Prostate cancer detection through unbiased capture of methylated cell-free DNA.

Prostate cancer screening using prostate-specific antigen (PSA) has been shown to reduce mortality but with substantial overdiagnosis, leading to unnecessary biopsies. The identification of a highly specific biomarker using liquid biopsies, represents an unmet need in the diagnostic pathway for prostate cancer. In this study, we employed a method that enriches for methylated cell-free DNA fragments coupled with a machine learning algorithm which enabled the detection of metastatic and localized cancers with AUCs of 0.96 and 0.74, respectively. The model also detected 51.8% (14/27) of localized and 88.7% (79/89) of patients with metastatic cancer in an external dataset. Furthermore, we show that the differentially methylated regions reflect epigenetic and transcriptomic changes at the tissue level. Notably, these regions are significantly enriched for biologically relevant pathways associated with the regulation of cellular proliferation and TGF-beta signaling. This demonstrates the potential of circulating tumor DNA methylation for prostate cancer detection and prognostication.

Is Bigger Better? Comparison of 150 µm and 200 µm Thulium Fiber for In Situ Lower-Pole Lithotripsy.

Introduction: The thulium fiber laser (TFL) generates a focused beam, which can be transmitted to laser fibers with small core diameters and may facilitate in situ lower-pole lithotripsy. This study compares lithotripsy performance of the 150 and 200 µm TFL in a lower pole benchtop kidney model. Materials and Methods: Using a 3D model printed from an actual kidney, in situ laser lithotripsy was performed on 1 cm lower-pole BegoStones (calcium oxalate monohydrate consistency) using four different settings (all 20W) and two fiber sizes (150 and 200 µm). Procedure time, laser time, total pulse energy, and fiber stripping were compared between the two fibers using an ANOVA or independent t-test. Results: The 150 µm fiber at 0.2 J × 100 Hz had the shortest lasing and procedure time (17.3 and 18.5 minutes) and lowest total pulse energy (20.75 kJ) compared with other study arms (p < 0.001). Overall procedure time, lasing time, and total pulse energy were significantly different between the 8 settings (p < 0.001 for all). At higher frequency (100 and 200 Hz), lasing time was significantly faster compared with 20 and 50 Hz (19.9 vs 27.3 minutes; p < 0.001). Furthermore, the average total procedure time was shorter with 150 µm compared with 200 µm regardless of settings (23.2 vs 29.8 minutes; p < 0.001). Conclusion: The 150 µm fiber results in shorter procedure and lasing time at lower total energy levels during lower-pole in situ lithotripsy. Overall, the fastest setting was 0.2 J and 100 Hz with the 150 µm fiber. Smaller laser fibers can potentially allow more efficient in situ laser lithotripsy with better irrigation and visibility at higher deflection angles.

Prone vs supine percutaneous nephrolithotomy: does position affect renal pelvic pressures?

The purpose of this study was to measure and compare renal pelvic pressure (RPP) between prone and supine percutaneous nephrolithotomy (PCNL) in a benchtop model. Six identical silicone kidney models were placed into anatomically correct prone or supine torsos constructed from patient CT scans in the corresponding positions. A 30-Fr renal access sheath was placed in either the upper, middle, or lower pole calyx for both prone and supine positions. Two 9-mm BegoStones were placed in the respective calyx and RPPs were measured at baseline, irrigating with a rigid nephroscope, and irrigating with a flexible nephroscope. Five trials were conducted for each access in both prone and supine positions. The average baseline RPP in the prone position was significantly higher than the supine position (9.1 vs 2.7 mmHg; p < 0.001). Similarly, the average RPP in prone was significantly higher than supine when using both the rigid and flexible nephroscopes. When comparing RPPs for upper, middle, and lower pole access sites, there was no significant difference in pressures in either prone or supine positions (p > 0.05 for all). Overall, when combining all pressures at baseline and with irrigation, with all access sites and types of scopes, the mean RPP was significantly higher in the prone position compared to the supine position (14.0 vs 3.2 mmHg; p < 0.001). RPPs were significantly higher in the prone position compared to the supine position in all conditions tested. These differences in RPPs between prone and supine PCNL could in part explain the different clinical outcomes, including postoperative fever and stone-free rates.