Sterile Water Versus Glycine in Transurethral Resection of Bladder Tumors-Immunogenic and Clinical Implications.

BACKGROUND AND OBJECTIVE: We compared the oncologic outcomes of patients with non-muscle invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumor (TUBRT) using sterile water vs glycine irrigation. The tumoricidal and immunogenic effects of these solutions on urothelial cancer cell lines were investigated. METHODS: The medical records of 530 consecutive patients who underwent TURBT using sterile water or glycine irrigation for NMIBC were reviewed. Recurrence and progression rates were evaluated using time dependent analyses.Bladder cancer cell lines (RT4, T24 and 5637) were treated with glycine and sterile water. Cell viability was evaluated with the XTT assay. Cell membrane calreticulin levels were evaluated with flow cytometry. Extracellular high mobility group box 1 (HMGB1) and heat shock 70 (HSP70) protein levels were evaluated using western blots. KEY FINDINGS AND LIMITATIONS: After propensity score matching each study arm comprised 161 patients. Median follow-up was 13.6 months (IQR 6.2, 24.5). The 2-year recurrence free survival was significantly lower in the sterile water vs glycine group (43% vs 71%, respectively, p<0.0001). Similarly, the 2-years progression free survival was significantly lower in the sterile water vs glycine group (85% vs 94%, respectively, p<0.014). Sterile water treatment resulted in the lowest number of viable cells. Early and late immunogenic cell death markers were markedly elevated in cells treated with glycine. CONCLUSIONS AND CLINICAL IMPLICATIONS: Sterile water compared to glycine irrigation during TURBT for NMIBC was associated with higher recurrence and progression rates. Possible explanation for these findings is the diminished immune response associated with sterile water reflected in a comparatively lesser expression of immune response inducers. PATIENT SUMMARY: We compared two irrigation fluids in non-muscle-invasive bladder cancer surgery: glycine and sterile water. Glycine outperformed sterile water in cancer recurrence, possibly boosting immunogenicity over sterile water.

Assessing renal tissue temperature changes and perfusion effects during laser activation in an in vivo porcine model.

INTRODUCTION: High fluid temperatures have been seen in both in vitro and in vivo studies with laser lithotripsy, yet the thermal distribution within the renal parenchyma has not been well characterized. Additionally, the heat-sink effect of vascular perfusion remains uncertain. Our objectives were twofold: first, to measure renal tissue temperatures in response to laser activation in a calyx, and second, to assess the effect of vascular perfusion on renal tissue temperatures. METHODS: Ureteroscopy was performed in three porcine subjects with a prototype ureteroscope containing a temperature sensor at its tip. A needle with four thermocouples was introduced percutaneously into a kidney with ultrasound guidance to allow temperature measurement in the renal medulla and cortex. Three trials of laser activation (40W) for 60 s were conducted with an irrigation rate of 8 ml/min at room temperature in each subject. After euthanasia, three trials were repeated without vascular perfusion in each subject. RESULTS: Substantial temperature elevation was observed in the renal medulla with thermal dose in two of nine trials exceeding threshold for tissue injury. The temperature decay time (t½) of the non-perfused trials was longer than in the perfused trials. The ratio of t½ between them was greater in the cortex than the medulla. CONCLUSION: High-power laser settings (40W) can induce potentially injurious temperatures in the in vivo porcine kidney, particularly in the medullary region adjacent to the collecting system. Additionally, the influence of vascular perfusion in mitigating thermal risk in this susceptible area appears to be limited.

Revisiting the issue of "beach balls" in holmium laser enucleation of prostate: clinical and histological characterization.

PURPOSE: To clinically and histologically characterize prostatic nodules resistant to morcellation ("beach balls," BBs). PATIENTS AND METHODS: We reviewed a consecutive cohort of 559 holmium laser enucleation of the prostate (HoLEP) procedures performed between January 2020 and November 2023. The BBs group comprised 55 men (10%) and the control group comprised 504 men (90%). The clinical, intraoperative, outcome, and histologic data were statistically processed for the prediction of the presence of BBs and their influence on the perioperative course and outcome. RESULTS: The BBs group in comparison to the controls was older (75 vs 73 years, respectively, p = 0.009) and had higher rates of chronic retention (51 vs 29%, p = 0.001), larger prostates on preoperative abdominal ultrasound (AUS) (140 vs 80 cc, p = 0.006E-16), longer operating time (120 vs 80 min, p = 0.001), higher weights of removed tissue (101 vs 60 gr, p = 0.008E-10), higher complication rates (5 vs 1%, p = 0.03), and longer hospitalization (p = 0.014). A multivariate analysis revealed that larger prostates on preoperative AUS and older age independently predicted the presence of BBs which would prolong operating time. ROC analyses revealed that a threshold of 103 cc on AUS predicted BBs with 94% sensitivity and 84% specificity. BBs were mostly characterized histologically by stromal component (p = 0.005). CONCLUSIONS: BBs are expected in older patients and cases of chronic retention. Prostatic volume is the most reliable predictor of their presence. They contribute to prolonged operating time and increased risk of complications. The predominantly stromal composition of the BBs apparently confers their resistance to morcellation.

