Publications by authors named "Sudhir Isharwal"

30 Publications

  • Page 1 of 1

Single-port robotic inguinal lymph node dissection: A safe and feasible option for penile cancer.

Surg Oncol 2021 Sep 16;38:101633. Epub 2021 Jul 16.

Department of Urology, Oregon Health and Science University, Portland, OR, USA.

Introduction: Inguinal lymph node dissection (ILND) is essential to the accurate staging of advanced penile cancer and in determining prognosis. Open ILND is associated with significant morbidity. The robotic-assisted approach has been described with comparable nodal yield with the advantage of decreased postoperative complications when studied with the multiport robotic platform. This video shows our approach for an ILND with the Intuitive single port (SP) robotic platform.

Method: A 54-year-old man underwent a partial penectomy for a penile mass that revealed squamous cell carcinoma invading the corpus spongiosum (pT2). Patient had non-palpable lymph nodes on physical examination. We proceeded with the bilateral inguinal lymph node dissection using the Intuitive da Vinci Single-Port Robot.

Results: A standard template dissection was performed on both sides. Due to nodal enlargement noted on the pre-operative CT scan on the right side, superficial and deep ILND were performed on that side. Intra-operative frozen section pathologies of superficial lymph nodes were negative on the left side. Bilateral saphenous veins were preserved. Total procedure time was 4 hours and 51 minutes in duration with minimal blood loss noted (<30 mL). Pathology revealed one 4.5cm superficial positive node on the right with no extra-nodal extension and no other positive nodes. No complications were noted. He was discharged on post-operative day 1 with minimal pain or leg swelling.

Conclusions: We describe the technique and feasibility of ILND using the SP robotic platform. This approach has the potential to reduce morbidity with comparable nodal dissection as the open approach.
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http://dx.doi.org/10.1016/j.suronc.2021.101633DOI Listing
September 2021

Primary Focal Therapy for Localized Prostate Cancer: A Review of the Literature.

Oncology (Williston Park) 2021 May 13;35(5):261-268. Epub 2021 May 13.

Department of Urology, Oregon Health & Science University, Portland, OR.

This article describes the available focal therapy options for primary treatment of localized PCa, along with their respective outcomes, drawbacks, and applicability.
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http://dx.doi.org/10.46883/ONC.2021.3505.0261DOI Listing
May 2021

Gender Representation in American Urological Association Guidelines.

Urology 2021 Mar 4. Epub 2021 Mar 4.

Department of Urology, Oregon Health and Science University, Portland, OR.

Objective: To study patterns and factors associated with female representation in the American Urological Association (AUA) guidelines.

Methods: We gathered publicly available information about the panelists, including the AUA section, practice setting, academic rank, fellowship training, years in practice, and H-index. The factors associated with the proportion of female panelists and trends were investigated. We also examined the proportion of female panelists in the European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) urology guidelines.

Results: There were 483 non-unique panelists in AUA guidelines, and 17% are female. Non-urologist female panelists in AUA guidelines represented a higher proportion than female urologists (30% vs 13%, P<0.0001). Compared with male panelists, females had lower H-indices (median 23 vs 35, P<0.001), and fewer were fellowship-trained (77.2% vs 86.8%; P=0.042). On multivariate analysis, non-urologists and panelists with lower H-indices were more likely to be female but there was no association between guideline specialties, academic ranking, geographic section, years in practice, and fellowship training with increased female authorship. Overtime, the proportion of female participation in guidelines remained stable. In the EAU and NCCN guideline panels, 12.2% and 10.7% were female, respectively.

Conclusion: Female representation among major urologic guidelines members is low and unchanged overtime. Female urologist participation was proportional to their representation in the urology workforce. Being a non-urologist and lower H-indices were associated with female membership in guideline panels.
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http://dx.doi.org/10.1016/j.urology.2021.02.027DOI Listing
March 2021

In-Bore Versus Fusion MRI-Targeted Biopsy of PI-RADS Category 4 and 5 Lesions: A Retrospective Comparative Analysis Using Propensity Score Weighting.

AJR Am J Roentgenol 2021 Sep 9:1-8. Epub 2021 Sep 9.

Department of Diagnostic Radiology, Oregon Health and Science University, Mail Code L340, 3181 SW Sam Jackson Park Rd, Portland, OR 97239.

Few published studies have compared in-bore and fusion MRI-targeted prostate biopsy, and the available studies have had conflicting results. The purpose of this study was to compare the target-specific cancer detection rate of in-bore prostate biopsy with that of fusion MRI-targeted biopsy. The records of men who underwent in-bore or fusion MRI-targeted biopsy of PI-RADS category 4 or 5 lesions between August 2013 and September 2019 were retrospectively identified. PI-RADS version 2.1 assessment category, size, and location of each target were established by retrospective review by a single experienced radiologist. Patient history and target biopsy results were obtained by electronic medical record review. Only the first MRI-targeted biopsy of the dominant lesion was included for patients with repeated biopsies or multiple targets. In-bore and fusion biopsy were compared by propensity score weights and multivariable regression to adjust for imbalances in patient and target characteristics between biopsy techniques. The primary endpoint was target-specific prostate cancer detection rate. Secondary endpoints were detection rate after application of propensity score weighting for cancers in International Society of Urological Pathology (ISUP) grade group 2 (GG2) or higher and detection rate with the use of off-target systematic sampling results. The study sample included 286 men (in-bore biopsy, 191; fusion biopsy, 95). Compared with fusion biopsy, in-bore biopsy was associated with significantly greater likelihood of detection of any cancer (odds ratio, 2.28 [95% CI, 1.04-4.98]; = .04) and nonsignificantly greater likelihood of detection of ISUP GG2 or higher cancer (odds ratio, 1.57 [95% CI, 0.88-2.79]; = .12) in a target. When off-target sampling was included, in-bore biopsy and combined fusion and systematic biopsy were not different for detection of any cancer (odds ratio, 1.16 [95% CI, 0.54-2.45]; = .71) or ISUP GG2 and higher cancer (odds ratio, 1.15 [95% CI, 0.66-2.01]; = .62). In this retrospective study in which propensity score weighting was used, in-bore MRI-targeted prostate biopsy had a higher target-specific cancer detection rate than did fusion biopsy. Pending a larger prospective randomized multicenter comparison between in-bore and fusion biopsy, in-bore may be the preferred approach should performing only biopsy of a suspicious target, without concurrent systematic biopsy, be considered clinically appropriate.
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http://dx.doi.org/10.2214/AJR.20.25207DOI Listing
September 2021

Urethral Mucinous Adenocarcinoma of the Prostate: An Uncommon and Diagnostically Complex Disease.

