Potential of Perfusion Magnetic Resonance Imaging to Predict Residual Renal Function after Radical Nephroureterectomy.

INTRODUCTION: The diffusion-weighted imaging (DWI) technique with intravoxel incoherent motion model enables the estimation of capillary blood volume as a perfusion-related parameter- (PP-) value. Therefore, the PP-value of the kidney theoretically reflects renal capillary blood volume. We analyzed the usefulness of the PP-value in estimating postoperative renal function in upper-tract urothelial carcinoma (UTUC) patients. METHODS: Forty-eight consecutive patients who underwent magnetic resonance imaging before radical nephroureterectomy from 2011 to 2018 were analyzed. A PP-map displaying PP-values on a pixel-by-pixel basis was created from DWI signals (b-values of 0, 500, and 1,000 s/mm2). Two readers independently analyzed the renal PP-value. DWI-based split renal function (SRF) of the intact kidney was calculated by splitting serum Cr-based preoperative estimated glomerular filtration rates (eGFRs). The predictive accuracy of the method was evaluated using renography as the reference standard. RESULTS: Interobserver analysis revealed an excellent correlation value of 0.97. The SRF value showed a good linear correlation with the observed postoperative eGFR (r = 0.76, p < 0.001). The predictive accuracy of the DWI-based method was similar to that of the nuclear-based method. CONCLUSION: This DWI-based evaluation of capillary blood volume provides a noninvasive tool for predicting the postoperative renal function, thereby facilitating the management of UTUC patients.

Sex differences in upper tract urothelial carcinomas.

PURPOSE OF REVIEW: To evaluate contemporary sex-specific differences in upper tract urothelial carcinoma (UTUC) by reviewing diagnostic considerations, clinicopathologic features, oncologic outcomes, environmental exposures, and regional variation in UTUC by sex. RECENT FINDINGS: Although some contemporary studies implicate sex-based differences in UTUC, the literature concerning the effect of sex on clinicopathologic features and oncologic outcomes in UTUC reveals mixed findings. Factors accounting for the time to diagnosis in UTUC seem to differ between men and women. The epidemiology and outcomes of UTUC are largely influenced by geographic variation in the disease, which may be due to differences in exposure to environmental risk factors. Sex-based variations and potential differences in disease biology remain to be elucidated. SUMMARY: A global consensus on the effect of sex on clinicopathologic characteristics and oncologic outcomes in UTUC has not been established definitively. Review of this topic does, however, shed light on important considerations given differences in the time to diagnosis, risk factors, and regional variation by sex. Further studies evaluating genetic, anatomic, physiologic, and socioeconomic differences between men and women with UTUC may provide further insight into understanding the effect of sex in UTUC.

Treatment Approaches for Cisplatin-Ineligible Patients with Invasive Bladder Cancer.

OPINION STATEMENT: Cisplatin has been established as an important agent in the neoadjuvant setting prior to radical cystectomy (RC) surgery for muscle-invasive urothelial cancer (MIUC) as well as in the unresectable or metastatic urothelial carcinoma (mUC) setting. Unfortunately, many patients in practice are felt to be "cisplatin-ineligible." Thus, it is vital that we develop treatment approaches and novel therapeutics for this population. We evaluate therapeutic alternatives to cisplatin-based treatment. For patients undergoing RC, there is no recommended alternative to neoadjuvant cisplatin-based combination therapy, and upfront RC or clinical trials are preferable. For patients receiving "bladder-sparing" radiation, concurrent radiosensitizing chemotherapies may be used, and several trials are also underway. For cisplatin-ineligible patients with mUC who are eligible for chemotherapy, carboplatin-based or split-dose cisplatin-based regimens may be employed. Pembrolizumab and atezolizumab offer options as first-line therapy for cisplatin-ineligible patients with high PD-L1 expression. The results of trials combining checkpoint inhibitors or platinum-based chemotherapy plus PD1/PD-L1 inhibitors are eagerly awaited. For platinum or chemotherapy-ineligible patients with mUC, immune checkpoint inhibitors such as inhibitors of programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) are approved regardless of PD-L1 expression. However, given limited effectiveness of first-line PD-1/PD-L1 inhibitor monotherapy in tumors with low PD-L1 expression, trials in this space are critical.

