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Purpose:Poor prognosis of patients with muscle-invasive bladder cancer that often metastasizes drives the need for discovery of molecular determinants of bladder cancer progression. Chondroitin sulfate proteoglycans, including CD44, regulate cancer progression; however, the identity of a chondroitinase (Chase) that cleaves chondroitin sulfate from proteoglycans is unknown. HYAL-4 is an understudied gene suspected to encode a Chase, with no known biological function. We evaluated HYAL-4 expression and its role in bladder cancer.Experimental Design:In clinical specimens, HYAL-4 wild-type (Wt) and V1 expression was evaluated by RT-qPCR, IHC, and/or immunoblotting; a novel assay measured Chase activity. Wt and V1 were stably expressed or silenced in normal urothelial and three bladder cancer cell lines. Transfectants were analyzed for stem cell phenotype, invasive signature and tumorigenesis, and metastasis in four xenograft models, including orthotopic bladder.Results:HYAL-4 expression, specifically a novel splice variant (V1), was elevated in bladder tumors; Wt expression was barely detectable. V1 encoded a truncated 349 amino acid protein that was secreted. In bladder cancer tissues, V1 levels associated with metastasis and cancer-specific survival with high efficacy and encoded Chase activity. V1 cleaved chondroitin-6-sulfate from CD44, increasing CD44 secretion. V1 induced stem cell phenotype, motility/invasion, and an invasive signature. CD44 knockdown abrogated these phenotypes. V1-expressing urothelial cells developed angiogenic, muscle-invasive tumors. V1-expressing bladder cancer cells formed tumors at low density and formed metastatic bladder tumors when implanted orthotopically.Conclusions:Our study discovered the first naturally-occurring eukaryotic/human Chase and connected it to disease pathology, specifically cancer. V1-Chase is a driver of malignant bladder cancer and potential predictor of outcome in patients with bladder cancer.

Four Supplementary Figures and Seven Supplementary Tables

Critical evaluation of minimally invasive techniques for bladder cancer has emerged in the last 5 years, with several single and multi-institutional case series, randomized controlled trials, and systematic reviews devoted to the discussion of outcomes following robotic-assisted radical cystectomy (RARC). Potential advantages to the robotic technique exist, and despite the arguably steep learning curve, the approach is rapidly becoming more familiar in the field of urologic oncology. This chapter describes the evidence which shows that RARC appears to have acceptable oncologic efficacy when compared to ORC for high-grade invasive bladder cancer. Offering advantages of decreased pain, early recovery, and reduced blood loss in addition to better cosmesis, RARC appears to be an excellent procedure with increasing use in academic and nonacademic centers. Ultimately, the choice of the technique should be tailored to patient characteristics, expertise, and experience of the surgeon and availability of technology.

Background: Aberrantly expressed miRNAs promote renal cell carcinoma (RCC) growth and metastasis and are potentially useful biomarkers for metastatic disease. However, a consensus clinically significant miRNA signature has not been identified. To identify an miRNA signature for predicting clinical outcome in RCC patients, we used a four-pronged interconnected approach. Methods: Differentially expressed miRNAs were identified and analyzed in 113 specimens (normal kidney: 59; tumor: 54). miRNA profiling was performed in matched normal and tumor specimens from 8 patients and extended to 32 specimens. Seven aberrantly expressed miRNAs were analyzed by qPCR, and their levels were correlated with RCC subtypes and clinical outcome. miRNA signature was confirmed in The Cancer Genome Atlas RCC dataset (n = 241). Results: Discovery phase identified miR-21, miR-142-3p, miR-142-5p, miR-150, and miR-155 as significantly upregulated (2–4-fold) and miR-192 and miR-194 as downregulated (3–60-fold) in RCC; miR-155 distinguished small tumors ( Conclusions: The interconnected discovery–validation approach identified a three-miRNA signature as a potential predictor of disease outcome in RCC patients. Impact: With 10% survival at 5 years, metastatic disease presents poor prognosis for RCC patients. The three-miRNA signature discovered and validated may potentially at an early stage detect and predict metastasis, to allow early intervention for improving patient prognosis. Cancer Epidemiol Biomarkers Prev; 27(4); 464–72. ©2018 AACR.

