Background: Patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) are at risk for upper urinary tract recurrence (UUTR), especially in case of carcinoma in situ (CIS). Data on the impact of CIS in the urinary bladder on ureteral tumour involvement or UUTR are conflicting. We presently evaluate the accuracy of intraoperative frozen section analysis (FSA) of the ureteral margin, the incidence of ureteral tumour involvement and their impact on UUTR in patients undergoing RC for UCB with versus without CIS of the bladder. Material and Methods: Between 2003 and 2007, 243 patients underwent RC in our department. 176 of these for UCB, either without CIS (n = 117, group I) or solitary/concomitant CIS (n = 59, group II). FSA was performed. Patients were followed up for UUTR. Results: Overall, 403 ureteral margins - including re-resections - were analysed (group I, n = 232; group II, n = 171). One patient (0.85%) in group I and 21 patients (35.6%) in group II had tumour involvement of the ureter (p < 0.0001) at the time of RC. The false-negative rate of FSA compared to final histopathology was 0.4% (1/232) for group I and 2.9% (5/171) for group II, respectively. Mean duration of follow-up was 26 months (1-72). In group II, 2 patients (1.1%) had UUTR in the follow-up; both had initially positive and subsequently false-negative FSA. Conclusions: Tumour involvement of the ureter is found significantly more often in solitary or concomitant CIS of the bladder. Intraoperative ureteral FSA is accurate and should be recommended in these patients. Ureteral tumour involvement predisposes to UUTR especially with initial positive margins mandating careful follow-up.

Keywords:
Bladder cancer, Radical cystectomy, Ureter, Surgical margin, Frozen section analysis
1.
Stenzl A, Cowan NC, De Santis M, Kuczyk MA, Merseburger AS, Ribal MJ, Sherif A, Witjes JA, European Association of Urology (EAU): Treatment of muscle-invasive and metastatic bladder cancer: update of the EAU guidelines. Eur Urol 2011;59:1009-1018.
2.
Schumacher MC, Scholz M, Weise ES, et al: Is there an indication for frozen section examination of the ureteral margins during cystectomy for transitional cell carcinoma of the bladder? J Urol 2006;176:2409-2413.
3.
Tran W, Serio AM, Raj GV, et al: Longitudinal risk of upper tract recurrence following radical cystectomy for urothelial cancer and the potential implications for long-term surveillance. J Urol 2008;179:96-100.
4.
Lee SE, Byun SS, Hong SK, et al: Significance of cancer involvement at the ureteral margin detected on routine frozen section analysis during radical cystectomy. Urol Int 2006;77:13-17.
5.
Otto W, Shariat SF, Fritsche HM, Gupta A, Matsumoto K, Kassouf W, Martignoni G, Walton TJ, Tritschler S, Baba S, Bastian PJ, Martínez-Salamanca JI, Seitz C, Pycha A, Burger M, Karakiewicz PI, Ficarra V, Novara G: Concomitant carcinoma in situ as an independent prognostic parameter for recurrence and survival in upper tract urothelial carcinoma: a multicenter analysis of 772 patients. World J Urol 2011;29:487-494.
6.
Nuhn P, Bastian PJ, Novara G, Svatek RS, Karakiewicz PI, Skinner E, Fradet Y, Izawa JI, Kassouf W, Montorsi F, Müller SC, Fritsche HM, Sonpavde G, Tilki D, Isbarn H, Ficarra V, Dinney CP, Shariat SF: Concomitant carcinoma in situ in cystectomy specimens is not associated with clinical outcomes after surgery. Urol Int 2011;87:42-48.
7.
Sauter G, Algaba F, Amin MB, et al: Non-invasive urothelial neoplasias: WHO classification of non-invasive papillary urothelial tumors; in Eble JN, Sauter G, Epstein JI, Sesterhenn IA (eds): World Health Organization Classification of Tumors Pathology and Genetics: Tumors of the Urinary System and Male Genital Organs. Lyon, IARC Press, 2004.
8.
Moussa S, Yafi FA, El-Hakim A, et al: Outcome of surgical treatment of patients with upper versus lower urinary tract urothelial carcinoma: stage-by-stage comparison. Urol Int 2010;84:50-55.
9.
Gunia S, Kakies C, Erbersdobler A, Koch S, May M: Scoring the percentage of Ki-67-positive nuclei is superior to mitotic count and the mitosis marker phosphohistone-H3 (PHH3) in terms of differentiating flat lesions of the bladder mucosa. J Clin Pathol 2012;65:715-720.
10.
Tollefson MK, Blute ML, Farmer SA, Frank I: Significance of distal ureteral margin at radical cystectomy for urothelial carcinoma. J Urol 2010;183:81-86.
11.
Osman Y, El-Tabey N, Abdel-Latif M, et al: The value of frozen-section analysis of ureteric margins on surgical decision-making in patients undergoing radical cystectomy for bladder cancer. BJU Int 2007;99:81-84.
12.
Sanderson KM, Cai J, Miranda G, et al: Upper tract urothelial recurrence following radical cystectomy for transitional cell carcinoma of the bladder: an analysis of 1,069 patients with 10-year follow-up. J Urol 2007;177:2088-2094.
13.
Volkmer BG, Schnoeller T, Kuefer R, Gust K, Finter F, Hautmann RE: Upper urinary tract recurrence after radical cystectomy for bladder cancer - who is at risk? J Urol 2009;182:2632-2637.
14.
Takayanagi A, Masumori N, Takahashi A, Takagi Y, Tsukamoto T: Upper urinary tract recurrence after radical cystectomy for bladder cancer: incidence and risk factors. Int J Urol 2012;19:229-233.
15.
Song YS, Cho JS, Cho KS, Doo SH, Chung BH, Kim SJ, Yang WJ, Song KH, Kim CI, Hong SJ: Efficacy of adjuvant gemcitabine-cisplatin chemotherapy: a comparative study between locally advanced transitional cell carcinoma of the bladder and upper urinary tract. Urol Int 2010;85:47-51.
16.
Johnson DE, Wishow KI, Tenney D: Are frozen section examinations of ureteral margins required for all patients undergoing radical cystectomy for bladder cancer. Urology 1989;33:451-454.
17.
Sobin LH, Gospodarowicz MK, Wittekind C: Urological tumours; in Sobin LH, Gospodarowicz MK, Wittekind C (eds): TNM Classification of Malignant Tumours, ed 7. Oxford, Wiley-Blackwell, 2009, pp 262-265.
© 2013 S. Karger AG, Basel
2013
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