Nephroureterectomy For Upper Urinary Tract Urothelial Carcinoma Research Articles

MP70-01 EXTIRPATIVE TREATMENT OF UPPER URINARY TRACT UROTHELIAL CARCINOMA: A 15-YEAR COMPREHENSIVE REVIEW

INTRODUCTION AND OBJECTIVES: Extirpative treatment of Upper Urinary Tract Urothelial Carcinoma (UTUC) has long been the standard of care regardless of tumor grade. We herein stratify oncologic outcomes based on tumor grade with implications for the role of systemic chemotherapy. We present long-term oncologic outcomes of all patients treated with nephroureterectomy (NU) for UTUC over a 15 year time period. METHODS: All patients (N1⁄480) were treated by a single surgeon with extirpative surgery for UTUC as a primary treatment. The majority (90%) underwent laparoscopic NU via a retroperitoneal approach, with transurethral incision of the ureteric orifice and then open bladder-cuff excision through a Gibson incision. The open surgical approach was used in 6 (7.5%) cases and distal/ segmental ureterectomy only was used sparingly (2.5%). Data was prospectively collected and concurrent outpatient follow up data were retrospectively reviewed. Statistical analysis was performed using Kaplan Meier methodology to calculate overall survival (OS), cancer specific survival (CSS), and metastasis-free survival (MFS). RESULTS: The mean age of patients was 72.5 (range 46-90), 50 male (62.5%) and mean Charlston Comorbidity Index of 5.1 (range 0-13). Mean follow-up time was 30.4 months (range 1-185.3) with median overall survival 109.2 months. Twenty-three patients (28.8%) with low grade tumors, treated with primary NU, had 2-, 5-, and 10-year OS of 100, 88, 73%. In contrast, 57 (71.3%) with high grade tumors had a lower 2-, 5-, and 10-year OS of 83, 68, 0%. Table 1 summarizes the oncologic outcomes based on histologic grade. Lymph node positive disease portends a particularly grim prognosis with 2and 5-year OS and CSS of 24 and 0% respectively CONCLUSIONS: Grade is a significant predictor of OS, CSS, and MFS in patients treated with nephroureterectomy for UTUC. Extirpative therapy was found to result in relatively poor long-term CSS in patients with high grade disease, underscoring the need for adjuvant or neoadjuvant therapies.

Two-micron thulium laser resection of the distal ureter and bladder cuff during nephroureterectomy for upper urinary tract urothelial carcinoma

The thulium laser (Tm-laser) technique has been used in the management of many urologic conditions. The present study aimed to evaluate the use of this technique for distal ureter and bladder cuff (DUBC) excision during nephroureterectomy for upper urinary tract urothelial carcinoma (UUT-UC). Fifty-eight patients with UUT-UC who underwent radical nephroureterectomy were included in this retrospective study. DUBC was managed by open excision in 24 cases, by transurethral electrosurgery in 17 cases, and by transurethral Tm-laser in 17 cases. Perioperative measures and oncologic outcomes were compared among the three groups. Furthermore, 11 human ureteral segments were collected to measure the burst pressure and show physical pressure tolerance, and six ureteral segments were assessed histologically to investigate the sealing effect. Operative time and hospital stay were significantly longer, and intraoperative blood loss was significantly greater in the open excision group than in the electrosurgery and Tm-laser groups (P < 0.05 for all). There were no significant differences in these parameters between the electrosurgery and Tm-laser groups. In addition, there were no significant differences in the incidences of bladder tumors and retroperitoneal recurrence of urothelial carcinoma among the three groups. The coagulation time and resection time were significantly shorter in the Tm-laser group than in the electrosurgery group. The mean burst pressure did not differ significantly between the tissues sealed by electrosurgery and by Tm-laser. Histopathological analyses showed that distal ureters were completely sealed by both electrosurgery and Tm-laser. The Tm-laser technique is superior to open excision and comparable to transurethral electrosurgery in the management of DUBC during nephroureterectomy for UUT-UC, offering an alternative treatment option for this condition.