8-armed octopus: Evaluation of clinicopathologic prognostic factors of urothelial carcinoma of the upper urinary system

Background/aim: This study was designed to determine the characteristic features of upper urinary system urothelial carcinomas (UUSUCs) and to evaluate the clinicopathological parameters associated with prognosis. Materials and methods: A total of 74 cases of UUSUC were included, from three different centers. Demographic data and histopathological features such as tumor localization, concomitant tumor in the urinary system, distant metastasis with overall survival and disease-free survival obtained from the hospital records were evaluated retrospectively. Histopathologic prognostic features such as grade, perineural invasion, lymphovascular invasion, tumor necrosis, and surgical margin status were also evaluated. Results: Seventy cases (94.6%) underwent open nephroureterectomy whereas 4 cases (5.4%) had laparoscopic nefroureterectomy. Thirty-eight (51.4%) cases were located in the pelvis, 7 (9.5%) in the ureter, 29 (39.2%) both in the pelvis and ureter. Fifty-six (75.7%) cases were alive; however, 18 (24.3%) patients were found to be dead. pTa, pT1, pT2, pT3, and pT4 tumors were reported in 16 (21.6%), 13 (17.6%), 4 (5.4%), 28 (37.8%), and 13 (17.6%) patients, respectively. Histopathologically, 17 cases (23%) were low-grade, 57 cases (77%) were high-grade. Statistically significant correlation was observed between overall survival and lymph node metastasis, distant metastasis, tumor necrosis, and differentiation by univariate analysis. Only distant metastasis was statistically associated with overall survival by multivariate analysis. We found no significant relationship between disease-free survival and all parameters. Conclusion: Differentiation and necrosis of tumor, lymph node involvement, and presence of distant metastasis is associated with the overall survival of urothelial carcinoma of the upper urinary system.

[A rare case of metastatic tumor of heart from bladder cancer].

The article presents a case report of metastatic heart damage which developed in association with urothelial bladder carcinoma in a 79-year old female patient. Various masses may be found in the heart. In tumors, a secondary damage to the heart is observed much more frequently than a primary damage; however, metastasis of bladder carcinoma to the heart is extremely rare. Of interest is the fact of metastatic damage to all layers of the heart, including the endocardium, pericardium, and myocardium.

Preoperative hydronephrosis is associated with less decline in renal function after radical nephroureterectomy for upper tract urothelial carcinoma.

INTRODUCTION: To compare renal function changes after radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) based on the presence of preoperative hydronephrosis. MATERIALS AND METHODS: Clinicopathologic data of 208 patients with UTUC treated surgically from 1998 to 2013 were compiled. Patients with bilateral disease, less than 1 month follow up, missing hydronephrosis data, or who underwent nephron-sparing approaches were excluded. Estimated glomerular filtration rate (eGFR) was calculated preoperatively, at first follow up (within 3 months) and at last follow up using the Modification of Diet in Renal Disease equation. Events were defined as new-onset stage III chronic kidney disease (CKD) or worsening of CKD stage in preexisting CKD. Kaplan-Meier event-free survival was assessed. Cox regression was performed to identify predictors of events. RESULTS: A total of 132 patients were analyzed, including 62 (47.0%) with hydronephrosis. Median follow up was 28.6 months. Patients with hydronephrosis had larger tumors (p = 0.045) and higher pathologic stage (p = 0.010) than those without hydronephrosis. Baseline eGFR was comparable between groups (p = 0.088). Patients without hydronephrosis experienced greater declines in eGFR following surgery (p < 0.001) and higher event rates at first (42.8% versus 24.2%, p = 0.028) and last (54.2% versus 30.6%, p = 0.008) follow up. On Cox regression, hydronephrosis predicted lower event likelihood in the long term (univariate HR 0.54, p = 0.033), while ureteral tumor location predicted lower event likelihood in the short term (HR 0.52, p = 0.030). CONCLUSIONS: Patients with hydronephrosis undergoing RNU for UTUC experience less decline in renal function than those without hydronephrosis. Given the prevalence of renal dysfunction in patients with UTUC, our results may help inform preoperative counseling.

Robot-assisted intracorporeal pyramid neobladder.

