Adult Urology

2020


December 4, 2020 - AUA Western Section

Suzanne M. Lange, MD and 4th year urology resident at the University of Utah presents at the AUA Western Section on Updated Imaging Trends in Men with Newly Diagnosed Prostate Cancer. Objectives of the study include: 1. Evaluate recent imaging trends in prostate cancer staging by risk group and 2. Characterize imaging utilization by appropriateness and understand risk factors for inappropriate use.

Suzanne M. Lange MD, Mouneeb M. Choudry, Trevor C. Hunt, Jacob P. Ambrose MS, William T. Lowrance MD MPH MBA, Heidi A. Hanson PhD, Brock B. O’Neil MD

View the full poster here:


aast nomogram validaation research poster

Validation of a Nomogram Predicting Bleeding Control Interventions After High-Grade Renal Trauma

Sorena Keihani MD,MSc, Joel Gross MD, Ryan Joyce MD, Sherry Wang MD, Douglas Rogers MD, Judith Hagedorn MD, J. Patrick Selph MD, Rachel Sensenig MD, Rachel Moses MD,MPH, Shubham Gupta MD, Nima Baradaran MD, Joshua Broghammer MD, Angela Presson PhD, Raminder Nirula M.D.,M.P.H., Jeremy Myers MD Department of Surgery, University of Utah

Introduction

Renal trauma grading has a limited ability to distinguish patients who will need interventions after renal trauma. A nomogram incorporating both clinical and radiologic factors has been previously developed to predict bleeding control interventions after high-grade renal trauma (HGRT). We aimed to externally validate this nomogram using multi-center data from level-1 trauma centers.

Methods

We gathered HGRT (AAST grades III-V) data from 7 Level-1 trauma centers. Two radiologists, blinded to the intervention data, reviewed the initial CT scans, when available. Nomogram variables included: 1. trauma mechanism (penetrating vs. blunt); 2. hypotension/shock; 3. concomitant injury (i.e. any solid organ, gastrointestinal, spinal cord, or major vascular injury, or pelvic fracture); 4. vascular contrast extravasation (VCE); 5. pararenal hematoma extension (beyond aorta on left or IVC on right or into the pelvis); and 6. hematoma rim distance (HRD, i.e. largest measure from the edge of the kidney to the hematoma). Bleeding interventions included nephrectomy, partial nephrectomy, renorrhaphy, renal packing, and renal angioembolization. Mixed-effect logistic regression, with clustering by facility, was used to assess the associations. The prediction accuracy of the nomogram was assessed using the area under the receiver operating characteristic curve (AUC) and its 95% confidence interval (CI).

Results

A total of 560 HGRT patients with a median (interquartile range) age of 32 (23-47) years were included. Median injury severity score was 27 (17-38). Trauma mechanism was blunt in 89%. Injuries were grade III, IV, and V in 58%, 35%, and 7%. Overall, 71% had concomitant injuries and 21% presented in shock. Using initial CT scans, 14% had VCE and 37% had pararenal extension of hematoma. Median HRD was 1.7 (0.9-2.6) cm and 14% had an HRD≥3.5 cm. Overall, 88% underwent expectant management and 12% underwent bleeding control interventions including 34 angioembolizations and 26 nephrectomies. Presence of VCE was associated with 7.5-fold increase in odds of bleeding interventions (95% CI: 4.3–13.2). Every cm increase in HRD was associated with 88% increase in odds of bleeding interventions (OR:1.88; 95% CI: 1.61–2.19) and an HRD≥3.5 cm was associated with 7.7-fold increase in odds of intervention (95% CI: 4.4–13.6). In the multivariable analysis validating the nomogram variables, the model provided excellent discrimination (AUC: 0.88; 95% CI: 0.84–0.92).