632 BUBR1 OVEREXPRESSION MAY PREDICT DISEASE-SPECIFIC SURVIVAL AFTER NEPHROURETERECTOMY IN UPPER URINARY TRACT UROTHELIAL CARCINOMA

You have accessJournal of UrologyUrothelial Cancer: Upper Tract Tumors1 Apr 2012632 BUBR1 OVEREXPRESSION MAY PREDICT DISEASE-SPECIFIC SURVIVAL AFTER NEPHROURETERECTOMY IN UPPER URINARY TRACT UROTHELIAL CARCINOMA Yoshiaki Yamamoto, Jun Nishigima, Yoshihiro Miyachika, Yoshihisa Kawai, Hiroaki Matsumoto, Kazuhiro Nagao, Takahiko Hara, Shigeru Sakano, Kohsuke Sasaki, and Hideyasu Matsuyama Yoshiaki YamamotoYoshiaki Yamamoto Ube, Japan More articles by this author , Jun NishigimaJun Nishigima Ube, Japan More articles by this author , Yoshihiro MiyachikaYoshihiro Miyachika Ube, Japan More articles by this author , Yoshihisa KawaiYoshihisa Kawai Ube, Japan More articles by this author , Hiroaki MatsumotoHiroaki Matsumoto Ube, Japan More articles by this author , Kazuhiro NagaoKazuhiro Nagao Ube, Japan More articles by this author , Takahiko HaraTakahiko Hara Ube, Japan More articles by this author , Shigeru SakanoShigeru Sakano Ube, Japan More articles by this author , Kohsuke SasakiKohsuke Sasaki Ube, Japan More articles by this author , and Hideyasu MatsuyamaHideyasu Matsuyama Ube, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.711AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There are few reliable markers to distinguish tumors with aggressive characteristics from others in upper urinary tract urothelial carcinoma (UUTUC). The purpose of this study was to identity a biomarker related to genetic instability (chromosomal instability or microsatellite instability) that allows for the prediction of prognosis for UUTUC. METHODS Expression of BUBR1, p53, polo-like kinase 1 (PLK1), MLH1 and MSH2 proteins were immunohistochemically assessed in 102 patients who had nephroureterectomy for UUTUC. Numerical aberrations of chromosomes 7, 9 and 17 were evaluated by fluorescence in situ hybridization which allowed for the estimation of the degree of chromosomal instability. Relationship between BUBR1 expression and the BUB1B copy number gain, the gene encoding BUBR1, was examined by array-based comparative genomic hybridization (CGH) in 32 patients with UUTUC. The clinical records were reviewed retrospectively and the mean follow-up was 46.6 months. RESULTS Overexpression of BUBR1, p53 and PLK1 were detected in 41 of 102 (40.2%), 52 of 101 (51.5%), and 27 of 102 (26.5%) of tumors, respectively. MLH1 and MSH2 protein expression decreased in 32 of 101 (31.7%) and 21 of 101 (20.8%) tumors, respectively. Overexpression of BUBR1 significantly correlated with higher histological grade, advanced pathological stage, lymph node metastasis and chromosomal instability (P < 0.0001, 0.0024, 0.0063 and 0.0060, respectively). Array CGH revealed that no tumors (0%) showed BUB1B amplification and gain, indicating that the overexpression of BUBR1 in these UUTUC was independent of BUB1B copy number gain. Univariate analyses showed that BUBR1, pT stage, pN stage and MSH2 were significantly related to disease-specific survival (P = 0.0008, 0.0061, 0.0146 and 0.0329, respectively). Multivariate analysis using the Cox proportional hazard model showed that BUBR1 overexpression was the only prognostic factor with independent significance for disease-specific survival (hazard ratio, 3.35; 95% confidence interval, 1.13-11.33; P = 0.0289). CONCLUSIONS These data suggest that overexpression of BUBR1 may have great potential as a biomarker for estimating disease-specific survival in patients with UUTUC treated by nephroureterectomy. The BUBR1 status could be useful for selecting patients and determining the efficacy of adjuvant therapy strategies. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e257 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yoshiaki Yamamoto Ube, Japan More articles by this author Jun Nishigima Ube, Japan More articles by this author Yoshihiro Miyachika Ube, Japan More articles by this author Yoshihisa Kawai Ube, Japan More articles by this author Hiroaki Matsumoto Ube, Japan More articles by this author Kazuhiro Nagao Ube, Japan More articles by this author Takahiko Hara Ube, Japan More articles by this author Shigeru Sakano Ube, Japan More articles by this author Kohsuke Sasaki Ube, Japan More articles by this author Hideyasu Matsuyama Ube, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