OBJECTIVE: To describe a robot-assisted intracorporeal pyramid neobladder reconstruction technique and report operative and perioperative metrics, postoperative upper tract imaging, neobladder functional outcomes, and oncological outcomes. PATIENTS AND METHODS: In all, 20 patients (19 male and one female) with a mean (sd; range) age of 57.2 (12.4; 31.0-78.2) years underwent robot-assisted radical cystectomy (RARC). Most cases were ≤pT1 (17 patients) and the remaining three patients had muscle-invasive bladder cancer (MIBC) at RARC histopathology. Although half of the patients (10) actually had MIBC at transurethral resection histopathology. All patients underwent RARC, bilateral pelvic lymphadenectomy, and intracorporeal neobladder formation using a pyramid detubularised folding pouch configuration. RESULTS: The median estimated blood loss was 250 mL and operating time was 5.5 h. The mean (sd) number of lymph nodes removed was 16.5 (7.8) and median hospital stay was 10 days. Early postoperative complications included urinary tract infection (UTI) (four patients), ileus (four), diarrhoea and vomiting (three), postoperative collection (two), and blocked stent (one). Late postoperative complications included UTI (seven patients), neobladder stone (two), voiding Hem-o-Loc (two), neobladder leak (two), diarrhoea and vomiting (one), uretero-ileal stricture (one), vitamin B12 deficiency (one), and port-site hernia (one). There was no evidence of hydronephrosis in 18 patients with a median follow-up of 21.5 months. At 24 months, recurrence-free survival was 86% and overall survival was 100%. In all, 19 patients and 13 patients reported 6-month day time and night time continence, respectively. CONCLUSIONS: The pyramid neobladder is technically feasible using a robotic platform and provides satisfactory functional outcomes at median of 21.5 months.

Urothelial carcinogen resistance driven by stronger Toll-like receptor 2 (TLR2) and Uroplakin III (UP III) defense mechanisms: a new model.

OBJECTIVE: The objective of the study was to illustrate the applicability and significance of the novel Lewis urothelial cancer model compared to the classic Fisher 344. METHODS: Fischer 344 and Lewis females rats, 7 weeks old, were intravesical instilled N-methyl-N-nitrosourea 1.5 mg/kg every other week for a total of four doses. After 15 weeks, animals were sacrificed and bladders analyzed: histopathology (tumor grade and stage), immunohistochemistry (apoptotic and proliferative indices) and blotting (Toll-like receptor 2-TLR2, Uroplakin III-UP III and C-Myc). Control groups received placebo. RESULTS: There were macroscopic neoplastic lesions in 20 % of Lewis strain and 70 % of Fischer 344 strain. Lewis showed hyperplasia in 50 % of animals, normal bladders in 50 %. All Fischer 344 had lesions, 20 % papillary hyperplasia, 30 % dysplasia, 40 % neoplasia and 10 % squamous metaplasia. Proliferative and apoptotic indices were significantly lower in the Lewis strain (p < 0.01). The TLR2 and UP III protein levels were significantly higher in Lewis compared to Fischer 344 strain (70.8 and 46.5 % vs. 49.5 and 16.9 %, respectively). In contrast, C-Myc protein levels were significantly higher in Fischer 344 (22.5 %) compared to Lewis strain (13.7 %). CONCLUSIONS: The innovative Lewis carcinogen resistance urothelial model represents a new strategy for translational research. Preservation of TLR2 and UP III defense mechanisms might drive diverse urothelial phenotypes during carcinogenesis in differently susceptible individuals.

Prediction of renal function after nephroureterectomy in patients with upper tract urothelial carcinoma.

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.

Preoperative predictors of renal function decline after radical nephroureterectomy for upper tract urothelial carcinoma.