Performance of brushite plaster as kidney stone phantoms for laser lithotripsy.

Artificial phantoms used in photothermal near-infrared laser lithotripsy research generally fail to mimic both the chemical and the physical properties of human stones. Though high-energy, 1 J pulses are capable of fracturing hard human stones into several large fragments along natural boundaries, similar behavior has not been observed in commonly used gypsum plasters like BegoStone. We developed a new brushite-based plaster formulation composed of ≈90% brushite that undergoes rapid fracture in the manner of human stones under fragmentation pulse regimes. Single-pulse (1 J) ablation crater volumes for phantoms were not significantly different from those of pure brushite stones. Control over crater volumes was demonstrated by varying phosphorous acid concentration in the plaster formulation. Fragmentation of cylindrical brushite phantoms was filmed using a high-speed camera which demonstrated rapid fragmentation in < 100 µs during the bubble expansion phase of a short pulse from a high-powered Ho:YAG laser (Lumenis Pulse 120 H). The rapid nature of observed fracture suggests increasing laser pulse energy by increasing laser pulse duration will not improve fragmentation performance of laser lithotripters. Brushite plaster phantoms are a superior alternative to gypsum plasters for laser lithotripsy research due to their better mimicry of stone composition, controllable single-pulse crater volumes, and fragmentation behavior.

Change in renal blood flow in response to intrarenal pressure alterations induced by ureteroscopy in an in-vivo porcine model.

INTRODUCTION: High irrigation rates are commonly used during ureteroscopy and can increase intrarenal pressure (IRP) substantially. Concerns have been raised that elevated IRP may diminish renal blood flow (RBF) and perfusion of the kidney. Our objective was to investigate the real-time changes in RBF while increasing IRP during Ureteroscopy (URS) in an in-vivo porcine model. METHODS: Four renal units in two porcine subjects were used in this study, three experimental units and one control. For the experimental units, RBF was measured by placing an ultrasonic flow cuff around the renal artery, while performing ureteroscopy in the same kidney using a prototype ureteroscope with a pressure sensor at its tip. Irrigation was cycled between two rates to achieve targeted IRPs of 30 mmHg and 100 mmHg. A control data set was obtained by placing the ultrasonic flow cuff on the contralateral renal artery while performing ipsilateral URS. RESULTS: At high IRP, RBF was reduced in all three experimental trials by 10-20% but not in the control trial. The percentage change in RBF due to alteration in IRP was internally consistent in each porcine renal unit and independent of slower systemic variation in RBF encountered in both the experimental and control units. CONCLUSION: RBF decreased 10-20% when IRP was increased from 30 to 100 mmHg during ureteroscopy in an in-vivo porcine model. While this reduction in RBF is unlikely to have an appreciable effect on tissue oxygenation, it may impact heat-sink capacity in vulnerable regions of the kidney.

Thermal Safety Boundaries for Laser Power and Irrigation Rate During Ureteroscopy: In Vivo Porcine Assessment With a Ho:YAG Laser.

OBJECTIVE: To map thermal safety boundaries during ureteroscopy (URS) with laser activation in two in vivo porcine subjects to better understand the interplay between laser power, irrigation rate, and fluid temperature in the collecting system. METHODS: URS was performed in two in vivo porcine subjects with a prototype ureteroscope containing a thermocouple at its tip. Up to 6 trials of 60 seconds laser activation were carried out at each selected power setting and irrigation rate. Thermal dose was calculated for each trial, and laser power-irrigation rate parameter pairs were categorized based on number of trials that exceeded a thermal dose of 120 equivalent minutes. RESULTS: The collecting fluid temperature was increased with greater laser power and slower irrigation rate. In the first porcine subject, 25 W of laser power could safely be applied if irrigation was at least 15 mL/min, and 48 W with at least 30 mL/min. Intermediate values followed a linear curve between these bounds. For the second subject, where the calyx appeared larger, 15 W laser power required 9 mL/min irrigation, 48 W required 24 mL/min, and intermediate points also followed a near-linear curve. CONCLUSION: This study validates previous bench research and provides a conceptual framework for selection of safe laser lithotripsy settings and irrigation rates during URS with laser lithotripsy. Additionally, it provides insight and guidance for future development of thermal mitigation strategies and devices.

