EUROPEAN UROLOGY 57 (2010)

Transcription

1 EUROPEAN UROLOGY 57 (2010) available at journal homepage: Platinum Priority Urothelial Cancer Editorial by Alexandre R. Zlotta on pp of this issue Oncologic Outcomes Following Three Different Approaches to the Distal Ureter and Bladder Cuff in Nephroureterectomy for Primary Upper Urinary Tract Urothelial Carcinoma Wei-Ming Li a, Jung-Tsung Shen b, Ching-Chia Li a,c, Hung-Lung Ke a,d, Yu-Ching Wei e, Wen-Jeng Wu a,c, *, Yii-Her Chou a,c, Chun-Hsiung Huang a,c a Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan b Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan c Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan d Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan e Department of Pathology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University-College of Medicine, Kaohsiung, Taiwan Article info Article history: Accepted December 25, 2009 Published online ahead of print on January 5, 2010 Keywords: Renal pelvis Recurrence Survival Ureter Urothelial carcinoma Abstract Background: There is a lack of consensus regarding the prognostic significance of different approaches to the bladder cuff at surgery for primary upper urinary tract urothelial carcinoma (UUT-UC). Objectives: To compare the oncologic outcomes following radical nephroureterectomy using three different methods of managing the bladder cuff. Design, setting, and participants: From January 1990 to December 2007, 414 patients with primary UUT-UC underwent radical nephroureterectomy at our institution. Of these, 301 were included in our study. Intervention: Three methods of bladder cuff excision intravesical incision, extravesical incision, and transurethral incision (TUI) were performed. Measurements: Patients medical records were reviewed retrospectively. The clinicopathologic data and oncologic outcomes were compared among groups. Results and limitations: Of the 301 patients, 81 (26.9%) underwent the intravesical method, 129 (42.9%) underwent the extravesical technique, and 91 (30.2%) underwent TUI. There were no differences in clinical and histopathologic data among the three groups. When comparing the intravesical, extravesical, and TUI techniques, bladder recurrence developed in, respectively, 23.5%, 24.0%, and 17.6% cases ( p = 0.485); local retroperitoneal recurrence in 7.4%, 7.8%, and 5.5% ( p =0.798); contralateral recurrence in 4.9%, 3.9%, and 2.2% ( p = 0.632); and distant metastasis in 7.4%, 10.4%, and 5.5% ( p = 0.564). There were no differences in recurrence-free and cancer-specific survival among the three groups ( p = and 0.502, respectively). Conclusions: The three techniques had comparable oncologic outcomes. Our data validate the TUI method of bladder cuff control in patients with primary UUT-UC without coexistent bladder tumors. # 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Urology, Kaohsiung Medical University Hospital No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan. Tel ; Fax: address: wejewu@kmu.edu.tw (W.-J. Wu) /$ see back matter # 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi: /j.eururo

2 964 EUROPEAN UROLOGY 57 (2010) Introduction 2. Methods Upper urinary tract (UUT) urothelial carcinoma (UC; UUT-UC) is rare, representing only 5% of all urothelial tumors. Nephroureterectomy with bladder cuff excision is the standard treatment for UUT-UC [1 3]. The conventional open nephroureterectomy technique still represents the gold standard for the management of UUT-UC; however, the laparoscopic approach has emerged as a feasible, minimally invasive method of managing these tumors. The oncologic efficacy of laparoscopic nephroureterectomy does not differ from traditional open surgery [4,5]. A standard technique for the management of the distal ureter and bladder cuff has not been established yet and many different methods have been described. These approaches include an open technique, a transurethral incision (TUI) of the ureteral orifice, an intussusception technique, a transvesical laparoscopic detachment, and a laparoscopic stapling method [6,7]. Each technique has distinct advantages and disadvantages. Although open dissection remains one of the most common methods of managing the bladder cuff, an endoscopic approach can provide a minimally invasive technique for treating UUT- UC. Urologists are concerned with both technical differences and oncologic outcomes. However, there are no broad series in the literature that have enrolled enough patients and applied adequate follow-up to