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Transitional Cell Cancer of the Renal Pelvis and Ureter

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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Liu JY, Dai YB, Zhou FJ, et al.
Laparoscopic versus open nephroureterectomy to treat localized and/or locally advanced upper tract urothelial carcinoma: oncological outcomes from a multicenter study.
BMC Surg. 2017; 17(1):8 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Many studies have reported the oncological outcomes between open radical nephroureterectomy (ONU) and laparoscopic radical nephroureterectomy (LNU) of upper tract urothelial carcinoma (UTUC). However, few data have focused on the oncological outcomes of LNU in the subgroup of localized and/or locally advanced UTUC (T1-4/N0-X). The purpose of this study was to compare the oncological outcomes of LNU vs. ONU for the treatment in patients with T1-4/N0-X UTUC.
METHODS: We collected and analyzed the data and clinical outcomes retrospectively for 265 patients who underwent radical nephroureterectomy for T1-4/N0-X UTUC between April 2000 and April 2013 at two Chinese tertiary hospitals. Survival was estimated using the Kaplan-Meier method. Cox's proportional hazards model was used for univariate and multivariate analysis.
RESULTS: The mean patient age was 62.0 years and the median follow-up was 60.0 months. Of the 265 patients, 213 (80.4%) underwent conventional ONU, and 52 (19.6%) patients underwent LNU. The groups differed significantly in their presence of previous hydronephrosis, presence of previous bladder urothelial carcinoma, and management of distal ureter (P < 0.05). The predicted 5-year intravesical recurrence- free survival (RFS) (79% vs. 88%, P = 0.204), overall RFS (47% vs. 59%, P = 0.076), cancer-specific survival (CSS) (63% vs. 70%, P = 0.186), and overall survival (OS) (61% vs. 55%, P = 0.908) rates did not differ between the ONU and LNU groups. Multivariable Cox proportional regression analysis showed that surgical approach was not significantly associated with intravesical RFS (odds ratio [OR] 1.23, 95% confidence interval [CI] 0.46-3.65, P = 0.622), Overall RFS (OR 0.99, 95% CI 0.54-1.83, P = 0.974), CSS (OR 1.38, 95% CI 0.616-3.13, P = 0.444), or OS (OR 1.61, 95% CI 0.81-3.17, P = 0.17).
CONCLUSIONS: The results of this retrospective study showed no statistically significant differences in intravesical RFS, overall RFS, CSS, or OS between the laparoscopy and the open groups. Thus, LNU can be an alternative to the open procedure for T1-4/N0-X UTUC. Further studies, including a multi-institutional, prospective study are required to confirm these findings.

Kishimoto N, Takao T, Kuribayashi S, et al.
The neutrophil-to-lymphocyte ratio as a predictor of intravesical recurrence in patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy.
Int J Clin Oncol. 2017; 22(1):153-158 [PubMed] Related Publications
BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation associated with recurrence and poor prognosis in numerous cancer types. The aim of this study was to evaluate the use of the NLR as a biomarker for intravesical recurrence (IVR) in patients undergoing radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC) for the first time.
METHODS: We retrospectively analyzed the records of 100 patients with UTUC who had undergone RNU between 1999 and 2015 at our institution. The association between the preoperative NLR and IVR were assessed using multivariate models.
RESULTS: Among the 100 patients enrolled in the study, 33 developed IVR during a median follow-up of 34 months. The receiver operating characteristic analysis revealed that the optimum cut-off value for the preoperative NLR was >3.8. A high preoperative NLR (n = 21) was associated with a significantly increased risk of lymph node involvement (p = 0.036) and IVR (p = 0.034) compared with a low preoperative NLR (n = 79). IVR-free survival in patients with a high preoperative NLR was significantly worse than that of patients with a low preoperative NLR (p = 0.018). On multivariate analysis, the preoperative NLR [hazard ratio (HR) 2.49; p = 0.015] and tumor multifocality (HR 2.96; p = 0.024) were independent risk factors predictive of IVR.
CONCLUSION: In our study population of patients with UTUC who had undergone RNU the preoperative NLR was associated with a significantly increased risk of IVR, suggesting that the NRL could be a useful biomarker for predicting IVR.

Huang H, Li X, Jin J
Association of ABO blood types and clinicopathological features of ureteral transitional cell carcinoma in a single-center in China.
J Cancer Res Ther. 2016 Apr-Jun; 12(2):601-4 [PubMed] Related Publications
PURPOSE: The purpose of this study was to evaluate the correlation of ABO blood types and clinicopathological characteristics of patients with ureteral transitional cell carcinoma.
MATERIALS AND METHODS: In our study, an entire cohort of 239 patients who were pathological diagnosed as ureteral transitional cell carcinoma (TCC) between February 2002 and March 2010 were reviewed retrospectively. Variables including demographic features, tumor grades, tumor stages, type of surgery and number of tumors as well as ABO blood types status were evaluated. The relationship between the ABO blood group and clinicopathological variables was assessed by Chi-squared analysis.
RESULTS: The ratio of male to female was 1: 1.12. The median age at diagnosis was 68.5 years. A total of 111 neoplasms located in the right ureter. A total of 218 patients had radical nephroureterectomy (RNU). Multifocality was observed in 32 patients. The pathology was as follow: Grade 1 (seven cases), Grade 2 (110 cases) and Grade 3 (122 cases); Ta and T1 (83 cases), T2-T4 (156 cases). The distribution of ABO blood types was A, B, O and AB in 70 (29.3%), 76 (31.8%), 66 (27.6%) and 27 (11.3%), respectively. There were no significant differences in the clinicopathological variables among individuals with different ABO blood types. In a subgroup analysis, B and O group showed a worse tumor stage compared with A and AB groups (P = 0.01).
CONCLUSION: B and O blood types are at higher risk of muscle invasive ureteral TCC as compared with A and AB blood types. We suggest ABO blood types to be taken into consideration when urologists select therapeutic schemes for individuals with ureteral TCC.