Effect of outflow resistance on intrarenal pressure at different irrigation rates during ureteroscopy: in vivo evaluation.

To maintain visualization and control temperature elevation during ureteroscopy, higher irrigation rates are necessary, but this can increase intrarenal pressure (IRP) and lead to adverse effects like sepsis. The IRP is also dependent on outflow resistance but this has not been quantitatively evaluated in a biological system. In this study, we sought to characterize the IRP as a function of irrigation rate in an in vivo porcine model at different outflow resistances. Ureteroscopy was performed in a porcine model with a 9.5 Fr prototype ureteroscope containing a pressure sensor. A modified ureteral access sheath (UAS) (11/13 Fr, 36 cm) was configured to adjust outflow resistance. IRP-irrigation rate curves were generated at four different outlet resistances representing different outflow scenarios. At lower irrigation rates, the pressure change in response to increased irrigation was gradual and non-linear, likely reflecting a "compliant" phase of the renal collecting system. Once IRP reached the range of 35-50 cm H2O, the pressure increased in a linear fashion with irrigation rate, suggesting that the distensibility of the collecting system had become saturated. The relationship between IRP and irrigation rate becomes linear during in vivo porcine studies once the initial compliance of the system is saturated. IRP is more sensitive to changes in irrigation rate in systems with higher outflow resistance. The modified UAS is a novel research tool which allows variance of outflow resistance to mimic different clinical scenarios. Knowledge of outflow resistance may simplify the decision to use an UAS.

Impact of COVID-19 pandemic on patients with obstructing urinary stones complicated by infection.

Objective: To assess the influence of COVID-19-imposed life changes on presentation and outcomes of patients with obstructing urinary stones complicated by infection. Patients and methods: All patients presenting with obstructing urinary stones and infection 1 year before the pandemic (March 2019 to February 2020; n = 66) and 1 year since its onset (March 2020 to February 2021; n = 45) were enrolled. Demographics, clinical presentation, laboratory panel, stone characteristics and outcomes were compared between groups. Univariate and multivariate logistic regression models were performed for analysis. Results: The COVID-19 period was characterised by younger patients, female predominance, higher temperature at presentation and more bilateral obstructing stones (p < 0.05). The admission rate to intensive care units was double that of the pre-pandemic period, whereas time between diagnosis and treatment was similar. The univariate analysis revealed higher rates of severe sepsis (odds ratio [OR] = 3, p = 0.01), systemic inflammatory response syndrome (SIRS) ≥ 2 (OR = 2.9, p = 0.01) and risk, injury, failure, loss of kidney function and end-stage kidney (RIFLE) criteria ≥ 1 (OR = 2.2, p = 0.04) in the pandemic period group. The multivariate analyses revealed the COVID-19 period as being the sole variable associated with severe sepsis (OR = 3.1, p = 0.02), SIRS ≥ 2 (OR = 3.8, p = 0.005) and RIFLE ≥ 1 (OR = 2.6, p = 0.05). Conclusions: The pandemic period was characterised by a worse clinical state at presentation of patients with obstructing urinary stones complicated by infection, probably reflecting delay in arrival to emergency services.

Querying the significance of patient position during computerized tomography on the reliability of pre-percutaneous nephrolithotomy planning.

BACKGROUND: Computerized tomography (CT) is considered indispensable in percutaneous nephrolithotomy (PCNL) planning. We aimed to define the reliability of pre-PCNL CT for planning renal access by assessing renal positional changes between supine and prone CTs. SUBJECTS AND METHODS: CT urographies (CTU) of 30 consecutive patients were reviewed for distances upper pole (UP)-diaphragm, UP-diaphragm attachment, renal pelvis (RP)-lateral body wall, RP- posterior body wall, and lower pole (LP)- anterior-superior iliac spine (ASIS). The posterior and lateral renal axes angles were also calculated. RESULTS: The most consistent overall movement in transition from prone to supine was backward rotation, as demonstrated by a decrease in distance UP-posterior body wall (p = 0.010) and increase in the posterior renal angle (p < 0.0001). This finding correlated with the patient's body mass index (BMI) (p = 0.029). The left kidney was more mobile than the right one, moving significantly for five of the measured parameters compared to the right kidney which moved significantly for only two parameters. The UP-diaphragm distance of the left kidney correlated with age (p = 0.014), the RP-lateral wall distance correlated with previous abdominal surgery (p = 0.006), and the RP-posterior wall distance with BMI (p = 0.017). On the right, the UP-diaphragm distance correlated with gender (p = 0.002) and the lateral renal rotation was smaller (p = 0.046). CONCLUSIONS: Kidneys present significant mobility between supine and prone positions. CT assessment should be performed in the position expected during surgery and should be interpreted with caution, while a real-time imaging modality should be used in the operating room.