Background: Molecular markers of clinical outcome may aid in designing targeted treatments for bladder cancer. However, only a few bladder cancer biomarkers have been examined as therapeutic targets. Methods: Data from The Cancer Genome Atlas (TCGA) and bladder specimens were evaluated to determine the biomarker potential of the hyaluronic acid (HA) family of molecules – HA synthases, HA receptors and hyaluronidase. The therapeutic efficacy of 4-methylumbelliferone (4MU), a HA synthesis inhibitor, was evaluated in vitro and in xenograft models. Results: In clinical specimens and TCGA data sets, HA synthases and hyaluronidase-1 levels significantly predicted metastasis and poor survival. 4-Methylumbelliferone inhibited proliferation and motility/invasion and induced apoptosis in bladder cancer cells. Oral administration of 4MU both prevented and inhibited tumour growth, without dose-related toxicity. Effects of 4MU were mediated through the inhibition of CD44/RHAMM and phosphatidylinositol 3-kinase/AKT axis, and of epithelial–mesenchymal transition determinants. These were attenuated by HA, suggesting that 4MU targets oncogenic HA signalling. In tumour specimens and the TCGA data set, HA family expression correlated positively with β-catenin, Twist and Snail expression, but negatively with E-cadherin expression. Conclusions: This study demonstrates that the HA family can be exploited for developing a biomarker-driven, targeted treatment for bladder cancer, and 4MU, a non-toxic oral HA synthesis inhibitor, is one such candidate.

BACKGROUND Patients with prostate cancer and their providers face uncertainty as they consider adjuvant radiotherapy (ART) or salvage radiotherapy (SRT) after undergoing radical prostatectomy. The authors prospectively evaluated the impact of the Decipher test, which predicts metastasis risk after radical prostatectomy, on decision making for ART and SRT. METHODS A total of 150 patients who were considering ART and 115 who were considering SRT were enrolled. Providers submitted a management recommendation before processing the Decipher test and again at the time of receipt of the test results. Patients completed validated surveys on prostate cancer (PCa)-specific decisional effectiveness and PCa-related anxiety. RESULTS Before the Decipher test, observation was recommended for 89% of patients considering ART and 58% of patients considering SRT. After Decipher testing, 18% (95% confidence interval [95% CI], 12%-25%) of treatment recommendations changed in the ART arm, including 31% among high-risk patients; and 32% (95% CI, 24%-42%) of management recommendations changed in the salvage arm, including 56% among high-risk patients. Decisional Conflict Scale (DCS) scores were better after viewing Decipher test results (ART arm: median DCS before Decipher, 25 and after Decipher, 19 [P

Prostate cancer is the most common solid organ malignancy in men in the USA with an annual incidence of 105 and an annual mortality rate of 19 per 100,000 people. With the advent of PSA screening, the majority of prostate cancer diagnosed is organ confined. Recent studies including the SPCG-4 and PIVOT trials have demonstrated a survival benefit for those undergoing active treatment for localized prostate cancer. The foremost surgical option has been radical prostatectomy (RP). The gold standard has been open radical retropubic prostatectomy (RRP); however, minimally invasive approaches including laparoscopic and robotic approaches are commonplace and increasing in popularity. We aim to describe the surgical options for the treatment of localized prostate cancer by reviewing the literature. A review of the literature was undertaken using MEDLINE and PubMed. Articles addressing the topic of radical prostatectomy by open, laparoscopic and robotic approaches were selected. Studies comparing the different modalities were also identified. These articles were reviewed for data pertaining to perioperative, oncological and functional outcomes. There is a paucity of randomized studies comparing the three modalities. The published data has demonstrated a benefit in favour of robotically assisted laparoscopic prostatectomy (RALP) over laparoscopic radical prostatectomy (LRP) and traditional open RRP in perioperative outcomes. When reviewing the best-reported outcomes for RALP compared to LRP and RRP, operative times are lower (105 vs. 138 vs. 138 min), estimated blood loss rates are lower (111 vs. 200 vs. 300 ml) and blood transfusion rates are lower as in the length of stay (1 vs. 2 vs. 2.3 days) and overall complication rates (4.3 vs. 5 vs. 20%). Similarly, when reviewing functional outcomes, RALP compared to LRP was not inferior. At 12 months, the reported continence was 97 vs. 94 vs. 89% and potency was 94 vs. 77 vs. 90%. In comparative studies, however, these differences did not always meet statistical significance. With respect to oncological outcomes, there was no clear evidence of superiority of one modality over another. RALP is now the most common modality for surgical treatment of organ-confined prostate cancer. Individual series appear to support better perioperative outcomes and perhaps quicker return to functional outcomes. There does not appear to be a clear advantage to date in oncological parameters; however, RALP does not appear to be inferior to either LRP or RRP. It is anticipated that further high quality randomized studies will shed more light on the clinical and statistical significance in the comparison between these modalities.