Conclusions

Our results reinforce the importance of select radiologic findings in predicting interventions after renal trauma. The prediction accuracy of the proposed nomogram remains high using external data. These variables can help to better risk stratify renal injuries and to potentially reduce the number of unnecessary renal explorations.


acs utah chapter nx mortality

Nephrectomy for High-Grade Renal Trauma is Associated with Higher In-Hospital Mortality Rates

Sorena Keihani, Ross E. Anderson, Judith C. Hagedorn, J. Patrick Selph, Rachel L. Sensenig, Rachel A. Moses, Shubham Gupta, Nima Baradaran, Joshua A. Broghammer, Richard A. Santucci, Frank N. Burks, Sean P. Elliott, Bradley A. Erickson, Benjamin B. Breyer, Bryan B. Voelzke, Raminder Nirula, & Jeremy B. Myers

Introduction

Nephrectomy can be avoided in most patients even in cases of high-grade renal trauma (HGRT) and is often reserved for hemodynamically unstable patients. However, the consequences of nephrectomy in acute trauma management are unknown. We hypothesized that undergoing nephrectomy would be associated with higher mortality rates after trauma.

Methods

We gathered renal trauma data from 21 Level-1 trauma centers through the Multi-institutional Genito-Urinary Trauma Study. Patients with HGRT (AAST grades III-V) were included. Mixed-effect univariable Poisson regression, with clustering by facility, was used to assess the association between nephrectomy and mortality. Multivariable regression was performed to control for age, injury severity score (ISS), shock, and Glasgow Coma Scale (GCS).

Results

A total of 1,176 HGRT patients were included. Mean age was 36.2±16.8 and trauma mechanism was blunt in 78%. Injuries were submitted as grades III, IV, and V in 55%, 35%, and 10%. There were 96 (8%) mortalities and 129 (11%) nephrectomies. Rate of mortality was higher in the nephrectomy group (21.7% vs. 6.5%, P<0.001). Those who died were older, had higher ISS, lower GCS, and higher rates of shock. Nephrectomy was associated with higher risk of death in both univariable (RR: 3.34; 95% CI: 2.15–5.19) and multivariable models (RR: 2.62, 95% CI: 1.61–4.24).

Conclusions

Nephrectomy was associated with higher mortality in the acute trauma setting even when controlling for shock, overall injury severity, and head injury. These results should be confirmed using larger databases controlling for multiple factors to find the potential causes behind this association.


aua decision fatigue poster

Decision Fatigue in Prostate-Specific Antigen (PSA) Testing

Trevor C. Hunt*, Jacob P. Ambrose, Benjamin Haaland, Heidi A. Hanson, Brock B. O'Neil, Salt Lake City, UT

Introduction and Objective

Low-value PSA testing is responsible for substantial waste and potential harm to patients, yet it accounts for nearly half of prostate cancer (PCa) screening. Decision fatigue, the progressive decline in consistency and quality of choices with repetitive decision-making, has been observed in breast and colorectal cancer care. Our aim was to determine whether low-value PSA testing patterns by outpatient providers are consistent with decision fatigue.

Methods

Men without PCa at a large academic health system from July 2011eJune 2018 were identified. Outpatient encounters across various specialties were stratified by clinical guidelines as whether a PSA test order would be appropriate or low-value. The primary endpoint was whether a PSA test was ordered. Logistic generalized estimating equations were used to analyze PSA test likelihood by appropriateness, with spline functions representing trends by hour. Models were adjusted for patient-, provider-, and appointment-level factors and stratified by specialty.

Results

Of 1,761,815 outpatient encounters, a PSA test was ordered during 3.7% when it would be considered appropriate and 1.8% when it was low-value. The overall likelihood of an encounter resulting in any PSA test was greatest at 8:00am, tapering off by 12:00pm (OR [0.66; 0.58e0.75) and persisting through 4:00pm (OR[0.65; 0.56e0.77). Testing patterns differed between specialties (Figure), with non-urologists exhibiting a proportionately greater decline in the likelihood of an appropriate test as the day progressed. Urologists showed a different pattern, with appropriate decisions relatively preserved even as inappropriate testing declined in the middle of the day.