Introducing in clinical practice a new laser suction handpiece for percutaneous nephrolithotomy.

OBJECTIVE: To assess a novel combined laser suction handpiece (LSH) for performing PCNL in a clinical setting. METHODS: The study comprised 40 consecutive PCNLs performed between May 2019 and February 2020. The first 20 procedures (Group A) were performed with conventional ultrasonic or pneumatic devices and the other 20 (Group B) were performed with the use of the new LSH. All patients were treated by tubeless supine PCNL. The groups were compared for demographics, clinical data, operative time, lithotrite effectiveness, stone clearance rate (SCR), and outcome. RESULTS: Groups A and B were similar in age, and in stone size, complexity, and density (Hounsfield units) (p < 0.05). The average operative time was 99 and 78 min, SCR 143 and 200 mm3/min, hospital stay 1.6 and 1.1 days, and stone-free rate 90% and 95%, respectively. Despite a trend toward better results with the new LSH, none of these comparisons reached statistical significance. Ineffective lithotripsy with the initial device (ultrasonic) requiring conversion to another modality (ballistic) occurred in six (30%) procedures in Group A, while all procedures were effectively accomplished with the LSH in Group B (p = 0.02). There were two complications in Group A and none in Group B (p > 0.05). CONCLUSIONS: The LSH is as effective and safe as the traditional lithotrites for performing PCNLs. This new tool completes the capabilities of the holmium laser high-power machines, enabling them to serve as the sole platform for all endourological treatments.

Anterior and apical samplings during transperineal image-guided prostate biopsy.

INTRODUCTION: Concurrent systematic biopsies during image-guided targeted biopsies of the prostate were found to improve the detection rate of clinically significant prostate cancer (CSPC). However, these biopsies do not routinely include anterior or apical sampling. We aimed to evaluate the significance of anterior and apical samplings during combined biopsies. METHODS: After obtaining institutional review board approval we identified 303 consecutive patients who underwent transperineal combined biopsies of the prostate between 2017-2020. Systematic biopsies were obtained from the peripheral zone, anterior zone, and apex. Study outcomes included CSPC and any cancer on anterior or apical biopsies. Logistic regression analyses were used to evaluate the association between pre-biopsy characteristics and study outcomes. RESULTS: Median prostatic-specific-antigen value was 6.8 ng/dL. Most patients had stage T1c disease (77%). Overall, combined biopsies detected CSPC in 87 patients (29%). Any cancer and CSPC in the anterior zone were found in 54 (18%) and 19 (6%) patients, respectively. Any cancer and CSPC in the apex were found in 54 (18%) and 16 (5%) patients, respectively. Anterior/apical samplings upgraded the pathological result in 19 patients (6%). Logistic regression analyses demonstrated that PI-RADS 5 lesions predicted the presence of CSPC in both the anterior zone (OR = 8, 95%CI = 3-22, P <0.001) and apex (OR = 4, 95%CI = 1-10, P = 0.01). CONCLUSIONS: Avoiding anterior and apical samplings during prostate biopsy does not result in substantial under-diagnosis of significant cancer. However, these areas are easily accessible using the transperineal approach and should be sampled in selected patients, particularly those with PI-RADS 5 lesions.

Novel ultrasound-based volume estimation of prostatic benign enlargement to improve decision-making on surgical approach.