OBJECTIVES: To model renal function after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). To identify predictors of renal function decline after surgery, thereby allowing the identification of patients likely to be ineligible for cisplatin-based chemotherapy in the adjuvant setting. PATIENTS AND METHODS: We retrospectively identified 374 patients treated with RNU for UTUC at three centres between 1995 and 2010. Estimated glomerular filtration rate (eGFR) was calculated using Chronic Kidney Disease Epidemiology Collaboration equation before RNU and at early (1-5 months after RNU) and late (>5 months) time points after RNU. Only patients deemed eligible for cisplatin-based chemotherapy before RNU (preoperative glomerular filtration rate [GFR] ≥60 mL/min/1.73 m(2) ) were included. Multivariable analysis identified the preoperative predictors of eGFR after RNU at early postoperative and late postoperative time points. RESULTS: A total of 163 patients had an eligible early post-RNU eGFR measurement and 172 had an eligible late eGFR measurement. The median eGFR declined by 32% and did not show a significant trend toward recovery over time (P = 0.4). On multivariable analysis preoperative eGFR and patient age were significantly associated with early and late postoperative eGFR, while Charlson comorbidity index score was significantly associated with late postoperative eGFR alone. CONCLUSIONS: In patients with normal preoperative eGFR (≥60 mL/min/1.73 m(2) ), renal function decreases by one-third after RNU and does not show evidence of recovery over time. Elderly patients and those with pre-RNU eGFR closer to 60 mL/min/1.73 m(2) (lower eGFR in the present cohort) are more likely to be ineligible for adjuvant cisplatin-based chemotherapy regimens because of renal function loss after RNU.

Noncoding RNA in bladder cancer: a specific focus upon high-risk nonmuscle invasive disease.

PURPOSE OF REVIEW: Bladder cancer is a common disease whose natural history can be unpredictable. As such, there is an urgent clinical need to identify biomarkers that will improve the care of patients by allowing a more individualized approach. Noncoding RNAs (ncRNAs) are a recently identified subgroup of RNAs whose mature species are not translated into proteins. Here, we review knowledge of ncRNA in bladder cancer, with a focus upon their role in high-risk nonmuscle invasive tumors. RECENT FINDINGS: There have been a number of articles reporting the ability of microRNAs to help evaluate patients with nonmuscle invasive bladder cancer. New long ncRNA species have been evaluated for the first time in bladder cancer. Competing endogenous RNAs and enhancer RNAs show interesting functional and regulatory effects in other cancers, but have yet to be evaluated in bladder cancer. SUMMARY: Novel RNA species are increasingly being used to help prognosticate patients with bladder cancer and to understand key oncological events in the evolution of this disease. Future work is needed to validate potential clinical utility of the RNA species described.

Sex steroids and gender differences in nonmuscle invasive bladder cancer.

PURPOSE OF REVIEW: To review and summarize current knowledge on gender differences and sex steroid hormones in nonmuscle invasive bladder cancer. RECENT FINDINGS: Beyond the proven role of gender as a risk factor for the development of bladder cancer, recent studies indicate that women present with more advanced bladder cancer tumor stages than men, which may be due to differences in both bladder cancer care and biology. In addition, female gender has been identified as an independent prognostic factor for both recurrence and progression and may be associated with worse response to Bacillus Calmette-Guérin instillation therapy. Overall, sex steroid hormones and their receptors impact bladder carcinogenesis, recurrence and progression. Basic and transitional research evidence suggests that estrogens may initially protect against bladder cancer development, but later promote bladder cancer progression. Androgens, in contrast, seem to initiate and drive bladder cancer with its receptor playing a central role. Promising novel research shows a potential role of sex steroid hormones as therapeutic targets. SUMMARY: Whereas men are more likely to develop bladder cancer, women present generally with more advanced disease and have worse oncologic outcomes even after adjusting for tumor stage. Sex steroid hormones and their receptors play an active role in bladder cancer development and progression and represent attractive therapeutic targets for gender-specific care.

Progress made in the use of animal models for the study of high-risk, nonmuscle invasive bladder cancer.

PURPOSE OF REVIEW: High-risk, nonmuscle invasive bladder cancer (HR-NMIBC) represents a costly and difficult-to-treat disease, the molecular pathogenesis of which has a limited understanding. Most preclinical models for the study of bladder cancer are more appropriate for the study of advanced disease. However, recent key advances in preclinical animal models places us at an opportune position to better understand HR-NMIBC. RECENT FINDINGS: Discoveries in the basic sciences allow us to better understand tumor biology when building models of bladder cancer. Of note, a key study on urothelial progenitor cells recently highlighted an important role for Sonic hedgehog-positive cells and retinoid signaling that is essential for urothelial development and regeneration. In the translational realm, transgenic mouse models continue to be used, with a recent interest in the role of Wnt/beta-catenin in urothelial carcinomas. Tissue recombination models are also being increasingly utilized to better recreate the tissue microenvironment and better understand stromal-epithelial interactions and the impact of genetic alterations on tissue differentiation. Lastly, the avatar mouse systems, which involve direct xenotransplantation of human tumor specimens into immunocompromised mice, represent an additional approach to study cancer characteristics in a preserved tissue context. SUMMARY: With molecular alterations remaining an unclear area of our understanding of HR-NMIBC, preclinical models of bladder cancer serve as essential tools to discover specific genetic compromises in disease pathogenesis and the therapeutics to treat them.

