Publications by authors named "Wei Phin Tan"

48 Publications

Oncological and Functional Outcomes of Patients Undergoing Individualized Partial Gland Cryoablation of the Prostate: A Single Institution Experience.

J Endourol 2021 Feb 9. Epub 2021 Feb 9.

Duke University Health System, 213852, Surgery, Durham, North Carolina, United States;

Objectives: We aim to report the functional and oncological outcomes in men with localized prostate cancer who underwent individualized partial gland cryoablation of the prostate using validated quality of life instruments.

Methods: We retrospectively reviewed our cryosurgery database between July 2003 and September 2019 for men who were treated with individualized partial gland cryoablation of the prostate at our tertiary care center. Baseline and periodic urinary and sexual function surveys were administered throughout the post-treatment period.

Results: A total of 82 men were included in the study. Median follow-up was 28 months (IQR: 10.5 - 59.3 months). A total of 71 men underwent primary individualized partial gland cryoablation whereas 11 men underwent salvage partial gland ablation. Failure-free survival at 1 to 5 years was 98%, 89%, 84%, 75%, 75% in the primary therapy group, and 100%, 80% and 40% in the salvage group at 1 to 3 years, respectively. In the primary therapy group, all 71 patients remained free of pads at 3 months and throughout the follow-up period. Men who have undergone primary focal cryoablation had a higher post-treatment IIEF score, followed by men treated with primary hemi-cryoablation and primary subtotal cryoablation. AUA symptom scores decreased regardless of type of partial gland ablation performed, with subtotal ablation having the lowest score compared to hemiablation and focal cryoablation. No patient developed a fistula in the primary group and 1 (9%) patient developed a fistula in the salvage group.

Conclusion: Individualized partial gland cryoablation of the prostate is able to achieve excellent oncological and functional outcomes in select men with localized prostate cancer.
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http://dx.doi.org/10.1089/end.2020.0740DOI Listing
February 2021

The nephroureterectomy: a review of technique and current controversies.

Transl Androl Urol 2020 Dec;9(6):3168-3190

Division of Urology, Duke University Medical Center, Durham, NC, USA.

The nephroureterectomy (NU) is the standard of care for invasive upper tract urothelial carcinoma (UTUC) and has been around for well over one hundred years. Since then new operative techniques have emerged, new technologies have developed, and the surgery continues to evolve and grow. In this article, we review the various surgical techniques, as well as present the literature surrounding current areas of debate surrounding the NU, including the lymphatic drainage of the upper urinary tract, management of UTUC involvement with the adrenals and caval thrombi, surgical management of the distal ureter, the use of intravesical chemotherapy as well as perioperative systemic chemotherapy, as well as various outcome measures. Although much has been studied about the NU, there still is a dearth of level 1 evidence and the field would benefit from further studies.
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http://dx.doi.org/10.21037/tau.2019.12.07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807352PMC
December 2020

Molecular biomarkers in the context of focal therapy for prostate cancer: recommendations of a Delphi Consensus from the Focal Therapy Society.

Minerva Urol Nefrol 2021 01 13. Epub 2021 Jan 13.

Department of Urology, Institut Mutualiste Montsouris, Paris, France.

Background: Focal Therapy (FT) for Prostate Cancer (PCa) is promising. However, long-term oncological results are awaited and there is no consensus on follow-up strategies. Molecular biomarkers (MB) may be useful in selecting, treating and following up men undergoing FT, though there is limited evidence in this field to guide practice. We aimed to conduct a consensus meeting, endorsed by the Focal Therapy Society, amongst a large group of experts, to understand the potential utility of MB in FT for localised PCa.

Materials And Methods: A 38-item questionnaire was built following a literature search. The authors then performed three rounds of a Delphi Consensus using DelphiManager, using the GRADE grid scoring system, followed by a face-to-face expert meeting. Three areas of interest were identified and covered concerning MB for FT, i) the current/present role; ii) the potential/future role; iii) the recommended features for future studies. Consensus was defined using a 70% agreement threshold.

Results: Of 95 invited experts, 42 (44.2%) completed the three Delphi rounds. Twenty-four items reached a consensus and they were then approved at the meeting involving (n=15) experts. Fourteen items reached a consensus on uncertainty, or they did not reach a consensus. They were re-discussed, resulting in a consensus (n=3), a consensus on a partial agreement (n=1), and a consensus on uncertainty (n=10). A final list of statements were derived from the approved and discussed items, with the addition of three generated statements, to provide guidance regarding MB in the context of FT for localised PCa. Research efforts in this field should be considered a priority.

Conclusions: The present study detailed an initial consensus on the use of MB in FT for PCa. This is until evidence becomes available on the subject.
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http://dx.doi.org/10.23736/S0393-2249.20.04160-0DOI Listing
January 2021

The Use of Serum Procalcitonin in the Setting of Infected Ureteral Stones: A Prospective Observational Study.