Conclusions 

In a framework where PSA testing decisions are considered complex and the default position is to not test, PSA testing among non-urologists is consistent with decision fatigue. That is, testing is most likely early in the day when complex decisions are easiest. The pattern of PSA testing among urologists is different and may not be explained by decision fatigue. This may be due to differences in the default position for testing or greater PSA testing expertise, which lightens the cognitive load of decision-making.


aua germline research poster

Patient-level factors are not associated with improved identification of germline pathogenic variants in men with prostate cancer

Trevor C. Hunt1, Samantha E. Greenberg2, Jacob P. Ambrose1,3, Brock B. O’Neil1x, Jonathan D. Tward4x

Affiliations

1Division of Urology, Department of Surgery; 2Genetic Counseling Shared Resource; 3Population Sciences, Department of Surgery; 4Department of Radiation Oncology; 1-4Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA; XCo-senior authors

Background

Pathogenic variants (PV) in genes associated with hereditary cancer risk account for over 10% of cases in men with metastatic prostate cancer (PCa). National Comprehensive Cancer Network (NCCN) guidelines encouraging germline testing (GT) in metastatic PCa were recently expanded to include all men with high risk, very high risk, or regional PCa. Previously, we showed that the rate of PV findings did not significantly decrease after expansion of these criteria. In this study, we sought to identify factors associated with a PV finding.

Methods

Men with PCa underwent multi-gene GT for PVs from April 2016 – December 2018 according to NCCN guidelines pre- (2016-17) and post-expansion (2018). The association of patient-level factors of interest with a positive GT result, where at least one PV was identified, was modeled with univariate logistic regression while overall model significance was validated with ANOVA.

Results

Of 410 men undergoing GT, 44 (10.7%) positive and 366 (89.3%) negative tests resulted. Mean age at diagnosis was 62.2 years. Positive testing remained stable from 9.4% to 11.2% following guideline expansion (p=0.62). None of the patient-level factors of interest were significantly associated with increased odds of a positive GT result in any model generated. These factors included age at diagnosis, race, pretreatment PSA, Gleason grade group, NCCN risk group, and family history of cancer (breast and ovarian, prostate, any cancer). Model p-values ranged from 0.84 for Gleason grade group to 0.12 for family history of any cancer.

Conclusions

Future work will need to further elucidate the role of patient-level factors in identifying men with PCa at increased risk for harboring a germline PV. Nonetheless, the lack of identification of other factors associated with positive GT results and a stable PV detection rate of roughly 10% support the recent expansion of NCCN testing guidelines. Given these findings, consideration of even broader NCCN criteria for GT may be justified.

2019


asa az+cc predictors research poster

Obesity Is an Independent Predictor for Combination Therapy with Anastrozole in Hypogonadal Men Treated with Clomiphene Citrate

Sorena Keihani *, Nathan J Alder, Philip J Cheng, Alexander W. Pastuszak, James M. Hotaling

Introduction and Objectives

Clomiphene citrate (CC) can be used in treatment of male hypogonadism, with one of its side effects being hyperestrogenemia, necessitating addition of aromatase inhibitors. We hypothesized that obese men started on CC are more likely to need combination therapy with anastrozole (AZ) and aimed to assess the conversion rate from CC monotherapy to combination CC+AZ therapy and its predictors.

Methods

Review of data from hypogonadal men treated with CC in a single center from 2013-2018 was performed. Patient age, body mass index (BMI), blood pressure, and hormones (follicle stimulating hormone [FSH], luteinizing hormone [LH], total testosterone [TT], estradiol [E], sex-hormone binding globulin [SHBG], and albumin) were obtained at baseline. Obesity was defined as BMI≥30 kg/m2. Cox proportional hazards models were used to identify predictors of conversion to combination CC+AZ therapy.