Purpose: Poor prognosis of patients with muscle-invasive bladder cancer that often metastasizes drives the need for discovery of molecular determinants of bladder cancer progression. Chondroitin sulfate proteoglycans, including CD44, regulate cancer progression; however, the identity of a chondroitinase (Chase) that cleaves chondroitin sulfate from proteoglycans is unknown. HYAL-4 is an understudied gene suspected to encode a Chase, with no known biological function. We evaluated HYAL-4 expression and its role in bladder cancer. Experimental Design: In clinical specimens, HYAL-4 wild-type (Wt) and V1 expression was evaluated by RT-qPCR, IHC, and/or immunoblotting; a novel assay measured Chase activity. Wt and V1 were stably expressed or silenced in normal urothelial and three bladder cancer cell lines. Transfectants were analyzed for stem cell phenotype, invasive signature and tumorigenesis, and metastasis in four xenograft models, including orthotopic bladder. Results: HYAL-4 expression, specifically a novel splice variant (V1), was elevated in bladder tumors; Wt expression was barely detectable. V1 encoded a truncated 349 amino acid protein that was secreted. In bladder cancer tissues, V1 levels associated with metastasis and cancer-specific survival with high efficacy and encoded Chase activity. V1 cleaved chondroitin-6-sulfate from CD44, increasing CD44 secretion. V1 induced stem cell phenotype, motility/invasion, and an invasive signature. CD44 knockdown abrogated these phenotypes. V1-expressing urothelial cells developed angiogenic, muscle-invasive tumors. V1-expressing bladder cancer cells formed tumors at low density and formed metastatic bladder tumors when implanted orthotopically. Conclusions: Our study discovered the first naturally-occurring eukaryotic/human Chase and connected it to disease pathology, specifically cancer. V1-Chase is a driver of malignant bladder cancer and potential predictor of outcome in patients with bladder cancer.

Purpose The optimal management of men with prostate cancer at high risk of recurrence postradical prostatectomy is controversial. The clinical utility of the Decipher test was evaluated prospectively on postoperative treatment decisions and patient-reported outcomes. Methods and Materials In the study, 246 eligible men across 19 centers were enrolled. Patients were dichotomized into those considering adjuvant or salvage radiation therapy (ART or SRT). Participating providers submitted a management recommendation before and after receiving the Decipher test results. Treatment received within 12 months and a validated survey on prostate cancer–related anxiety were collected longitudinally. Results Pre-Decipher, treatment was recommended for 12% and 40% for the ART and SRT arms, respectively. Post-Decipher, 17% and 30% of treatment recommendations changed in the ART and SRT arms, respectively. Post-Decipher treatment recommendation was administered 78% and 76% of the time in the ART and SRT arms, respectively. Multivariable analysis confirmed that the Decipher score was an independent predictor for change in management for both adjuvant and salvage patients. The number needed to test to change management for one patient was 4. Cancer-specific anxiety decreased among Decipher risk categories in both arms. Conclusions Use of Decipher postradical prostatectomy test was associated with postoperative treatment decisions. Overall, high Decipher risk was associated with an increase in treatment intensity whereas low risk scores were associated with a decrease in therapy administered independent of clinical and pathologic risk factors.