J Endourol 2020 Nov 5. Epub 2020 Nov 5.

Department of Urology, Rush University Medical Center, Chicago, Illinois, USA.

Infected ureteral stones are a urologic emergency and require urgent decompression. We set out to determine whether serum procalcitonin (PCT) could aid in the diagnosis of infected ureteral stones. All consecutive patients presenting to the emergency room from November 9, 2016, to November 10, 2018, with an obstructing ureteral stone were included. All patients had complete blood count, urinalysis (UA), PCT, and urine culture (UCx). Subgroup analysis was performed in a "clinically equivocal" cohort of afebrile patients defined as a leukocytosis >10/μL and UA with <50 white blood cells (WBCs) per high powered field (hpf). Patients with positive and negative UCx were compared. A total of 231 patients were included, of whom 56 had a positive UCx. Of all covariates, UA WBCs with a cutoff of 9 per hpf performed best at predicting positive UCx with an area under the curve (AUC) of 0.87. PCT did not perform as well with an ideal cutoff of 0.08 ng/mL, having an AUC of 0.77, sensitivity 70.6%, specificity 73.9%, positive predictive value (PPV) 34.3%, and negative predictive value (NPV) 92.9%. When looking at the clinically equivocal cohort, UA WBCs with a cutoff of 6 per hpf appeared to perform best at predicting a positive UCx with an AUC of 0.72. PCT was less predictive in this cohort with an ideal cutoff of 0.3 ng/mL, having an AUC of 0.32, sensitivity 47.1%, specificity 85.2%, PPV 38.1%, and NPV 89.3%. PCT does not appear to be a superior marker for diagnosing urinary tract infection in the setting of obstructing ureterolithiasis when compared with components of the standard work-up.
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http://dx.doi.org/10.1089/end.2020.0308DOI Listing
November 2020

National Quality Improvement Program in Transurethral Resection of Bladder Tumor: A Model for the Rest of Us, Even if We Cannot Share All Results.

Eur Urol 2020 10 9;78(4):531-532. Epub 2020 Aug 9.

Division of Urology, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA. Electronic address:

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http://dx.doi.org/10.1016/j.eururo.2020.07.020DOI Listing
October 2020

Safety and efficacy of intravesical chemotherapy and hyperthermia in the bladder: results of a porcine study.

Int J Hyperthermia 2020 ;37(1):854-860

Division of Urology, Duke University Medical Center, Durham, NC, USA.

Background: Hyperthermia (heating to 43 °C) activates the innate immune system and improves bladder cancer chemosensitivity.

Objective: To evaluate the tissue penetration and safety of convective hyperthermia combined with intravesical mitomycin C (MMC) pharmacokinetics in live porcine bladder models using the Combat bladder recirculation system (BRS).

Methods: Forty 60 kg-female swine were anesthetized and catheterized with a 3-way, 16 F catheter. The Combat device was used to heat the bladders to a target temperature of 43 °C with recirculating intravesical MMC at doses of 40, 80, and 120 mg. Dwell-heat time varied from 30-180 min. Rapid necropsy with immediate flash freezing of tissues, blood and urine occurred. MMC concentrations were measured by liquid chromatography tandem-mass spectrometry.

Results: The Combat BRS system was able to achieve target range temperature (42-44 °C) in 12 mins, and this temperature was maintained as long as the device was running. Two factors increased tissue penetration of MMC in the bladder: drug concentration, and the presence of heat. In the hyperthermia arm, MMC penetration saturated at 80 mg, suggesting that with heating, drug absorption may saturate and not require higher doses to achieve the maximal biological effect. Convective hyperthermia did not increase the MMC concentration in the liver, heart, kidney, spleen, lung, and lymph node tissue even at the 120 mg dose.

Conclusions: Convective bladder hyperthermia using the Combat BRS device is safe and the temperature can be maintained at 43 °C. Hyperthermia therapy may increase MMC penetration into the bladder wall but does not result in an increase of MMC levels in other organs.
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http://dx.doi.org/10.1080/02656736.2020.1780328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700761PMC
January 2020

Salvage Focal Cryotherapy Offers Similar Short-term Oncologic Control and Improved Urinary Function Compared With Salvage Whole Gland Cryotherapy for Radiation-resistant or Recurrent Prostate Cancer.

Clin Genitourin Cancer 2020 06 5;18(3):e260-e265. Epub 2019 Dec 5.

Division of Urology, Department of Surgery, Duke University Medical Center, Durham, NC. Electronic address:

Background: We compared the short-term oncologic and functional outcomes of salvage focal cryotherapy (SFC) with those of salvage total cryotherapy (STC) for radiotherapy (RT)-persistent/recurrent prostate cancer.