Urology 2020 Dec 10;146:e1-e2. Epub 2020 Oct 10.

Department of Urology, Oregon Health & Science University, Portland, OR.

A 66-year-old male presented with hematuria and mucosuria. A transurethral resection of the prostate revealed adenocarcinoma in situ with mucinous features. He underwent a robotic-assisted radical prostatectomy with lymph node dissection. Pathology confirmed T2 primary mucin-producing urothelial type adenocarcinoma in the prostatic urethra. Urothelial adenocarcinoma arising in the prostatic urethra is an uncommon disease that warrants clear differentiation from other malignancies due to its aggressive nature. The differential includes urologic and gastrointestinal malignancies making diagnosis complex. Accurate diagnosis is critical to providing appropriate treatment as these patients are at high risk of developing recurrence and metastatic disease.
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http://dx.doi.org/10.1016/j.urology.2020.09.039DOI Listing
December 2020

Survival outcomes and practice trends for off-label use of adjuvant targeted therapy in high-risk locoregional renal cell carcinoma.

Urol Oncol 2020 06 31;38(6):604.e1-604.e7. Epub 2020 Mar 31.

Oregon Health & Science University, Department of Urology, Portland, OR; Portland VA Healthcare System, Operative Care Division, Urology Section, Portland, OR.

Importance: The appropriate use of adjuvant targeted therapy (TT) for high-risk locoregional renal cell carcinoma (RCC) after nephrectomy is currently unclear due to mixed results from the relevant randomized controlled trials. National-level survival outcomes and practice trends for the use of adjuvant TT in the United States have not been reported.

Objective: To compare overall survival for patients who did and did not receive adjuvant TT after nephrectomy for high-risk locoregional RCC.

Design, Setting, And Participants: This cohort study reviewed the National Cancer Database from 2006 to 2015. Patients with nonmetastatic clear cell RCC who underwent nephrectomy with either stage pT3a or greater or pN+ were included.

Main Outcomes And Measures: Adjuvant TT was defined as receipt of TT within 3 months of nephrectomy. The primary end point was overall survival from initial diagnosis to date of death or censored at last follow-up. Baseline characteristics were described, and a multivariable analysis identified associations for receipt of adjuvant TT. Nearest-neighbor propensity matching was performed to create similar groups for comparison. A survival analysis was performed using Kaplan-Meier analysis and log-rank test.

Results: The final study population included 41,127 patients. Two thousand seventy-one patients (5.04%) received off-label adjuvant TT. Younger age, white race, private insurance, positive margins, pT4, and pN+ were associated with receipt of adjuvant TT. After nearest-neighbor propensity matching for clinically and statistically relevant covariates, 1,604 patients remained in the matched cohort, with statistically nonsignificant differences between the groups for all baseline characteristics. Median overall survival was 52 months for patients in the Adjuvant TT group versus 79 months for those who did not receive adjuvant TT (P < 0.001). Decreased overall survival for patients receiving adjuvant therapy was also seen in pathologic subgroups with and without lymph node involvement.

Conclusions: The propensity matched survival analysis revealed significantly decreased overall survival in patients who received off-label adjuvant TT for high-risk locoregional RCC.
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http://dx.doi.org/10.1016/j.urolonc.2020.02.028DOI Listing
June 2020

Vascularized Parenchymal Mass Preserved with Partial Nephrectomy: Functional Impact and Predictive Factors.

Eur Urol Oncol 2019 02 14;2(1):97-103. Epub 2018 Jul 14.

Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address:

Background: Percentage parenchymal mass preserved (PPMP) is a key determinant of functional outcomes after partial nephrectomy (PN); however, predictors of PPMP have not been defined.

Objective: To provide a comprehensive analysis of the functional impact of and potential predictive factors for PPMP.

Design, Setting, And Participants: We analyzed data for 464 patients managed with PN at our center with necessary studies to determine vascularized parenchymal mass and function preserved within the operated kidney. PPMP was measured from computed tomography scans <2 mo before and 3-12 mo after PN.

Intervention: PN.

Outcome Measurements/statistical Analysis: Recovery from ischemia was defined as percentage ipsilateral glomerular filtration rate (GFR) preserved normalized by PPMP. We used Pearson correlation to evaluate the relationships between GFR preserved and PPMP. Multivariable logistic regression was used to assess predictors of PPMP.

Result And Limitations: Ninety-six patients (21%) had a solitary kidney. The median tumor size and RENAL score were 3.5cm and 8, respectively. Cold/warm ischemia were utilized in 183/281 patients for which the median ischemia time were 28/20min. The median preoperative and postoperative vascularized parenchymal mass in the operated kidney were 194 and 157cm, respectively, resulting in median PPMP of 84%. GFR preservation correlated strongly with PPMP (r=0.64; p<0.001). Recovery from ischemia was suboptimal (<80%) in 71 patients (15%), while suboptimal PPMP (<80%) was a more common adverse event, occurring in 160 patients (34%; p<0.001). Multivariable analysis demonstrated that greater tumor size and complexity were associated with lower PPMP (p≤0.04), while solitary kidney and hypothermia were associated with higher PPMP (p<0.001). Longer ischemia time was also associated with lower PPMP (p=0.003), probably reflecting the complexity of the surgery. Limitations include the retrospective design.

Conclusion: PPMP correlates strongly with functional outcomes after PN, and lower PPMP is the most common and important source of functional decline after PN. Larger tumors, greater tumor complexity, and prolonged ischemia time were associated with lower PPMP, while PPMP tended to be greater for solitary kidneys, confirming that PPMP is a modifiable factor.

Patient Summary: Kidney function after partial nephrectomy primarily depends on the amount of vascularized kidney preserved by the procedure. Lower recovery of function is seen when operating on larger tumors in unfavorable locations, but preservation of the parenchymal mass can be improved when truly necessary, such as when operating on a tumor in a solitary kidney.
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http://dx.doi.org/10.1016/j.euo.2018.06.009DOI Listing
February 2019

Cystectomy for benign disease: readmission, morbidity, and complications.

Can J Urol 2018 10;25(5):9473-9479

Department of Urology, University of Kentucky, Lexington, Kentucky, USA.

Introduction: We sought to elucidate outcomes and risks associated with cystectomy and urinary diversion for benign urological conditions compared to malignant conditions.

Materials And Methods: We identified patients who underwent cystectomy and urinary diversion for benign and malignant diseases through the American College of Surgeons National Surgery Quality Improvement Program database for the period 2007-2015. Patients were selected for inclusion based upon their current procedure terminology and International Classification of Disease, Ninth revision codes. Primary outcome was 30 day morbidity including return to the operating room (OR); infectious, respiratory, and/or cardiovascular complications; readmission to the hospital; and mortality. Multivariable regression analyses were performed to identify associated factors.