Equivalent survival and improved preservation of renal function after distal ureterectomy compared with nephroureterectomy in patients with urothelial carcinoma of the distal ureter: a propensity score-matched multicenter study.

OBJECTIVES: To investigate the oncological and functional outcome of distal ureterectomy compared with nephroureterectomy in the management of distal ureteral urothelial carcinoma. METHODS: Using a database including upper urinary tract urothelial carcinoma patients (n = 1329), 282 patients were identified with urothelial carcinoma localized in the distal ureter on clinical evaluation. To adjust for potential baseline differences between groups, 43 patients undergoing distal ureterectomy were matched with 86 patients undergoing nephroureterectomy using propensity scoring. Cox regression models tested the effect of surgery type on recurrence-free survival and cancer-specific survival. Estimated glomerular filtration rate was measured before and after surgery. RESULTS: The median follow-up period was 50 months. There were no significant differences in 5-year recurrence-free survival and cancer-specific survival rates between the distal ureterectomy and nephroureterectomy groups (P = 0.22 and P = 0.70, respectively). Multivariate analysis showed that surgery type was not associated with recurrence-free survival and cancer-specific survival (P = 0.90 and P = 0.28, respectively). In the subanalysis, recurrence-free survival and cancer-specific survival in the distal ureterectomy group were equivalent to those of the nephroureterectomy group in both pTa-1 and pT2-4 patients. Renal function was better preserved in the distal ureterectomy group than in the nephroureterectomy group (rate of change in estimated glomerular filtration rate 2% vs -20%; P < 0.001). CONCLUSIONS: The oncological outcome of distal ureterectomy is comparable with that of nephroureterectomy in distal ureteral urothelial carcinoma patients, and distal ureterectomy provides better preservation of renal function. Distal ureterectomy would be feasible for carefully selected patients with distal ureteral urothelial carcinoma.

Impact of renal function on eligibility for chemotherapy and survival in patients who have undergone radical nephro-ureterectomy.

UNLABELLED: What's known on the subject? and what does the study add?: Radical nephroureterectomy (RNU), the standard of care treatment for high-risk urothelial carcinoma of the upper tract (UTUC), results in loss of a renal unit. Loss of renal function decreases eligibility for systemic chemotherapies and results in decreased overall survival in various malignancies. The study shows that only a small proportion of patients had a preoperative renal function that would allow cisplatin-based chemotherapy. Moreover, eGFR significantly decreased after RNU, thereby lowering the rate of cisplatin eligibility to only 16 and 52% of patients based on the thresholds of 60 and 45 mL/min/1.73 m(2) , respectively. Taken together with the rest of the literature, the findings of the study support the use of cisplatin-based chemotherapy, when indicated, in the neoadjuvant rather than adjuvant setting. OBJECTIVE: To report (i) the estimated glomerular filtration rate (eGFR) changes in patients undergoing radical nephro-ureterectomy (RNU) for upper tract urothelial carcinoma (UTUC); (ii) the rate of change in eGFR in patients eligible for cisplatin-based chemotherapy; and (iii) the association of preoperative, postoperative and rate of change of renal function variables with survival outcomes. PATIENT AND METHODS: We performed a retrospective analysis of 666 patients treated with RNU for UTUC at seven international institutions from 1994 to 2007. The eGFR was calculated at baseline and at 3-6 months (Modification of Diet in Renal Disease formula (MDRD) and Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EP) equations). RESULTS: The median (interquartile range) eGFR decreased by 18.2 (8-12)% after RNU. A total of 37% of patients had a preoperative eGFR ≥ 60 mL/min/1.73 m(2) , which decreased to 16% after RNU (P < 0.001); 72% of patients had a preoperative eGFR ≥ 45 mL/min/1.73 m(2) , which decreased to 52% after RNU (P < 0.001). The distributions were similar when analyses were restricted to patients with locally advanced disease (pT3-pT4) and/or lymph node metastasis. Patients older than the median age of 70 years were more likely to have a decrease in eGFR after RNU (P < 0.001). None of the renal function variables was associated with clinical outcomes such as disease recurrence, cancer-specific and overall mortality; however, when analyses were restricted to patients who had no adjuvant chemotherapy and did not experience disease recurrence (n = 431), a preoperative eGFR ≥ 60 mL/min/1.73 m(2) (P = 0.03) and a postoperative eGFR ≥ 45 mL/min/1.73 m(2) (P = 0.04) were associated with better overall survival in univariable analyses. CONCLUSIONS: In patients who had UTUC, eGFR was low and furthermore, it significantly decreased after RNU. Renal function did not affect cancer-specific outcomes after RNU.