Objective To identify factors that are not available at the time of prostate cancer diagnosis and are associated with the risk of biopsy progression in active surveillance (AS) patients. Materials and Methods The study included 314 AS patients who had at least 1 repeat biopsy. We used logistic regression to analyze the association between prostate-specific antigen (PSA) and its derivatives, including PSA density, PSA velocity (PSAV) and doubling time (PSADT); presence of bilateral disease and number of previous successive negative surveillance biopsies; and the risk of progression on the surveillance biopsies first through fourth. Results Over a median follow-up of 3.1 years, patients had a mean of 2.4 biopsies. The median time from diagnosis to the last biopsy was 2.3 years. The biopsies were performed at fairly equal intervals. For surveillance biopsies 1 through 3, none of the studied factors was adding significant prognostic information to the baseline characteristics. PSAV and PSADT were associated with the risk of progression on the fourth biopsy; this association was independent of baseline characteristics. No progression on the fourth biopsy was noted in 23 patients with negative PSAV. Among 54 patients with PSADT of more than 3 years only, 2 progressed whereas 6 out of 9 patients with a PSADT less than 3 years had biopsy progression on the fourth surveillance biopsy. Conclusion PSA kinetics may be helpful in defining the indications for prostate biopsy in AS patients who are followed with regular biopsies for more than 3-4 years.

Currently there is no global agreement as to how ex- tensively a radical prostatectomy specimen should be sectioned and histologically examined. We analyzed the ability of different methods of partial sampling in detecting positive margin (PM) and extraprostatic extension (EPE)—2 pathologic features of prostate cancer that are most easily missed by partial sampling of the prostate. Radical prostatectomy specimens from 617 pa- tients treated with open radical prostatectomy between 1992 and 2011 were analyzed. Examination of the entirely submitted prostate detected only PM in 370 (60%), only EPE in 100 (16%), and both in 147 (24%) specimens. We determined whether these pathologic features would have been diagnosed had the examination of the specimen been limited only to al- ternate sections (method 1), alternate sections representing the posterior aspect of the gland in addition to one of the mid- anterior aspects (method 2), and every section representing the posterior aspect of the gland in addition to one of the mid- anterior aspects, supplemented by the remaining ipsilateral an- terior sections if a sizeable tumor is seen (method 3). Methods 1 and 2 missed 13% and 21% of PMs and 28% and 47% of EPEs, respectively. Method 3 demonstrated better results missing only 5% of PMs and 7% of EPEs. Partial sampling techniques missed slightly more PMs and EPEs in patients with low-risk to intermediate-risk prostate cancer, although even in high-risk cases none of the methods detected all of the studied aggressive pathologic features.

BACKGROUND Patients with prostate cancer and their providers face uncertainty as they consider adjuvant radiotherapy (ART) or salvage radiotherapy (SRT) after undergoing radical prostatectomy. The authors prospectively evaluated the impact of the Decipher test, which predicts metastasis risk after radical prostatectomy, on decision making for ART and SRT. METHODS A total of 150 patients who were considering ART and 115 who were considering SRT were enrolled. Providers submitted a management recommendation before processing the Decipher test and again at the time of receipt of the test results. Patients completed validated surveys on prostate cancer (PCa)‐specific decisional effectiveness and PCa‐related anxiety. RESULTS Before the Decipher test, observation was recommended for 89% of patients considering ART and 58% of patients considering SRT. After Decipher testing, 18% (95% confidence interval [95% CI], 12%‐25%) of treatment recommendations changed in the ART arm, including 31% among high‐risk patients; and 32% (95% CI, 24%‐42%) of management recommendations changed in the salvage arm, including 56% among high‐risk patients. Decisional Conflict Scale (DCS) scores were better after viewing Decipher test results (ART arm: median DCS before Decipher, 25 and after Decipher, 19 [P, Use of the Decipher test appears to result in a change in treatment decision making in a substantial percentage of men with prostate cancer who are considering adjuvant or salvage radiotherapy after radical prostatectomy. Decisional effectiveness improves for both patients and providers with use of the Decipher test.