Results: A total of 317 patients underwent cystectomy and urinary diversion for benign disease, and 5510 patients underwent radical cystectomy with urinary diversion for cancer. Rates of major morbidity (43.2% versus 38.6%), mortality (0.9% versus 1.9%), return to OR (5% versus 5.8%), readmission (19.7% versus 21.4%), postoperative sepsis (14.5% versus 12%), and wound complications (16.1% versus 14.2%) were similar among patients undergoing cystectomy for benign and malignant conditions. In the group with cystectomy for benign conditions, smoking (OR: 3.11) and longer operative duration (OR: 1.06) were significantly associated with increased overall morbidity. Wound complications were significantly higher in smokers (OR: 3.09) and with an ASA ≥ III (OR: 5.71) CONCLUSIONS: Patients undergoing cystectomy and urinary diversion for benign disease are at similar risk for 30 day morbidity and mortality as patients undergoing surgery for malignant conditions. Risk factors are identified that can potentially be targeted for morbidity reduction.
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October 2018

The 17-Gene Genomic Prostate Score Assay Predicts Outcome After Radical Prostatectomy Independent of PTEN Status.

Urology 2018 Nov 22;121:132-138. Epub 2018 Aug 22.

Department of Urology, Glickman Urology and Kidney Institute, Cleveland Clinic, Cleveland, OH. Electronic address:

Objective: To compare the ability of loss of phosphatase and tensin homolog (PTEN) and Genomic prostate score assay (GPS) in predicting the biochemical-recurrence (BCR) and clinical-recurrence (CR) after radical prostatectomy (RP) for clinically localized prostate cancer (PCa).

Methods: Three hundred seventy seven patients with and without CR were retrospectively selected by stratified cohort sampling design from RP database. PTEN status (by immunohistochemistry [IHC] and fluorescence in situ hybridization [FISH]) and GPS results were determined for RP specimens. BCR was defined as Prostate Specific Antigen (PSA) ≥ 0.2 ng/mL or initiation of salvage therapy for a rising PSA. CR was defined as local recurrence and/or distant metastases.

Results: Baseline mean age, PSA, and GPS score for the cohort were 61.1 years, 8 ng/dL, and 32.8. PTEN loss was noted in 38% patients by FISH and 25% by IHC. The concordance between FISH and IHC for PTEN loss was 66% (Kappa coefficient 0.278; P < .001). On univariable analysis, loss of PTEN by FISH or IHC was associated with BCR and CR (P < .05). However, after adjusting for GPS results, PTEN loss was not a significant predictor for CR or BCR (P > .1). The GPS result remained strongly associated with CR and BCR after adjusting for PTEN status (P < .001). PTEN status and GPS results only weakly correlated. GPS was widely distributed regardless of PTEN status indicating the biological heterogeneity of PCa even in PTEN-deficient cases.

Conclusion: GPS is a significant predictor of aggressive PCa, independent of PTEN status. After adjustment for GPS results, PTEN was not independently associated with recurrence for PCa.
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http://dx.doi.org/10.1016/j.urology.2018.07.018DOI Listing
November 2018

Acute Kidney Injury after Partial Nephrectomy of Solitary Kidneys: Impact on Long-Term Stability of Renal Function.

J Urol 2018 12 20;200(6):1295-1301. Epub 2018 Jul 20.

Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address:

Purpose: Acute kidney injury often leads to chronic kidney disease in the general population. The long-term functional impact of acute kidney injury observed after partial nephrectomy has not been adequately studied.

Materials And Methods: From 2004 to 2014 necessary studies for analysis were available for 90 solitary kidneys managed by partial nephrectomy. Functional data at 4 time points included preoperative serum creatinine, peak postoperative serum creatinine, new baseline serum creatinine 3 to 12 months postoperatively and long-term followup serum creatinine more than 12 months postoperatively. Adjusted acute kidney injury was defined by the ratio, observed peak postoperative serum creatinine/projected postoperative serum creatinine adjusted for parenchymal mass loss to reveal the true effect of ischemia. The long-term change in renal function (the long-term functional change ratio) was defined as the most recent glomerular filtration rate/the new baseline glomerular filtration rate. The relationship between the grade of the adjusted acute kidney injury and the long-term functional change was assessed by Spearman correlation analysis and multivariable regression.

Results: Median patient age was 64 years and median followup was 45 months. Median parenchymal mass preservation was 80%. Adjusted acute kidney injury occurred in 42% of patients, including grade 1 injury in 20 (22%) and grade 2/3 in 18 (20%). On univariable analysis the degree of the adjusted acute kidney injury did not correlate with the long-term glomerular filtration rate change (p = 0.55). On multivariable analysis adjusted acute kidney injury was not associated with a long-term functional change (p >0.05) while diabetes and warm ischemia were modestly associated with a long-term functional decline (each p <0.05).

Conclusions: Acute kidney injury after partial nephrectomy was not a significant or independent predictor of long-term functional decline in our institutional cohort. A prospective study with larger sample sizes and longer followup is required to evaluate factors associated with long-term nephron stability.
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http://dx.doi.org/10.1016/j.juro.2018.07.042DOI Listing
December 2018

Current Therapeutic Strategies in Clinical Urology.

Mol Pharm 2018 08 28;15(8):3010-3019. Epub 2018 Jun 28.

Glickman Urological and Kidney Institute, Cleveland Clinic Foundation 9500 Euclid Ave , Cleveland , Ohio 44195 , United States.

The field of urology encompasses all benign and malignant disorders of the urinary tract and the male genital tract. Urological disorders convey a huge economic and patient quality-of-life burden. Hospital acquired urinary tract infections, in particular, are under scrutiny as a measure of hospital quality. Given the prevalence of these pathologies, there is much progress still to be made in available therapeutic options in order to minimize side effects and provide effective care. Current drug delivery mechanisms in urological malignancy and the benign urological conditions of overactive bladder (OAB), interstitial cystitis/bladder pain syndrome (IC/BPS), and urinary tract infection (UTI) will be reviewed herein. Both systemic and local therapies will be discussed including sustained release formulations, nanocarriers, hydrogels and other reservoir systems, as well as gene and immunotherapy. The primary focus of this review is on agents which have passed the preclinical stages of development.
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http://dx.doi.org/10.1021/acs.molpharmaceut.8b00383DOI Listing
August 2018

Tumor Contact Surface Area As a Predictor of Functional Outcomes After Standard Partial Nephrectomy: Utility and Limitations.

Urology 2018 Jun 6;116:106-113. Epub 2018 Mar 6.

Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH. Electronic address:

Objective: To evaluate contact surface area (CSA) between the tumor and parenchyma as a predictor of ipsilateral parenchyma and function preserved after partial nephrectomy (PN). Previous studies suggested that CSA is a strong predictor of functional outcomes but the limitations of CSA have not been adequately explored.

Patients And Methods: Four hundred nineteen patients managed with standard PN for solitary tumor with necessary studies to evaluate and analyze ipsilateral preoperative or postoperative parenchymal mass and function. Parenchymal mass and CSA were measured using contrast-enhanced computed tomography <2 months prior and 3-12months after PN. CSA was calculated: 2πrd, where r = radius and d = intraparenchymal depth. Pearson-correlation evaluated relationships between CSA and ipsilateral parenchymal mass or function preserved. Multivariable regression assessed predictors of function preserved. Conceptually, the CSA paradigm should function better for exophytic tumors than endophytic ones.

Results: Median tumor size was 3.5 cm and R.E.N.A.L. was 8. Median global and ipsilateral glomerular filtration rate preserved were 89% and 79%, respectively. Median ipsilateral parenchymal mass preserved was 85% and significantly higher for exophytic masses (P = .001). Median CSA was 22.8 cm and significantly less for exophytic masses (P = .02). CSA associated with both ipsilateral function and mass preserved (both P < .05), but the correlations were only modest (r = 0.25 and 0.36, respectively). On multivariable analysis, CSA associated with function preserved for exophytic masses (P = .01), but not for endophytic ones (P = .27).

Conclusion: CSA associates with functional outcomes after standard PN, although the strength of the correlations was modest, unlike previous studies, and CSA was not an independent predictor for endophytic tumors. Further study will be required to evaluate the utility of CSA in various clinical settings.
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http://dx.doi.org/10.1016/j.urology.2018.02.030DOI Listing
June 2018

Kidney, Ureteral, and Bladder Cancer: A Primer for the Internist.

Med Clin North Am 2018 Mar;102(2):231-249

Center for Urologic Oncology, Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Q10-1, Cleveland, OH 44195, USA. Electronic address:

Malignancies of the urinary tract (kidney, ureter, and bladder) are distinct clinical entities. Hematuria is a unifying common presenting symptom for these malignancies. Surgical management of localized disease continues to be the mainstay of treatment, and early detection is important in the prognosis of disease. Patients often require life-long follow-up and assessment for recurrence.
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http://dx.doi.org/10.1016/j.mcna.2017.10.002DOI Listing
March 2018

Impact of Comorbidities on Functional Recovery from Partial Nephrectomy.

J Urol 2018 06 7;199(6):1433-1439. Epub 2017 Dec 7.

Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address:

Purpose: Parenchymal mass preservation, and ischemia type and/or duration can influence functional recovery after partial nephrectomy. Some groups have hypothesized that relevant comorbidities may also impact nephron stability and functional recovery but this has not been adequately investigated.

Materials And Methods: At our center 405 patients treated with partial nephrectomy from 2007 to 2015 had the necessary data to determine the function and parenchymal mass preserved in the ipsilateral kidney. Comorbidities potentially associated with renal functional status were reviewed, including various degrees of hypertension, diabetes, cardiovascular disease, obesity, smoking status and related medications. Multivariable linear regression was done to assess factors associated with functional recovery, defined as the percent of preserved ipsilateral glomerular filtration rate.

Results: Median tumor size was 3.5 cm and the median R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines and tumor touching main renal artery or vein) score was 8. Warm and cold ischemia were done in 264 (65%) and 141 patients for a median duration of 21 and 27 minutes, respectively. The median preserved ipsilateral glomerular filtration rate was 79%. Patient age, comorbidity index, hypertension and proteinuria were each associated with the preoperative glomerular filtration rate (all p <0.01). On univariable and multivariable analyses the preserved parenchymal mass, and ischemia type and duration were significantly associated with functional recovery (all p <0.001). On univariable analysis of comorbidities only hypertension was significantly associated with functional recovery. However, on multivariable analysis none of the analyzed comorbidities were associated with functional recovery.

Conclusions: Recovery of function after partial nephrectomy depends primarily on parenchymal mass preservation and ischemia characteristics. Comorbidities failed to be associated with functional outcomes. Comorbidities can impact function, leading to surgery, and may influence long-term functional stability. However, our data suggest that they do not influence short-term recovery after partial nephrectomy.
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http://dx.doi.org/10.1016/j.juro.2017.12.004DOI Listing
June 2018

Post-prostatectomy radiation therapy for locally recurrent prostate cancer.

Expert Rev Anticancer Ther 2017 11 18;17(11):1003-1012. Epub 2017 Sep 18.

a Department of Urology , Glickman Urology and Kidney Institute, Cleveland Clinic , Cleveland , OH , USA.

Introduction: Approximately 15-30% of men with localized prostate cancer will experience biochemical recurrence (BCR) after radical prostatectomy. Postoperative radiation therapy is used in men with adverse pathological features to reduce the risk of BCR or with curative intent in men with known BCR. In this study, we review the evidence for the adjuvant and salvage radiation therapy after radical prostatectomy. Areas covered: A literature review of the Medline and Embase databases was performed. The search strategy included the following terms: prostate cancer, adjuvant radiotherapy, salvage radiotherapy, radical prostatectomy, biochemical recurrence, and prostate cancer recurrence. Prospective randomized trials for the adjuvant radiotherapy and observational studies supporting salvage radiotherapy were included for discussion. Expert commentary: As postoperative radiotherapy is associated with non-trivial risks of acute and long-term toxicity and given the absence of compelling data supporting adjuvant over early salvage radiotherapy, the authors advocate, with rare exceptions, close observation and timely (early) salvage radiotherapy for patients with BCR and long life expectancy. Adjuvant radiotherapy may be considered in patients at high-risk for recurrence. Observation is appropriate in patients with limited life expectancy and/or absence of adverse features.
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http://dx.doi.org/10.1080/14737140.2017.1378575DOI Listing
November 2017

Predictors of Long-Term Survival after Renal Cancer Surgery.

J Urol 2018 02 30;199(2):384-392. Epub 2017 Aug 30.

Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address:

Purpose: Renal cancer surgery can adversely impact long-term function and survival. We evaluated predictors of chronic kidney disease 5 years and nonrenal cancer mortality 10 years after renal cancer surgery.

