Metabolic syndrome and the urinary microbiome of patients undergoing percutaneous nephrolithotomy.

Objective: To identify possible stone-promoting microbes, we compared the profiles of microbes grown from stones of patients with and without metabolic syndrome (MetS). The association between MetS and urinary stone disease is well established, but the exact pathophysiologic relationship remains unknown. Recent evidence suggests urinary tract dysbiosis may lead to increased nephrolithiasis risk. Methods: At the time of percutaneous nephrolithotomy, bladder urine and stone fragments were collected from patients with and without MetS. Both sample types were subjected to expanded quantitative urine culture (EQUC) and 16 S ribosomal RNA gene sequencing. Results: Fifty-seven patients included 12 controls (21.1%) and 45 MetS patients (78.9%). Both cohorts were similar with respect to demographics and non-MetS comorbidities. No controls had uric acid stone composition. By EQUC, bacteria were detected more frequently in MetS stones (42.2%) compared to controls (8.3%) (p=0.041). Bacteria also were more abundant in stones of MetS patients compared to controls. To validate our EQUC results, we performed 16 S ribosomal RNA gene sequencing. In 12/16 (75.0%) sequence-positive stones, EQUC reliably isolated at least one species of the sequenced genera. Bacteria were detected in both "infectious" and "non-infectious" stone compositions. Conclusion: Bacteria are more common and more abundant in MetS stones than control stones. Our findings support a role for bacteria in urinary stone disease for patients with MetS regardless of stone composition.

F-SHARP: a Phase I/II trial of focal salvage high-dose-rate brachytherapy for Radiorecurrent prostate cancer.

BACKGROUND: Intraprostatic local radiorecurrence (LRR) after definitive radiation is being increasingly identified due to the implementation of molecular positron emission tomography (PET)/computed tomography (CT) imaging for the evaluation of biochemical recurrence. Salvage high-dose rate (HDR) brachytherapy offers a promising local therapy option, with encouraging toxicity and efficacy based on early series. Furthermore, the incorporation of advanced imaging allows for focal HDR to further reduce toxicity to maximise the therapeutic ratio. The objectives of the 'focal salvage HDR brachytherapy for locally recurrent prostate cancer in patients treated with prior radiotherapy' (F-SHARP) trial are to determine the acute and late toxicity and efficacy outcomes of focal salvage HDR brachytherapy for LRR prostate cancer. STUDY DESIGN: The F-SHARP is a multi-institutional two-stage Phase I/II clinical trial of salvage focal HDR brachytherapy for LRR prostate cancer enrolling patients at three centres. ENDPOINTS: The primary endpoint is the acute radiation-related Grade ≥3 Common Terminology Criteria for Adverse Events (CTCAE, version 4.03) genitourinary (GU) and gastrointestinal (GI) toxicity rate, defined as within 3 months of brachytherapy. Secondary endpoints include acute and late CTCAE toxicity, biochemical failure, patterns of clinical progression, disease-specific and overall survival, and health-related quality of life, as measured by the International Prostate Symptom Score and 26-item Expanded Prostate Cancer Index Composite instruments. PATIENTS AND METHODS: Key eligibility criteria include: biopsy confirmed LRR prostate adenocarcinoma after prior definitive radiation therapy using any radiotherapeutic modality, no evidence of regional or distant metastasis, and cT1-3a Nx or N0 prostate cancer at initial treatment. All patients will have multiparametric magnetic resonance imaging and molecular PET/CT imaging if possible. In Stage 1, seven patients will be accrued. If there are two or more GI or GU Grade ≥3 toxicities, the study will be stopped. Otherwise, 17 additional patients will be accrued (total of 24 patients). For Stage 2, the cohort will expand to 62 subjects to study the efficacy outcomes, long-term toxicity profile, quality of life, and compare single- vs multi-fraction HDR. Transcriptomic analysis of recurrence biopsies will be performed to identify potential prognostic and predictive biomarkers.

Using Intraoperative Portable CT Scan to Minimize Reintervention Rates in Percutaneous Nephrolithotomy: A Prospective Trial.