CyberKnife for inoperable renal tumors: Canadian pioneering experience.

INTRODUCTION: Stereotactic ablative body radiotherapy (SABR) is currently under study regarding its clinical application in management of patients with kidney tumors. CyberKnife can accurately deliver ablative tumor radiation doses while preserving kidney function. We report Canada's first use of CyberKnife SABR system in treating primary kidney tumors. MATERIALS AND METHODS: Between January 2011 and February 2012, we treated three patients with renal tumors using CyberKnife SABR. Two patients had tumors in solitary kidney. The third patient had a recurrent tumor after two previous radiofrequency ablation treatments. Platinum seed fiducials were used for real time tumor tracking. Magnetic resonance imaging registration was used for tumor delineation in all cases. The patients were followed with regular renal scans and renal function tests. RESULTS: The mean age was 79 years. Mean tumor size was 21.3 cm3. A dose of 39 Gy in 3 fractions was delivered. The post treatment follow up times were 15 months, 13 months and 12 months. Local control was obtained in all three patients. No acute or chronic toxicity was reported. Kidney functions remained unaffected after treatment. CONCLUSION: CyberKnife is technically feasible for treatment of medically inoperable renal tumors or tumors in a solitary kidney.

Renal function and oncologic outcomes of parenchymal sparing ureteral resection versus radical nephroureterectomy for upper tract urothelial carcinoma.

PURPOSE: We compared renal function and oncologic outcomes of parenchymal sparing ureteral resection with radical nephroureterectomy for the treatment of upper tract urothelial carcinoma confined to the ureter. MATERIALS AND METHODS: Review of a large institutional database identified 367 patients treated for primary upper tract urothelial carcinoma with radical nephroureterectomy or parenchymal sparing ureteral resection from 1994 to 2009. Patients with known renal pelvis tumors, muscle invasive urothelial carcinoma, prior cystectomy, contralateral upper tract urothelial carcinoma, metastatic disease or chemotherapy were excluded, leaving 120 patients for analysis. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease equation. Recurrence-free, cancer specific and overall survival were estimated using Kaplan-Meier analysis. RESULTS: Radical nephroureterectomy was performed in 87 patients and parenchymal sparing ureteral resection in 33. Median age at surgery was 73 years in the radical nephroureterectomy group (IQR 64-76) vs 70 years (IQR 59-77) in the parenchymal sparing ureteral resection group (p = 0.5). The radical nephroureterectomy and parenchymal sparing ureteral resection cohorts had several disparate clinicopathological variables including preoperative hydronephrosis (80% vs 45%, p = 0.0006), stage (pT3 or greater 26% vs 9%, p = 0.01) and baseline estimated glomerular filtration rate (51 vs 63 ml/minute/1.73 m(2), p = 0.009). Patients who underwent radical nephroureterectomy experienced a significantly greater decrease in estimated glomerular filtration rate after surgery (median -7 vs 0 ml/minute/1.73 m(2), p <0.001). Median followup was 4.2 years. Of the patients 79 experienced cancer recurrence and 44 died (28 of upper tract urothelial carcinoma). There were no obvious differences in the rates of recurrence, cancer specific death or overall death by procedure type. However, due to the limited number of events we cannot exclude the possibility that there are large differences in oncologic outcomes by procedure type. CONCLUSIONS: Parenchymal sparing ureteral resection is associated with superior postoperative renal function. However, the impact on cancer control cannot be determined conclusively due to the small sample size and putative selection bias.