compare the outcomes of these surgical techniques. In Taiwan, an unusually high incidence of UUT-TCC has been reported [8 10]. At our institution, three different techniques intravesical, extravesical, and transurethral have been used to manage the distal ureter and bladder cuff. Thus, in this context, our intention of analyzing oncologic outcomes of three bladder cuff excision techniques by using a large cohort of patients was possible. Furthermore, evaluation was made to determine whether different methods of bladder cuff excision are possible risk factors for bladder, local, or contralateral UUT recurrences and cancer-related deaths in patients who underwent radical nephroureterectomy for primary UUT-UC Patients This was an institutional review board approved study. From January 1990 to December 2007, 414 patients were diagnosed with UUT-UC and underwent radical nephroureterectomy at our institution. Among the 414 patients, 113 were excluded from this study because 59 had previous or concomitant urinary bladder tumors, 23 had lymph node or distant metastasis at the time of diagnosis, 5 had bilateral synchronous UUT tumors, and 26 had incomplete data. The remaining 301 patients who received nephroureterectomy and bladder cuff excision for primary UUT-UC were included in this study. None of them received preoperative chemotherapy or radiotherapy. Nephroureterectomy was performed either openly or laparoscopically, as chosen by the operating surgeons. The method of managing distal ureter and bladder cuff was also decided by the surgeons. In all methods, a Foley catheter was left in the bladder for 1 wk postoperatively and bladder integrity checked via cystography Surgical technique The intravesical technique is performed via a lower midline incision. It involves creating an anterior cystotomy in the bladder and confirming the contralateral ureteral orifice. The ipsilateral ureteral orifice is circumferentially incised through the full thickness of the bladder. The nephroureterectomy specimen with a cuff of bladder mucosa is removed en bloc, and the residual defect and anterior cystotomy are closed with two layers of absorbable sutures. The extravesical technique is performed via a Gibson or a lower midline incision to completely dissect the intramural portion of the ureter. With gentle traction on the ureter, a right angle clamp is used to transect the ureter with a bladder cuff. In TUI of the bladder cuff, the patient is placed in the lithotomy position and undergoes cystoscopy to rule out coexisting bladder tumor. A resectoscope is inserted into the bladder via the urethra using sterile water for irrigation and the ipsilateral ureteral orifice is endoscopically coagulated. The bladder is kept semidistended to prevent excessive extravasation during the procedure. A hook electrode is used to incise a circumferential 10-mm cuff of bladder mucosa around the ureteral orifice. Endoscopic-guided dissection and incision deep to the level of perivesical fat and detachment of the intramural ureter are performed (Fig. 1). After complete hemostasis, the bladder is catheterized. The patient is repositioned for nephroureterectomy. Fig. 1 Resectoscopic appearance of bladder (A) before and (B) after transurethral incision of intramural ureter and bladder cuff. The instrument is ahook electrode.

3 EUROPEAN UROLOGY 57 (2010) Table 1 Patient characteristics Variables Total (%) Intravesical (%) Extravesical (%) TUI (%) p value Patients, No. 301 (100) 81 (100) 129 (100) 91 (100) Age, yr (46.8) 44 (54.3) 58 (45.0) 39 (42.9) > (53.2) 37 (45.7) 71 (55.0) 52 (57.1) Sex Male 131 (43.5) 33 (40.7) 63 (48.8) 35 (38.5) Female 170 (56.5) 48 (59.3) 66 (51.2) 56 (61.5) Smoke Yes 75 (24.9) 24 (29.6) 32 (17.1) 19 (20.9) No 226 (75.1) 57 (70.4) 97 (82.9) 72 (79.1) Gross hematuria Yes 233 (77.4) 60 (74.1) 96 (74.4) 77 (84.6) No 68 (22.6) 21 (25.9) 33 (25.6) 14 (15.4) Tumor side Right 147 (48.8) 38 (46.9) 69 (53.5) 47 (51.6) Left 154 (51.2) 43 (53.1) 60 (46.5) 44 (48.4) Tumor location Renal pelvis or calyx 105 (34.9) 25 (30.9) 43 (33.3) 37 (40.6) Upper ureter 49 (16.3) 14 (17.3) 19 (14.7) 16 (17.6) Middle ureter 43 (14.3) 8 (9.9) 22 (17.1) 13 (14.3) Lower ureter 50 (16.6) 16 (19.7) 27 (20.9) 7 (7.7) Multiple 54 (17.9) 18 (22.2) 18 (14.0) 18 (19.8) Type of NU Open 246 (81.7) 77 (95.1) 102 (79.1) 67 (73.6) Laparoscopy 55 (18.3) 4 (4.9) 27 (20.9) 24 (26.4) pt stage Ta/Tis/T1 122 (40.5) 25 (30.9) 56 (43.4) 41 (45.0) T2 88 (29.2) 30 (37.0) 31 (24.0) 27 (29.7) T3 77 (25.6) 22 (27.2) 35 (27.2) 20 (22.0) T4 14 (4.7) 4 (4.9) 7 (5.4) 3 (3.3) Tumor grade Low 130 (43.2) 32 (39.5) 63 (48.8) 35 (38.5) High 171 (56.8) 49 (60.5) 66 (51.2) 56 (61.5) TUI = transurethral incision of the bladder cuff; NU = nephroureterectomy. The first step of nephroureterectomy is to identify and ligate the ureter below the level of the tumor prior to mobilizing the kidney. After completing nephrectomy, the distal ureter including the bladder cuff is gently withdrawn and removed. The ureter is checked for complete extraction by identifying the coagulated edge of the bladder cuff at the distal ureteral end Tumor staging and follow-up The clinicopathologic data were recorded retrospectively. Pathologic staging (pt) was based on the 2002 TNM staging system, and tumors were graded according to the 1998 World Health Organization classification. Postoperative follow-up consisted of interval history and physical examination, urinalysis, urine cytology, chest x-ray, abdominal ultrasound, intravenous urography (IVU), and abdominal computed tomography (CT). Cystoscopy was performed every 3 mo for the first 2 yr, every 6 mo for the next 2 yr, and annually thereafter. IVU or contrast CT scans were obtained annually during follow-up or when clinically indicated Statistics Statistical analyses were performed using SPSS v.15.0 statistical software (SPSS Inc., Chicago, IL, USA). The percentage frequencies of the three groups were compared by means of chi-square. Recurrence-free and cancer-specific survival were calculated by the Kaplan-Meier method with the log-rank test. For all statistical analyses, p < 0.05 was considered statistically significant. 3. Results We analyzed data from 131 men and 170 women (mean age: yr, range: yr), with a median followup of 33 mo (range: mo). The patients demographic and clinicopathologic characteristics are listed in Table 1. Of the 301 patients, 105 (34.9%) had tumors only in the renal pelvis, 142 (47.2%) had tumors only in the ureter, and 54 (17.9%) had multiple tumors in the UUT urothelium at presentation. The stage distribution of UUT-UC in this cohort was 40.5% pta/pt1/ptis, 29.2% pt2, 25.6% pt3, and 4.7% pt4. At follow-up there were 41 cancer-related deaths (13.6%) and 16 (5.3%) deaths from other causes. At the time of analysis, 254 patients (81.1%) remained alive. Of the 301 patients, 81 (26.9%) underwent the intravesical method for managing the bladder cuff, 129 (42.9%) underwent the extravesical technique, and 91 (30.2%) underwent TUI. Median follow-up for the intravesical, extravesical, and TUI groups was 33 mo (range: 1 196), 39 mo (range: 1 186), and 30 mo (range 1 155), respectively ( p = 0.221). There were no differences in patient age, gender, smoking status, gross hematuria history, tumor side, location, stage, and grade among the three groups (Table 1). In laparoscopic nephroureterectomy, most surgeons chose extravesical or TUI technique to control the bladder cuff ( p = 0.001).

4 966 EUROPEAN UROLOGY 57 (2010) Table 2 Oncologic outcomes Total Intravesical Extravesical TUI p value Median follow-up, mo Bladder recurrence, No. (%) 66 (21.9) 19 (23.5) 31 (24.0) 16 (17.6) Median mo to recurrence Local recurrence, No. (%) 21 (7.0) 6 (7.4) 10 (7.8) 5 (5.5) Median mo to recurrence Contralateral recurrence, No. (%) 11 (3.7) 4 (4.9) 5 (3.9) 2 (2.2) Median mo to recurrence Distant metastasis, No. (%) 24 (8.0) 6 (7.4) 13 (10.1) 5 (5.5) Median mo to metastasis Dead of disease, No. (%) 41 (13.6) 15 (18.5) 17 (13.2) 9 (9.9) TUI = transurethral incision of the bladder cuff. Table 2 lists the oncologic results of this cohort. Of the 301 patients, 66 (21.9%) developed subsequent bladder tumors, 21 (7.0%) developed local recurrence, 11 (3.7%) developed metachronous contralateral UUT tumors, and 24 (8.0%) developed distant metastases. When comparing the intravesical, extravesical, and TUI techniques, bladder recurrence developed in, respectively, 23.5%, 24.0%, and 17.6% of cases ( p = 0.485), local retroperitoneal recurrence in 7.4%, 7.8%, and 5.5% ( p = 0.798), contralateral recurrence in 4.9%, 3.9%, and 2.2% ( p = 0.632), and distant metastasis in 7.4%, 10.1%, and 5.5% ( p = 0.564). None of these differences were statistically significant. Fig. 2 (A) Cancer-specific survival by tumor stage; (B) cancer-specific survival by different methods of bladder cuff excision; (C) bladder recurrence-free survival by different methods of bladder cuff excision; and (D) local recurrence-free survival by different methods of bladder cuff excision. TUI = transurethral incision.