Materials And Methods: We queried the Cryo On-Line Database registry for men who had undergone SFC and STC of the prostate for RT-persistent or recurrent disease. Propensity score weighting was used to match age at treatment, presalvage therapy prostate-specific antigen level, Gleason sum, and presalvage cryotherapy androgen deprivation therapy status. The primary outcome was progression-free survival.

Results: A total of 385 men with biopsy-proven persistent or recurrent prostate cancer after primary RT were included in the present study. The median follow-up, age, prostate-specific antigen, and Gleason sum before salvage cryotherapy was 24.4 months (first and third quartile, 9.8 and 60.3), 70 years (first and third quartile, 66 and 74 years), 4 ng/dL (first and third quartile, 2.7 and 5.6 ng/dL), and 7 (first and third quartile, 6 and 8), respectively. After propensity score weighting, the difference in progression-free survival was not statistically significant between the patients who had undergone STC and those who had undergone SFC (79.8% vs. 76.98%; P = .11 on weighted log-rank test). SFC was associated with a lower probability of post-treatment transient urinary retention (5.6% vs. 22.4%; P < .001). No significant differences were found in the incidence of rectal fistula (1.4% vs. 3.8; P = .30), new-onset urinary incontinence within 12 months (9.3% vs. 15.1%; P = .19), or new-onset erectile dysfunction within 12 months (52.6% vs. 59.6%; P = .47) between the SFC and STC groups, respectively.

Conclusions: STC resulted in similar 2-year oncologic outcomes compared with SFC in the RT-persistent/recurrent disease population. However, the patients who had undergone SFC had a lower urinary retention rate compared with those who had undergone STC.
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http://dx.doi.org/10.1016/j.clgc.2019.11.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272259PMC
June 2020

PD-L1/PD-1 Biomarker for Metastatic Urothelial Cancer that Progress Post-platinum Therapy: A Systematic Review and Meta-analysis.

Bladder Cancer 2019 Nov 22;5(3):211-223. Epub 2019 Nov 22.

Division of Urology, Duke University Medical Center, Durham, NC, USA.

Background: Immune checkpoint inhibitors (ICI) are extremely expensive and most patients with metastatic urothelial carcinoma (mUC) do not benefit significantly from their use.

Objective: We performed a systematic review and meta-analysis to determine response rates and survival outcomes on patients with mUC progressing despite prior platinum-based chemotherapy receiving ICI stratified by biomarker status.

Methods: We performed a comprehensive literature search for all articles in PubMed and Embase up to 06/15/2019 to identify all studies pertaining to programmed death-ligand 1 (PD-L1) and programmed death 1 (PD-1) receptor targeted therapies for mUC that reported biomarkers. Given that biomarkers are reported on different scales and with different metrics, we defined each biomarker as either positive or negative using the definitions implemented in each individual trial. We meta-analyzed the data, reconstructed overall (OS) and progression-free survival (PFS) curves, and analyzed response rates by biomarker status. OS and PFS were analyzed in a pooled Kaplan-Meier analysis and pseudo-individualized patient data (IPD) extracted.

Results: We identified 1429 manuscripts of which 8 met inclusion criteria, with a total of 1837 treated patients with outcomes data. On proportional hazards survival analysis, patients in the biomarker negative group were associated with a lower PFS (HR 1.48, 95% CI: 1.18 - 1.85,  < 0.001) and lower OS (HR 1.54, 95% CI: 1.32 - 1.80,  < 0.001) when compared to the biomarker positive group. Response data was available for 1641 patients and random effects proportion show complete response in 8% and 3% in biomarker positive and negative patients, respectively.

Conclusions: ICI therapy for metastatic UC post platinum therapy has a higher overall response rate, OS and PFS in patients who are biomarker positive compared to those who are negative. However, some patients who are biomarker negative do achieve complete responses. A better biomarker for patient selection is essential before biomarkers can be used to stratify candidates for ICI therapy.
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http://dx.doi.org/10.3233/BLC-190238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6919639PMC
November 2019

Renal Thermal Ablation Trends of American Urologists.

J Endourol 2020 04 22;34(4):409-416. Epub 2020 Jan 22.

Division of Urology, Duke University Medical Center, Durham, North Carolina, USA.