Materials And Methods: We analyzed the records of 4,283 patients who underwent renal cancer surgery from 1997 to 2008. Radical and partial nephrectomy were performed in 46% and 54% of patients, respectively. Cumulative probability ordinal modeling was used to predict chronic kidney disease status 5 years after surgery and multivariable logistic regression was used to predict nonrenal cancer mortality at 10 years. Relevant patient, tumor and functional covariates were incorporated, including the preoperative glomerular filtration rate (A), the new baseline glomerular filtration rate after surgery (B) and the glomerular filtration rate loss related to surgery (C), that is C = A - B. In contrast, partial or radical nephrectomy was not used in the models due to concerns about strong selection bias associated with the choice of procedure.

Results: Multivariable modeling established the preoperative glomerular filtration rate and the glomerular filtration rate loss related to surgery as the most important predictors of the development of chronic kidney disease (Spearman ρ = 0.78). Age, gender and race had secondary roles. Significant predictors of 10-year nonrenal cancer mortality were the preoperative glomerular filtration rate, the new baseline glomerular filtration rate, age, diabetes and heart disease (all p <0.05). Multivariable modeling established age and the preoperative glomerular filtration rate as the most important predictors of 10-year nonrenal cancer mortality (c-index 0.71) while the glomerular filtration rate loss related to surgery only changed absolute mortality estimates 1% to 3%.

Conclusions: Glomerular filtration rate loss related to renal cancer surgery, whether due to partial or radical nephrectomy, influences the risk of chronic kidney disease but it may have less impact on survival. In contrast, age and the preoperative glomerular filtration rate, which reflects general health status, are more robust predictors of nonrenal cancer mortality, at least in patients with good preoperative function or mild chronic kidney disease.
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http://dx.doi.org/10.1016/j.juro.2017.08.096DOI Listing
February 2018

Ischemia and Functional Recovery from Partial Nephrectomy: Refined Perspectives.

Eur Urol Focus 2018 07 3;4(4):572-578. Epub 2017 Mar 3.

Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address:

Background: Nephron mass preservation is a key determinant of functional outcomes after partial nephrectomy (PN), while ischemia plays a secondary role. Analyses focused specifically on recovery of the operated kidney appear to be most informative, yet have only included limited numbers of patients.

Objective: To evaluate the relative impact of parenchymal preservation and ischemia on functional recovery after PN using a more robust cohort allowing for more refined perspectives about ischemia.

Design, Setting, And Participants: A total of 401 patients managed with PN with necessary studies were analyzed for function and nephron mass preserved specifically within the kidney exposed to ischemia.

Intervention: PN.

Outcome Measurements And Statistical Analysis: The nephron mass preserved was measured from computed tomography scans <2 mo before and 3-12 mo after PN. Patients with two kidneys were required to have nuclear renal scans within the same timeframes. Recovery from ischemia was defined as the percent function preserved normalized by the percent nephron mass preserved. Pearson correlation was used to evaluate relationships between functional recovery and nephron mass preservation or ischemia time. Multivariable linear regression assessed predictors for recovery from ischemia.

Results And Limitations: The median tumor size was 3.5cm and the median RENAL score was 8. Cold and warm ischemia were utilized in 151 and 250 patients, and the median ischemia time was 27 and 21min, respectively. The function preserved was strongly correlated with nephron mass preserved(r=0.63; p<0.001). Median recovery from ischemia was significantly higher for hypothermia (99% vs 92%; p<0.001) and remained consistently strong even with longer duration. Multivariable analysis demonstrated that recovery from ischemia, which normalizes for nephron mass preservation, was significantly associated with ischemia type and duration (both p<0.05). However, each additional 10min of warm ischemia was associated with only a 2.5% decline in recovery from ischemia. Limitations include the retrospective design.

Conclusions: Our data suggest that functional recovery from clamped PN is most reliable with hypothermia. Longer intervals of warm ischemia are associates with reduced recovery; however, incremental changes are modest and may not be clinically significant in patients with a normal contralateral kidney.

Patient Summary: Functional recovery after clamped partial nephrectomy is primarily dependent on preservation of nephron mass. Recovery is most reliable when hypothermia is applied. Longer intervals of warm ischemia are associated with reduced recovery; however, the incremental changes are modest.
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http://dx.doi.org/10.1016/j.euf.2017.02.001DOI Listing
July 2018

Functional Comparison of Renal Tumor Enucleation Versus Standard Partial Nephrectomy.

Eur Urol Focus 2017 10 16;3(4-5):437-443. Epub 2017 Jun 16.

Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address:

Background: Tumor enucleation (TE) optimizes parenchymal preservation and could yield better function than standard partial nephrectomy (SPN), although data on this are conflicting.

Objective: To compare functional outcomes for TE and SPN strategies.

Design, Setting, And Participants: Patients managed with partial nephrectomy (PN) with necessary data for analysis of preservation of ipsilateral parenchymal mass (IPM) and global glomerular filtration rate (GFR) from two centers were included. All studies were required <2 mo before and 3-12 mo after surgery. Patients with a solitary kidney or multifocal tumors were excluded.

Intervention: Partial nephrectomy.

Outcome Measurements And Statistical Analysis: Vascularized IPM was estimated from contrast-enhanced CT scans preoperatively and postoperatively. Serum creatinine-based estimates of global GFR were also obtained in the same timeframes. Univariable and multivariable linear regression evaluated factors associated with new-baseline global GFR.

Results/limitations: Analysis included 71 TE and 373 SPN cases. The median preoperative global GFR was comparable for TE and SPN (75 vs 78ml/min/1.73m; p=0.6). The median tumor size was 3.0cm for TE and 3.3cm for SPN (p=0.03). The median RENAL score was 7 in both cohorts. For TE, warm ischemia and zero ischemia were used in 51% and 49% of cases, respectively. For SPN, warm ischemia and cold ischemia were used in 72% and 28% of patients, respectively. Capsular closure was performed in 46% of TE and 100% of SPN cases (p<0.001). Positive margins were found in 8.5% of TE and 4.8% of SPN patients (p=0.2). The median vascularized IPM preserved was 95% (interquartile range [IQR] 91-100%) for TE and 84% (IQR 76-92%) for SPN (p<0.001). The median global GFR preserved was 101%(IQR 93-111%) and 89% (IQR 81-96%) for TE and SPN, respectively (p<0.001). On multivariable analysis, resection strategy, preoperative GFR, and vascularized IPM preserved were all significantly associated (p<0.001) with new-baseline global GFR. Limitations include the retrospective design and the lack of resection outcome data.

Conclusions: Our analysis suggests that TE has potential for maximum IPM preservation compared to SPN and may provide optimized functional recovery. Further investigation will be required to evaluate the clinical significance of these findings.