Kondo T, Hara I, Takagi T, et al.
Template-based lymphadenectomy reduces the risk of regional lymph node recurrence among patients with upper/middle ureteral cancer.
Int J Clin Oncol. 2017; 22(1):145-152 [PubMed] Related Publications
BACKGROUND: Our previous nonrandomized prospective study showed that template-based lymphadenectomy improved survival among patients with renal pelvic cancer but not among patients with ureteral cancer. However, regional node sites vary according to the tumor's location in relation to the ureter. Therefore, this retrospective study examined the therapeutic role of lymphadenectomy for ureteral cancer according to tumor location.
METHODS: Between January 1988 and September 2015, we performed nephroureterectomy for 154 patients with nonmetastatic urothelial carcinoma of the ureter at two Japanese institutions. The tumors' locations were classified as the lower ureter or the upper/middle ureter (before the cranial crossing of the common iliac artery). The appropriate regional nodes were identified based on our previous mapping study. Dissection was classified as complete lymphadenectomy (all regional sites were dissected), incomplete lymphadenectomy (not all sites were dissected), or no lymphadenectomy. We focused the analyses on patients with ≥pT2 disease to clarify the effect of the lymphadenectomy.
RESULTS: Among the 48 patients with upper/middle ureteral cancer, recurrence-free and cancer-specific survival were significantly higher in the complete lymphadenectomy group (vs. the incomplete or no lymphadenectomy groups). However, there were no differences in recurrence-free and cancer-specific survivals among the 56 patients with lower ureteral cancer. In the patients with upper/middle ureteral cancer, multivariate analysis revealed that template-based lymphadenectomy was independently associated with a reduced risk of cancer-specific mortality.
CONCLUSIONS: Template-based lymphadenectomy has a therapeutic benefit for treating patients with upper/middle ureteral cancer but not for treating patients with lower ureteral cancer.

Ishihara H, Kondo T, Omae K, et al.
Sarcopenia predicts survival outcomes among patients with urothelial carcinoma of the upper urinary tract undergoing radical nephroureterectomy: a retrospective multi-institution study.
Int J Clin Oncol. 2017; 22(1):136-144 [PubMed] Related Publications
BACKGROUND: We aimed to evaluate the effect of sarcopenia, a condition of low muscle mass, on the survival among patients who were undergoing radical nephroureterectomy (RNU) for urothelial carcinoma of the upper urinary tract (UCUT).
METHODS: We retrospectively reviewed consecutive patients with UCUT (cT[any]N0M0) who underwent RNU between 2003 and 2013 at our department and its affiliated institutions. Preoperative computed tomography images were used to calculate each patient's skeletal muscle index, an indicator of whole-body muscle mass. Sarcopenia was defined according to the sex-specific consensus definitions, based on the patient's skeletal muscle and body mass indexes. We analyzed the relapse-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) after RNU to identify factors that predicted patient survival.
RESULTS: A total of 137 patients were included, and 90 patients (65.7 %) were diagnosed with sarcopenia. Compared to the non-sarcopenic patients, the sarcopenic patients had a significant inferior 5-year RFS (48.8 vs. 79.6 %, p = 0.0002), CSS (57.1 vs. 92.6 %, p < 0.0001), and OS (48.2 vs. 90.6 %, p < 0.0001). Multivariate analyses revealed that sarcopenia was an independent predictor of shorter RFS, CSS, and OS (all, p < 0.0001).
CONCLUSIONS: Sarcopenia was an independent predictor of survival among patients with UCUT who were undergoing RNU.

Popovska-Jankovic K, Noveski P, Jankovic-Velickovic L, et al.
MicroRNA Profiling in Patients with Upper Tract Urothelial Carcinoma Associated with Balkan Endemic Nephropathy.
Biomed Res Int. 2016; 2016:7450461 [PubMed] Free Access to Full Article Related Publications
Balkan endemic nephropathy (BEN) is a disease that affects people that live in the alluvial plains along the tributaries of the Danube River in the Balkan region. BEN is a chronic tubulointerstitial disease with a slow progression to terminal renal failure and has strong association with upper tract urothelial carcinoma (UTUC). There are several hypotheses about the etiology of BEN, but only the toxic effect of aristolochic acid has been confirmed as a risk factor in the occurrence of the disease. Aberrantly expressed miRNAs have been shown to be associated with many types of cancers. A number of studies have investigated the expression of microRNAs in urothelial carcinoma, mainly on urothelial bladder cancer, and only a few have included patients with UTUC. Here we present the first study of microRNA profiling in UTUC tissues from patients with BEN (BEN-UTUC) and patients with UTUC from nonendemic Balkan regions (non-BEN-UTUC) in comparison to normal kidney tissues. We found 10 miRNAs that were differentially expressed in patients with BEN-UTUC and 15 miRNAs in patients with non-BEN-UTUC. miRNA signature determined in BEN-UTUC patients differs from the non-BEN-UTUC patients; only miR-205-5p was mutual in both groups.

Chen JS, Lu CL, Huang LC, et al.
Chronic Kidney Disease is Associated With Upper Tract Urothelial Carcinoma: A Nationwide Population-Based Cohort Study in Taiwan.
Medicine (Baltimore). 2016; 95(14):e3255 [PubMed] Free Access to Full Article Related Publications
Increased urinary tract malignancy has been reported in end-stage renal disease (ESRD). However, little is known about chronic kidney disease (CKD). This study is designed to explore the association between CKD and upper tract urothelial carcinoma (UTUC).Using Taiwan's Longitudinal Health Insurance Database, we studied CKD patients between January 2000 and December 2011. The non-CKD controls were selected at a ratio of 4:1 and frequency matched by gender, age group, and index date. We used the chi-square test and t test to analyze the sociodemographic information and comorbidities. Cox regression analysis was used to calculate the hazard ratio (HR) and 95% confidence interval (CI).The selected cases included 45,321 CKD cases and 181,284 controls. A significantly higher incidence of UTUC was noted in the CKD group (0.22% vs 0.07%, P < 0.001). In univariate analysis, CKD, female gender, age, hypertension, hematuria, repeated urinary tract infection, bladder cancer, and ESRD were all associated with UTUC. In multivariate analysis, only CKD, female gender, age, hematuria, bladder cancer, and ESRD were significantly associated. The HR for CKD was 1.63 (95% CI: 1.26-2.13). Females had a higher HR of 1.38 (95% CI: 1.11-1.71). After excluding those patients who progressed to dialysis or kidney transplantation, the risk for CKD was still high, with an HR of 1.72 (95% CI: 1.33-2.33).CKD is a significant factor associated with UTUC. We should pay attention to the possibility of UTUC for CKD patients before they progress to ESRD.

Chopra S, Metcalfe C, Satkunasivam R, et al.
Initial Series of Four-Arm Robotic Completely Intracorporeal Ileal Ureter.
J Endourol. 2016; 30(4):395-9 [PubMed] Related Publications
Ileal ureter formation has been found to be a suitable treatment option for long, chronic ureteral strictures not amendable to less invasive forms of repair. Minimally invasive surgical techniques for this condition have been investigated. We report the first series of robotic completely intracorporeal ileal ureter using a four-arm robotic technique. Three patients underwent this procedure, including one patient with a solitary kidney. All procedures were performed effectively with a median operative time of 450 minutes (range: 420-540) and median estimated blood loss of 100 mL (range: 50-200). Postoperatively, one patient suffered volvulus and subsequent necrosis of small bowel and ileal ureter, which required re-operation and small bowel resection, including the ileal ureter. The other two patients report no surgical complications to date. This early series represents preliminary technical procedure feasibility. Further experience is necessary.

