figs. 1, 2). The space between the window and the mesentery of the reservoir was closed with interrupted 3-0 silk sutures. The ureters were anastomosed to the 14-cm proximal afferent tubular portion of the reservoir with interrupted 5-0 polyglactin sutures using the Bricker ureterointestinal anastomosis. The ureters were stented with 7 Fr catheters and the ureteral stents were moved anteriorly through separate stab wounds. An 8- to 10-mm-diameter hole was cut from the most caudal part of the reservoir away from the suture line, and urethral anastomosis was then performed. Analysis of outcomes We reviewed perioperative outcomes of operative time, estimated blood loss, transfusion rate, and complications
Int Urol Nephrol Fig. 1 Schematic illustration of the surgical technique. a Dissection plane showing preservation of the peritoneum in males. b Construction of Studer type ileal neobladder. c Extraperitonealization of the neobladder and ureter anastomosis. d Dissection plane showing preservation of the peritoneum and genital tract in females. e Extraperitonealization of the neobladder and urethral anastomosis in females
between the two cohorts. The distribution of clinicopathologic parameters was tested using chi-square and Student t tests. Complications were reviewed for any adverse events that occurred following RCEN or traditional cystectomy, and postoperative surgical complications were defined according to the Clavien classification system [12].
Results A total of 15 patients who underwent RCEN were reviewed and matched to a contemporary cohort of 15 patients who
underwent traditional cystectomy with orthotopic ileal neobladder substitution by the same surgeon. Demographic data are summarized in Table 1. There was no significant difference between the two cohorts with respect to age, sex, BMI, ASA score, or tumor characteristics. The operative time was not significantly different between the two cohorts (RCEN vs. traditional technique = 387.6 vs. 370.1 min) (Table 2). The estimated blood loss and transfusion rate was similar between the cohorts. There were no differences of ureteral size and length between two cohorts. Postoperative complications occurred in seven cases in the traditional group including
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Int Urol Nephrol Fig. 2 Preservation of the peritoneum and gynecological organs in a female patient. a The bladder was dissected from the overlying peritoneum, uterus, and anterior vaginal wall in sequence. The urethra was divided 1 cm below the bladder neck. b Intact entire peritoneum, uterus, and vagina. c A small window is made in the right side of the peritoneum for neobladder extraperitonealization. d The neobladder is pulled out into the pelvic cavity through the window
Table 1 Baseline characteristics
Characteristics
RCEN
Traditional technique
N
15
15
Mean age (years) ± SD
64.5 ± 7.3
63.2 ± 3.4
Male (%)
10 (66.7)
10 (66.7)
Female (%)
5 (33.3)
5 (33.3)
Mean BMI (kg/m ) ± SD
25.48 ± 3.47
25.14 ± 2.73
Mean ASA score
1.5
1.6
p value
0.870
Gender
2
Preoperative tumor stage RCEN radical cystectomy with extraperitonealization of orthotopic neobladder, BMI body mass index, ASA American society of Anesthesiologist
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0.280 0.981
T1
13
13
T2a
2
2
Low grade
1
2
High grade
14
13
Preoperative tumor grade
four bowel-related complications. There were no bowelrelated complications in the RCEN group. Resumption of a normal diet occurred earlier in the RCEN group than the traditional group (6.3 vs. 9.8 days, p = 0.010). The time
0.161
0.748
until return of normal gas pattern was also shorter in the RCEN group (3.8 vs. 6.7 days, p = 0.015). None of the patients in the RCEN group suffered any delay in resuming an oral diet or any abdominal pain. The time for Levin tube
Int Urol Nephrol Table 2 Perioperative outcomes compared RCEN and traditional technique for bladder cancer
Variables
RCEN
Traditional technique
p value
N
15
15
Operative time (min) ± SD
387.6 ± 34.1
370.1 ± 12.8
0.178
Estimated blood loss (cc) ± SD
277.5 ± 197.4
314.9 ± 241.1
0.444
Transfusion (%)
2 (13.3)
3 (20)
0.281
Complications
1
7
Clavien-Dindo classification 1
1 (wound problem)
3 (wound problem)
2
0
3 (ileus)
3
0
1 (bowel obstruction)
Bowel-related complication (mean ± SD)
RCEN radical cystectomy with extraperitonealization of orthotopic neobladder
Resumption of normal diet (days)
6.3 ± 1.7
9.8 ± 2.1
0.010
Time for Levin tube indwelling (days)
2.1 ± 0.8
4.5 ± 2.7
0.021
3.8 ± 1.0
6.7 ± 3.4
0.015
9.9 ± 1.4
12.5 ± 5.4
0.014
Time for return of normal gas pattern (days) Mean hospital stay (days) ± SD
indwelling time was significantly shorter in RCEN group than traditional group (2.1 vs. 4.5 days, p = 0.021), and mean hospital stay of the RCEN group was 9.9 days, which was shorter than that of the traditional group (12.5 days). The pathological findings confirmed clear surgical margins, and none of the patients developed local recurrence or metastasis during the follow-up period. Mean 15.5 lymph nodes were removed in RCEN group; however, mean 20.1 lymph nodes were removed in traditional technique group. Only one patient had positive lymph node in RCEN group and two patients in traditional technique group. The neobladder functions were similar between the two cohorts in male patients. However, among female patients, maximal flow rate and residual urine volume significantly improved in the RCEN group compared with the traditional group (data not shown). All patients remained continent during the day without catheterization for residual urine but had varying degrees of night incontinence requiring no more than one pad.