5 EUROPEAN UROLOGY 57 (2010) Cancer-specific survival was significantly associated with tumor stage ( p < 0.001, Fig. 2A) and tumor grade ( p = 0.002). Five-year cancer-specific survival rates of patients with tumors staged pta/ptis/pt1, pt2, pt3, and pt4 were 98.7%, 88.3%, 66.5%, and 0%, respectively. Five-year cancer-specific survival rates of low-grade and high-grade cancers were 92.9% and 76.4%, respectively. Cancer-specific survival was not associated with the three bladder cuff control techniques we evaluated ( p = 0.502, Fig. 2B) or other variables. Bladder (Fig. 2C), local (Fig. 2D), and contralateral UUT recurrence-free survival was also not associated with the three bladder cuff control techniques ( p =0.759, 0.855, and 0.930, respectively). When bladder, local, and contralateral UUT recurrences and distant metastasis were combined to calculate recurrence-free survival, only tumor stage ( p < 0.001) significantly affected recurrence-free survival. Five-year recurrence-free survival rates of patients with stage pta/ptis/pt1, pt2, pt3, and pt4 tumors were 76.6%, 65.4%, 41.2%, and 0%, respectively. Recurrence-free survival was not associated with bladder cuff control methods ( p = 0.680) and other variables. 4. Discussion Radical nephroureterectomy with bladder cuff excision is the gold standard treatment for UUT-UC. From the oncologic viewpoint, with intermediate follow-up, cancer-related outcomes seem similar between the open and laparoscopic surgical modalities [4,5,11]. However, the method of controlling distal ureter and bladder cuff has not been standardized yet. Open, laparoscopic, and endoscopic techniques, as well as other approaches have been described with varying degrees of oncologic safety [6,7]. Traditionally, nephroureterectomy is performed with two major incisions: subcostal or lumbar for nephrectomy and Gibson s or lower midline for bladder cuff excision or with an extended lumboabdominal incision. McDonald et al described the first endoscopic method a ureteral stripping technique for managing the bladder cuff at time of nephrectomy without an additional incision [12]. Since then, various other endoscopic techniques have been described [6,7]. Whether the endoscopic approaches increase the risk of tumor recurrence and affect the longterm prognosis remains unclear. The current answer is restricted due to the limited number of studies that enrolled enough patients and had an adequate follow-up period when comparing the different methods of bladder cuff excision. To our knowledge, we are the first group to analyze the oncologic outcomes among three different techniques of bladder cuff excision in a single-center experience with a relatively larger cohort and comparable patient and pathologic characteristics. Furthermore, only patients with primary UUT-UC without previous or concomitant bladder cancer, lymph node or distant metastases, and bilateral synchronous UUT tumor at the time of diagnosis were included in this study to decrease the selection bias. Several concerns about TUI remain in comparison with intravesical and extravesical methods. Reviewing the endoscopic distal ureteral approach to determine whether the TUI procedure would increase the risk of tumor recurrence in the bladder, Laguna et al reported a 24% intravesical recurrence rate with TUI in a total 129 patients from nine series [7]. However, the patient characteristics and follow-up period data from these studies were different. In a study comparing oncologic outcomes of 51 patients undergoing nephroureterectomy via intravesical or TUI techniques, Ko et al indicated that the bladder tumor recurrence rates were similar between the two groups (22.2% and 26.3%, respectively) [13]. There were no pelvic recurrences in either group. After excluding patients with previous or concomitant bladder tumors, our study found that intravesical recurrent rate in the TUI group was 17.6%, which did not differ from the other two groups ( p = 0.485). Bladder tumor recurrence might arise from microscopic tumor seeding or chronic carcinogen stimulation. During TUI, two procedures are suggested to prevent the implantation of tumor cells. First, the ureteral orifice must be coagulated endoscopically before the transurethral resection procedure. Second, the ureter below the distal border of the tumor should be ligated before performing nephrectomy. Another concern regarding TUI is local retroperitoneal or perivesical tumor recurrence. Hall et al reported a series of 252 patients treated surgically and noted a 9% local recurrence rate [1]; Li et al reported a 6.2% local recurrence