Background and Purpose: More than 40% of patients undergoing percutaneous nephrolithotomy (PCNL) are left with residual stone fragments and often require secondary procedures. Portable CT (PCT) technology allows surgeons to obtain intraoperative cross-sectional imaging, identify and extract residual stones immediately, and thereby reduce the need for subsequent procedures. This prospective trial evaluates how incorporation of PCT during PCNL affects perioperative outcomes. Patients and Methods: We prospectively enrolled eligible patients undergoing initial PCNL for this trial (n = 60), which entailed a single intraoperative CT abdomen and ipsilateral antegrade ureteroscopy when the surgeon felt stone treatment was visually complete. If residual fragments were identified, the surgeon continued nephroscopy to find and remove them; if not, the procedure was concluded. These patients were compared with a retrospective cohort (n = 174) who underwent initial PCNL with postoperative imaging performed the following day. Results: The two cohorts had similar demographic properties and stone characteristics, and location of percutaneous access. In the prospective arm, 50% of intraoperative PCT scans identified residual fragments, prompting continuation of surgery to remove them. This cohort had significantly higher stone-free rate (82% vs 36%, p < 0.01), lower rate of planned reintervention (7% vs 32%, p < 0.01), lower rate of urgent presentation with ureteral obstruction (0% vs 7%, p = 0.04), lower total CT-based effective radiation dose (8.4 mSv vs 14.6 mSv, p < 0.01), and shorter length of stay (2.3 days vs 3.5 days, p < 0.01) when compared with the retrospective cohort that did not use intraoperative PCT. Conclusions: Obtaining an intraoperative PCT scan during PCNL can substantially improve perioperative outcomes. Further evaluation of this modality through a randomized controlled trial is warranted. Clinical Trial Registration Number: NCT04556396.

Gender-Based Pay Gap in Urology: A Review of the Literature and Potential Solutions.

Studies have repeatedly demonstrated salary-based gender disparities in the field of Urology. These disparities persist even when accounting for contributing factors such as years of experience, hours worked, and practice setting, suggesting that inherent gender bias exists. In addition to salary discrepancies, female urologists are also less likely to be promoted and less likely to hold leadership positions as compared to male urologists. We review the data supporting these disparities and provide tangible, evidence-based solutions for the field of Urology going forward.

Health-Related Quality of Life and Toxicity After Definitive High-Dose-Rate Brachytherapy Among Veterans With Prostate Cancer.

PURPOSE: High-dose-rate (HDR) brachytherapy (BT) is a well-tolerated and effective treatment for prostate cancer. There is limited research, however, investigating toxicity outcomes with HDRBT treatment among veterans. The objective of this study is to assess the impact on health-related quality of life (hrQOL) and physician-graded toxicities associated with HDRBT as monotherapy among veterans treated at Edward Hines, Jr. Veterans Affairs Hospital in Hines, Illinois. METHODS: Between 2016 and 2019, 74 veterans with low- or intermediate-risk prostate cancer were treated with HDRBT as monotherapy with 27 Gy in 2 fractions, delivered over 2 implants. Veteran-reported hrQOL in the genitourinary (GU), gastrointestinal (GI), and sexual domains was assessed using the International Prostate Symptoms Score (IPSS) and Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire. Mixed linear effect models were used to assess differences in the hrQOL scores at follow-up compared with baseline scores. Statistically significant differences in hrQOL scores from baseline were further assessed for clinical significance, using minimal clinically important difference (MCID) evaluations. RESULTS: Median follow-up was 18 months. Veterans reported declines in GU, GI, and sexual hrQOL scores immediately after treatment, with the IPSS and EPIC-26 hrQOL scores all displaying significant decrease from baseline over time. The majority of the declines in hrQOL scores met criteria for MCID. These hrQOL scores trended toward a return to baseline, with the EPIC-26 urinary obstruction score returning to baseline at the 18-month follow-up assessment and the EPIC-26 bowel score returning to baseline at the 12-month follow-up. The IPSS, urinary incontinence, and sexual scores did not return to baseline at 18 months. The grade 2 maximum physician-graded GU, GI, and sexual toxicity rates were 65%, 5%, and 53%, respectively. There was 1 incidence of grade 3 GU toxicity but no grade 3 GI or sexual toxicity. CONCLUSIONS: HDRBT as monotherapy is a well-tolerated treatment option for veterans with low- or intermediate-risk prostate cancer, with favorable veteran-reported and physician-graded toxicities. Veterans should be educated about HDRBT as an option when counseled regarding treatment for localized prostate cancer.