Jinzaki M, Kikuchi E, Akita H, et al.
Role of computed tomography urography in the clinical evaluation of upper tract urothelial carcinoma.
Int J Urol. 2016; 23(4):284-98 [PubMed] Related Publications
Intravenous urography has been widely used for the evaluation of upper tract urothelial carcinoma. However, computed tomography urography presently has a higher diagnostic accuracy for upper tract urothelial carcinoma (94.2-99.6%) than intravenous urography (80.8-84.9%), and has replaced intravenous urography as the first-line imaging test for investigating patients with a high risk of upper tract urothelial carcinoma. Although the detection rate for bladder tumors using standard computed tomography urography is not yet high enough to replace cystoscopy, the addition of a 60- to 80-s delayed scan after the administration of contrast material for the whole pelvis improves the detection rate. A drawback to computed tomography urography is the higher radiation dose of 15-35 mSv, compared with a mean effective dose of 5-10 mSv for intravenous urography. Among several approaches to reducing the radiation dose, the use of an iterative reconstruction algorithm is most likely to become an effective solution because of its simplicity. One advantage of computed tomography urography over intravenous urography is its ability to reliably differentiate between upper tract urothelial carcinoma and calculi or blood clots. Computed tomography urography also shows characteristic findings of other benign conditions. These findings, in combination with negative cytology, are very important diagnostic clues for avoiding an unnecessary nephroureterectomy. For the clinical staging, a recent study has reported the high diagnostic accuracy of computed tomography urography with respect to ≥pT3 tumors. The present review shows the current status of computed tomography urography for the evaluation of upper tract urothelial carcinoma.

Kim HS, Lee JS, Jeong CW, et al.
Adjuvant chemotherapy for locally advanced upper tract urothelial carcinoma: updated results of the Seoul National University Hospital experience.
Int Braz J Urol. 2015 Nov-Dec; 41(6):1067-79 [PubMed] Free Access to Full Article Related Publications
OBJECTIVES: The objective of this study was to update the long-term outcome in the treatment of locally advanced upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU) regarding the role of adjuvant chemotherapy.
MATERIALS AND METHODS: Clinical data from 138 patients who underwent RNU for locally advanced UTUC (pT3/4 or pN+) were analyzed.
RESULTS: The adjuvant chemotherapy group comprised 66 patients, and other 72 patients did not receive adjuvant chemotherapy. Cisplatin-based chemotherapy was the most common regimen, depending on the patient's eligibility and renal function. The median follow-up period was 48.7 months (interquartile range: 29.2-96.9 months). The 3-and 5-year disease-specific survival (DSS) rates were 76.0% and 69.9% for the non- -adjuvant chemotherapy group versus 74.6% and 54.5% for the adjuvant chemotherapy group (p=0.301, log-rank test). Overall survival (OS) rates for the same time period were 70.1% and 62.9% for the non-adjuvant chemotherapy group versus 73.8% and 53.2% for the adjuvant chemotherapy group (p=0.931, log-rank test). On multivariate analysis, adjuvant chemotherapy could not predict DSS and OS after surgery. When patients who received cisplatin-based adjuvant chemotherapy (n=59) were compared to those who did not receive adjuvant chemotherapy, similar results were found.
CONCLUSIONS: There does not appear to be a significant DSS or OS benefit associated with adjuvant chemotherapy. Prospective randomized clinical trials are necessary to verify the effect of adjuvant chemotherapy on locally advanced UTUC.

Stojnev S, Krstić M, Velicković LJ, et al.
Impact of Ki-67 and E-cadherin expression on lymphovascular invasion in upper urinary tract urothelial carcinoma.
Vojnosanit Pregl. 2015; 72(11):982-8 [PubMed] Related Publications
UNLABELLED: BACGROUND/AIM: Upper urinary tract urothelial carcinoma (UUT-UC) constitutes 5% of malignant neoplasms arising from transitional epithelium, but is more invasive than bladder cancer. Lzmphovascular invasion (LVI) is associated with biologically aggressive carcinoma and with occult metastases. The aim of this study was to investigate the correlation between LVI and immunohistochemical expression of two frequently routinely applied immunohistochemical biomarkers, Ki-67 and E-cadherin, in UUT-UC.
METHODS: The specimens from 106 patients with UUT-UC who had undergone nephroureterectomy were analyzed for pathologic parameters and LVI, while Ki-67 and E-cadherin expression were assessed by immunohistochemistry.
RESULTS: Ki-67 was overexpressed in 38% of the cases, while 45% of tumors demonstrated aberrant E-cadherin staining. The presence of LVI was significantly associated with tumor stage, grade, non-papillary growth, nodular invasion pattern, high Ki-67 labeling index and altered E-cadherin expression. Analyzing logistic regression models, we have shown that tumor properties such as stage, grade, growth and invasion pattern (p < 0.001), as well as the expression of Ki-67 and E-cadherin (p < 0.001) significantly predicted the presence of LVI. In the first model, only solid tumor architecture (p < 0.05) and nodular invasion pattern (p < 0.05) were significant predictors of LVI. In the second model, Ki-67 expression was found to improve the prediction of LVI (p < 0.05).
CONSLUSION: Our results suggest that Ki-67 overexpression is an independent predictor of LVI in UUT-UC, indicating the progression of the disease. E-cadherin staining adds no valuable information to LVI probability assessment. This emphasizes the importance of Ki-67 staining of UUT-UC sections in routine pathological practice. Patients with Ki-67 overexpression, especially in solid tumors with nodular invasion, should be monitored more closely after surgery.

Inokuchi J, Naito S, Fujimoto H, et al.
Impact of multimodal treatment on prognosis for patients with metastatic upper urinary tract urothelial cancer: Subanalysis of the multi-institutional nationwide case series study of the Japanese Urological Association.
Int J Urol. 2016; 23(3):224-30 [PubMed] Related Publications
OBJECTIVES: To describe the nature of metastatic upper urinary tract urothelial cancer and determine the prognostic predictors or treatment modality associated with all-cause mortality.
METHODS: Within the nationwide case series study of the Japanese Urological Association, consisting of 1509 patients with urinary tract urothelial cancer diagnosed in 2005, we identified 102 patients with metastatic urinary tract urothelial cancer. Univariate and multivariate survival analyses identified prognostic outcome variables.
RESULTS: Predominant sites of distant metastasis at diagnosis were the lungs (54.9%), distant lymph nodes (37.3%), bone (32.4%) and liver (19.6%). Of 102 patients, 70 patients (68.6%) died during the median follow-up period of 6 months, and the 2-year overall survival rate was estimated at 22%. The median survival time to all-cause mortality was 8.5 months (95% confidence interval 6.4-10.7 months). On multivariate analysis, independent predictive factors for all-cause mortality were age (hazard ratio 2.36, P = 0.015) and liver metastasis (hazard ratio 2.35, P = 0.037). Patients who received multimodal treatment including chemotherapy and surgery showed significantly better prognosis (median survival time 25.8 months) compared with patients treated with chemotherapy alone (median survival time 7.3 months) or best supportive care (median survival time 4.3 months).
CONCLUSIONS: Age at diagnosis and the presence of liver metastasis seem to have an impact on survival of metastatic urinary tract urothelial cancer patients. Multimodal treatment including systemic chemotherapy and surgery might result in better prognosis in some of these patients.