Patient Summary: Tumor enucleation for kidney cancer involves dissection along the tumor capsule and optimally preserves normal kidney tissue, which may lead to better functional recovery. The importance of this approach in various clinical settings will require further investigation.
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http://dx.doi.org/10.1016/j.euf.2017.06.002DOI Listing
October 2017

Devascularized Parenchymal Mass Associated with Partial Nephrectomy: Predictive Factors and Impact on Functional Recovery.

J Urol 2017 10 9;198(4):787-794. Epub 2017 Apr 9.

Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address:

Purpose: Parenchymal mass loss is the predominant factor associated with functional outcomes after partial nephrectomy. It is primarily due to excised and/or devascularized parenchymal mass. We evaluated the importance of excised and devascularized parenchymal mass relative to functional recovery after partial nephrectomy.

Materials And Methods: In 168 patients who underwent partial nephrectomy the necessary studies were done to determine excised and devascularized parenchymal mass, and evaluate parenchymal mass changes and functional loss of the operated kidney. Parenchymal mass loss in the ipsilateral kidney was measured on contrast enhanced computerized tomography less than 2 months before and 3 to 12 months after partial nephrectomy. Excised parenchymal mass was estimated by subtracting tumor volume from specimen volume. Devascularized parenchymal mass was defined as total parenchymal mass loss minus excised parenchymal mass. We used the Pearson correlation to evaluate relationships between glomerular filtration rate preservation and parenchymal mass loss. Multivariable analysis was done to assess factors associated with devascularized parenchymal mass.

Results: Median tumor size was 3.4 cm and median R.E.N.A.L. (radius, exophytic/endophytic tumor properties, nearness of tumor to collecting system or sinus, anterior/posterior and location relative to polar lines) score was 7. Warm and cold ischemia was used in 100 and 68 patients, respectively. Median excised parenchymal and devascularized parenchymal mass was 9 and 16 cm, respectively (p <0.001). Total parenchymal mass loss and devascularized parenchymal mass were associated strongly with glomerular filtration rate preservation in the operated kidney (each r ≥0.55, p <0.001). However, excised parenchymal mass was only weakly associated with functional outcomes (r = 0.23). The preoperative glomerular filtration rate and endophytic status were associated with devascularized parenchymal mass on multivariable analysis.

Conclusions: To our knowledge we report the first study to specifically evaluate the relative contributions of devascularized and excised parenchymal mass to functional recovery after partial nephrectomy. Our study suggests that devascularized parenchymal mass has more impact, which may have implications regarding surgical technique. Prospective study is required to further evaluate the relative contributions of excised and devascularized parenchymal mass in various settings.
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http://dx.doi.org/10.1016/j.juro.2017.04.020DOI Listing
October 2017

Excised Parenchymal Mass During Partial Nephrectomy: Functional Implications.

Urology 2017 May 21;103:129-135. Epub 2016 Dec 21.

Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH. Electronic address:

Objective: To evaluate whether excised parenchymal mass (EPM) during partial nephrectomy (PN) correlates with functional decline and can serve as a surrogate for functional outcomes.

Materials And Methods: All 215 patients managed with PN for unifocal renal mass with necessary studies to determine EPM and percent glomerular filtration rate (GFR) and parenchymal mass preserved (both global and specific to the operated kidney) were analyzed. EPM was estimated from the pathologic specimen by subtracting the tumor mass from the specimen mass, with both calculated using the elliptical formula. Vascularized parenchymal mass preserved was measured from computed tomography scans obtained <2 months prior and 3-12 months after surgery. All functional analyses were required to be within the same time frames, and patients with a contralateral kidney were also required to have nuclear renal scans.

Results: The median tumor size was 3.5 cm and the median R.E.N.A.L. was 7. Warm and cold ischemia were utilized in 123 and 92 patients, respectively (median ischemia time = 23 minutes). The median global GFR preserved was 89%, the median total parenchymal mass preserved was 93%, and the median estimated EPM was 16 cm. Whereas percent parenchymal mass preserved correlated strongly with global and ipsilateral GFR preserved (both P < .001), EPM failed to correlate with functional outcomes on both univariable and multivariable analyses.

Conclusion: Our data suggest that parenchymal mass preserved with standard PN by experienced surgeons associates strongly with function preserved, whereas EPM fails to correlate with functional outcomes. Further study of the functional impact of EPM in other circumstances will be required, such as enucleation or PN performed by less-experienced surgeons.
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http://dx.doi.org/10.1016/j.urology.2016.12.021DOI Listing
May 2017

Does endorectal coil MRI increase the accuracy of preoperative prostate cancer staging?

Can J Urol 2016 Dec;23(6):8564-8567

Division of Urology, University of Nebraska Medical Center, Omaha, Nebraska, USA.

Introduction: We sought to investigate the association of preprostatectomy magnetic resonance imaging (MRI) and surgical pathologic findings in patients with prostate cancer.

Materials And Methods: All patients with prostate cancer and preprostatectomy MRI available between 2002 and 2015 were included. Age, prostate-specific antigen at diagnosis, Gleason score at biopsy, MRI technique, radiology report suggestive of prostate cancer, extraprostatic invasion and seminal vesicle involvement, lymphadenopathy and final pathology report were retrospectively reviewed. Data was analyzed for sensitivity, specificity, positive and negative predictive values of MRI findings for predicting T3 disease. Consistency of MRI findings with pathology report was compared between MRIs with or without endorectal coil (ERC).

Results: A cohort of 83 patients was identified. Eighty-seven percent of the patients had MRI findings suggestive of prostate cancer. MRI was performed with and without ERC in 21 (25.3%) and 62 (74.3%) patients respectively. Eighty-five percent of patients with ERC and 88.7% of those without ERC had MRI findings suggestive of prostate cancer (p = 0.659). MRI correlated with final surgical pathology stage T3 in 53 patients (64%). MRI findings were consistent with final pathology report in 70% of ERC group and 61.3% of non ERC group (p = 0.482). In terms of extra prostatic invasion or seminal vesicle involvement, MRI had specificity, sensitivity, positive and negative predictive values of 84.44%, 37.84%, 66.67% and 62.3% respectively.

Conclusions: MRI was specific but not sensitive in determining extraprostatic or seminal vesicle invasion. MRI was not accurate for lymph node involvement. In addition, using an ERC did not increase the accuracy of prostate MRI in this small cohort.
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December 2016

Clinical Correlates of Benefit From Radium-223 Therapy in Metastatic Castration Resistant Prostate Cancer.

Prostate 2017 04 19;77(5):479-488. Epub 2016 Dec 19.

Fred Hutchinson Cancer Research Center, Seattle, Washington.

Background: We sought to identify potential clinical variables associated with outcomes after radium-223 therapy in routine practice.