Axial Diameter is Superior to Volumetric Measurement in Predicting Ureteral Stone Passage.

INTRODUCTION: We sought to investigate the clinical utility of volumetric measurements in predicting passage of symptomatic ureteral calculi. METHODS: We performed a retrospective review of patients seen in the emergency department for computerized tomography-confirmed symptomatic ureteral calculi with a subsequent discharge for trial of passage. Patient demographics and results of the passage trial were recorded. Stone parameters including location, 2-dimensional linear measurements and 3-dimensional volume measurements were calculated. Univariate and multivariate analyses were performed to evaluate the association between the aforementioned stone parameters and stone passage. RESULTS: A total of 70 patients were analyzed, of whom 37 (53%) passed their stones. On univariate analysis, patients who passed their stones had shorter axial diameters (mean±SD 3.3±1.3 mm vs 5.1±1.7 mm, p <0.01) and smaller volumes (0.03±0.02 cm3 vs 0.10±0.08 cm3, p <0.01). Stones that passed had traversed 79% of the ureter on presentation, compared to 41% for the stones that did not pass (p <0.01). Multivariate analysis demonstrated that shorter axial diameter was independently associated with stone passage (OR 0.46 [CI 0.29-0.71], p <0.01). Inclusion of stone volume measurements into the logistic regression model, however, provided no additional benefit for predicting stone passage rates (p=0.28). CONCLUSIONS: Although a stone's volume is expectedly correlated with passage, it does not seem to provide additional benefit when the stone's axial diameter and location within the ureter are known. Based on our findings, additional investment of time and resources into 3-dimensional modalities may not be warranted in this setting.

Initial Extracorporeal Shockwave Lithotripsy versus Ureteroscopy: A Re-treatment and Cost Analysis Using a Longitudinal, Population-Based Database.

INTRODUCTION: We sought to compare re-treatment rates between shockwave lithotripsy and ureteroscopy to evaluate the effectiveness of these modalities. Additionally, we aimed to compare costs associated with re-treatment. METHODS: The Healthcare Cost and Utilization Project State Ambulatory Surgery Database for Florida from 2009 to 2015 was used to identify patients who underwent shockwave lithotripsy or ureteroscopy. Patients were tracked for subsequent stone surgeries within 3 months, 6 months and 1 year. Costs of care were estimated and descriptive analyses were performed. A multivariable logistic regression model was used to determine predictors of a second procedure. RESULTS: A total of 98,011 patients underwent initial shockwave lithotripsy or ureteroscopy. Of those who underwent initial shockwave lithotripsy 21.2% had a second surgery (shockwave lithotripsy or ureteroscopy) within 3 months compared to 10% of patients who underwent initial ureteroscopy (p <0.01). On multivariable analysis, patients who underwent initial shockwave lithotripsy were more than twice as likely (OR 2.4, 95% CI 2.3-2.5) to undergo a second procedure within 3 months. Older patients were also more likely to undergo a second surgery, while African Americans, Hispanics, uninsured patients and patients with more comorbidities had decreased odds of undergoing a second surgery (all p <0.05). The per patient cost of the initial procedure plus re-treatment at the 3-month mark was $6,239 for initial shockwave lithotripsy and $5,319 for initial ureteroscopy (p <0.01). CONCLUSIONS: Patients undergoing shockwave lithotripsy are more likely than those undergoing ureteroscopy to have additional stone procedures, making shockwave lithotripsy a more expensive intervention.

Proton-pump inhibitors associated with decreased urinary citrate excretion.

INTRODUCTION: Proton-pump inhibitors (PPIs) may increase the risk of kidney stone formation, but the mechanism has not been elucidated. There is a paucity of literature evaluating the effects of PPIs on urinary metabolites and urine pH. METHODS: We performed a retrospective review of nephrolithiasis patients treated at our institution and compared patients who were taking PPIs to those who were not at the time of their 24-h urine collections. Hierarchical multivariate linear regression was used to evaluate the independent relationship between PPI use and urinary mineral composition. RESULTS: We identified 301 consecutive patients, 88 (29%) of whom were taking PPIs at the time of their 24-h urine collections. Patients taking PPIs were older and more likely to have medical comorbidities associated with metabolic syndrome such as hypertension, diabetes, and dyslipidemia (p < 0.01). Controlling for these factors, patients taking PPIs were found to have 12% lower 24-h urine citrate excretion (ß = - 0.12, ΔF = 4.24, p = 0.04). There were no other differences in urinary mineral composition between the groups. CONCLUSION: Our findings suggest that patients who take PPIs regularly may be at risk for decreased urinary citrate excretion. The consequent decrease in urinary citrate may become clinically significant for patients with other predisposing factors for hypocitraturia.