To define current trends in the utilization of renal thermal ablation by urologists in the United States. A six-month case log data for renal procedures submitted by certifying and recertifying American urologists from 2003 to 2018 were obtained from the American Board of Urology and stratified by current procedural terminology code. The utilization of thermal ablative techniques was examined with respect to overall trends, surgeon, and practice characteristics associated with its use. Six thousand two hundred eleven unique urologists performed 54,075 renal procedures, including 1916 (3.5%) thermal ablations, 630 (1.2%) renal biopsies, 17,361 (32.1%) partial nephrectomies, 20,403 (37.8%) radical nephrectomies, and 7957 (14.7%) nephroureterectomies. Eight hundred twenty-five (13.3%) unique urologists performed renal ablations, including 1344 (70.2%), 418 (21.8%), and 154 (8.0%) laparoscopic, percutaneous, and open ablation procedures, respectively. The annual volume of ablation was highest in 2008, followed by 2010 and 2009. On multivariate modeling of those performing renal interventions, the first decade of practice, self-declared endourologist, urologist who completed an endourology fellowship, urologist who practices in the Mid Atlantic, North Central, South Central, and South Eastern United States (compared with New England) were more likely to perform thermal ablation for renal masses. Urologists who perform renal biopsies and partial nephrectomies are also more likely to perform ablation of renal masses. Thermal ablation accounted for a small percentage of renal interventions performed by urologists in the last 1.5 decades with definable associations to practice characteristics. Renal ablation was most commonly performed laparoscopically, with declining use in recent years.
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http://dx.doi.org/10.1089/end.2019.0774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194313PMC
April 2020

Heated Intravesical Chemotherapy: Biology and Clinical Utility.

Urol Clin North Am 2020 Feb;47(1):55-72

Division of Urology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address:

Non-muscle-invasive bladder cancer can be a challenging disease to manage. In recent years, hyperthermia therapy in conjunction with intravesical therapy has been gaining traction as a treatment option for bladder cancer, especially if Bacillus Calmette-Guerin might not be available. Trials of intravesical chemotherapy with heat are few and there has been considerable heterogeneity between studies. However, multiple new trials have accrued and high-quality data are forthcoming. In this review, we discuss the role of combined intravesical hyperthermia and chemotherapy as a novel approach for the treatment of bladder cancer.
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http://dx.doi.org/10.1016/j.ucl.2019.09.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917042PMC
February 2020

Re: Association of Black Race with Prostate Cancer-specific and Other-cause Mortality Dess RT, Hartman HE, Mahal BA, et al JAMA Oncol 2019;5:975-83.

Eur Urol 2020 01 17;77(1):129-130. Epub 2019 Oct 17.

Division of Urology, Department of Surgery, Duke University Medical Center, Durham, NC, USA. Electronic address:

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http://dx.doi.org/10.1016/j.eururo.2019.08.036DOI Listing
January 2020

Diet and Exercise Are not Associated with Skeletal Muscle Mass and Sarcopenia in Patients with Bladder Cancer.

Eur Urol Oncol 2019 May 25. Epub 2019 May 25.

Division of Urology, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA. Electronic address:

Background: There is limited understanding about why sarcopenia is happening in bladder cancer, and which modifiable and nonmodifiable patient-level factors affect its occurrence.

Objective: The objective is to determine the extent to which nonmodifiable risk factors, modifiable lifestyle risk factors, or cancer-related factors are determining body composition changes and sarcopenia in bladder cancer survivors.

Design, Setting, And Participants: Patients above 18 yr of age with a histologically confirmed diagnosis of bladder cancer and a history of receiving care at Duke University Medical Center between January 1, 1996 and June 30, 2017 were included in this study.

Outcome Measurements And Statistical Analysis: Bladder cancer survivors from our institution were assessed for their dietary intake patterns utilizing the Diet History Questionnaire II (DHQ-II) and physical activity utilizing the International Physical Activity Questionnaire long form (IPAQ-L) tools. Healthy Eating Index 2010 (HEI2010) scores were calculated from DHQ-II results. Body composition was evaluated using Slice-O-Matic computed tomography scan image analysis at L3 level and the skeletal muscle index (SMI) calculated by three independent raters.

Results And Limitations: A total of 285 patients were evaluated in the study, and the intraclass correlation for smooth muscle area was 0.97 (95% confidence interval: 0.94-0.98) between raters. The proportions of patients who met the definition of sarcopenia were 72% for men and 55% of women. Univariate linear regression analysis demonstrated that older age, male gender, and black race were highly significant predictors of SMI, whereas tumor stage and grade, chemotherapy, and surgical procedures were not predictors of SMI. Multivariate linear regression analysis demonstrated that modifiable lifestyle factors, including total physical activity (p=0.830), strenuousness (high, moderate, and low) of physical activity (p=0.874), individual nutritional components (daily calories, p=0.739; fat, p=0.259; carbohydrates, p=0.983; and protein, p=0.341), and HEI2010 diet quality (p=0.822) were not associated with SMI.

Conclusions: Lifestyle factors including diet quality and physical activity are not associated with SMI and therefore appear to have limited impact on sarcopenia. Sarcopenia may largely be affected by nonmodifiable risk factors.