Methods: Consecutive non-trial mCRPC patients who received ≥1 dose of radium dichloride-223 at four academic and one community urology-specific cancer centers from May 2013 to June 2014 were retrospectively identified. Association of baseline and on-therapy clinical variables with number of radium doses received and clinical outcomes including overall survival were analyzed using chi-square statistics, cox proportional hazards, and Kaplan-Meier methods. Bone Scan Index (BSI) was derived from available bone scans using EXINI software.

Results: One hundred and forty-five patients were included. Radium-223 was administered for six cycles in 74 patients (51%). One-year survival in this heavily pre-treated population was 64% (95%CI: 54-73%). In univariate and multivariate analysis, survival was highly associated with receiving all six doses of Radium-223. Receipt of six doses was associated with ECOG PS of 0-1, lower baseline PSA & pain level, no prior abiraterone/enzalutamide, <5 BSI value, and normal alkaline phosphatase. In patients who reported baseline pain (n = 72), pain declined in 51% after one dose and increased in 7%. PSA declined ≥50% in 16% (18/110). Alkaline phosphatase declined ≥25% in 48% (33/69) and ≥50% in 16/69 patients. BSI declined in 17 (68%) of the 25 patients who had bone scan available at treatment follow-up. Grade ≥3 neutropenia, anemia, and thrombocytopenia occurred in 4% (n = 114), 4% (n = 125), and 5% (n = 123), respectively.

Conclusions: Patients earlier in their disease course with <5 BSI, low pain score, and good ECOG performance status are optimal candidates for radium-223. Radium-223 therapy is well tolerated with most patients reporting declines in pain scores and BSI. Prostate 77:479-488, 2017. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/pros.23286DOI Listing
April 2017

Urinalysis findings are not predictive of positive urine culture in patients with indwelling stents.

Can J Urol 2016 Oct;23(5):8446-8450

Division of Urology, University of Nebraska Medical Center, Omaha, Nebraska, USA.

Introduction: Indwelling stents produce symptoms and urinalysis findings mimicking urinary tract infection (UTI). In this study, we investigated the correlation of urinalysis findings with urine culture in patients with indwelling ureteral stents.

Materials And Methods: All patients with ureteral stents who underwent stent removal in urology clinic from July 2013 to January 2015 and had urine culture available immediately prior to stent removal were included in this study. Urine culture results as well as age, gender, duration of indwelling stent, and reason for stent placement were collected.

Results: A total of 122 patients were included in this study. The two most common reasons for ureteral stent placement included urolithiasis (65.6%) and renal transplant (22.1%). Red blood cell (RBC), leukocytes and nitrite were positive in 92.9%, 70.2% and 17.9% of urine samples respectively. Only 17 patients (13.9%) had positive urine culture. Although renal transplant patients had significantly longer duration of stent retention, no statistically significant difference was noted in rate of positive urine culture compared to urolithiasis patients (p = 1.0). Among patients with positive urine culture, 62.5% had resistant bacteria to common antibiotic treatments and two patients had yeast in urine culture (12.5%). The duration of stent retention did not correlate with bacterial resistance. Multivariate analysis failed to show significant correlation of gender, reason for stent, stent duration, RBC and nitrite with positive urine culture.

Conclusions: Positive findings on urinalysis in patients with indwelling ureteral stent have poor correlation to positive urine culture and therefore the use of urine culture to diagnose UTI is warranted.
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October 2016

Preoperative frailty predicts postoperative complications and mortality in urology patients.

World J Urol 2017 Jan 12;35(1):21-26. Epub 2016 May 12.

Division of Urology, University of Nebraska Medical Center, 984110 Nebraska Medical Center, Omaha, NE, 68198-4110, USA.

Purpose: Our objective was to determine the impact of preoperative frailty, as measured by validated Risk Analysis Index (RAI), on the occurrence of postoperative complications after urologic surgeries in a national database comprised of diverse practice groups and cases.

Study Design: The National Surgical Quality Improvement Program (NSQIP) database was queried from 2005 to 2011 for a list of abdominal, vaginal, transurethral and scrotal urological surgeries using Current Procedural Terminology codes. The study population was subdivided into two groups based on the nature of procedures performed: complex procedures (inpatient) and simple procedures (outpatient). Risk Analysis Index score was calculated using preoperative NSQIP variables to determine preoperative frailty. Major postoperative morbidities (pulmonary, cardiovascular, renal and infectious), mortality, return to operating room, discharge destination and readmission to the hospital were examined.

Results: The study identified 42,715 patients who underwent urological procedures, 25,693 complex and 17,022 simple procedures. Mean RAI score (range) was 7.75 (0-53). The majority of patients scored low on the RAI (90.57 % with RAI < 10). As the RAI score increased, there was a significant increase in postoperative complication and mortality rate (both p < 0.0001). Similarly, the rate of return to operating room and hospital readmission rate increased as RAI increased (both p < 0.0001). Additionally, rate of discharge to home decreased. Interestingly, mortality rate in patients with high RAI did not differ comparing simple to complex procedures (p = 0.90), whereas complications were significantly greater in the complex operation (p = 0.01).

Conclusions: Increase in frailty, as measured by RAI score, is associated with increased postoperative complications and mortality. RAI may allow for rapid identification and counseling of patients who are at high risk of adverse perioperative outcomes.
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http://dx.doi.org/10.1007/s00345-016-1845-zDOI Listing
January 2017

Histone deacetylase inhibitors in castration-resistant prostate cancer: molecular mechanism of action and recent clinical trials.

Ther Adv Urol 2015 Dec;7(6):388-95

Section of Urology, and Department of Biochemistry, University of Nebraska Medical Center, Omaha, NE, USA.

Historically, androgen-deprivation therapy has been the cornerstone for treatment of metastatic prostate cancer. Unfortunately, nearly majority patients with prostate cancer transition to the refractory state of castration-resistant prostate cancer (CRPC). Newer therapeutic agents are needed for treating these CRPC patients that are unresponsive to androgen deprivation and/or chemotherapy. The histone deacetylase (HDAC) family of enzymes limits the expression of genomic regions by improving binding between histones and the DNA backbone. Modulating the role of HDAC enzymes can alter the cell's regulation of proto-oncogenes and tumor suppressor genes, thereby regulating potential neoplastic proliferation. As a result, histone deacetylase inhibitors (HDACi) are now being evaluated for CRPC or chemotherapy-resistant prostate cancer due to their effects on the expression of the androgen receptor gene. In this paper, we review the molecular mechanism and functional target molecules of different HDACi as applicable to CRPC as well as describe recent and current clinical trials involving HDACi in prostate cancer. To date, four HDAC classes comprising 18 isoenzymes have been identified. Recent clinical trials of vorinostat, romidepsin, and panobinostat have provided cautious optimism towards improved outcomes using these novel therapeutic agents for CPRC patients. Nevertheless, no phase III trial has been conducted to cement one of these drugs as an adjunct to androgen-deprivation therapy. Consequently, further investigation is necessary to delineate the benefits and drawbacks of these medications.
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http://dx.doi.org/10.1177/1756287215597637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647138PMC
December 2015

Patient-Provider Communication About Prostate Cancer Screening and Treatment: New Evidence From the Health Information National Trends Survey.