Systemic chemotherapy in patients with advanced transitional cell carcinoma of the urothelium and impaired renal function.

Cisplatin is the backbone of chemotherapeutic regimens used in the treatment of advanced transitional cell carcinoma of the urothelium. However, about 50% of patients cannot be administered cisplatin because of impaired renal functions. A review of the different approaches that have been developed in this patient population was performed through a Medline search from 1 January 1998 to 31 December 2010. Twenty-six studies including 25 phase II and one randomized phase II/III studies were analyzed. All regimens, except one, were based on gemcitabine and/or carboplatin and/or paclitaxel. Only five (20%) out of 25 phase II studies actually include homogeneous patients with an impaired renal function defined by a creatinine clearance below 60 ml/min. One hundred and eight patients with a median creatinine clearance ranging from 28 to 48 ml/min received four different chemotherapy regimens including one to four drugs. The results showed the response rates to vary from 24 to 56% and survival to range from 7 to 15 months. No standard chemotherapy can be recommended from literature data. Future randomized studies will have to solve the following questions: what is the optimal definition of cisplatin eligibility? Which platinum salt should be used? Is a platinum salt necessary? How many drugs should be delivered?

Transitional cell carcinoma of the upper urinary tract: optimizing image interpretation with 3D reconstructions.

PURPOSE: This article reviews the pathophysiology of transitional cell carcinoma (TCC), CT urography (CTU) protocols, different possible 3D reconstruction techniques, and the importance of 3D reconstructions for appropriate interpretation. RESULTS/CONCLUSION: CTU has largely replaced conventional IV pyelography in the evaluation of the upper urinary tract for TCC. The majority of large lesions can be easily seen on standard axial images with multiplanar reformats. However, it is imperative to also use 3D reconstructions when interpreting these studies, as subtle lesions can be difficult to visualize on the more traditional images. In this pictorial essay, we present multiple cases of upper urinary tract TCC which illustrate the value of 3D reconstructions for increasing the conspicuity of lesions, particularly at the junction of the infundibulum and calyx and in the ureters. As these cases demonstrate, each of the three possible 3D reconstruction techniques (maximum intensity projection, volume rendering, and volume rendered "virtual ureteroscopy") has its own distinct advantages, although the pitfalls of each technique must also be kept in mind.

Segmental ureterectomy vs. radical nephroureterectomy for ureteral carcinoma in patients with a preoperative glomerular filtration rate less than 90 ml/min/1.73 m2: A multicenter study.

OBJECTIVES: To compare segmental ureterectomy (SU) and radical nephroureterectomy (RNU) in terms of overall survival (OS) and impact on postoperative renal function in patients treated for upper tract urothelial carcinoma (UTUC) of the ureter with preoperatively reduced estimated glomerular filtration rate (eGFR). MATERIALS AND METHODS: We retrospectively collected the data of consecutive patients treated for UTUC, in 6 Italian tertiary referral centers, from 2003 to 2013, and analyzed those treated with RNU or SU for ureteral cancer and with a preoperative eGFR <90 ml/min/1.73m2. The primary outcome was to compare the postoperative eGFR variation and the OS according to the surgical technique chosen. RESULTS: Out of 521 patients with UTUC, 228 patients had preoperative reduced eGFR. Out of these patients, 93 had ureteral cancer and were included in the primary analyses - 67 (72.0%) treated with RNU and 26 (28.0%) with SU. Preoperative characteristics were similar in the 2 groups. The overall median follow-up period was 26.5 months. A nonsignificant postoperative eGFR decrease of 3.0 ml/min/1.73m2 was found overall (P = 0.094), with nonsignificant difference between the 2 groups (P = 0.735). A comparable 5-year OS was calculated for RNU and SU patients (P = 0.99). CONCLUSIONS: The type of surgery (SU vs. RNU) has a low impact on postoperative renal function and OS in patients with ureteral cancer and preoperative eGFR <90 ml/min/1.73m2. The indications for kidney sparing surgery for UTUC should be based on the surgical and oncological risks in these patients.