Impact of a negative confirmatory biopsy on risk of disease progression among men on active surveillance for prostate cancer.

OBJECTIVE: Most prostate cancer active surveillance (AS) protocols suggest a confirmatory biopsy within 12 to 18 months of diagnosis to mitigate the risk of unsampled high-grade disease. We investigate whether the results of confirmatory biopsy impact AS outcomes and could be used to tailor surveillance intensity. METHODS: We retrospectively reviewed our institutional database of prostate cancer patients managed by AS from 1997 to 2019 who underwent confirmatory biopsy and ≥3 biopsies overall. Biopsy progression was defined as either an increase in grade group or an increase in the proportion of positive biopsy cores to >34% and was compared between patients with a negative vs positive confirmatory biopsy using the Kaplan-Meier method and Cox proportional hazards regression. RESULTS: We identified 452 patients meeting inclusion criteria for this analysis, of whom 169 (37%) had a negative confirmatory biopsy. With a median follow-up of 6.8 years, 37% of patients progressed to treatment, most commonly due to biopsy progression. A negative confirmatory biopsy was significantly associated with biopsy progression-free survival in multivariable analysis (HR 0.54, 95% CI 0.34-0.88, P = 0.013), adjusting for known clinical and pathologic factors, including use of mpMRI prior to confirmatory biopsy. Negative confirmatory biopsy was also associated with an increased risk of adverse pathologic features at prostatectomy but not with biochemical recurrence among men who ultimately underwent definitive treatment. CONCLUSIONS: A negative confirmatory biopsy is associated with a lower risk of biopsy progression. While the increased risk of adverse pathology at time of definitive treatment sounds a small cautionary note regarding decreasing surveillance intensity, the majority of such patients have a favorable outcome on AS.

Evaluation of fluid absorption during flexible ureteroscopy in an in vivo porcine model.

OBJECTIVE: To evaluate the relationship between renal pelvis pressure and fluid absorption during ureteroscopy (URS) in a live porcine model. MATERIALS AND METHODS: Flexible URS (fURS) was performed in anaesthetised female Yorkshire pigs. Prior to performing fURS, a 0.3556-mm (0.014″) pressure-sensing guidewire (Comet™, Boston Scientific) was placed to monitor renal pelvis pressure. A simulated fURS procedure was then performed for 1 h. Infusion of irrigation fluid (5% ethanol in saline) at target renal pelvis pressures (37-150 mmHg) was maintained for 1 h using a pressure bag and real-time feedback from the pressure-sensing guidewire. Venous blood was sampled every 10 min. The volume of irrigation fluid absorbed was estimated with established equations. RESULTS: A URS procedure was performed in vivo in 18 porcine kidneys and the volume of irrigation fluid absorbed during the 1 h URS was calculated. The mean (SD) volume of irrigation fluid absorbed after 1 h of simulated URS was 7.6 (5.7), 10.8 (7.1), 26.0 (15.8), and 56.8 (22.3) mL at renal pelvis pressures of 37, 55, 75, and 150 mmHg, respectively. Compared with URS with renal pelvis pressure of 37 mmHg, the volume of fluid absorption was significantly greater at renal pelvis pressures of 75 and 150 mmHg (P = 0.026 and P = 0.047, respectively). In addition, compared with URS with renal pelvis pressure of 37 mmHg, the rate of absorption was significantly greater at renal pelvis pressures of 75 and 150 mmHg (both P < 0.001). CONCLUSION: In this study of an in vivo porcine model of URS, increasing renal pelvis pressures during URS were associated with increases in irrigation fluid absorption and increases in the rate of fluid absorption.

The Metabolic Phenotype of Prostate Cancer.

Prostate cancer is the most common non-cutaneous cancer in men in the United States. Cancer metabolism has emerged as a contemporary topic of great interest for improved mechanistic understanding of tumorigenesis. Prostate cancer is a disease model of great interest from a metabolic perspective. Prostatic tissue exhibits unique metabolic activity under baseline conditions. Benign prostate cells accumulate zinc, and this excess zinc inhibits citrate oxidation and metabolism within the citric acid cycle, effectively resulting in citrate production. Malignant cells, however, actively oxidize citrate and resume more typical citric acid cycle function. Of further interest, prostate cancer does not exhibit the Warburg effect, an increase in glucose uptake, seen in many other cancers. These cellular metabolic differences and others are of clinical interest as they present a variety of potential therapeutic targets. Furthermore, understanding of the metabolic profile differences between benign prostate versus low- and high-grade prostate cancers also represents an avenue to better understand cancer progression and potentially develop new diagnostic testing. In this paper, we review the current state of knowledge on the metabolic phenotypes of prostate cancer.

Contract Costs Associated with Maintaining Flexible Ureteroscopes: A Single Center Experience.

INTRODUCTION: We compared the cost of flexible ureteroscope processing and maintenance contracts offered by a scope manufacturer and a third-party company. METHODS: Use and repairs of the Storz 11278AU1 Flex X2 Flexible Ureteroscope are prospectively recorded at our large, 371-bed, acute care hospital. A retrospective analysis of the processing of ureteroscopic instruments during a 3-year period (2011 to 2013) was completed. We compared the handling of ureteroscopes between 1 year under a third-party contractor (Integrated Medical Systems International, Inc. [IMS]) and 2 prior years under the manufacturer (KARL STORZ) contract. RESULTS: From January 1, 2011 through October 1, 2012 our institution used the manufacturer for the processing of ureteroscopic instruments. From January 1, 2013 through December 9, 2013 our institution used the third-party contractor IMS for repairs. The number of procedures performed per repair/exchange during the manufacturer contract was 19.9 and the number of procedures performed per repair/exchange during the third-party contract was 11. The third-party contract resulted in a reduction of procedures performed per repair/exchange by 52%. Adjusted for inflation, the yearly cost of ureteroscope repairs was $125,715 during the manufacturer contract and $158,040 during the third-party contract. By analyzing the costs incurred in 2013, if our institution had maintained the manufacturer contract for all 3 years, the estimated repair cost would have resulted in a savings of $32,325. CONCLUSIONS: Using the manufacturer repair contract is more cost-effective than using that of third-party companies.

Metabolic targets for potential prostate cancer therapeutics.

PURPOSE OF REVIEW: Prostate cancer (PCa) demonstrates characteristic changes in metabolism and bioenergetics in the transition from benign to malignant tissue. It is feasible that some of these changes may be targetable for therapeutic purposes. This review will highlight some of the current metabolically targeted therapies being investigated for the treatment of prostate cancer. RECENT FINDINGS: The transition from benign to malignant prostate cells is characterized by decreased intracellular zinc concentration and subsequent release of inhibition of the tricarboxylic acid cycle enzyme m-aconitase, which leads to the decrease in citrate concentration within the cancer tissue. Instead of the largely glycolytic phenotype exhibited by most cancers, PCa relies on glutamine and lipids for survival and proliferation. Early studies are beginning to demonstrate that targeting some of the upregulated pathways with inhibitors of key enzymes, such as glutaminase, fatty acid synthase, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, hexokinase, zinc transport, or complex I in the mitochondria may have significant metabolic effects and therapeutic potential. SUMMARY: The unique metabolic profile of PCa allows for many potential avenues of treatment. Future studies will continue to test if the metabolic characterization and treatment of PCa could be an important approach to provide personalized treatment for the disease.