RESULTS: We identified 195 lesions in the PZ and 123 lesions in the TZ. Among lesions found in the TZ, 54% were reported as probably malignant, compared to 46% of lesions seen in the PZ. Cancer was diagnosed in 25% of the lesions in the PZ, compared to only in 9.7% in the TZ (p 4 were associated with a three-fold increase in the odds of detecting cancer compared to lesions with PI-RADS < 4 (OR 3.53; CI 95% 1.7-7.31, p

Our goal was to compare the ability of active surveillance (AS) criteria and preoperative nomograms to identify patients with pathologically low-risk prostate cancer.The study cohort consisted of 402 radical prostatectomy patients with Gleason 6 prostate cancer on at least 10-core biopsy. In this group, we analyzed the ability of Kattan and Truong nomograms to select patients with Gleason 3+3 or 3+4 organ-confined prostate cancer, and compared it with that of AS criteria of John Hopkins (JH) and University of California at San Francisco (UCSF) medical centers, and Prostate Cancer Research International: Active Surveillance (PRIAS) study. The performance of each tool was evaluated with respect to discrimination and predictive accuracy.About 30% of patients were upgraded and 8% were upstaged in the final pathology. The nomograms demonstrated slightly higher discrimination in detecting organ-confined Gleason 3+3 and 3+4 disease. The predictive accuracy of the nomograms in selecting patients with low-grade organ-confined prostate cancer was superior to that of JH and UCSF criteria but not to PRIAS criteria. Furthermore, the nomograms were unable to select larger subgroups of patients with the same prevalence of Gleason 3+3 organ-confined prostate cancer as in men who met the PRIAS criteria. No difference was seen between the studied nomograms and AS criteria in their ability to identify patients with Gleason 3+4 organ-confined prostate cancer.PRIAS criteria demonstrate optimal balance between sensitivity and specificity and are not inferior to the available pathological nomograms in selecting patients with low-grade organ-confined prostate cancer.

Prostate cancer treatment presents multiple challenges that can negatively affect health-related quality of life (HrQoL), and which may be further compromised by maladaptive personality styles and psychological adjustment difficulties. This study examined the utility of a comprehensive psychosocial screening tool to identify psychosocial traits that prospectively predict HrQoL status among men treated for localized prostate cancer. The Millon Behavioral Medicine Diagnostic (MBMD) was administered to 66 men (mean age 68 years, 59% Caucasian) treated by either radical prostatectomy or radiotherapy along with standard measures of general and prostate cancer-specific quality of life assessed at a 12-month follow-up. Higher scores on both summary MBMD Management Guides (Adjustment Difficulties and Psych Referral) and higher scores on personality styles characterized by avoidance, dependency, depression, passive aggressiveness and self-denigration predicted lower HrQoL (β range = −.21 to −.50). Additionally, higher scores on the MBMD Depression, Tension-Anxiety and Future Pessimism scales predicted lower HrQoL. Finally, higher scores on the MBMD Intervention Fragility and Utilization Excess scale, also consistently predicted poorer mental and physical health functioning over time. These results point to the utility of the MBMD to help screen for potential impairments in mental and physical health functioning in men undergoing treatment for prostate cancer.