Results

319 males were included. Mean age was 35.2±7.2 years and patients were followed for a median (IQR) of 9 (4–17) months on therapy. Following CC therapy, 97 (30%) were started on combination therapy (due to increased E [>50 pg/ml] and/or hyperestrogenic symptoms) at a median (IQR) of 2 (2–4) months. Patients who received combination therapy had higher baseline BMI (34.8±8.5 vs. 30.2±6.0 kg/m2; P<0.001), as well as higher estradiol levels and systolic blood pressure than those who did not. Lower baseline TT and albumin were also observed in men on CC+AZ. Overall, 50% of included men were obese and the obesity rate was higher in men on combination therapy (65% vs. 43%, P<0.001). In multivariable regression after controlling for baseline age, TT, blood pressure, and albumin, obesity (HR:1.7, 95% CI:1.03–3.00, P=0.04) [Figure 1], and baseline E level (HR: 1.07, 95% CI: 1.04–1.11, P<0.001) were significant predictors of conversion to combination therapy.

Conclusions

Following CC monotherapy, 30% of men required combination therapy with AZ. Higher baseline BMI and estradiol levels predict the need for combination therapy, and obese patients are more likely to require AZ. These data can facilitate identification of patients at risk for significant elevations in estradiol levels who may require CC+AZ therapy.


aua grading agreement research poster

Reproducibility of the American Association for the Surgery of Trauma (AAST) Renal Injury Grading for High-Grade Renal Injuries

Sorena Keihani, MD, Gregory Stoddard*, MS, Douglas Rogers*, MD, Bryn Putbrese*, MD, Bradley Erickson, MD, MS, Sean Elliott, MD, MS, Benjamin Breyer, MD, MAS, Richard Santucci, MD, Frank Burks, MD, Marta Heilbrun*,MD, James Hotaling, MD, MS, Raminder Nirula*, MD, MPH, & Jeremy Myers, MD,
for the Genito-Urinary Trauma Study Group: Salt Lake City, UT

(Presentation to be made by Dr. Sorena Keihani)

Introduction

The American Association for the Surgery of Trauma (AAST) organ injury scaling is the most widely used grading system for renal trauma. However, reproducibility of the AAST grading is not well studied. We aimed to assess the agreement for AAST renal trauma grading between radiologists and the grades entered in a multi-center database of high-grade renal trauma.

Methods

Data on high-grade renal trauma (AAST grades III-V) was collected from 14 Level-1 trauma centers from 2014-2017. Patients with initial CT scans were included. 2 radiologists, blinded to the provided grades and outcomes, reviewed the scans to re-grade the injuries according to the 1989 original AAST grading (O-AAST) and were allowed to re-grade the injuries as grades I-V. After measuring the inter-radiologist agreement, both radiologists were asked to reach consensus on the discrepancies. The reproducibility of AAST grading was evaluated using weighted Kappa analysis for ordinal variables. Inter-radiologists agreement as well as final agreement between re-graded readings (O-AAST) and the injury grades submitted by the centers (C-AAST) were measured. Agreement was interpreted based on the kappa coefficient as slight (0-0.20), fair (0.21-0.40), moderate (0.41-0.60), substantial (0.61-0.80), and almost perfect (0.81-1.00).

Results

322 patients met the inclusion criteria. Injuries were submitted by centers as grade III (59.8%), grade IV (33.1%), and grade V (7.1%). Upon re-grading the injuries, inter-radiologist agreement was substantial for O-AAST (Kappa: 0.76, 95% CI: 0.66-0.84). After resolving the discrepancies, injuries were re-graded using the O-AAST as non-gradable (1.2%), grade I (0.9%), grade II (4.6%), grade III (71.5%), grade IV (16.6%), and grade V (5.2%). Comparing the O-AAST re-grading and C-AAST, the agreement was moderate (Kappa: 0.50, 95% CI: 0.40-0.60). Overall, 27% of injuries were downgraded, 5% were upgraded, and 68% remained the same.