Motamedinia P, Keheila M, Leavitt DA, et al.
The Expanded Use of Percutaneous Resection for Upper Tract Urothelial Carcinoma: A 30-Year Comprehensive Experience.
J Endourol. 2016; 30(3):262-7 [PubMed] Related Publications
INTRODUCTION: The gold standard treatment for upper tract urothelial carcinoma (UTUC) is radical nephroureterectomy (RNU). The role of endoscopic resection is limited to low-risk patients. In this study, we present our 30-year experience in the endoscopic management of UTUC.
METHODS: In this retrospective study, we identified 141 patients who underwent percutaneous UTUC resection. Demographic and clinical data were collected, including tumor characteristics, bacillus Calmette-Guérin (BCG) and mitomycin use, tumor recurrence, progression to RNU, and overall survival (OS), and compared in univariate and multivariate analyses.
RESULTS: Median follow-up was 66 months. Recurrence occurred in 37% of low-grade patients and 63% of high-grade (HG) patients, with a median time to recurrence of 71.4 vs 36.4 months, respectively. Grade was the only predictor of recurrence (HR 2.12, p = 0.018). The latest time to recurrence occurred after 116 months of surveillance. RNU was avoided by 87% of patients. Age, imperative indications for endoscopy, a history of bladder cancer, and tumor stage and grade were predictors of OS; however, in multivariate analysis, grade and stage lost significance. BCG and mitomycin did not protect against recurrence, progression to RNU, or death over resection alone.
CONCLUSION: Percutaneous management of UTUC allows for renal preservation in the majority of patients with resectable disease. Patients with HG tumors are more likely to experience recurrence, but are not at an increased risk of death. Intraluminal BCG and mitomycin continue to have a limited adjuvant role to resection. Recurrence may occur many years following initial resection and therefore prolonged surveillance is advised.

Tully CM, Apolo AB, Zabor EC, et al.
The high incidence of vascular thromboembolic events in patients with metastatic or unresectable urothelial cancer treated with platinum chemotherapy agents.
Cancer. 2016; 122(5):712-21 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The current study compared the incidence of vascular thromboembolic events (VTEs) in patients with metastatic or unresectable urothelial carcinoma (UC) who were treated with gemcitabine and carboplatin (GCb); gemcitabine, carboplatin, and bevacizumab (GCbBev); or gemcitabine and cisplatin (GCis).
METHODS: Patients with UC who were treated with GCbBev on protocol were analyzed prospectively and 2 contemporary control cohorts receiving GCb or GCis were evaluated retrospectively. VTE was defined as either venous or arterial (myocardial infarctions or cerebral vascular accidents) thrombosis. VTEs were considered to be related to treatment if they occurred during treatment or within 4 weeks of the completion of treatment. Associations with chemotherapy regimen were tested using either the Fisher exact test or Kruskal-Wallis test. Clinical factors associated with VTEs were analyzed using conditional logistic regression stratified by treatment regimen.
RESULTS: Among 198 patients, VTEs occurred in 13 of 51 patients treated with GCbBev (26%), 22 of 92 patients treated with GCb (24%), and 8 of 55 patients treated with GCis (15%). Patient characteristics were significantly different between the treatment cohorts in terms of age, prior cystectomy, tumor location near pelvic vessels, Khorana risk group, and receipt of antiplatelet therapy. The incidence of VTE and type of VTE (arterial vs venous) did not differ by type of chemotherapy. Prior cystectomy was associated with an increased risk of VTE (odds ratio, 2.2; 95% confidence interval, 1.0-4.9 [P = .047]).
CONCLUSIONS: The incidence of VTE in Cis-treated patients was similar to prior reports. However, the VTE rate in Cb-treated patients was > 20%, a figure not previously defined in patients with UC and higher than expected. This high incidence of both Cis-related and Cb-related VTEs warrants greater awareness by treating physicians and deserves further study. Cancer 2016;122:712-721. © 2015 American Cancer Society.

Seisen T, Nison L, Remzi M, et al.
Oncologic Outcomes of Kidney Sparing Surgery versus Radical Nephroureterectomy for the Elective Treatment of Clinically Organ Confined Upper Tract Urothelial Carcinoma of the Distal Ureter.
J Urol. 2016; 195(5):1354-61 [PubMed] Related Publications
PURPOSE: We compared the oncologic outcomes of radical nephroureterectomy, distal ureterectomy and endoscopic surgery for elective treatment of clinically organ confined upper tract urothelial carcinoma of the distal ureter.
MATERIALS AND METHODS: From a multi-institutional collaborative database we identified 304 patients with unifocal, clinically organ confined urothelial carcinoma of the distal ureter and bilateral functional kidneys. Rates of overall, cancer specific, local recurrence-free and intravesical recurrence-free survival according to surgery type were compared using Kaplan-Meier statistics. Univariable and multivariable Cox regression analyses were performed to assess the adjusted outcomes of radical nephroureterectomy, distal ureterectomy and endoscopic surgery.
RESULTS: Overall 128 (42.1%), 134 (44.1%) and 42 patients (13.8%) were treated with radical nephroureterectomy, distal ureterectomy and endoscopic surgery, respectively. Although rates of overall, cancer specific and intravesical recurrence-free survival were equivalent among the 3 surgical procedures, 5-year local recurrence-free survival was lower for endoscopic surgery (35.7%) than for nephroureterectomy (95.0%, p <0.001) or ureterectomy (85.5%, p = 0.01) with no significant difference between nephroureterectomy and distal ureterectomy. On multivariable analyses only endoscopic surgery was an independent predictor of decreased local recurrence-free survival compared to nephroureterectomy (HR 1.27, p = 0.001) or distal ureterectomy (HR 1.14, p = 0.01). Distal ureterectomy and endoscopic surgery did not significantly correlate to cancer specific or intravesical recurrence-free survival. However, when adjustment was made for ASA(®) (American Society of Anesthesiologists(®)) score, distal ureterectomy (HR 0.80, p = 0.01) and endoscopic surgery (HR 0.84, p = 0.02) were independent predictors of increased overall survival, although no significant difference was found between them.
CONCLUSIONS: Because of better oncologic outcomes, distal ureterectomy could be considered the elective first line treatment of clinically organ confined urothelial carcinoma of the distal ureter.