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)

BackgroundStandard treatment for upper urinary tract urothelial carcinoma (UUTUC) is nephroureterectomy. Subsequently, around 40% of patients will develop a bladder tumour potentially because of implantation from the primary tumour. ObjectiveTo prevent bladder tumour after nephroureterectomy with a single postoperative dose of intravesical mitomycin C (MMC). Design, setting, and participantsA prospective, randomised, nonblinded trial (ODMIT-C: One Dose Mitomycin C) was undertaken in 46 British centres between July 2000 and December 2006. The study recruited 284 patients with no previous or concurrent history of bladder cancer undergoing nephroureterectomy for suspected UUTUC. InterventionA single postoperative intravesical dose of MMC (40mg in 40ml saline) or standard management on removal of the urinary catheter. MeasurementsBladder tumour formation was judged by visual appearance at cystoscopy at 3, 6, and 12 mo following nephroureterectomy. Results and limitationsOne hundred forty-four patients were randomised to receive MMC and 140 patients to receive standard care. In the MMC arm, 105 of 144 patients (73%) and 115 of 140 patients (82%) in the standard care arm received their allocated treatment. Thirteen of 105 patients who received MMC and 20 of 115 patients allocated to standard treatment did not complete follow-up. By modified intention-to-treat analysis, 21 of 120 patients (17%) in the MMC arm developed a bladder recurrence in the first year compared to 32 of 119 patients (27%) in the standard treatment arm (p=0.055). By treatment as per protocol analysis, 17 of 105 patients (16%) in the MMC arm and 31 of 115 patients (27%) in the standard treatment arm developed a recurrence (p=0.03). No serious adverse events were reported. A limitation is that histologic proof of recurrence was not required in this trial. ConclusionsA single postoperative dose of intravesical MMC appears to reduce the risk of a bladder tumour within the first year following nephroureterectomy for UUTUC. The absolute reduction in risk is 11%, the relative reduction in risk is 40%, and the number needed to treat to prevent one bladder tumour is nine.

669 PROSPECTIVE RANDOMIZED PHASE II TRIAL OF SINGLE EARLY INTRAVESICAL INSTILLATION OF (2′R)-4′-O-TETRAHYDROPYRANYL-DOXORUBICIN (THP) FOR PREVENTION OF BLADDER RECURRENCE AFTER NEPHROURETERECTOMY FOR UPPER URINARY TRACT UROTHELIAL CARCINOMA (UUT-UC)