What's known on the subject? and What does the study add? Active surveillance is an established management option for patients with favourable-risk prostate cancer. However, about 25–30% of active surveillance patients demonstrate biopsy progression within the first 3–5 years of follow-up. Although several factors, such as the results of the diagnostic and surveillance biopsies, are known to be associated with the risk of progression, our ability to accurately predict this risk remains limited. Our analysis demonstrated that the overall number of positive cores in the diagnostic and first surveillance biopsies is strongly associated with the risk of progression in active surveillance patients. Furthermore, combined results of diagnostic and first surveillance biopsies provide more information about the probability of progression than they do separately. The most important variable affecting the progression-free survival was the overall number of cores positive for cancer. By 3 years of active surveillance, most of the patients who had four positive cores in the diagnostic and surveillance biopsies progressed, while those who had only one positive core had an excellent prognosis. These findings could be used to improve the accuracy of assessments of the prognosis of patients with low-risk prostate cancer and to help them make informed decisions about their treatment. Objective To analyse the prognostic importance of information provided by the diagnostic biopsy, the first surveillance biopsy and a combination thereof to identify active surveillance patients with a particularly high risk of progression. Materials and Methods The present study included 161 active surveillance patients who had at least two surveillance biopsies. The first surveillance biopsy was performed within 1 year of the diagnosis. Further surveillance biopsies usually took place every 1–2 years. Progression on the surveillance biopsy was defined as the presence of Gleason 4/5 cancer, > two positive cores or >20% involvement of any core. Cox proportional hazards regression analysis was used to examine the relationship between biopsy characteristics and progression. Three distinct statistical models were built using characteristics of diagnostic biopsies, surveillance biopsies, and a combination thereof. Harrell's c-index was used to quantify the predictive accuracy of each multivariate Cox model. Results The median follow-up was 3.6 years; 46 (28.6%) patients progressed. In multivariate analysis the major factor associated with progression was the number of positive cores. The model based on the combined results of diagnostic and first surveillance biopsies was significantly more predictive than the models based on the individual results of each biopsy. Patients with four positive cores in the diagnostic and first surveillance biopsies had estimated 5-year progression rate of 100%. Conclusion The total number of positive cores in the diagnostic and first surveillance biopsies provides important information about the risk of prostate cancer progression in active surveillance patients.

The occurrence of low-risk, localized prostate cancer (PCa) has increased in the prostate-specific antigen era. A significant amount of low-risk PCas progress slowly and may not impact patient survival. Thus, these patients may be subjected to unnecessary interventions that result in physical and psychological complications. The active surveillance (AS) protocol has been used over the few past decades. It was designed so that patients with low-risk PCa can be monitored for a period of time, during which they are free from complication of interventions, and can be treated with curative intention on evidence of disease progression. Institutions have developed different selection criteria and follow-up schedules for suitable patients with PCa. Recently, long-term data have emerged suggesting that AS is a reasonable option for appropriately selected patients with low-risk PCa who have a life expectancy of < 10 years. Subsequently, the AS protocol has been recognized by various guidelines as part of the treatment strategy for PCa. However, the challenges that remain for AS are the risk of under-staging of PCa and the low uptake and high attrition rate of AS, and questions remain regarding its long-term efficacy. Recent advances in AS for PCa, such as better imaging modality, combining AS with limited local therapy, as well as the role of AS in association with chemoprevention, are discussed.

Active surveillance is an established management option for patients with low risk prostate cancer. However, little is known about the characteristics associated with the increased probability of progression in patients on active surveillance. We analyzed our active surveillance cohort in search of such features.A total of 272 men with prostate cancer have enrolled in our active surveillance program since 1994, of whom 249 underwent at least 1 surveillance biopsy and were included in analysis. Our active surveillance inclusion criteria are biopsy Gleason grade less than 7, 2 or fewer positive biopsy cores, 20% or less tumor in any core and clinical stage T1-T2a. Changes in any of these parameters during followup that went beyond these limits were considered progression. Univariate and multivariate Cox regression analysis was done to determine patient characteristics associated with an increased risk of progression.A total of 64 patients (26%) showed progression at a median 2.9-year followup on a mean of 2.3 surveillance biopsies. The progression risk was significantly increased in black patients (adjusted HR 3.87-4.12), and in men with a smaller prostate and higher prostate specific antigen density. The latter 2 variables had no specific cutoff for an association with progression.Black men with low risk prostate cancer should be advised that the risk of progression on active surveillance may be higher than that in the available literature. Integral prognostic tools incorporating race and prostate specific antigen density may be useful to accurately assess the individual risk of progression in patients on active surveillance.