Stroman LA, Sharma N, Sullivan M
Upper ureteric transitional cell carcinoma, extending to the renal pelvis, presenting as duodenal obstruction.
BMJ Case Rep. 2015; 2015 [PubMed] Related Publications
A 61-year-old man presented with weight loss, dysphagia and vomiting. A barium swallow revealed a duodenal obstruction at D3. CT of the abdomen and pelvis showed a left upper ureteric tumour extending to the renal pelvis compressing the duodenum and causing left-sided hydronephrosis. Cystoscopy and left-sided ureteroscopy proved difficult and were unable to visualise or biopsy the mass, but a left ureteric stent was placed. Laparoscopic biopsy of the mass was completed and histology revealed transitional cell carcinoma. The patient went on to receive palliative chemotherapy, which relieved the small bowel obstruction, and the patient was able to eat solid food 8 weeks later. This case highlights a previously unreported cause of duodenal obstruction.

Sung HH, Jeon HG, Han DH, et al.
Diagnostic Ureterorenoscopy Is Associated with Increased Intravesical Recurrence following Radical Nephroureterectomy in Upper Tract Urothelial Carcinoma.
PLoS One. 2015; 10(11):e0139976 [PubMed] Free Access to Full Article Related Publications
Diagnostic ureterorenoscopy is powerful tool to confirm upper tract urothelial cancer (UTUC). However, URS and associated manipulation may be related to the risk of intravesical recurrence (IVR) following radical nephroureterectomy (RNU). We aimed to investigate whether preoperative ureterorenoscopy would increase IVR after RNU in patients with UTUC. We performed a retrospective analysis of 630 patients who had RNU with bladder cuff excision due to UTUC. Diagnostic URS was performed in 282 patients (44.7%). Patients were divided into two groups according to the URS. Survival analysis and multivariate Cox regression model were performed to address risk factors for the IVR. The interval from URS to RNU was measured. During URS, manipulation such as biopsy and resection was determined. The median age was 64 (IQR 56-72) years with follow-up duration of 34.3 (15.7-64.9) months. Median time from URS to RNU was 16 (0-38) days. The IVR developed in 42.5% (n = 268) patients at 8.2 (4.9-14.7) months. The five-year IVR-free survival rate was 42.6 ± 8.0% and 63.6 ± 6.9% in patients with and without preoperative URS, respectively (P < 0.001). In multivariate analysis, previous history of bladder tumour, extravesical excision of distal ureter, multifocal tumour, and URS (HR, 95% CI; 1.558, 1.204-2.016, P = 0.001) were independent predictors for higher IVR. The IVR rate in patients without manipulation during URS was not different to those with manipulation (P = 0.658). The duration from URS to RNU was not associated with IVR (P = 0.799). Diagnostic URS for UTUC increased IVR rate after RNU. However, the lessening of interval from URS to radical surgery or URS without any manipulation could not reduce the IVR rate.

Potretzke AM, Knight BA, Potretzke TA, et al.
Is Ureteroscopy Needed Prior to Nephroureterectomy? An Evidence-Based Algorithmic Approach.
Urology. 2016; 88:43-8 [PubMed] Related Publications
OBJECTIVE: To develop an evidence-based approach to the diagnostic workup of suspicious upper urinary tract lesions.
METHODS: The PubMed database was searched using the following terms with a filter for English language: "upper tract urothelial carcinoma" and "upper tract transitional cell carcinoma," along with the following corresponding terms: "cost," "epidemiology," "diagnosis," "ureteroscopy," and "workup." A total of 404 articles were returned, and 33 were reviewed in full based on relevance.
RESULTS: Computed tomography urogram is both sensitive and specific (96% and 99%). Cytology is utilized for its specificity (89%-100%). Ureteroscopy and biopsy of an upper tract lesion can be helpful in equivocal cases but can pose challenges in terms of yield and eventual pathologic upstaging. Due to the high sensitivity and specificity of other noninvasive tests, ureteroscopy can be obviated in select cases. We assess the available evidence and devise an algorithm for the evaluation of an upper tract urothelial carcinoma lesion.
CONCLUSION: Ureteroscopy can be omitted as part of the diagnostic workup in appropriately selected cases of upper tract urothelial carcinoma.

van Osch FH, Jochems SH, van Schooten FJ, et al.
Significant Role of Lifetime Cigarette Smoking in Worsening Bladder Cancer and Upper Tract Urothelial Carcinoma Prognosis: A Meta-Analysis.
J Urol. 2016; 195(4 Pt 1):872-9 [PubMed] Related Publications
PURPOSE: Although cigarette smoking is a well established risk factor for urothelial cancer, its role in urothelial cancer prognosis is still undetermined. In this meta-analysis we quantify the role of lifetime smoking history in bladder cancer recurrence, progression and survival by pooling available data on nonmuscle invasive bladder cancer, muscle invasive bladder cancer and upper tract urothelial carcinoma.
MATERIALS AND METHODS: A total of 24 studies, comprising data from 13,114 patients with bladder cancer and 2,259 patients with upper tract urothelial carcinoma, were included in this meta-analysis. Publication bias was addressed through Egger's test, and the heterogeneity among studies was assessed by the I(2) test statistic and subgroup analyses.
RESULTS: Current smokers at diagnosis are at increased risk for local recurrence in nonmuscle invasive bladder cancer (HR 1.27, 95% CI 1.09-1.46) and smokers with muscle invasive bladder cancer have an increased risk of dying of bladder cancer (HR 1.23, 95% CI 1.02-1.44). In the upper tract urothelial carcinoma population smokers have an increased risk of recurrence in the operative bed (HR 1.57, 95% CI 1.19-1.95) and of death from upper tract urothelial carcinoma (HR 1.53, 95% CI 1.13-1.92). We did not identify significant heterogeneity among included studies.
CONCLUSIONS: The body of evidence is limited due to the absence of prospective studies. However, the results from this meta-analysis unambiguously support the hypothesis that lifetime cigarette smokers are at increased risk for a more malignant type of urothelial carcinoma associated with a worse prognosis.