Conclusion

The agreement between center-reported renal injury grades and re-grading of injuries by readers blinded to the outcomes was moderate as most injuries were downgraded upon re-reading. These findings may imply over-grading of the renal injuries as reported by the centers and may have implications for using AAST grading for both predicting the need for interventions, as well as using administrative data for research purposes.

Table: Comparison of renal trauma grades as submitted by the centers (C-AAST) and as re-graded by radiologists blinded to the outcome (O-AAST). Each cells represent number of injuries and the percentage in relation to all patients.

 

O-AAST

 

C-AAST

Grade-I

Grade-II

Grade-III

Grade-IV

Grade-V

Total

Grade-III

2 (0.6%)

12 (3.7%)

171 (53.1%)

8 (2.5%)

1 (0.3%)

194 (60.2%)

Grade-IV

1 (0.3%)

3 (0.9%)

58 (18.0%)

39 (12.1%)

6 (1.9%)

107(33.2%)

Grade-V

0 (0%)

0 (0%)

4 (1.3%)

7 (2.2%)

10 (3.1%)

21 (6.6%)

Total

3 (0.9%)

15 (4.6%)

233 (72.4%)

54 (16.8%)

17 (5.3%)

322 (100%)

 


smsna clomid research poster

Introduction

Clomiphene citrate (CC) is commonly used in the treatment of male hypogonadism/infertility and stimulates pituitary gonadotropin release. Patients variably respond to CC treatment, but whether baseline gonadotropin levels can be used to select patients for CC treatment is unknown.

Objective

To investigate the role of baseline gonadotropins in predicting the biochemical response to CC treatment.

Methods

Retrospective review of data from hypogonadal men treated with CC in two high-volume fertility centers was performed between 2013 and 2018. Patient age, body mass index (BMI), and baseline hormones (follicle stimulating hormone [FSH], luteinizing hormone [LH], and total testosterone [TT]) were obtained. Men on exogenous testosterone or gonadotropins within 6 months of CC treatment were excluded. CC starting dose varied from 25-50 mg every day to every other day. Response in treatment was measured as changes in continuous TT levels within 6 months of initiating CC treatment. Linear and curvilinear (quadratic fit) correlations were assessed between baseline gonadotropins and changes in TT levels. We defined the optimal slope transition point, fitting a piecewise linear regression at a threshold that maximized the multiple R statistics. Linear regression models adjusted for age, BMI, and time on CC therapy were fitted to assess the associations between baseline LH and FSH levels with treatment response.

Results

A total of 332 men were included. Mean age was 36.2±8.2 years. Median time to initial follow-up was 6 weeks (25th–75th interquartile range [IQR]: 4-9 weeks). Median FSH and LH levels at baseline were 4.3 mIU/L (1.7–7.3) and 4.2 mIU/L (2.8–6.2), respectively. TT levels increased significantly on CC treatment (mean change: 361 ng/dL, 95% CI: 325–397) with 73% of men having at least 200 ng/dL increase over baseline TT levels. In univariable linear regression models, only age was significantly associated with TT response (beta coefficient: -5.7, 95% CI: -8.3 to -3.1). Neither the baseline LH nor FSH significantly predicted TT response in linear regression. A quadratic correlation better fit the data for gonadotropins with optimal transition points of 10 mIU/L for FSH and 4.5 mIU/L for LH (Figure 1). No correlation between FSH and TT response was observed when baseline FSH was <10 mIU/L. For patients with FSH≥10 (n=43, 14%), TT response decreased for each unit increase in FSH (slope: -10.6, 95% CI: -18.0 to -3.1) although they still demonstrated a robust average increase in TT (mean TT change: 325.6 ng/dL, 95% CI: 300.7–350.6 vs. mean TT change: 332.8 ng/dL, 95% CI: 265.8–399.8). For patients with baseline LH<4.5, TT response increased with increasing LH levels (beta coefficient: +51.2, 95%CI: +12.7 to +89.8). No correlation between LH and TT response was observed if baseline LH was ≥4.5 mIU/L (P-value=0.12) [n=114, 45%].