AIM: To assess the precision of preoperative ultrasonography (US)-determined prostate volume and to propose formulas for improving it. METHODS: This retrospective study comprised 155 consecutive men who underwent open prostatectomy for benign prostatic hyperplasia (BPH) between 2013 and 2019. Preoperative prostate volume was estimated by either abdominal US (AUS) (n = 92) or transrectal US (TRUS) (n = 63), and was compared with the weight of surgically enucleated tissue at a conversion rate of 1 ml (US) = 1 g tissue. Statistical analysis was conducted and a novel formula for prostate volume was constructed. RESULTS: The median prostate volumes by AUS and TRUS were 140 ml [interquartile ratio (IQR) 111-182] and 108 ml (IQR 93-120), respectively. Enucleated tissue weight was lower than the AUS assessment by a median difference of 50 g (IQR 28.7-75.7; p < 0.001), and lower than the TRUS assessment by a median difference of 27 g, IQR 10-43, p < 0.001). Using a cutoff of 80 ml, 30 (33%) AUS patients and 23 (36%) TRUS patients underwent unneeded open procedures. Mathematical calculations revealed two formulas that significantly adjusted for the actual weight: 1.082*Age + 0.523*AUS - 53.845 for AUS and 0.138*age + 2.22*prostate-specific antigen + 0.453*TRUS + 11.682 for TRUS (p < 0.001). These formulas increased the overall US prostate volume accuracy from 65% to 85%. CONCLUSION: Assessment of prostate volume by US is imprecise for decision-making of whether to perform open simple prostatectomy for BPH. Our novel formulas may enhance stratification of patients with prostatic enlargement to a more optimal surgical approach. Future studies in larger cohorts are needed to substantiate our results.

Long-Term Follow-Up of Yearly Replaced Double Internal Stents for Extrinsic Malignant Ureteral Obstruction.

Introduction: To assess long-term outcomes of double internal stents (DIS) for the relief of external malignant ureteral obstruction (MUO). Materials and Methods: DIS (7F each; 12-month indwelling time) were inserted under general anesthesia in 62 consecutive patients (75 renal units) with MUO during 2007-2018. Surveillance was performed every 3 months, and stents were exchanged routinely every year. The need for permanent stent retrieval was considered stent failure. Maintenance of stent patency and disease-specific survival (DSS) were estimated (Kaplan-Meier). Risk factors were also assessed (univariate and multivariable Cox regression analyses). Results: The median follow-up was 27 months (interquartile range [IQR] 20-27). The most frequent tumors causing obstruction were colorectal and ovarian cancers. Six patients (10%) had stent failure caused by sepsis, creatinine elevation, or hematuria. The average time to failure was 15 months (range 1-27). A history of radiation and an estimated glomerular filtration rate (eGFR) ≤45 mL/(min/1.73 m2) were associated with stent failure (p = 0.038 and p = 0.001, respectively). Thirty-nine patients died with a median DSS of 21 months (IQR 8.6-not reached). Multivariate analysis identified eGFR ≤60 mL/(min/1.73 m2) (hazard ratio [HR] 2.1, 95% confidence interval [CI] 1.1-4.2, p = 0.02) and need for balloon dilation (HR 2.1, 95% CI 1.1-4.1, p = 0.02) as independent predictors for disease-related mortality. Twenty-six patients (42%) had stent-related complications, for example, irritative symptoms, hematuria, and infections, of whom only two failed. Conclusions: One-year indwelling DIS provide effective long-term relief of MUO and represent a simple and effective alternative to other methods of urinary diversion. They avoid the need for external tubes and contribute to improved patient satisfaction.

The effect of delaying transperineal fusion biopsy of the prostate for patients with suspicious MRI findings-Implications for the COVID-19 era.

OBJECTIVE: Image guided biopsies are an integral part of prostate cancer evaluation. The effect of delaying biopsies of suspicious prostate mpMRI lesions is uncertain and clinically relevant during the COVID-19 crisis. We evaluated the association between biopsy delay time and pathologic findings on subsequent prostate biopsy. MATERIALS AND METHODS: After obtaining IRB approval we reviewed the medical records of 214 patients who underwent image-guided transperineal fusion biopsy of the prostate biopsy between 2017 and 2019. Study outcomes included clinically significant (ISUP grade group ≥2) and any prostate cancer on biopsy. Logistic regression was used to evaluate the association between biopsy delay time and outcomes while adjusting for known predictors of cancer on biopsy. RESULTS: The study cohort included 195 men with a median age of 68. Median delay between mpMRI and biopsy was 5 months, and 90% of patients had a ≤8 months delay. A significant association was found between PI-RADS 5 lesions and no previous biopsies and shorter delay time. Delay time was not associated with clinically significant or any cancer on biopsy. A higher risk of significant cancer was associated with older age (P = 0.008), higher PSA (0.003), smaller prostate volume (<0.001), no previous biopsy (0.012) and PI-RADS 5 lesions (0.015). CONCLUSIONS: Our findings suggest that under current practice, where men with PI-RADS 5 lesions and no previous biopsies undergo earlier evaluation, a delay of up to 8 months between imaging and biopsy does not affect biopsy findings. In the current COVID-19 crisis, selectively delaying image-guided prostate biopsies is unlikely to result in a higher rate of significant cancer.