UNLABELLED What's known on the subject? and What does the study add? The surgical implications of renal cell carcinoma with coexisting bland and tumour thrombi of the inferior vena cava is not well described. In this study we review our experience managing these tumours. On multivariate analysis, we found that the presence of bland thrombus was associated with an increased need for surgical interruption of the inferior vena cava. OBJECTIVE • To study the role of interruption of the inferior vena cava (IVC) in patients with renal cell carcinoma (RCC) and associated bland and tumour thrombi. METHODS • We reviewed 129 consecutive patients with the preoperative diagnosis of RCC with tumour thrombus who underwent radical nephrectomy and tumour thrombectomy in one academic institution between May 1997 and February 2011. RESULTS • Percentages of patients with levels I, II, III and IV tumour thrombus were 29%, 13%, 48% and 9%, respectively. • The perioperative mortality rate was 2.3%. There were 29 (22%) perioperative complications recorded. • In all, 19 patients underwent surgical interruption of the IVC by ligation or segmental resection, including one level II, 14 level III and four level IV thrombi. • A total of 15 patients (12%) had bland thrombus associated with the tumour thrombus; four of these underwent intraoperative IVC filter placement and eight underwent surgical IVC interruption. • Advanced level of tumour thrombus was the only significant factor predicting association of bland thrombus (odds ratio [OR]= 2.09, 95% confidence interval [CI]: 1.082-4.037, P= 0.028). • On multivariate analysis, level of thrombus (OR = 3.1, 95% CI: 1.30-7.74, P= 0.011) and association of bland thrombus (OR = 9.07, 95% CI: 2.42-34.01, P= 0.001) were significant factors for IVC interruption. CONCLUSIONS • Surgical interruption of the IVC is a feasible option in selected patients with chronic IVC obstruction. Association of bland thrombus with tumour thrombus should alert the surgical team to the potential for a challenging surgery. • Precise preoperative imaging to assess the degree of venous obstruction and to help with differentiation between bland and tumour thrombus is key to achieving a surgical outcome with minimal morbidity.

BACKGROUND The purpose of our analysis was to determine if delays in treatment caused by active surveillance result in significant pathological changes when patients no longer meet the criteria on repeat biopsy and to study whether or not these changes may affect treatment outcomes. METHODS Out of 207 men who were on active surveillance, 47 (23%) no longer met the criteria after one of the repeat biopsies. Twenty-two underwent radical prostatectomy at our institution and formed the main group (Group 1) of this study. One hundred sixty-four patients met the criteria for active surveillance but underwent immediate surgery. Of these patients, we selected 38 (23%) with the lowest predicted biochemical recurrence-free survival. These patients formed the comparison group (Group 2). Pathological features as well as postoperative biochemical outcomes were compared between the groups. RESULTS Seven patients (32%) in Group 1 and four (11%) in Group 2 have predominantly high-grade cancer (i.e., ≥4/5 + 3) at pathology. The visually estimated percent of carcinoma was also higher in patients initially managed by active surveillance (median 12.5 vs. 5.0 in Groups 1 and 2, respectively, P = 0.009). Other pathological characteristics were similar in both groups. With limited duration of follow-up, postoperative biochemical recurrence-free survival did not differ significantly between the groups. CONCLUSIONS Our study has demonstrated that both tumor grade and volume may increase during active surveillance. However, the clinical significance of these changes with respect to the outcomes of delayed treatment remains to be established. Prostate 72:1573–1579, 2012. © 2012 Wiley Periodicals, Inc.

BACKGROUND: Molecular profiling of renal cell carcinomas (RCCs) may improve the distinction between oncocytoma and malignant RCC subtypes and aid in early detection of metastasis. The hyaluronic acid (HA) family includes HA synthases (HAS1, HAS2, HAS3), hyaluronidases (HYAL-1, HYAL-2, HYAL-3, HYAL-4, PH20, HYAL-P1), and HA receptors (CD44s, CD44v, RHAMM). HA family members promote tumor growth and metastasis. The authors evaluated the expression of HA family members in kidney specimens. METHODS: By using quantitative polymerase chain reaction, mRNA levels of 12 HA family members were measured in tumor specimens obtained from 86 consecutive patients undergoing nephrectomy; 80 of them also provided normal specimens. Mean and median follow-up were 15.2 ± 8.8 and 13.8 months. RCC specimens included clear cell RCC: 65; papillary: 10; chromophobe: 5; oncocytoma: 6; metastasis positive: 17. RESULTS: Median HAS1, CD44s, and RHAMM transcript levels were elevated 3- to 25-fold in clear cell RCC and papillary and chromophobe tumors when compared with normal tissues. HYAL-4, CD44s, and RHAMM levels were elevated 4- to 12-fold in clear cell RCC and papillary tumors when compared with oncocytomas; only HYAL-4 levels distinguished between chromophobe and oncocytoma (P = .009). CD44s and RHAMM levels were significantly higher in tumors

BACKGROUND The clinical and prognostic significance of unifocal prostatic carcinoma is not clearly understood. In the current study, we sought to characterize the clinical and pathologic characteristics of unifocal and multifocal prostate cancers and to investigate the effects of tumor focality on biochemical outcome after radical prostatectomy. METHODS Our analysis included 1,444 radical prostatectomy patients with available information concerning the number and location of tumor foci in the specimen. Each patient was assigned to one of three groups depending on whether they had unifocal, multifocal, or extensive cancer. Clinical and pathological features as well as biochemical outcomes were compared between the groups. RESULTS Two hundred and seventy-two mens in the study cohort (18.8%) had unifocal cancer. The rates of unifocal cancer did not differ significantly between the three studied time intervals (17.3% in 1992–1998, 20.5% in 1999–2004, and 17.8% in 2005–2011). The number of positive biopsy cores was slightly lower in the unifocal group, while the overall amount of biopsy tissue containing cancer was similar in both groups. The patients in the multifocal group had higher pathologic Gleason scores, increased incidence of positive surgical margin, and larger tumors. The rate of clinically significant Gleason score upgrade was significantly higher in the multifocal group compared to the unifocal group (35.7% vs. 21.7%, respectively, P

Purpose: The desirable outcomes after open radical prostatectomy (RP) for localized prostate cancer (PC) are to: a) achieve disease recurrence free, b) urinary continence (UC), and c) maintain sexual potency (SP). These 3 combined desirable outcomes we called it the “Trifecta”. Our aim is to assess the likelihood of achieving the Trifecta, and to analyze the influencing the Trifecta . Materials and Methods: A total of 1738 men with localized PC underwent RP from 1992-2007 by a single surgeon. The exclusion criteria for this analysis were: preoperative hormonal or radiation therapy, preoperative urinary incontinence or erectile dysfunction, follow-up less than 24 months or insufficient data. Post-operative Trifecta factors were analyzed, including biochemical recurrence (BR).. We defined: BR as PSA ≥ 0.2 ng/mL, urinary continence as wearing no pads, and sexual potency as having erections sufficient for intercourse with or without a phosphodiesterase-5 inhibitor . Results: A total of 831 patients met the inclusion criteria. The mean age of the entire cohort was 59 years old. The median follow-up was 52 months (mean 60, range 24-202). The BR, UC and SP rates were 18.7%, 94.5%, and 71% respectively. Trifecta was achieved in 64% at 2 year follow-up, and 61% at 5 year follow-up. Multivariate analysis revealed age at time of surgery, pathologic Gleason score (PGS), pathologic stage, specimen weight, and nerve sparing (NS) were independent factors. Conclusions: Age at time of surgery, pathologic GS, pathologic stage, specimen weight and NS were independent predictors to achieve the Trifecta following radical prostatectomy. This information may help patients counseling undergoing radical prostatectomy for localized prostate cancer.

Abnormalities of the inferior vena cava (IVC) and renal veins are extremely rare. However, with the increasing use of computed tomography (CT), these anomalies are more frequently diagnosed. The majority of venous anomalies are asymptomatic and they include left sided IVC, duplicated IVC, absent IVC as well as retro-aortic and circumaortic renal veins. The embryological development of the IVC is complex and involves the development and regression of three sets of paired veins. During renal surgery, undiagnosed venous anomalies may lead to major complications. There may be significant hemorrhage or damage to vascular structures. In addition, aberrant vessels may be mistaken for lymphadenopathy and may be biopsied. In this review we discuss the embryology of the IVC and the possible anomalies of IVC and its tributaries paying particular attention to diagnosis and implications for renal surgery.