Patient Summary: In this report, we aim to determine whether lifestyle factors such as diet and physical activity were the primary drivers of body composition changes and sarcopenia in bladder cancer survivors. We found that lifestyle factors including dietary habits, individual nutritional components, and physical activity do not demonstrate an association with skeletal muscle mass, and therefore may have limited impact on sarcopenia.
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http://dx.doi.org/10.1016/j.euo.2019.04.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875605PMC
May 2019

Correction: Predictors of fluoroquinolone-resistant bacteria in the rectal vault of men undergoing prostate biopsy.

Prostate Cancer Prostatic Dis 2019 May;22(2):350

Department of Urology, University of Illinois Chicago, Chicago, IL, USA.

The original version of this article contained an error in the name of author Alfredo Mena Lora. This has now been corrected.
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http://dx.doi.org/10.1038/s41391-019-0133-6DOI Listing
May 2019

Predictors of fluoroquinolone-resistant bacteria in the rectal vault of men undergoing prostate biopsy.

Prostate Cancer Prostatic Dis 2019 05 2;22(2):268-275. Epub 2018 Oct 2.

Department of Urology, University of Illinois Chicago, Chicago, IL, USA.

Importance: Fluoroquinolone (FQ)-resistant rectal vault flora is associated with infectious complications in men undergoing transrectal ultrasound-guided prostate needle biopsy (TRUS-PNB).

Objective: To determine the patient factors that predict FQ-resistant rectal cultures in men who are undergoing transrectal ultrasound-guided prostate needle biopsy.

Methods: An IRB approved retrospective review of 6183 consecutive men who had undergone a rectal swab culture in preparation for TRUS-PNB between January 2013 and December 2014 was performed. Multivariable logistic regression was used to determine the clinical and demographic factors associated with FQ-resistant Enterobacteriaceae in the rectal vault.

Results: Of the 6179 rectal swabs analyzed, 4842 (78%) were FQ-sensitive, and 1337 (22%) were FQ-resistant. On univariable analysis, increasing age, prior TRUS-PNB, higher number of biopsy cores obtained, diabetes mellitus, antimicrobial use within the past 6 months and non-Caucasian race were predictors of FQ-resistance (all p < 0.05). Men with FQ-resistant cultures were more likely to have benign pathology on TRUS-PNB (p = 0.004). On multivariable analysis, increasing patient age (OR = 1.01/year [1.00-1.02]), use of antimicrobials in the last 6 months (OR = 2.85[2.18-3.72]), African American (OR = 1.99 [1.66-2.37]), Asian (OR = 3.39 [2.63-4.37]), and Hispanic (OR = 2.10 [1.72-2.55]) races were independently associated with FQ-resistant rectal cultures. The overall infectious rate was 1.1% (56/5214) and the sepsis rate was 0.46% (24/5214). The infection rate in the FQ-resistant group was 3.9% (43/1107) compared to FQ-sensitive group 0.3% (13/4107), p < 0.001.

Conclusion: In this cohort, increasing age, recent antimicrobial-use, and non-Caucasian race were independent predictors of FQ-resistance in the rectal vault. As FQ-resistance is associated with infectious complications from transrectal ultrasound-guided prostate needle biopsy, understanding risk factors may assist infection control efforts.
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http://dx.doi.org/10.1038/s41391-018-0092-3DOI Listing
May 2019

Lowering positive margin rates at radical prostatectomy by color coding of biopsy specimens to permit individualized preservation of the neurovascular bundles: is it feasible? a pilot investigation.

Int Braz J Urol 2018 Nov-Dec;44(6):1081-1088

Department of Urology, Rush University Medical Center, Chicago, IL, USA.

Objective: To evaluate whether color-coding of prostate core biopsy specimens aids in preservation of the neurovascular bundles from an oncological perspective.

Materials And Methods: MRI guided transrectal ultrasound and biopsy of the prostate were performed in 51 consecutive patients suspected of being at high risk for harboring prostate cancer. Core specimens were labeled with blue dye at the deep aspect and red dye at the superficial peripheral aspect of the core. The distance from the tumor to the end of the dyed specimen was measured to determine if there was an area of normal tissue between the prostate capsule and tumor.

Results: Of the 51 patients undergoing prostate biopsy, 30 (58.8%) were found to have cancer of the prostate: grade group 1 in 13.7%, 2 in 25.5%, 3 in 7.8%, 4 in 7.8% and 5 in 3.9% of the cohort. A total of 461 cores were analyzed in the cohort, of which 122 showed cancer. Five patients opted to undergo robotic assisted laparoscopic radical prostatectomy. No patients had a positive surgical margin (PSM) or extra prostatic extension (EPE) on radical prostatectomy if there was a margin of normal prostatic tissue seen between the dye and the tumor on prostate biopsy.