Lee KH, Chen YT, Chung HJ, et al.
Kidney disease progression in patients of upper tract urothelial carcinoma following unilateral radical nephroureterectomy.
Ren Fail. 2016; 38(1):77-83 [PubMed] Related Publications
OBJECTIVES: To compare the renal outcomes in patients of unilateral renal cell carcinoma (RCC) with upper tract urothelial carcinoma (UTUC) following surgical resection of the tumor-bearing kidney, and to investigate the potential predictors in renal function decline.
PATIENTS AND METHODS: In this retrospective cohort study, 319 RCC patients undergoing radical nephrectomy (RN) and 297 UTUC patients undergoing radical nephroureterectomy were recruited from a tertiary medical center between 2001 and 2010. Demographic data, co-morbidity, smoking habit, baseline estimated glomerular filtration rate (eGFR) calculated by chronic kidney disease-epidemiology equation, as well as tumor staging of RCC and UTUC, were recorded. The primary endpoint was serum creatinine doubling and/or end-stage renal disease (ESRD) necessitating long-term dialysis. Cox proportional hazard model and Fine and Gray's competing risk regression accounting for death were used to model renal outcome.
RESULTS: UTUC patients had a higher incidence rate of renal function deterioration than RCC patients did (15.01 vs. 2.68 per 100 person-years, p<0.001). In Cox proportional hazard model and Fine and Gray's competing risk regression, UTUC was significantly associated with increased risk of creatinine doubling and/or ESRD necessitating dialysis (hazard ratio, 3.13; 95% confidence interval, 2.01-4.87) as compared to RCC following unilateral RN. Nevertheless, our study is observational in nature and cannot prove causality.
CONCLUSIONS: UTUC per se is strongly associated with kidney disease progression as compared to RCC following unilateral nephrectomy. Further studies are needed to elucidate this association.

Woodford R, Ranasinghe W, Aw HC, et al.
Trends in incidence and survival for upper tract urothelial cancer (UTUC) in the state of Victoria--Australia.
BJU Int. 2016; 117 Suppl 4:45-9 [PubMed] Related Publications
OBJECTIVE: To investigate the incidence and mortality trends of upper tract urothelial cancers (UTUC) in Victoria over the last decade.
PATIENTS AND METHODS: Age-adjusted incidence and mortality rates were calculated for UTUC. These were identified using data from the Victorian Cancer Registry from 2001 until 2011 based on histological diagnoses. Age at diagnosis, sex and demographical location were compared.
RESULTS: The age-standardised incidence of UTUC remained stable from 2001 to 2011. There were 278 deaths from UTUC over this period with an overall 5-year survival rate of 32%. There was no significant difference in survival between 2001-06 and 2007-11 (30% vs 36%, respectively). Lower age at diagnosis was associated with a significant improvement in survival (P = 0.01). Sex and geographical location appeared to have no effect on survival.
CONCLUSION: The 5-year survival rates for UTUC in Victoria are poor, particularly in comparison to worldwide data. In contrast to worldwide trends, the incidence of UTUC appears to be stable. No significant improvement in 5-year survival rates over the short study period was identified. These findings highlight the difficulties in managing this rare yet deadly malignancy.

Villa L, Cloutier J, Cotè JF, et al.
Confocal Laser Endomicroscopy in the Management of Endoscopically Treated Upper Urinary Tract Transitional Cell Carcinoma: Preliminary Data.
J Endourol. 2016; 30(2):237-42 [PubMed] Related Publications
PURPOSE: To describe our initial experience with confocal laser endomicroscopy (CLE) for the evaluation and treatment of patients with upper urinary tract transitional cell carcinoma (UUT-TCC).
MATERIALS AND METHODS: Preliminary data were analyzed from 11 patients with suspicion of UUT-TCC scheduled for flexible ureteroscopy (f-URS) and consensual holmium-YAG laser tumor ablation. CLE was performed before endoscopic biopsy and laser photoablation of the suspected lesion using a 3F-diameter flexible probe UroFlex™ B (Cellvizio® system; Mauna Kea Technologies, Paris, France), which allows to obtain microscopic resolution imaging (3.5 μm), with a field of view of 325 μm and a depth of tissue imaging of 40 to 70 μm. Video sequences were analyzed offline and thereafter compared with histopathologic findings.
RESULTS: CLE technique was feasible and showed good quality imaging in all patients. Overall, the Cellvizio system provided reliable images of healthy urothelium when the probe was pointed toward normal tissue, showing umbrella cells on the surface and vessels in the lamina propria. Moreover, CLE displayed the characteristic features of high-density cellular aggregates and fibrovascular stalks in four patients with pathologically confirmed low-grade UUT-TCC. In the patient with pathologically confirmed high-grade UUT-TCC, more distorted microarchitecture and tortuous vessels were clearly recognized with CLE.
CONCLUSIONS: These preliminary data showed the feasibility of CLE technique when applied to the diagnosis of UUT-TCC. Further clinical studies are required to confirm CLE accuracy in distinguishing healthy urothelial tissue from malignant lesions, thus helping clinicians in targeting ureteroscopic biopsy and improving the conservative management of UUT-TCC patients.

Wu P, Liu S, Zhang W, et al.
Low-level Ki-67 expression as an independent predictor of bladder tumour recurrence in patients with primary upper tract urothelial carcinoma after radical nephroureterectomy.
Jpn J Clin Oncol. 2015; 45(12):1175-81 [PubMed] Related Publications
OBJECTIVE: To evaluate the association of molecular markers and conventional clinicopathological factors with bladder tumour recurrence in patients with primary upper tract urothelial carcinoma after radical nephroureterectomy.
METHODS: The expressions of Ki-67 and P53 were measured by immunohistochemical staining prospectively in 115 consecutive patients with primary upper tract urothelial carcinoma from March 2004 to February 2014. The Cox proportional hazards regression model was used to identify independent predictors. The association between Ki-67 expression and clinicopathological variables was assessed by the χ(2) test.
RESULTS: Intravesical recurrence occurred in 13 out of 115 (11.3%) patients with a mean follow-up of 54.2 months (range: 7-130). Low-level Ki-67 expression (P = 0.010), older age (>65, P = 0.040) and lower ureter tumour (P = 0.001) were independent predictors of bladder tumour recurrence in Cox regression analysis. Ki-67 expression was elevated with the progression of tumour grade (P = 0.004) but not with stage (P = 0.186). Ki-67 overexpression was also significantly higher in aggressive pathological types (P = 0.008), but only shows an inclination towards poor oncologic outcomes in the cancer-specific survival rate (P = 0.107) and the overall survival rate (P = 0.063).
CONCLUSIONS: Low-level Ki-67 expression was an independent predictor for bladder tumour recurrence, while Ki-67 overexpression was associated with adverse clinicopathological parameters and poor prognosis in patients with primary upper tract urothelial carcinoma after radical nephroureterectomy.