Am J Mens Health 2017 Jan 7;11(1):134-146. Epub 2016 Jul 7.

1 The University of Memphis, Memphis, TN, USA.

The American Urological Association, American Cancer Society, and American College of Physicians recommend that patients and providers make a shared decision with respect to prostate-specific antigen (PSA) testing for prostate cancer (PCa). The goal of this study is to determine the extent of patient-provider communication for PSA testing and treatment of PCa and to examine the patient specific factors associated with this communication. Using recent data from the Health Information National Trends Survey, this study examined the association of patient characteristics with four domains of patient-provider communication regarding PSA test and PCa treatment: (1) expert opinion of PSA test, (2) accuracy of PSA test, (3) side effects of PCa treatment, and (4) treatment need of PCa. The current results suggested low level of communication for PSA testing and treatment of PCa across four domains. Less than 10% of the respondents report having communication about all four domains. Patient characteristics like recent medical check-up, regular healthcare provider, global health status, age group, marital status, race, annual household income, and already having undergone a PSA test are associated with patient-provider communication. There are few discussions about PSA testing and PCa treatment options between healthcare providers and their patients, which limits the shared decision-making process for PCa screening and treatment as recommended by the current best practice guidelines. This study helps identify implications for changes in physician practice to adhere with the PSA screening guidelines.
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http://dx.doi.org/10.1177/1557988315614082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675184PMC
January 2017

Desmoid tumor: an unusual case of gross hematuria.

Ther Adv Urol 2015 Feb;7(1):49-51

Division of Urology, University of Nebraska Medical Center, Omaha, NE, USA.

Desmoid tumors are rare soft-tissue masses originating from the proliferation of fibroblasts in the fibroconnective tissues. Intra-abdominal desmoid tumors pose special diagnostic challenge due to multiplicity of differential diagnoses, and difficulty to well characterize the lesions on imaging studies. Desmoid tumors can have atypical presentation making clinical correlation challenging to unsuspecting urologists. Only a few cases have been reported in the urology literature. In this report, we present a case of desmoid tumor presenting with gross hematuria.
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http://dx.doi.org/10.1177/1756287214553969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294801PMC
February 2015

Chronic lymphocytic leukemia of the bladder: an atypical etiology of gross hematuria.

Ther Adv Urol 2014 Oct;6(5):198-200

Omaha-VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA.

Chronic lymphocytic leukemia (CLL) is a rare hematologic disorder with affected patients having complications of frequent infections and possible transformation to a more aggressive malignancy. The occurrence of CLL in the bladder is a rare event, with few reported cases. As a result, its aggressiveness and the optimal course for treatment are unknown. Despite this, its presence in the bladder warrants continued surveillance, as recurrence and progression to other bladder malignancies are possible. We present a 71-year-old woman initially diagnosed with CLL who was plagued by recurrent hematuria and dysuria for over a decade, which lead to multiple negative urologic workups. However, these continued workups eventually lead to her diagnosis of bladder CLL with a subsequent finding of carcinoma in situ that was prompted by a suspicious surveillance cystoscopy performed 4 months after her initial bladder diagnosis. Hence, infiltration of CLL in the urinary bladder merits close follow up, including additional urologic procedures.
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http://dx.doi.org/10.1177/1756287214535461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144259PMC
October 2014

The N-terminal domain of the androgen receptor drives its nuclear localization in castration-resistant prostate cancer cells.

J Steroid Biochem Mol Biol 2014 Sep 22;143:473-80. Epub 2014 Mar 22.

Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, United States; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, United States; University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, United States. Electronic address:

Androgen-independent nuclear localization is required for androgen receptor (AR) transactivation in castration-resistant prostate cancer (CRPC) and should be a key step leading to castration resistance. However, mechanism(s) leading to androgen-independent AR nuclear localization are poorly understood. Since the N-terminal domain (NTD) of AR plays a role in transactivation under androgen-depleted conditions, we investigated the role of the NTD in AR nuclear localization in CRPC. Deletion mutagenesis was used to identify amino acid sequences in the NTD essential for its androgen-independent nuclear localization in C4-2, a widely used CRPC cell line. Deletion mutants of AR tagged with green fluorescent protein (GFP) at the 5'-end were generated and their signal distribution was investigated in C4-2 cells by fluorescent microscopy. Our results showed that the region of a.a. 294-556 was required for androgen-independent AR nuclear localization whereas a.a. 1-293 mediates Hsp90 regulation of AR nuclear localization in CRPC cells. Although the region of a.a. 294-556 does not contain a nuclear import signal, it was able to enhance DHT-induced import of the ligand binding domain (LBD). Also, transactivation of the NTD could be uncoupled from its modulation of AR nuclear localization in C4-2 cells. These observations suggest an important role of the NTD in AR intracellular trafficking and androgen-independent AR nuclear localization in CRPC cells.
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http://dx.doi.org/10.1016/j.jsbmb.2014.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4127361PMC
September 2014

Regenerated luminal epithelial cells are derived from preexisting luminal epithelial cells in adult mouse prostate.

Mol Endocrinol 2011 Nov 22;25(11):1849-57. Epub 2011 Sep 22.

Department of Urology, University of Pittsburgh School of Medicine, Pennsylvania 15232, USA.

Determining the source of regenerated luminal epithelial cells in the adult prostate during androgen deprivation and replacement will provide insights into the origin of prostate cancer cells and their fate during androgen deprivation therapy. Prostate stem cells in the epithelial layer have been suggested to give rise to luminal epithelium. However, the extent of stem cell participation to prostate regrowth is not clear. In this report, using prostate-specific antigen-CreER(T2)-based genetic lineage marking/tracing in mice, preexisting luminal epithelial cells were shown to be a source of regenerated luminal epithelial cells in the adult prostate. Prostatic luminal epithelial cells could survive androgen deprivation and were capable of proliferating upon androgen replacement. Prostate cancer cells, typically exhibiting a luminal epithelial phenotype, may retain this intrinsic capability to survive and regenerate in response to changes in androgen signaling, providing part of the mechanism for the ultimate failure of androgen deprivation therapy in prostate cancer.
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http://dx.doi.org/10.1210/me.2011-1081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198961PMC
November 2011
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