You have accessJournal of UrologyUrothelial Cancer: Upper Tract Tumors1 Apr 2011669 PROSPECTIVE RANDOMIZED PHASE II TRIAL OF SINGLE EARLY INTRAVESICAL INSTILLATION OF (2′R)-4′-O-TETRAHYDROPYRANYL-DOXORUBICIN (THP) FOR PREVENTION OF BLADDER RECURRENCE AFTER NEPHROURETERECTOMY FOR UPPER URINARY TRACT UROTHELIAL CARCINOMA (UUT-UC) Akihiro Ito, Makoto Satoh, Ichiro Shintaku, Shigeto Ishidoya, Yoichi Arai, and Tohoku Urological EBM Study Group Akihiro ItoAkihiro Ito Sendai, Japan More articles by this author , Makoto SatohMakoto Satoh Sendai, Japan More articles by this author , Ichiro ShintakuIchiro Shintaku Sendai, Japan More articles by this author , Shigeto IshidoyaShigeto Ishidoya Sendai, Japan More articles by this author , Yoichi AraiYoichi Arai Sendai, Japan More articles by this author , and Tohoku Urological EBM Study Group More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1599AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Approximately 5% to 50% patients have bladder recurrence after nephroureterectomy for UUT-UC. However standard prophylactic treatment against recurrence has not been established. We evaluated the efficacy of a single early intravesical instillation of THP for prevention of bladder recurrence after nephroureterectomy for UUT-UC. METHODS From December 2005 to November 2008, 77 patients from 11 institutions in the Tohoku Urological EBM Study Group who were clinically diagnosed with UUT-UC were pre-operatively enrolled in this study. Patients were randomly assigned to receive instillation of THP (30mg/30ml) into the bladder within 48 hours after nephroureterectomy or no instillation. The prophylactic and toxic effects of THP instillation were investigated. RESULTS Of the 77 patients, 3 were excluded after surgery because they did not have pathologically confirmed urothelial carcinoma and 2 were excluded for other reasons. The remaining 72 patients were evaluable for this study. Of the 72 patients, 21 (29.2%) had subsequent bladder recurrence; most recurrences were observed at the first cystoscopic examination after nephroureterectomy. Significantly fewer patients who had THP instilled had a recurrence compared with the control group (6/36 [16.7%] vs 15/36 [41.6%]; p = 0.0247). There were no significant differences in median time to first bladder recurrence between groups. No remarkable adverse events were observed in the THP- treated group. CONCLUSIONS The single intravesical instillation of THP immediately after nehproureterectomy was well tolerated and effective for preventing bladder recurrences. A phase III, large-scale, multicenter study is needed to confirm the therapeutic efficacy of THP instillation. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e270-e271 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Akihiro Ito Sendai, Japan More articles by this author Makoto Satoh Sendai, Japan More articles by this author Ichiro Shintaku Sendai, Japan More articles by this author Shigeto Ishidoya Sendai, Japan More articles by this author Yoichi Arai Sendai, Japan More articles by this author Tohoku Urological EBM Study Group More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Prospective clinical trial of the merits of retroperitoneal lymph node dissection at the time of nephroureterectomy for upper tract urothelial carcinoma.

293 Background: The role of retroperitoneal lymph node dissection (RPLND) in patients with upper urinary tract urothelial carcinoma (UUT-UC) remains controversial. The purpose of this prospective study was to assess the safety and feasibility of RPLND at the time of nephroureterectomy (NU) and to determine the incidence of lymph node metastasis and hence the clinical merit of this procedure at the time of NU. Methods: From March 2009 to October 2010, sixteen patients with UUT-UC underwent open (8), laparoscopic (4) or robotic (4) NU with modified RPLND. Each patient received the appropriate modified template dissection depending on the site of the UC. Demographic data, clinical and pathologic stage, histologic nodal status, perioperative complications and recurrence data were documented. Results: On final pathology, 11 (69%) patients had pTa disease, 1 (6%) had pT1, 3(19%) had pT3 disease and 1 (6%) had a benign angioma. The average lymph node count was 8 (range 3–27). No patient had positive lymph node metastasis. The median operative time was 252 minutes (range 146–371). Average EBL was 342 ml (range 100–950). Median hospital stay was 7 days (4–18). Median follow up was 5 months (range 0–16). There were four bladder tumor recurrences and one recurrence in the opposite renal pelvis and ureter. Two patients with pT3 disease as well as the patient with recurrence in the opposite UUT received chemotherapy. Four patients (25%) were given blood transfusions (median 1.2, range 1–2), one patient (6%) developed a chylous leak which resolved in four weeks, one patient (6%) developed postoperative ileus and one patient (6%) had a bowel injury during lysis of adhesions necessitating resection and anastomosis of small bowel. There was no injury to major vessels or other solid organs. Conclusions: Our preliminary results indicate that RPLND during NU for UUT-UC is a safe procedure with minimal morbidity. A larger prospective clinical trial as a multicenter study is required to adequately assess the pathological and treatment related outcomes. No significant financial relationships to disclose.