Patient and physician reported toxicity with two-fraction definitive high-dose-rate prostate brachytherapy: the impact of implant interval.

PURPOSE: High-dose-rate (HDR) brachytherapy is an effective method of treating localized prostate cancer. There are limited data on the relationship between implant interval and outcomes. This study aims to assess if the implant interval between HDR treatments has an impact on patient-reported health-related quality of life (QOL) and physician-graded toxicity in men treated for localized prostate cancer. MATERIAL AND METHODS: Patients were treated with HDR brachytherapy as monotherapy with 27 Gy in 2 fractions, given over two implants, performed 1-2 weeks apart. Patients were dichotomized into one-week and two-week cohorts. Patient-reported EPIC-26 genitourinary (GU), gastrointestinal (GI), and sexual QOL were assessed. Linear regression, chi-squared testing, and generalized linear mixed effect models were used to assess the differences in patient characteristics, patient-reported QOL, and physician-graded toxicity. RESULTS: Outcomes of 122 patients were analyzed. Median follow-up was 18 months. Patient-reported GU and GI QOL worsened after treatment with a return towards baseline over time, while patient-reported sexual QOL worsened after treatment, but did not return towards baseline. There were no differences in patient-reported health related QOL as a function of implant interval. Maximum physician-graded GU, GI, and sexual toxicity rates of grade 2 or 3 were 68%, 3%, and 53%, respectively. There was no difference in rates of grade 2 or 3 toxicity as a function of implants interval. CONCLUSIONS: HDR brachytherapy for prostate cancer is a well-tolerated treatment. The interval between treatments is not associated with differences in patient-reported QOL or physician-graded toxicities.

Association of Impaired Renal Function With Changes in Urinary Mineral Excretion and Stone Composition.

OBJECTIVE: To investigate the effect of kidney function on stone composition and urinary mineral excretion in patients undergoing surgical intervention for nephrolithiasis. METHODS: Using our institutional kidney stone database, we performed a retrospective review of stone patients who underwent surgical intervention between 2004 and 2015. Patients' demographic information, 24-hour urinary mineral excretion, and stone characteristics were reported. The patients' estimated glomerular filtration rates (eGFR) were compared with their stone compositions and 24-hour urine mineral excretions. RESULTS: A statistically significant difference was noted between the groups, with uric acid stones being associated with lower eGFR and calcium phosphate stones associated with higher eGFR. No relationship could be demonstrated between eGFR and calcium oxalate or struvite stones. Patients with lower eGFR also demonstrated a statistically significant association with lower urinary pH as well as lower urinary excretion of calcium and citrate. CONCLUSION: While various factors have been found to play significant roles in kidney stone formation and composition, our findings demonstrate a definite relationship between these and renal function. This paper highlights the fact that renal function evaluation should be considered an important component in the evaluation, counseling, and management of patients with nephrolithiasis.

Paravertebral block for percutaneous nephrolithotomy: a prospective, randomized, double-blind placebo-controlled study.

PURPOSE: Percutaneous nephrolithotomy (PCNL) is performed commonly in patients with large kidney stones, but the management of their postoperative pain presents a major challenge. While it is not routinely performed in PCNL patients, paravertebral block (PVB) has been described as an effective strategy for pain control after various non-urologic surgeries. This trial aims to assess the effect of paravertebral blockade on intraoperative and postoperative opioid use as well as postoperative pain control in patients undergoing PCNL. METHODS: This was a prospective, randomized, double-blind, placebo-controlled study. Patients who consented to participate were randomly assigned to undergo either PVB or a placebo intervention preoperatively. The patient, surgeon, and anesthesia team were all blinded to the randomization. The outcome parameters were intraoperative opioid requirement, postoperative visual analog scale (VAS) pain scores, postoperative opioid use, and postoperative antiemetic use. RESULTS: 23 patients were enrolled in each arm of the study, and the two groups had no significant differences in baseline demographic or clinical characteristics. Patients in the PVB group had significantly lower intraoperative opioid use, postoperative opioid use, frequency of opioid use, and antiemetic. Patients in the PVB group also had lower postoperative VAS pain scores. There were no patients who suffered from complications attributable to PVB. CONCLUSION: The results of this randomized, double-blind, placebo-controlled trial suggest that PVB should be considered an effective strategy to reduce opioid requirement and improve pain control for patients undergoing PCNL.