Liu P, Fang D, Xiong G, et al.
A Novel and Simple Modification for Management of Distal Ureter During Laparoscopic Nephroureterectomy Without Patient Repositioning: A Bulldog Clamp Technique and Description of Modified Port Placement.
J Endourol. 2016; 30(2):195-200 [PubMed] Related Publications
BACKGROUND AND PURPOSE: To describe a novel and pure laparoscopic approach using a custom-made bulldog clamp with modified port placement for management of distal ureter during laparoscopic nephroureterectomy.
PATIENTS AND METHODS: Between October 2013 and December 2014, 31 patients found to have upper tract urothelial carcinoma were treated using this technique. After finishing a standard laparoscopic transperitoneal nephrectomy in a 45° to 60° recumbent position, an additional 12-mm trocar was inserted at the lower abdomen to allow the surgeon to continue dissecting the ureter caudally toward the bladder wall without repositioning the patient. The intramural ureter was separated from the surrounding detrusor muscle and down to the bladder mucosa, until a tent-shaped bladder cuff and intramural ureter could be formed by retraction in the superior and lateral directions. Then, a custom-made laparoscopic bulldog clamp was placed at the bottom of the tent-shaped structure to prevent urine spillage, and the bladder was closed by two-layer running closure using a barbed suture.
RESULTS: All surgeries were completed uneventfully. The mean operative time and estimated blood loss were 146.6 minutes and 47.3 mL, respectively. The median duration of the postoperative hospital stay was 6 days. No complications were noted. There were no positive margins in any specimen. No patients experienced stone formation or local or bladder recurrence during the 10.5-month follow-up period.
CONCLUSIONS: Our novel technique fully replicates the open excision technique and conforms to the strictest oncologic principles while avoiding patient repositioning and the use of staplers (EndoGIA or Hemolock) to prevent stone formation.

Bui D, Mach KE, Zlatev DV, et al.
A Pilot Study of In Vivo Confocal Laser Endomicroscopy of Upper Tract Urothelial Carcinoma.
J Endourol. 2015; 29(12):1418-23 [PubMed] Free Access to Full Article Related Publications
PURPOSE: Tissue diagnosis of upper tract urothelial carcinoma (UTUC) is limited by variance in tumor sampling by standard ureteroscopic biopsy. Optical imaging technologies can potentially improve UTUC diagnosis, surveillance, and endoscopic treatment. We previously demonstrated in vivo optical biopsy of urothelial carcinoma of the bladder using confocal laser endomicroscopy (CLE). In this study, we evaluated a new 0.85-mm imaging probe in the upper urinary tract and demonstrated feasibility and compatibility with standard ureteroscopes to achieve in vivo optical biopsy of UTUC.
MATERIALS AND METHODS: Fourteen patients scheduled for ureteroscopy of suspected upper tract lesions or surveillance of UTUC were recruited. After intravenous (IV) administration of fluorescein, CLE was performed using a 0.85-mm-diameter imaging probe inserted through the working channel of standard ureteroscopes. Acquired confocal video sequences were reviewed and analyzed. A mosaicing algorithm was used to compile a series of images into a single larger composite image. Processed CLE images were compared with standard histopathologic analysis.
RESULTS: Optical biopsy of the UTUC using CLE was effectively achieved during standard ureteroscopy. There were no adverse events related to IV fluorescein administration or image acquisition. Confocal imaging of UTUC showed characteristic features similar to urothelial carcinoma of the bladder, including papillary structure, fibrovascular stalks, and pleomorphism. Lamina propria in normal areas of the renal pelvis and ureter was also identified.
CONCLUSIONS: We report an initial feasibility of CLE of UTUC. Pending further clinical investigation, CLE may become a useful adjunct to ureteroscopic biopsy, endoscopic ablation, and surveillance of UTUC.

Ketsuwan C, Sangkum P, Sirisreetreerux P, et al.
Laparoscopic Bilateral Nephro-Ureterectomy Approach for Complete Urinary Tract Extirpation for the Treatment of Multifocal Urothelial Carcinoma in a Kidney Transplant Patient: A Case Report and Literature Review.
Transplant Proc. 2015; 47(7):2265-9 [PubMed] Related Publications
BACKGROUND: Urothelial carcinoma of the transitional epithelium is the most common malignancy in the Thai kidney transplant population.
METHODS: We report our experience in managing simultaneous upper and lower urinary tract urothelial cancer in a post-kidney transplant recipient through the use of laparoscopic bilateral nephron-ureterectomy and anterior pelvic exenteration with the use of a Studer orthotopic neobladder. A 35-year-old woman with end-stage renal disease underwent living related kidney transplantation in 2009. She presented with gross hematuria 5 years later. Enhanced computer tomography revealed diffuse bladder wall thickening with an intravesical polypoid soft tissue mass at the right ureterovesical junction extending to the right distal ureter. Hydronephrosis of the left native kidney without any demonstrable cause of obstruction was also noted. On trans-urethral resection, the pathological finding was high-grade, non-invasive urothelial cell carcinoma.
RESULTS: The operation was successfully performed without intra- or post-operative complications. The patient could ambulate independently on post-operative day 2. The kidney graft function did not change from her pre-operative baseline. At 6 months' follow-up, the patient had no tumor recurrence, returned to normal activities, and was able to void spontaneously without any need of intermittent catheterization.
CONCLUSIONS: Laparoscopic bilateral nephron-ureterectomy for complete urinary tract extirpation is feasible, safe, and associated with low morbidity. This technique avoids a large abdominal midline incision or a bilateral flank incision for nephron-ureterectomy and is a good alternative surgical technique in post-kidney transplant patients who require complete urinary tract extirpation.

Zhang XK, Zhang ZL, Yang P, et al.
Tumor necrosis predicts poor clinical outcomes in patients with node-negative upper urinary tract urothelial carcinoma.
Jpn J Clin Oncol. 2015; 45(11):1069-75 [PubMed] Related Publications
OBJECTIVE: Tumor necrosis has been indicated as a factor for the poor clinical outcome in human cancers. We aim to disclose the association between tumor necrosis and overall survival and recurrence-free survival in node-negative upper urinary tract urothelial carcinoma patients treated with radical nephroureterectomy.
METHODS: A retrospective cohort of 100 patients with upper urinary tract urothelial carcinoma from January 1990 to June 2011 was enrolled in this study. Univariate analysis with Log-rank test and multivariate analysis with Cox proportional hazards regression models were conducted to determine the correlations of tumor necrosis with overall survival and recurrence-free survival.
RESULTS: Tumor necrosis was presented in 48 patients with upper urinary tract urothelial carcinoma and was significantly associated with the advanced pathological stage (P < 0.001), high tumor grade (P < 0.001), subsequent bladder tumor (P = 0.018), vascular invasion (P < 0.001) and lymph node metastasis (P = 0.026). Multivariate analysis revealed tumor necrosis as an independent unfavorable predictor of overall survival in node-negative upper urinary tract urothelial carcinoma patients by multivariate analysis (hazard ratio = 9.23, 95% confidence interval = 1.05-80.89, P = 0.045).
CONCLUSIONS: Tumor necrosis was an independent factor of adverse clinical outcomes in node-negative upper urinary tract urothelial carcinoma patients who received radical nephroureterectomy. Evaluation of tumor necrosis might be of clinical significance to determine whether patients with node-negative upper urinary tract urothelial carcinoma should be given further therapy after radical nephroureterectomy.