Conclusion: Color-coding of prostate biopsy core specimens may assist in tailoring the approach for preservation of the neurovascular bundles without compromising early oncological efficacy. Further study is required to determine whether this simple modification of the prostate biopsy protocol is valuable in larger groups of patients.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2017.0328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442172PMC
February 2019

Novel urinary biomarkers for the detection of bladder cancer: A systematic review.

Cancer Treat Rev 2018 Sep 29;69:39-52. Epub 2018 May 29.

Division of Surgery and Interventional Science, University College London, 3rd Floor Charles Bell House, 43-45 Foley Street, London W1W 7TS, UK; Department of Urology, University College London Hospital at Westmoreland Street, 16-18 Westmoreland Street, London W1G 8PH, UK.

Background: Urinary biomarkers for the diagnosis of bladder cancer represents an area of considerable research which has been tested in both patients presenting with haematuria and non-muscle invasive bladder cancer patients requiring surveillance cystoscopy. In this systematic review, we identify and appraise the diagnostic sensitive and specificity of reported novel biomarkers of different 'omic' class and highlight promising biomarkers investigated to date.

Methods: A MEDLINE/Pubmed systematic search was performed between January 2013 and July 2017 using the following keywords: (bladder cancer OR transitional cell carcinoma OR urothelial cell carcinoma) AND (detection OR diagnosis) AND urine AND (biomarker OR assay). All studies had a minimum of 20 patients in both bladder cancer and control arms and reported sensitivity and/or specificity and/or receiver operating characteristics (ROC) curve. QUADAS-2 tool was used to assess risk of bias and applicability of studies. The search protocol was registered in the PROSPERO database (CRD42016049918).

Results: Systematic search yielded 115 reports were included for analysis. In single target biomarkers had a sensitivity of 2-94%, specificity of 46-100%, positive predictive value (PPV) of 47-100% and negative predictive value (NPV) of 21-94%. Multi-target biomarkers achieved a sensitivity of 24-100%, specificity of 48-100%, PPV of 42-95% and NPV of 32-100%. 50 studies achieved a sensitivity and specificity of ≥80%. Protein (n = 59) and transcriptomic (n = 21) biomarkers represents the most studied biomarkers. Multi-target biomarker panels had a better diagnostic accuracy compared to single biomarker targets. Urinary cytology with urinary biomarkers improved the diagnostic ability of the biomarker. The sensitivity and specificity of biomarkers were higher for primary diagnosis compared to patients in the surveillance setting. Most studies were case control studies and did not have a predefined threshold to determine a positive test result indicating a possible risk of bias.

Conclusion: This comprehensive systematic review provides an update on urinary biomarkers of different 'omic' class and highlights promising biomarkers. Few biomarkers achieve a high sensitivity and negative predictive value. Such biomarkers will require external validation in a prospective observational setting before adoption in clinical practice.
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http://dx.doi.org/10.1016/j.ctrv.2018.05.012DOI Listing
September 2018

Urinary biomarker for the detection of recurrence following non-muscle invasive bladder cancer: are we there yet?

Transl Androl Urol 2018 Mar;7(Suppl 1):S109-S110

Division of Urology, Rush University Medical Center, Chicago, IL, USA.

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http://dx.doi.org/10.21037/tau.2017.12.18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881187PMC
March 2018

Genital Dermatillomania.

Curr Urol 2017 Nov 30;11(1):54-56. Epub 2017 Nov 30.

Department of Urology, Rush University Medical Center, Chicago, Illinois, USA.

Dermatillomania is a rare disease that seldom affects the genitals. Genital dermatillomania has not yet been recognized as a separate entity within the disease. The purpose of the report is to highlight a new facet of dermatillomania and inform urologists that dermatillomania could be a potential reason for genital ulcers. This report documents 2 cases of genital dermatillomania which vary in severity from mild (case 1), where the patient's ulcers healed after extensive counseling, to extremely dire (case 2), where the patient lost his penis after recurring ulcers and multiple reconstructive surgeries. Clinicians should be aware of the characteristics of dermatillomania to ensure that appropriate therapy can be promptly initiated to prevent morbidity.
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http://dx.doi.org/10.1159/000447195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814777PMC
November 2017

Microdenervation of the spermatic cord for post-vasectomy pain syndrome.

BJU Int 2018 04 9;121(4):667-673. Epub 2018 Feb 9.

Division of Urology, Rush University Medical Center, Chicago, IL, USA.

Objective: To evaluate the outcomes of patients who underwent microdenervation of the spermatic cord (MDSC) for post-vasectomy pain syndrome (PVPS) at our institution.