Transitioning From a Low-Dose-Rate to a High-Dose-Rate Prostate Brachytherapy Program: Comparing Initial Dosimetry and Improving Workflow Efficiency Through Targeted Interventions.

PURPOSE: We transitioned from a low-dose-rate (LDR) to a high-dose-rate (HDR) prostate brachytherapy program. The objective of this study was to describe our experience developing a prostate HDR program, compare the LDR and HDR dosimetry, and identify the impact of several targeted interventions in the HDR workflow to improve efficiency. METHODS AND MATERIALS: We performed a retrospective cohort study of patients treated with LDR or HDR prostate brachytherapy. We used iodine-125 seeds (145 Gy as monotherapy, and 110 Gy as a boost) and preoperative planning for LDR. For HDR, we used iridium-192 (13.5 Gy × 2 as monotherapy and 15 Gy × 1 as a boost) and computed tomography-based planning. Over the first 18 months, we implemented several targeted interventions into our HDR workflow to improve efficiency. To evaluate the progress of the HDR program, we used linear mixed-effects models to compare LDR and HDR dosimetry and identify changes in the implant procedure and treatment planning durations over time. RESULTS: The study cohort consisted of 122 patients (51 who received LDR and 71 HDR). The mean D90 was similar between patients who received LDR and HDR (P = .28). HDR mean V100 and V95 were higher (P < .0001), but mean V200 and V150 were lower (P < .0001). HDR rectum V100 and D1cc were lower (P < .0001). The HDR mean for the implant procedure duration was shorter (54 vs 60 minutes; P = .02). The HDR mean for the treatment planning duration dramatically improved with the implementation of targeted workflow interventions (3.7 hours for the first quartile to 2.0 hours for the final quartile; P < .0001). CONCLUSIONS: We successfully developed a prostate HDR brachytherapy program at our institution with comparable dosimetry to our historic LDR patients. We identified several targeted interventions that improved the efficiency of treatment planning. Our experience and workflow interventions may help other institutions develop similar HDR programs.

Socioeconomic Disparities in the Acute Management of Stone Disease in the United States.

INTRODUCTION: Patients admitted to the hospital with an acute, noninfected episode of urolithiasis are candidates for medical expulsive therapy, ureteral stent placement, or upfront ureteroscopy (URS). We sought to assess socioeconomic factors influencing treatment decisions in managing urolithiasis and to determine differences in outcomes based on treatment modality. MATERIALS AND METHODS: The Healthcare Cost and Utilization Project State Inpatient Database, State Ambulatory Surgery and Services Database, and State Emergency Department Database for California from 2007 to 2011 and for Florida from 2009 to 2014 were utilized. Patients who were admitted to the hospital with a primary diagnosis of kidney or ureteral stone were identified. The initial treatment modality utilized was assessed and factors that influenced that decision were analyzed. Multivariate logistic regression model was fit to determine factors independently associated with upfront URS. Lastly, outcomes of noninfected patients who underwent stent alone vs URS were compared. RESULTS: We identified 146,199 patients who had an inpatient admission with urolithiasis. Overall, 45% of patients had no intervention at the time of their evaluation. Of the 55% of patients who underwent surgical intervention, 42% underwent stent alone, 44% underwent upfront URS, 1% had a PCN tube placement, 8% underwent extracorporeal shockwave lithotripsy, while 5% underwent PCNL. On multivariate logistic regression model, minorities, younger patients, publicly uninsured patients, more comorbid patients, those admitted on the weekends, and those admitted to an academic institution had significantly lower odds of undergoing upfront URS. Secondary analysis demonstrated clinical and economic advantages of upfront URS vs stent alone in eligible patients. CONCLUSION: Upfront URS is an overlooked procedure that has clinical and cost-saving implications. Unfortunately, minorities, publicly insured patients, and those admitted on the weekend are less likely to undergo upfront URS, a disparity that should be addressed by urologist.