Conclusion

CC treatment results in significant increases in testosterone levels in most men. Baseline LH and FSH are not strong predictors for treatment response to CC. Patients with a diverse range of baseline gonadotropins can have good biochemical response with CC, and baseline FSH and LH should not be used as exclusion criteria for CC therapy.


nephrectomy urology research poster

Presented by Ross Anderson, GURS fellow, at the American Association for Surgery Trauma: Dallas, Texas, 2019

Nephrectomy is independently associated with increased mortality after renal trauma: An analysis from the National Trauma Data Bank 2007-2016

Ross Anderson, Sorena Keihani, Rupam Das, Heidi Hanson, Raminder Nirula, James Hotaling, Jeremy B. Myers

Introduction

The vast majority of high-grade renal trauma can be managed conservatively; however, nephrectomy is still common in the acute management setting. When controlling for multiple patient and injury severity measures, we sought to determine if nephrectomy was associated with increased mortality within the National Trauma Data Bank (NTDB).

Methods

We identified renal trauma patients from NTDB from 2007-2016. We excluded patients <18 years old, mechanisms other than blunt or penetrating trauma, missing facility codes, severe head injuries (abbreviated injury severity (AIS) score 6 or 7), and death within 4 hours of admission. We performed conditional logistic regression analysis to determine if nephrectomy was an independent predictor of mortality controlling for: age, sex, race (Caucasian / non-Caucasian), ethnicity (Hispanic / non-Hispanic), mechanism of injury (blunt / penetrating), shock (systolic BP <90 on admission), blood transfusion (yes/ no), Glasgow Coma Score (GCS), Revised Trauma Score (RTS), and Injury Severity Score (ISS).  We did not control for renal AIS score because of concern over inaccuracies in the NTDB.

Results

We identified 62,987 renal trauma patients that met our inclusion criteria; 75.8% were male, and 82.6% had a blunt mechanism of injury. Nephrectomy was performed in 3,348 (5.29%). In patients undergoing nephrectomy, 569 (17%) died vs 3,467 (5.81%) in the non-nephrectomy group. On multi-variable logistic regression, nephrectomy was associated with 72% increased odds of death (OR 1.72, 95%CI 1.56-1.91). Other significant associations with death included: age, non-Caucasian race, penetrating mechanism, hypotension, blood transfusion, lower GCS, lower RTS, and higher ISS (table 1).
 
Table 1: Logistic regression model for predicting mortality in renal trauma patients

Variables OR 95% CI Limit P-Value
Age* 1.0332 1.032-1.035 < 0.001
Sex (male) 0.9705 0.902-1.045 0.425
Race (non-caucasian) 1.115 1.031-1.206 0.006
Ethnicity (hispanic) 0.970 0.947-1.176 0.332
Mechanism (penetrating) 1.355 1.223-1.503 <0.001
Hypotension 1.249 1.133-1.376 < 0.001
Blood transfusion 1.479 1.368-1.599 <0.001
Glasgow Coma Score (GCS)* 0.912 0.894-0.930 < 0.001
Revised Trauma Score (RTS)* 0.836 0.794-0.881 < 0.001
Injury Severity Score (ISS)* 1.049 1.046-1.051 < 0.001
Nephrectomy 1.724 1.557-1.909 < 0.001
*Each 1-point increase in GCS improved survival by 8.8% and in RTS by 16.4%; each 1-point increase in ISS worsened survival by 4.9%; each year increase in age worsened survival by 3.3%

Discussion

In the NTDB, nephrectomy is associated with 72% increased risk of mortality even after adjusting for demographic, injury characteristics, and multiple measures of overall injury severity. In many circumstances, nephrectomy cannot be avoided in the management of acute trauma; however, nephrectomy may impact overall survival and is imperative to be avoided when possible.