Discussion Our RCEN technique that preserved the entire peritoneum and selectively preserved genital organs in female patients had excellent outcomes with respect to recovery of normal bowel function and reduction in bowel-related complications. Moreover, the RCEN technique might be favored for female patients who are sexually active as the gynecologic tract was fully preserved. The reported perioperative morbidity rate after radical cystectomy ranges from 20 to 64 % [13–16]. Among the reported complications, bowel-related complications such as prolonged ileus and bowel obstruction have been a major problem in patients undergoing radical cystectomy
with a prevalence of 20–30 % [17, 18]. Attempts to reduce bowel-related morbidity have mainly been studied in general surgery. In a meta-analysis, Noble et al. [7] showed that postoperative gum chewing significantly decreased the time of ileus. Traut et al. [8] investigated the effect of prokinetic agents on prolonged ileus and found that certain medications reduce time to flatus and duration of hospital stay. In the urological field, a surgical technique to reduce bowel-related complications was introduced by Reyblat et al. [9], who showed that an extraperitoneal technique during augmentation enterocystoplasty facilitated early postoperative recovery. Their results suggested that the incidence of postoperative major intestinal obstruction might be reduced by reconstituting the pelvic floor. During radical cystectomy, there is insufficient sigmoid colon and omentum available to fill the pelvis, which results in small bowel entrapment within the denuded pelvis and subsequent bowel obstruction. Preservation of the peritoneum, which prevents bowel entrapment within the pelvis, might reduce the possibility of major bowel obstruction requiring re-exploratory abdominal surgery. Additionally, Mandhani et al. [19] showed in their report with technique including extraperitonealization during radical cystectomy and orthotopic neobladder that extraperitonealization of orthotopic neobladder offered the advantage of reduction in length of hospitalization, early recovery and less bowelrelated complications. Likewise in our study, patients who underwent the RCEN technique preserving the entire peritoneum experienced earlier recovery of bowel function than those who underwent the traditional technique. A radical cystectomy in women traditionally removes the bladder along with surrounding perivesical soft tissue including the ovaries, fallopian tubes, uterus, cervix, and anterior vagina [20]. However, new data indicate that preserving the gynecological organs and urethra is
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Int Urol Nephrol
oncologically and clinically acceptable in appropriately selected female patients because urethral tumors occur rarely. The urethral involvement rate is approximately 12 %, even in female patients with high-grade invasive bladder cancer [10], and the incidence of secondary malignant involvement of the gynecological organs from bladder cancer is only 2.6 % [11]. Several studies have reported that radical cystectomy and orthotopic urinary diversion that spares the gynecological organs result in excellent oncological and functional outcomes [20, 21]. Performing RCEN technique in female invasive bladder cancer patients preserved the female genital organ effectively, and it would preserve the sexual function and reproductive function in selected patients. Patient selection is important in order to achieve promising oncological outcomes after organ-sparing techniques. The patient must have no evidence of lymph node metastasis, extravesical spread, or bladder neck invasion on clinical evaluation and imaging studies. Analysis of intraoperative frozen sections of the proximal urethra is an important way to identify candidates for orthotopic urinary diversion. Tumors located in the dome or posterior bladder wall should be carefully evaluated for appropriate invasion depth and should be analyzed by intra-operative frozen sections to achieve a safe margin. Additionally, application of RCEN technique had difficulty to remove lymph node in extended area; therefore, careful patient selection is more important. The main limitations of our preliminary data are the short follow-up duration and small study population. Oncologic outcomes after RCEN could not be investigated due to very short-term follow-up duration, and preliminary data with including only 15 cases were difficult to generalize our results. It should be overcome by validation in a large-scale study over a longer duration. Another variable that was hard to control was previous medical history that might change baseline bowel function. Although all patients received pain control according to the same protocol after surgery, use of postoperative analgesics differed somewhat between patients.
Conclusions The routine resection of the peritoneum overlying the bladder and the female genital tract during radical cystectomy may be unnecessary and undesirable. Our RCEN technique that preserves the peritoneum helps to reduce postoperative bowel-related complications and maintains pelvic support via the peritoneum to improve neobladder function. In selected patients, the RCEN technique could preserve the female genital organs, which should contribute to improved functional outcome with a positive impact on quality of life.
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Conflict of interest The authors have no conflict of interest with any institutions or products.
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