Hashimoto T, Ohno Y, Nakashima J, et al.
Prediction of renal function after nephroureterectomy in patients with upper tract urothelial carcinoma.
Jpn J Clin Oncol. 2015; 45(11):1064-8 [PubMed] Related Publications
OBJECTIVE: The estimated glomerular filtration rate is significantly decreased after nephroureterectomy. Deteriorating renal function likely affects the eligibility for cisplatin-based chemotherapy in patients with upper tract urothelial carcinoma. The present study was undertaken to identify preoperative factors for the prediction of postoperative renal function and develop a prediction model.
METHODS: Between June 1996 and January 2014, 110 patients who underwent radical nephroureterectomy at our institution were analyzed in this study. The estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease study equation. Univariate linear regression analyses were performed to investigate the correlation between postoperative estimated glomerular filtration rate and preoperative variables. A stepwise multivariate linear regression analysis was performed to identify independent predictors of postoperative estimated glomerular filtration rate.
RESULTS: Comparison of preoperative and postoperative estimated glomerular filtration rate for each patient showed a median difference of 13.1 ml/min/1.73 m(2). The postoperative estimated glomerular filtration rate was significantly lower than the preoperative estimated glomerular filtration rate (P < 0.001). On univariate analysis, age and preoperative estimated glomerular filtration rate were significantly correlated with postoperative estimated glomerular filtration rate. On multivariate analysis, age, preoperative estimated glomerular filtration rate and the presence of hydronephrosis were independent predictive factors of postoperative estimated glomerular filtration rate. The predicted postoperative estimated glomerular filtration rate, which was calculated using these independent factors, showed a significant correlation with the observed postoperative estimated glomerular filtration rate (correlation coefficient = 0.7533).
CONCLUSIONS: Age, preoperative estimated glomerular filtration rate and the presence of hydronephrosis were independent predictors of postoperative estimated glomerular filtration rate in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. The predicted postoperative estimated glomerular filtration rate based on these factors may be useful for choosing alternative management strategies such as neoadjuvant chemotherapy for patients with upper tract urothelial carcinoma.

Kim BW, Ha YS, Lee JN, et al.
Effects of Previous or Synchronous Non-Muscle Invasive Bladder Cancer on Clinical Results after Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Multi-Institutional Study.
Urol J. 2015; 12(4):2233-9 [PubMed] Related Publications
PURPOSE: To evaluate the effects of the presence of previous or synchronous non-muscle invasive bladder cancer (NMIBC) on the oncologic outcomes of radical nephroureterectomy in patients with upper tract urothelial carci­noma (UTUC).
MATERIALS AND METHODS: In total, 505 patients with UTUC were enrolled from four different institutions. The clinicopathologic parameters of patients with and without previous or synchronous NMIBC were compared, and Kaplan-Meier estimates and multivariate Cox regression analyses were performed.
RESULTS: The median follow-up period was 38.4 months. In all, 408 patients had primary UTUC, 45 (8.9%) had a history of NMIBC, 59 (11.7%) had concomitant bladder cancer, and seven (1.4%) had experienced both. Tumors in patients with associated NMIBC were more commonly multifocal (P = .001) and associ­ated with surgical margin positivity (P = .001). Kaplan-Meier estimates revealed that previous or synchro­nous NMIBC was significantly associated with bladder recurrence (P < .001) and locoregional recurrence/distant metastasis (P = .008). A multivariate Cox regression model identified previous or synchronous NMIBC as an independent predictor of bladder recurrence (P < .001). However, the presence of previ­ous or synchronous NMIBC was not a prognostic indicator of locoregional recurrence/distant metastasis.
CONCLUSION: In patients with UTUC, previous or synchronous NMIBC was significantly associated with an increased risk of cancer recurrences in the bladder after radical nephroureterectomy. The present find­ings suggest that a close monitoring should be required for the patients with previous or concomitant NMIBC.

Sfakianos JP, Cha EK, Iyer G, et al.
Genomic Characterization of Upper Tract Urothelial Carcinoma.
Eur Urol. 2015; 68(6):970-7 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Despite a similar histologic appearance, upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) tumors have distinct epidemiologic and clinicopathologic differences.
OBJECTIVE: To investigate whether the differences between UTUC and UCB result from intrinsic biological diversity.
DESIGN, SETTING, AND PARTICIPANTS: Tumor and germline DNA from patients with UTUC (n=83) and UCB (n=102) were analyzed using a custom next-generation sequencing assay to identify somatic mutations and copy number alterations in 300 cancer-associated genes.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We described co-mutation patterns and copy number alterations in UTUC. We also compared mutation frequencies in high-grade UTUC (n=59) and high-grade UCB (n=102).
RESULTS AND LIMITATIONS: Comparison of high-grade UTUC and UCB revealed significant differences in the prevalence of somatic alterations. Genes altered more commonly in high-grade UTUC included FGFR3 (35.6% vs 21.6%; p=0.065), HRAS (13.6% vs 1.0%; p=0.001), and CDKN2B (15.3% vs 3.9%; p=0.016). Genes less frequently mutated in high-grade UTUC included TP53 (25.4% vs 57.8%; p<0.001), RB1 (0.0% vs 18.6%; p<0.001), and ARID1A (13.6% vs 27.5%; p=0.050). Because our assay was restricted to genomic alterations in a targeted panel, rare mutations and epigenetic changes were not analyzed.
CONCLUSIONS: High-grade UTUC tumors display a spectrum of genetic alterations similar to high-grade UCB. However, there were significant differences in the prevalence of several recurrently mutated genes including HRAS, TP53, and RB1. As relevant targeted inhibitors are being developed and tested, these results may have important implications for the site-specific management of patients with urothelial carcinoma.
PATIENT SUMMARY: Comparison of next-generation sequencing of upper tract urothelial carcinoma (UTUC) with urothelial bladder cancer identified that similar mutations were present in both cancer types but at different frequencies, indicating a potential need for unique management strategies. UTUC tumors were found to have a high rate of mutations that could be targeted with novel therapies.

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