rate [9]. However, the local recurrence relative to the different methods of bladder cuff excision in those two articles was not analyzed separately. In our study, the local tumor recurrence rates after intravesical, extravesical, and TUI procedures were 7.4%, 7.8%, and 5.5%, respectively ( p = 0.798). Of the 21 patients with local recurrence in our series, 18 (85.7%) had high-stage (pt2 or higher) cancer. This finding implied that patients with invasive disease may have microscopic cancer cells left even after a radical surgery. Some authors described local recurrence with use of the TUI method and presumed that this recurrence occurred due to seeding at the point where the nonoccluded ureter and adjacent bladder cuff were dismembered from the bladder [14,15]. Based on above-mentioned evidence and our results, we suggest that the resectoscopic outflow should be kept patent during the procedure to prevent bladder overdistention and the ureteral orifice must be occluded first during the TUI procedure to prevent fluid extravasation to the perivesical and retroperitoneal spaces, possibly increasing the risk of local tumor recurrence. In an effort to minimize potential tumor seeding, some modifications of TUI have been described. Wong and Leveillee performed transperitoneal, hand-assisted, laparoscopic nephrectomy with early ligation of the ureter followed by transurethral cystoscopic excision [16]. The excision was assisted by the surgeon s intra-abdominal hand placing tension on the ureter; the cystoscopist excised transurethrally the bladder cuff and intramural ureter with a Collins knife. Kurzer et al performed this technique on 49 patients without evidence of pelvic or abdominal

6 968 EUROPEAN UROLOGY 57 (2010) recurrences postoperatively [17]. Gill et al described a novel, cystoscopic, secured detachment and ligation technique that incorporates intramural ureteral dissection with a Collins knife aided by two transvesical laparoscopic ports and an endoloop to ligate the ureteral lumen and minimize potential tumor spillage [18]. They reported an analysis of 60 patients, demonstrating fewer positive margins, and bladder and local recurrences with this technique compared with extravesical laparoscopic stapling [19]. With respect to risk factors for cancer-specific survival, previous studies reported different factors that influenced survival of patients with UUT-UC, including tumor grade, tumor stage, tumor location, history of bladder UC, and tumor multifocality [1 4,9,10,20 22]. All these studies revealed cancer-specific survival was most highly dependent upon pathologic stage and grade. This is consistent with our results showing that cancer-specific survival was significantly associated with tumor stage ( p < 0.001) and tumor grade ( p = 0.001). Laparoscopic nephroureterectomy and TUI technique for managing bladder cuff did not affect the clinical outcome. The limitations of our study are the duration of follow-up and the number of patients receiving laparoscopic nephroureterectomy. Although our follow-up is relatively short, many published series have indicated that tumor recurrences developed rapidly after surgery, even as soon as 1 mo postoperatively [1,22]. Bariol et al reviewed the technique of endoscopic excision of the distal ureter and showed that the median time to tumor recurrence was 7.7 mo [11]. A recent study, including 12 academic centers (>3000 patients), showed that the median time to tumor recurrence was 10.4 mo [22]. Given the small number of laparoscopic cases, the oncologic results in these patients require additional investigation. Moreover, although our series is relatively large, the absence of statistical significance in tumor recurrence among the three techniques may be explained by a lack of statistical power to determine a difference in oncologic outcomes. Consequently, the validity of our findings requires confirmation in prospective studies. 5. Conclusions Based on our 18-yr experience in 301 patients with primary UUT-UC undergoing radical nephroureterectomy, we conclude that the technique of TUI of the bladder cuff that we used in this study does not increase the incidence of bladder, local, or contralateral tumor recurrences. Furthermore, cancer-specific survival is not significantly different among the intravesical, extravesical, and TUI techniques. While using the TUI method, we suggest early coagulation of the ureteral orifice before dissecting the bladder cuff and early ligation of the ureter before nephroureterectomy to minimize the potential for tumor seeding. Our data validate the TUI method of bladder cuff control in patients with primary UUT-UC without coexistent bladder tumors. Author contributions: Wen-Jeng Wu had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Shen, Li, Wu. Acquisition of data: Shen, Li, Ke, Chou, Huang. Analysis and interpretation of data: Li, Wei, Wu. Drafting of the manuscript: Li, Wu. Critical revision of the manuscript for important intellectual content: Wu. Statistical analysis: Li, Ke. Obtaining funding: None. Administrative, technical, or material support: None. Supervision: None. Other (specify): None. Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/ affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None. Funding/Support and role of the sponsor: None. Acknowledgement statement: The authors thank Dr. Chien-Hung Lee at the Faculty of Public Health, College of Health Sciences, Kaohsiung Medical University for his support with the statistical analyses. References [1] Hall M, Womack S, Sagalowsky A, Carmody T, Erickstad MR, Roehrborn CC. Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract: a 30-year experience in 252 patients. Urology 1998;52: [2] Huben RP, Mounzer AM, Murphy GP. Tumor grade and stage as prognostic variables in upper tract urothelial tumors. Cancer 1988; 62: [3] Kirkali Z, Tuzel E. Transitional cell carcinoma of the ureter and renal pelvis. Crit Rev Oncol Hematol 2003;47: [4] Manabe D, Saika T, Ebara S, et al. Comparative study of oncologic outcome of laparoscopic nephroureterectomy and standard nephroureterectomy for upper urinary tract transitional cell carcinoma. Urology 2007;69: [5] Rassweiler JJ, Schulze M, Marrero R, Frede T, Palou Redorta J, Bassi P. Laparoscopic nephroureterectomy for upper urinary tract transitional cell carcinoma: is it better than open surgery? Eur Urol 2004; 46: [6] Steinberg JR, Matin SF. Laparoscopic radical nephroureterectomy: dilemma of the distal ureter. Curr Opin Urol 2004;14:61 5. [7] Laguna MP, de la Rosette JJ. The endoscopic approach to the distal ureter in nephroureterectomy for upper urinary tract tumor. J Urol 2001;166: [8] Chou YH, Huang CH. Unusual clinical presentation of upper urothelial carcinoma in Taiwan. Cancer 1999;85: [9] Li C-C, Chang T-H, Wu W-J, et al. Significant predictive factors for prognosis of primary upper urinary tract cancer after radical nephroureterectomy in Taiwanese patients. Eur Urol 2008;54: [10] Li WM, Li CC, Ke HL, Wu WJ, Huang CN, Huang CH. The prognostic predictors of primary ureteral transitional cell carcinoma after radical nephroureterectomy. J Urol 2009;182: [11] Bariol SV, Stewart GD, McNeill SA, Tolley DA. Oncological control following laparoscopic nephroureterectomy: 7-year outcome. J Urol 2004;172: [12] McDonald HP, Upchurch WE, Sturdevant CE. Nephro-ureterectomy: a new technique. J Urol 1952;67:804 9.

7 EUROPEAN UROLOGY 57 (2010) [13] Ko R, Chew BH, Hickling DR, et al. Transitional-cell carcinoma recurrence rate after nephroureterectomy in patients who undergo open excision of bladder cuff v transurethral incision of the ureteral orifice. J Endourol 2007;21: [14] Jones DR, Moisey CU. A cautionary tale of the modified pluck nephroureterectomy. Br J Urol 1993;71:486. [15] Arango O, Bielsa O, Carles J, Gelabert-Mas A. Massive tumor implantation in the endoscopic resected area in modified nephroureterectomy. J Urol 1997;157:1839. [16] Wong C, Leveillee RJ. Hand-assisted laparoscopic nephroureterectomy with cystoscopic en bloc excision of the distal ureter and bladder cuff. J Endourol 2002;16: [17] Kurzer E, Leveillee RJ, Bird VG. Combining hand-assisted laparoscopic nephroureterectomy with cystoscopic circumferential excision of the distal ureter without primary closure of the bladder cuff is it safe? J Urol 2006;175:63 7. [18] Gill IS, Soble JJ, Miller SD, Sung GT. A novel technique for management of the en bloc bladder cuff and distal ureter during laparoscopic nephroureterectomy. J Urol 1999;161: [19] Matin SF, Gill IS. Recurrence and survival following laparoscopic radical nephroureterectomy with various forms of bladder cuff control. J Urol 2005;173: [20] Van der Poel HG, Antonini N, van Tinteren H, Horenblas S. Upper urinary tract cancer: location is correlated with prognosis. Eur Urol 2005;48: [21] Novara G, De Marco V, Gottardo F, et al. Independent predictors of cancer-specific survival in transitional cell carcinoma of the upper urinary tract: multi-institutional dataset from 3 European centers. Cancer 2007;110: [22] Margulis V, Shariat SF, Matin SF, et al. Outcomes of radical nephroureterectomy: a series from the Upper Tract Urothelial Carcinoma Collaboration. Cancer 2009;115: