A comparative study of different surgical techniques for the management of distal ureter during laparoscopic radical nephroureterectomy

+Model

ARTICLE IN PRESS

Actas Urol Esp. 2019;xxx(xx):xxx---xxx

Actas Urol´ ogicas Espa˜ nolas www.elsevier.es/actasuro

ORIGINAL ARTICLE

A comparative study of different surgical techniques for the management of distal ureter during laparoscopic radical nephroureterectomy夽 A. Carrion a,∗ , M.J. Ribal c , J. Morote a , J. Huguet b , C. Raventós a , F. Lozano a , M. Costa-Grau c , A. Alcaraz c a

Departamento de Urología, Hospital Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain Departamento de Urología, Fundación Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain c Departamento de Urología, Hospital Clínic, Universidad de Barcelona, Barcelona, Spain b

Received 28 May 2019; accepted 14 July 2019

KEYWORDS Ureteral endoscopic detachment; Laparoscopic radical nephroureterectomy; Management of distal ureter; Oncological outcomes; Upper urinary tract urothelial carcinoma

Abstract Objectives: To compare the oncological outcomes between two open surgical techniques and two endoscopic approaches for the management of the distal ureter during laparoscopic radical nephroureterectomy (LRNU). Material and methods: Retrospective review of 152 patients submitted to LRNU for the management of upper urinary tract tumors between 2007 and 2014. We analyzed the potential impact of two different open surgical (extravesical vs intravesical) and two endoscopic (resection of ureteral oriˇce and fragment removal vs endoscopic bladder cuff) techniques on the development of bladder recurrence, distant/local recurrence and cancer-speciˇc survival (CSS). Results: A total of 152 patients with a mean age of 69.9 years (±10.1) underwent LRNU. We reported 62 pTa-T1 (41%), 35 pT2 (23%) and 55 pT3-4 (36%). Thirty-two were low grade (21.1%) and 120 high grade (78.9%). An endoscopic approach was performed in 89 cases (58.5%), 32 with resection (36%) and 57 with bladder cuff (64%), and open approach in 63 (41.5%), 42 intravesical (66.7%) and 21 extravesical (33.3%). Within a median follow-up of 32 months (3---120), 38 patients (25%) developed bladder recurrence, 42 distant/local recurrence (27.6%) and 34 died of tumor (22.4%). In the univariate analysis, the type of endoscopic technique was not related to bladder recurrence (p = 0.961), distant/local recurrence (p = 0.955) nor CSS (p = 0.802). The open extravesical approach was not related to bladder recurrence (p = 0.12) but increased distant/local recurrence (p = 0.045) and decreased CSS (p = 0.034) compared to intravesical approach.

夽 Please cite this article as: Carrion A, Ribal MJ, Morote J, Huguet J, Raventós C, Lozano F, et al. Estudio comparativo de diferentes técnicas quirúrgicas para el manejo del uréter distal durante la nefroureterectomía laparoscópica. Actas Urol Esp. 2019. https://doi.org/10.1016/j.acuro.2019.07.001 ∗ Corresponding author. E-mail address: [email protected] (A. Carrion).

2173-5786/© 2019 AEU. Published by Elsevier Espa~ na, S.L.U. All rights reserved.

ACUROE-1188; No. of Pages 7

+Model

ARTICLE IN PRESS

2

A. Carrion et al. Conclusions: LRNU outcomes are not dependant on the type of endoscopic approach performed. The open extravesical approach is a more difˇcult technique and could worsen the oncological outcomes when compared to the intravesical. © 2019 AEU. Published by Elsevier Espa~ na, S.L.U. All rights reserved.

PALABRAS CLAVE Desinserción ureteral endoscópica; Manejo del uréter distal; Nefroureterectomía radical laparoscópica; Resultados oncológicos; Tumor del tramo urinario superior

Estudio comparativo de diferentes técnicas quirúrgicas para el manejo del uréter distal durante la nefroureterectomía laparoscópica Resumen Objetivos: Comparar los resultados oncológicos de dos técnicas quirúrgicas abiertas y dos endoscópicas para el manejo del uréter distal durante nefroureterectomía laparoscópica (NUL). Material y métodos: Revisión retrospectiva de 152 pacientes sometidos a NUL por tumor del tramo urinario superior entre 2007 y 2014. Se analizó el potencial impacto de distintas técnicas de desinserción abierta (extravesical vs. intravesical) y endoscópica (resección meato con evacuación de fragmentos vs. rodete perimeático) sobre el desarrollo de recidiva vesical, extraurotelial y supervivencia cáncer-especíˇca (SCE). Resultados: Un total de 152 pacientes con edad media de 69,9 a~ nos (±10,1) fueron sometidos a NUL. Se reportaron 62 pTa-T1 (41%), 35 pT2 (23%) y 55 pT3-4 (36%). Treinta y dos fueron bajo grado (21,1%) y 120 alto grado (78,9%). Se realizó desinserción endoscópica en 89 casos (58,5%), 32 con resección (36%) y 57 con rodete (64%), y abierta en 63 (41,5%), 42 intravesical (66,7%) y 21 extravesical (33,3%). Con mediana de seguimiento de 32 meses (3-120), 38 pacientes (25%) desarrollaron recidiva vesical, 42 extraurotelial (27,6%) y 34 murieron por tumor (22,4%). En el análisis univariante, el tipo de técnica endoscópica no se relacionó con recidiva vesical (p = 0,961), extraurotelial (p = 0,955) ni SCE (p = 0,802). El abordaje abierto extravesical no se relacionó con recidiva vesical (p = 0,12) pero sí con aumento de recidiva extraurotelial (p = 0,045) y menor SCE (p = 0,034) respecto al intravesical. Conclusiones: El subtipo de desinserción endoscópica no in˚uye en los resultados de la NUL. La desinserción abierta extravesical es una técnica más compleja que la intravesical y podría empeorar los resultados oncológicos. © 2019 AEU. Publicado por Elsevier Espa~ na, S.L.U. Todos los derechos reservados.

Introduction

Material and methods

Upper urinary tract tumors (UTUC) account for 5% of all urothelial cancers. Approximately 60% are invasive at the time of diagnosis and 40% of patients die from recurrence despite having submitted to radical nephroureterectomy (RNU).1 RN including the distal ureter and ipsilateral bladder cuff is the treatment of choice for UTUC.2 Even though some studies have shown similar oncological results for the endoscopic management and the traditional open approach,3 the most appropriate surgical technique for the management of the distal ureter is still under debate. Open approach is mainly recommended for distal UTUC, and endoscopic access is more common for the treatment of proximal UTUC.4,5 In a previous study, our group reported a lower cancer-speciˇc survival (CSS) in patients undergoing open vs. endoscopic management, and it showed to be correlated with the greater aggressiveness of distal tumors.6 Multiple surgical techniques of open and endoscopic approaches have been described, but there is still no consensus on which should be the treatment of choice. The objective of the current study was to analyze the potential impact of the different techniques with open approach (extravesical vs. intravesical) and endoscopic (transurethral resection of the meatus vs. bladder cuff) on the development of vesical or extraurothelial recurrence and CSS.

Study population We retrospectively reviewed the medical records of 152 patients undergoing transperitoneal laparoscopic radical nephroureterectomy (LRNU) for the treatment of UTUC at the Hospital Clinic of Barcelona between 2007 and 2014. Lymphadenectomy was only performed in cases of suspicious lymph nodes, and neoadjuvant chemotherapy was not administered. Tumors were diagnosed with CT scan and conˇrmed with ureteroscopy and biopsy in case of doubt. All patients were also evaluated with cystoscopy and cytology.

Surgical techniques for ureteral detachment The management of the distal ureter was ˇrst classiˇed as open or endoscopic. Open detachment was performed after laparoscopic kidney release with Hem-o-lock® placement in the pelvic ureter. The extravesical technique consisted of dissection and resection of the intramural portion of the ureter from the posterior portion of the bladder without performing anterior cystotomy. The intravesical technique involved dissection of the intramural portion of the ureter from the posterior bladder wall with the performance of a bladder cuff through an anterior cystotomy. Endoscopic detachment was performed before laparoscopic time through transurethral resection of the meatus and evacuation of the fragments with Ellick® evac-

+Model

ARTICLE IN PRESS

A comparative study of different surgical techniques uator or bladder cuff excision with a Collin's knife. Both processes employed monopolar energy and coagulation of the meatus to avoid distal urothelial dissemination. The piece was removed en bloc through a Gibson incision, and with an endobag except for large or distal tumors. In case of concomitant bladder cancer, transurethral resection was performed in the same procedure. Immediate intravesical instillation was not administered in any case. Generally, open detachment was used for UTUC located below the intersection with the iliac vessels and the endoscopic approach for those located above. The technique (open intravesical or extravesical and resection or bladder cuff) was chosen based on the surgeon's preference (6 surgeons).

Perioperative and oncological results UTUC staging was reported according to the TNM classiˇcation of 2002,7 and the grade was deˇned according to the WHO (1973) and WHO/ISUP (2004)8,9 guidelines. A positive margin was deˇned as the presence of tumor in soft tissue areas with ink stains in the LRNU piece. Patients with pT ≥ 3 were evaluated individually to receive adjuvant chemotherapy. The follow-up included physical examination, blood tests, thoracoabdominal CT, cystoscopy and cytology every 3---6 months for 5 years and annually thereafter. Bone scintigraphy was performed when clinically indicated. Extraurothelial recurrence was deˇned as the presence of any type of local or distant recurrence evidenced in the CT scan and conˇrmed with biopsy in suspicious cases, excluding contralateral UTUC. The objective of the study was to analyze the potential impact of the different techniques of open detachment (extravesical vs. intravesical) and endoscopic (resection vs. bladder cuff) on the development of bladder or extraurothelial recurrence, and CSS.

Statistical analysis Statistical analysis was carried out with SPSS© version 20 (IBM Corp., Somers, NY, USA). The association between categorical variables was analyzed using the Chi-square test. The univariate and multivariate analyses for the study of potential prognostic factors of recurrence was performed using the Cox regression test. The CSS rates were estimated using the Kaplan---Meier method. A p < 0.05 value was considered signiˇcant.

Results A total of 152 patients with a mean age of 69.9 years (±10.1) underwent LNU for UTUC. Table 1 shows the characteristics of the entire series. 29 pTa (19.1%), 33 pT1 (22%), 35 pT2 (23%), 45 pT3 (29.6%) and 10 pT4 (6.6%) were reported. There were 32 (21.1%) low grade and 120 (78.9%) high grade. Table 2 compares the characteristics and results of the patients according to the type of endoscopic detachment (resection vs. bladder cuff) or open (extravesical vs. intravesical). Endoscopic detachment was performed in 89 cases (58.5%), from which 32 (36%) were through resection of the meatus and 57 (64%) with bladder cuff. There were 63 (41.5%) open detachments: 42 (66.7%) were intravesical and 21 (33.3%) extravesical. The detachment subgroups were comparable, except in the location of the UTUC among open approaches (p = 0.034) and the positive margins in endoscopic (p = 0.01) and in open (p = 0.045). The perioperative complications were similar between groups. Table 3 shows the oncological results of the entire series and according to the type of detachment. With a median follow-up of 32 months (3---120), 38 patients (25%) developed bladder recurrence (9 muscle-invasive), 42 (27.6%) extraurothelial recurrence and 34

3 Table 1 Descriptive characteristics of all patients undergoing LRNU for UUTT. All (n = 152) Age BMI

69.9 (10.1) 26.6 (3.9)

Sex Male Female

116 (76.3) 36 (23.7)

ASA I II III IV

4 (2.7) 102 (68.9) 34 (23) 8 (5.4)

UTUC laterality Left Right

85 (55.9) 67 (44.1)

Tumor location Pelvis-proximal ureter Distal ureter Both

113 (74.3) 28 (18.4) 11 (7.2)

Hydronephrosis

102 (68)

Cytology Positive/suspicious Negative

49 (48.5) 52 (51.5)

Concomitant BT Previous BT Lymphadenectomy Intraoperative complications Postoperative complications

36 (23.7) 41 (27) 26 (17.2) 21 (13.8) 36 (23.7)

pT pTa pT1 pT2 pT3 pT4

29 (19.1) 33 (22) 35 (23) 45 (29.6) 10 (6.6)

Grade Low High

32 (21.1) 120 (78.9)

Concomitant CIS Multifocality

32 (21.1) 21 (13.8)

Margins Positive Negative

21 (13.8) 131 (86.2)

pN pN− pN+ pNx

19 (12.5) 7 (4.6) 126 (82.9)

Data are shown as n (%) or mean (SD). ASA: American Society Anesthesiologists; CIS: carcinoma in situ; BMI: body mass index; LNU: laparoscopic nephroureterectomy; UTUC: upper urinary tract tumor; BT: bladder tumor.

+Model

ARTICLE IN PRESS

4

A. Carrion et al. Table 2

Descriptive characteristics of the patients according to the surgical approach: endoscopic or open. D. Endoscopic (n = 89) Resection (n = 32)

Cuff (n = 57)

Age BMI

70 (9.1) 26.3 (3.6)

70.1 (10.9) 26.7 (3.7)

Sex Male Female

25 (78.1) 7 (21.9)

42 (73.7) 15 (26.3)

ASA I II III IV

0 (0) 22 (68.8) 7 (21.9) 3 (9.4)

2 39 13 3

UTUC laterality Left Right

17 (53.1) 15 (46.9)

36 (63.2) 21 (36.8)

Tumor location Pelvis-proximal ureter Distal ureter Both

28 (87.5) 2 (6.2) 2 (6.2)

56 (98.2) 0 (0) 1 (1.8)

14 (48)

31 (55.4)

Cytology Positive/suspicious Negative

14 (63.6) 8 (36.4)

15 (45.5) 18 (54.5)

Concomitant BT Previous BT Lymphadenectomy Intraoperative complications Postoperative complications

5 (15.6) 6 (18.8) 8 (14) 5 (15.6) 9 (28.1)

8 (14) 7 (12.3) 2 (6.2) 5 (8.8) 9 (15.8)

pT pTa pT1 pT2 pT3 pT4

4 (12.5) 8 (25) 9 (28.1) 10 (31.2) 1 (3.1)

10 (17.5) 14 (24.6) 7 (12.3) 24 (42.1) 2 (3.5)

Grade Low High

7 (21.9) 25 (78.1)

11 (19.3) 46 (80.7)

8 (25) 3 (9.4)

12 (21.1) 5 (8.8)

Margins Positive Negative

5 (15.6) 27 (84.4)

1 (1.8) 56 (98.2)

pN pN− pN + pNx

1 (3.1) 1 (3.1) 30 (93.9)

6 (10.5) 2 (3.5) 49 (86)

Hydronephrosis

Concomitant CIS Multifocality

p

D. Open (n = 63) Extravesical (n = 21)

0.509 0.579

p

Intravesical (n = 42)

67.8 (10.1) 26 (2.2)

70.81 (9.92) 27.2 (4.9)

13 (61.9) 8 (38.1)

36 (85.7) 6 (14.3)

2 41 14 2

1 27 11 1

0.641

0.032*

0.649 (3.5) (68.4) (22.8) (5.3)

0.7 (3.4) (69.5) (23.7) (3.4)

(2.5) (67.5) (27.5) (2.5)

0.355

0.476 12 (57.1) 9 (42.9)

20 (47.6) 22 (52.4)

14 (66.7) 4 (19) 3 (14.3)

15 (35.7) 22 (52.4) 5 (11.9)

21 (100)

41 (97.6)

4 (25) 12 (75)

16 (53.3) 14 (46.7)

6 8 3 3 5

(28.6) (38.1) (14.3) (14.3) (23.8)

17 (40.5) 20 (47.6) 13 (31) 8 (19) 13 (31)

3 (14.3) 4 (19) 5 (23.8) 4 (19) 5 (23.8)

12 (28.6) 7 (16.7) 14 (33.3) 7 (16.7) 2 (4.8)

6 (28.6) 15 (71.4)

8 (19) 34 (81)

5 (23.8) 6 (28.6)

7 (16.7) 7 (16.7)

8 (38.1) 13 (61.9)

7 (17.7) 35 (83.3)

1 (4.7) 2 (9.6) 18 (85.7)

11 (26.2) 2 (4.8) 29 (69)

0.08

0.13

0.034*

0.186

0.839 0.407 0.253 0.326 0.164

0.057 0.065

0.429

0.355 0.473 0.152 0.639 0.554 0.179

0.772

0.669 0.924

0.293 0.375

0.391

0.012*

0.496 0.271 0.045*

0.215

0.117

Data are shown as n (%) or mean (standard deviation). ASA: American Society Anesthesiologists; CIS: carcinoma in situ; BMI: body mass index; UTUC: upper urinary tract tumor; BT: bladder tumor. * p < 0.05.

+Model

ARTICLE IN PRESS

A comparative study of different surgical techniques Table 3

5

Bladder/extraurothelial recurrence and cancer-speciˇc survival according to the type of detachment. All (n = 152)

D. Endoscopic (n = 89)

D. Open (n = 63)

Resection (n = 32)

Bladder cuff (n = 57)

Extravesical (n = 21)

Intravesical (n = 42)

Bladder recurrence No 112 (74.7) Yes 38 (25)

27 (84.4) 5 (15.6)

48 (84.2) 9 (15.8)

17 (81) 4 (19)

22 (52.4) 20 (47.6)

Extraurothelial recurrence No 110 (72.3) Yes 42 (27.6)

25 (78.1) 7 (21.9)

44 (77.2) 13 (22.8)

10 (47.6) 11 (52.4)

31 (73.8) 11 (26.2)

Death caused by UTUC No 118 (77.6) Yes 34 (22.4)

27 (84.8) 5 (15.6)

47 (82.5) 10 (17.5)

10 (47.6) 11 (52.4)

32 (76.2) 10 (23.8)

The data is shown as n (%). UTUC: upper urinary tract tumor.

died from UTUC (22.4%). The CSS rate at 2 years was 86% for the whole series. Table 4 shows the analysis of the potential prognostic factors associated with recurrence and CSS. The mean CSS values for patients undergoing endoscopic detachment with resection and bladder cuff were 84 (±6) and 89 (±5) months, respectively; 48 (±11) for open extravesical and 71 (±7) for open intravesical (Fig. 1). The type of endoscopic technique was not related to bladder (p = 0.961) or extraurothelial (p = 0.955) recurrence or CSS (p = 0.802) in the univariate analysis. The extravesical open approach was not related to bladder recurrence (p = 0.12). However, it did show increased extraurothelial recurrence rates (HR 2.7; 95% CI: 1.2---6.2; p = 0.045) and lower CSS rates (HR 2.9; 95% CI: 1.2---6.7; p = 0.034) when compared to the intravesical access. Tumor location appeared as an independent prognostic factor of bladder recurrence (p = 0.033) in the multivariate analysis. The pathological stage and positive margins were independent prognostic factors for extraurothelial recurrence (p = 0.022, p = 0.001) and CSS (p = 0.013, p = 0.006).

Discussion In this retrospective study, we analyzed the potential impact, regarding oncological outcomes, of the various surgical techniques for the management of the distal ureter, in patients undergoing LRNU for UTUC. Irrespective of the adopted technique, the current tendency is to ensure adherence to principles of reproducibility of results, patient safety, and oncological outcomes in the treatment of UTUC.4 Since 2007, laparoscopy has been increasing in our center and is currently performed in a standardized manner, except for large masses (T3---T4 or N+). It has been shown that the dissection of the distal ureter and excision of a bladder cuff including the ureteral meatus is mandatory for the optimal management of UTUC.2,10 In accordance with other studies, we mainly used an open approach for distal ureteral tumors and endoscopic for proximal or pyelocaliceal tumors.4,5 There were some cases of proximal tumors managed with open detachment at the beginning of the series, since there was less evidence on the safety of the endoscopic technique at that moment. The open intravesical approach has been the standard treatment to ensure complete resection of the distal ureter. However, other endoscopic techniques have recently been described with comparable results.3,11 The current study did not compare the open and endoscopic approaches, because the same group had previously reported lower CSS rates with the open technique, since it was

used primarily for more aggressive distal tumors associated to an increased risk of bladder recurrence.6,12 Although it has been suggested that immediate postoperative instillation of intravesical chemotherapy reduces the risk of recurrence during the ˇrst year,13 we did not administer it because our series ends in 2014, when it was not yet systematically recommended by the European Guidelines.

Endoscopic detachment: meatus resection vs. bladder cuff. There are few studies in the literature that compare variants of endoscopic detachment and are usually short series of novel techniques that have failed to consolidate as the ``gold standard''.14,15 The European Guidelines recommend several endoscopic techniques (depending on the disease) and only advise against ureteral stripping.2 Our group followed the recommendations in order to minimize the risk of urine extravasation and tumor dissemination during endoscopic detachment: exclude distal tumors, clamp the ureter early and coagulate the meatus.11 As shown in the literature, endoscopic detachment has not been associated to bladder/extraurothelial recurrences or CSS16 in our study. The positive margin rate was higher in the resection, although this was located in proximal UTUC and not in the distal ureteral margin, so it should not be associated to the endoscopic technique performed. Our bladder (16%) and extraurothelial (22%) recurrence rates after endoscopic detachment were comparable to those of other studies.17 There were no differences between both endoscopic techniques regarding perioperative complications.

Open detachment: extravesical vs. intravesical) An open incision provides better visual control of the removal of the distal ureter and allows its early clamping while minimizing the risk of spillage.10,18 On the other hand, the extravesical route is technically more complex than the intravesical, since it forces the mobilization and dissection of the ipsilateral base of the bladder and may increase the risk of incomplete resection of the intramural portion.16 This is why Krabbe et al. reported a higher rate of extraurothelial recurrence in patients submitted to open extravesical vs. intravesical detachment.19 We also found higher extraurothelial recurrence and lower CSS rates after the extravesical approach (52.4%) compared to the intravesical (26.2%). This ˇnding could be due to increased positive margins after using the extravesical route, thus conˇrming its technical difˇculty and the risk of incomplete resection of the distal tumor. We believe that the results

+Model

ARTICLE IN PRESS

6

A. Carrion et al. Table 4 Univariate and multivariate analysis of the potential prognostic factors of bladder/extraurothelial recurrence and CSS in patients undergoing LRNU for UTUC. Bladder recurrence Univariate p Sex Age BMI ASA UUTT laterality Location Hydronephrosis Cytology Concomitant BT Previous BT Resection vs. endoscopic cuff Open intravesical vs. Extravesical Intraoperative complications Postoperative complications Lymphadenectomy pT Grade Concomitant CIS Multifocality Margins pN

0.210 0.183 0.508 0.478 0.667 <0.001* 0.221 0.022* 0.139 0.013* 0.961 0.12 0.726 0.304 0.773 0.470 0.686 0.388 0.43 0.007* 0.467

Extraurothelial recurrence

Multivariate HR (95% CI)/p

Univariate p 0.644 0.327 0.206 0.113 0.214 0.769 0.273 0.62 0.325 0.542 0.955 0.045* 0.03* 0.4 0.098 <0.001* 0.071 0.166 0.012* <0.001* <0.001*

0.027* 0.380 0.634

0.218

Multivariate HR (95% CI)/p

CSS Univariate p 0.501 0.081 0.287 0.086 0.149 0.451 0.078 0.536 0.713 0.948 0.802 0.034* 0.039* 0.178 0.063 <0.001* 0.041* 0.242 0.015* <0.001* <0.001*

0.346 0.803

0.04*

0.426 0.001* 0.161

Multivariate HR (95% CI)/p

0.941 0.35

0.015* 0.17 0.992 0.001* 0.41

ASA: American Society Anesthesiologists; CIS: carcinoma in situ; HR: hazard ratio; CI: conˇdence interval; BMI: body mass index; LNU: laparoscopic nephroureterectomy; CSS: cancer-speciˇc survival; UTUC: upper urinary tract tumor; BT: bladder tumor. * p < 0.05.

A

B

Cancer-specific survival

Cancer-specific survival

Endoscopic approach

Open approach

1,0

1,0 Bladder cuff Resection Bladder cuff-censored Resection-censored

0,8

Cum survival

Cum survival

0,8

Bladder cuff Resection Bladder cuff-censored Resection-censored

0,6

0,4

0,2

0,6

0,4

0,2

0,0

0,0 ,00

20,00

40,00

60,00

80,00

100,00

120,00

Follow up time (months)

,00

20,00

40,00

60,00

80,00

100,00

120,00

Follow up time (months)

Figure 1 Kaplan---Meier curves showing the comparison of cancer-speciˇc survival in patients undergoing endoscopic detachment with cuff vs. resection (A) and open extravesical vs. intravesical approach (B).

were not statistically signiˇcant in the multivariate analysis due to the low number of extravesical vs. intravesical procedures. In addition, the open approach is especially complicated in tumors located below the intersection with the iliac artery, and the fact that the extravesical group includes more proximal UTUCs compared to the intravesical one, could favor its oncological results. Finally, the laparoscopic bladder cuff excision is equally complex and could also facilitate tumor implantation in a pneumoperitoneum

environment.20 The global extraurothelial recurrence rate for the group treated with an open approach was similar to those from previous studies (35%). On the other hand, the bladder recurrence (38%) and perioperative complications rates did not differ among the types of open access surgery. The present study could be useful as it reinforces the evidence that the endoscopic cuff as well as the resection of the ureteral meatus are safe and effective techniques for the management of

+Model

ARTICLE IN PRESS

A comparative study of different surgical techniques the distal ureter in proximal UTUC. Furthermore, it conˇrms that open detachment is more technically challenging as well as the recommended technique for the treatment of distal UTUC. Finally, this study shows that the intravesical technique allows greater control of the complete removal of the intramural portion, providing greater oncological safety than the extravesical one. Some limitations of this work are its retrospective nature, which includes few patients with recurrence and a relatively short followup time. On the other hand, the low number of extravesical open approach cases cannot provide statistically signiˇcant results. Also, several surgeons were included, and the selection of the technique was made according to their preferences (not randomly).

Conclusions LRNU outcomes are not dependant on the type of endoscopic approach performed. The open extravesical approach is a more difˇcult technique and could worsen the oncological outcomes when compared to the intravesical.

Conflicts of interest The authors declare no con˚icts of interest.

References 1. Hall MC, Womack S, Sagalowsky, Carmody T, Erickstad MD, Roehrborn CG. Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract: a 30-year experience in 252 patients. Urology. 1998;52:594---601. 2. Roupret M, Babjuk M, Compérat E, Zigeuner R, Sylvester RJ, Burger M, et al. European Association of Urology guidelines on upper urinary tract urothelial cell carcinoma: 2015 update. Eur Urol. 2015;68:868---79. 3. Berger A, Fergany A. Laparoscopic nephroureterectomy: oncologic outcomes and management of distal ureter; review of the literature. Adv Urol. 2009;2009, 8267258267254. 4. Stewart GD, Humphries KJ, Cutress ML, Riddick AC, McNeill SA, Tolley DA. Long-term comparative outcomes of open versus laparoscopic nephroureterectomy for upper urinary tract urothelialcell carcinoma after median follow-up of 13 years. J Endourol. 2011;25:1329---35. 5. Bariol SV, Stewart GD, McNeill SA, Tolley DA. Oncological control following laparoscopic nephroureterectomy: 7-year outcome. J Urol. 2004;172:1805---8. 6. Carrion A, Huguet J, García-Cruz E, Izquierdo L, Mateu L, Musquera M, et al. Intraoperative prognostic factors and atypical patterns of recurrence in patients with upper urinary tract urothelial carcinoma treated with laparoscopic radical nephroureterectomy. Scand J Urol. 2016;50:305---12. 7. International Union Against Cancer, Sobin L, Godspodarowicz M, Wittekind C. Renal pelvis and ureter. In: TNM classiˇcation of malignant tumours. Urological tumours. New York: Wiley; 2009. p. 258---61. 8. Mostoˇ FK, Sorbin L, Torloni H. International histologic classiˇcation of tumours: histological typing of urinary bladder tumours. World Health Organization; 1973.

7 9. Sauter G, Algaba F, Amin M. Tumors of the urinary system. In: World Health Organisation classiˇcation of tumors. Pathology and genetics of tumors of the urinary system and male genital organs. Lyon, France: IARC Press; 2004. p. 110---23. 10. Lughezzani G, Sun M, Perrotte P, Shariat SF, Jeldres C, Budaus L, et al. Should bladder cuff excision remain the standard of care at nephroureterectomy in patients with urothelial carcinoma of the renal pelvis? A population-based study. Eur Urol. 2010;57:956---62. 11. Li WM, Shen JT, Li CC, Ke HL, Wei YC, Wu WJ, et al. Oncologic outcomes following three different approaches to the distal ureter and bladder cuff in nephroureterectomy for primary upper urinary tract urothelial carcinoma. Eur Urol. 2010;57:963---9. 12. Mateu L, Huguet J, Carrión A, García-Cruz E, Izquierdo L, Musquera M, et al. Predictors, pathological characteristics and outcomes of bladder recurrences following nephroureterectomy. Actas Urol Esp. 2015;39:488---93. 13. British Association of Urological Surgeons Section of OncologyO'Brien T, Ray E, Singh R, Coker B, Beard R. Prevention of bladder tumours after nephroureterectomy for primary upper urinary tract urothelial carcinoma: a prospective, multicentre, randomised clinical trial of a single postoperative intravesical dose of mitomycin C (the ODMIT-C Trial). Eur Urol. 2011;60:703---10. 14. Agarwal DK, Khaira HS, Clarke D, Tong R. Modiˇed transurethral technique for the management of distal ureter during laparoscopic assisted nephroureterectomy. Urology. 2008;71:740---3. 15. Mueller TJ, DaJusta DG, Cha DY, Kim IY, Ankem MK. Ureteral ˇbrin sealant injection of the distal ureter during laparoscopic nephroureterectomy --- a novel and simple modiˇcation of the pluck technique. Urology. 2010;75:187---92. 16. Walton TJ, Sherwood BT, Parkinson RJ, Obakponovwe O, Thomas SA, Taylor MC, et al. Comparative outcomes following endoscopic ureteral detachment and formal bladder cuff excision in open nephroureterectomy for upper urinary tract transitional cell carcinoma. J Urol. 2009;181:532---9. 17. Fradet V, Mauermann J, Kassouf W, Rendon R, Jacobsen N, Fairey A, et al. Risk factors for bladder cancer recurrence after nephroureterectomy for upper tract urothelial tumors: results from the Canadian Upper Tract Collaboration. Urol Oncol. 2014;32:839. 18. Xylinas E, Rink M, Cha EK, Clozel T, Lee RK, Fajkovic H, et al. Impact of distal ureter management on oncologic outcomes following radical nephroureterectomy for upper tract urothelial carcinoma. Eur Urol. 2014;65:210---7. 19. Krabbe LM, Westernab NE, Bagrodia A, Gayed BA, Khalil D, Kapur P, et al. Surgical management of the distal ureter during radical nephroureterectomy is an independent predictor if oncological outcomes: results of a current series and a review of the literature. Urol Oncol. 2014;32:19---26. 20. Muntener M, Schaeffer EM, Romero FR, Nielsen ME, Allaf ME, Brito FA, et al. Incidence of local recurrence and port site metastasis after laparoscopic radical nephroureterectomy. Urology. 2007;70:864---8.