Methods: A retrospective study of all patients who underwent MDSC for PVPS by a single surgeon between March 2002 and October 2016 was performed. Pain was documented using the numerical rating scale (NRS). Spermatic cord block (SCB) was performed on all patients, and success was defined as NRS score ≤1 for >4 h. All patients had failed medical therapy prior to MDSC. All previous procedures for PVPS had been performed elsewhere. Surgical success was defined as a postoperative NRS score of ≤1.

Results: A total of 27 patients with 28 scrotal units underwent MDSC for PVPS. The median (1st quartile; 3rd quartile) follow-up was 10 (2; 16.5) months. The median (range) duration of pain prior to surgery was 57 (8-468) months. Pain was bilateral in 14 (52%), left-sided in eight (30%) and right-sided in five patients (19%). Data on SCB were available for 23 patients, with a success rate of 96%. The median (range) preoperative pain NRS score was 7 (2-10). The median (range) pain score after SCB on the NRS scale was 0 (0-5). The median (range) postoperative pain score on the NRS was 0 (0-9). Overall success was achieved in 20 of 28 testicular units (71%). Patients with involvement of multiple structures in the scrotum (i.e. testis, epididymis, spermatic cord) had a success rate of 81% and were more likely to have a successful surgery (P < 0.001). Five patients had failed a prior epididymectomy and three had failed a vaso-vasostomy for PVPS; this had no correlation with the success of MDSC (P = 0.89).

Conclusion: The MDSC procedure is a reasonably successful, durable and valuable approach for PVPS, especially when pain involves multiple structures in the scrotum (testis, epididymis, spermatic cord). MDSC was equally efficacious in patients who had previously failed a procedure for PVPS. No patient had a worsening NRS score after MDSC. This is the largest study to date evaluating MDSC for the treatment of PVPS.
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http://dx.doi.org/10.1111/bju.14125DOI Listing
April 2018

What Can We Do for Chronic Scrotal Content Pain?

World J Mens Health 2017 Dec;35(3):146-155

Department of Urology, Rush University Medical Center, Chicago, IL, USA.

Chronic scrotal content pain remains one of the more challenging urological problems to manage. This is a frustrating disorder to diagnose and effectively treat for both the patient and clinician, as no universally accepted treatment guidelines exist. Many patients with this condition end up seeing physicians across many disciplines, further frustrating them. The pathogenesis is not clearly understood, and the treatment ultimately depends on the etiology of the problem. This article reviews the current understanding of chronic scrotal content pain, focusing on the diagnostic work-up and treatment options.
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http://dx.doi.org/10.5534/wjmh.17047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746485PMC
December 2017

An Atypical Presentation of Retroperitoneal Fibrosis.

Curr Urol 2017 Aug 30;10(3):157-159. Epub 2017 Jul 30.

Department of Urology, Rush University Medical Center, Chicago, Illinois, USA.

A 69-year-old man with a psoriatic arthritis treated with infliximab for 1 month presented to the urology clinic for lower urinary tract symptoms. He was found to have a new diagnosis of elevated creatinine. Computed tomography of the abdomen and pelvis revealed bilateral severe hydronephrosis with abnormal soft tissue thickening of the right renal pelvis and proximal ureter. Bilateral stents were placed after ureteroscopy demonstrated no abnormalities. A computed tomography-guided biopsy of the peri-ureteral lesions revealed fibroadipose tissue with sclerosis and extensive chronic inflammation consistent with retroperitoneal fibrosis. Infliximab was discontinued and the patient was started on corticosteroids. Follow-up magnetic resonance imaging of the abdomen and pelvis at 2 months revealed total resolution of soft tissue and inflammation along the proximal ureter bilaterally. Repeat imaging demonstrated no hydronephrosis after stents removal, and the patient's creatinine remains normal at 12 months follow-up.
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http://dx.doi.org/10.1159/000447172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582446PMC
August 2017

Micro-Denervation of the Spermatic Cord for Post-Vasectomy Pain Management.

Sex Med Rev 2018 04 21;6(2):328-334. Epub 2017 Jul 21.

Department of Urology, Rush University Medical Center, Chicago, IL, USA. Electronic address:

Introduction: Post-vasectomy pain syndrome (PVPS) is a challenging problem for the practicing urologist because of its unclear pathophysiology and no clearly established protocol for evaluation or treatment. PVPS is defined as at least 3 months of chronic or intermittent scrotal content pain after a vasectomy procedure once other etiologies for the pain have been ruled out.

Aim: To systematically review the current literature on the effectiveness of micro-denervation of the spermatic cord (MDSC) for PVPS.

Methods: A systematic literature search using PubMed, Scopus, Medline, Embase, and Cochrane databases for all reports pertaining to PVPS using the Medical Subject Heading terms post vasectomy pain syndrome and micro-denervation of spermatic cord through February 2017.

Main Outcome Measures: Scrotal content pain after MDSC for PVPS.

Results: There were nine retrospective studies evaluating MDSC for chronic testicular pain. After omitting repeated series, there were 213 patients who underwent MDSC for chronic orchialgia. Only one study specifically reviewed the outcomes of patients who underwent MDSC for PVPS. In this study, 17 patients underwent MSDC for PVPS, with 13 (76.5%) reporting complete relief of pain at their first follow-up visit. The other four patients had significant improvement in pain and were satisfied with the results. Long-term follow-up data were not available for this study.

Conclusion: MDSC remains a valuable approach with high success rates and should be considered for PVPS that is refractory to medical therapy. MDSC appears to have the most success for patients who experience a temporary relief from a cord block and can significantly improve the patient's quality of life and ability to return to daily activities. Tan WP, Levine LA. Micro-Denervation of the Spermatic Cord for Post-Vasectomy Pain Management. Sex Med Rev 2018;6:328-334.
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http://dx.doi.org/10.1016/j.sxmr.2017.06.002DOI Listing
April 2018

Schistosoma haematobium: A Delayed Cause of Hematuria.

Urology 2017 Sep 23;107:e7-e8. Epub 2017 Jun 23.

Department of Urology, Rush University Medical Center, Chicago, IL.

A 22-year-old African American man with recurrent episodes of gross hematuria for 6 months presented to the clinic for evaluation. A thorough history revealed that the patient emigrated from Mozambique to the United States 12 years ago. Urine culture was negative for a urinary tract infection. Cystoscopy revealed 4 lesions in the bladder. Biopsy of the bladder lesion revealed severe cystitis and Schistosoma haematobium. The patient later confirmed that he used to swim in rivers and streams back in Africa. He completed a course of praziquantel and his gross hematuria resolved.
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http://dx.doi.org/10.1016/j.urology.2017.06.021DOI Listing
September 2017

Intentional Omission of Ureteral Stents During Robotic-assisted Intracorporeal Ureteroenteric Anastomosis: Is It Safe and Feasible?

Urology 2017 04 19;102:116-120. Epub 2017 Jan 19.

Department of Urology, Rush University Medical Center, Chicago, IL.

Objective: To describe the surgical technique we used to perform a stentless intracorporeal ureteroenteric anastomosis and to determine the outcomes in this initial series.

Methods: We performed a retrospective review of a prospective database of all patients undergoing robotic-assisted intracorporeal urinary diversion with stentless ureteroenteric anastomosis between March 2014 and July 2016. Diversions were performed at the time of either robotic-assisted laparoscopic cystectomy for bladder cancer or urinary diversion for other indications.

Results: A total of 10 patients underwent implantation of 20 ureters into the intestine via a robotic-assisted approach with intentional omission of stents. Median body mass index was 29.57 (first quartile 23.68, third quartile 34.69). Median American Society of Anesthesiologists score was 3 (range 2-3). Seven patients had intracorporeal ileal conduit reconstruction and 3 patients had an intracorporeal neobladder creation. There were no patients who developed a stricture of the ureter nor did any patient develop a leak at the ureteroenteric anastomosis. All patients had normal serum creatinine at least 4 weeks after surgery, and all patients had follow-up computed tomography of the kidneys, which were normal. The median follow-up was 8 months (first quartile = 3 months, third quartile = 17 months).

Conclusion: Robotic intracorporeal urinary diversion with intentional omission of ureteral stents is a safe and feasible option when establishing continuity of the genitourinary and gastrointestinal tracts.
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http://dx.doi.org/10.1016/j.urology.2017.01.014DOI Listing
April 2017

Upper Tract Urothelial Carcinoma in the Genetically Predisposed Patient: Role of Urinary Markers in Predicting Recurrence.

J Endourol Case Rep 2016 1;2(1):235-237. Epub 2016 Dec 1.

Department of Urology, Rush University Medical Center , Chicago, Illinois.

Upper tract urothelial carcinoma (UTUC) is an uncommon disease that is diagnosed clinically by the selective use of urine cytology, urine biomarkers, and imaging of the upper tract. We present a case of a patient with Lynch syndrome and high-grade UTUC that was diagnosed by an abnormal Cxbladder assay, prompting further endoscopic examination. A 59-year-old Caucasian female with a history of endometrial cancer and bladder cancer with Lynch syndrome presented for evaluation of recurrent urothelial carcinoma. Her previous bladder tumors have been T1 high grade and Ta high grade and have been treated with resection and multiple cycles of intravesical Bacillus Calmette-Guerin (BCG) therapy. She had also undergone a robotic left distal ureterectomy and psoas hitch for a high-grade distal ureteral tumor. Surveillance cystoscopy 7 months after revealed a biopsy-confirmed bladder tumor, which was resected, and she was started on maintenance BCG therapy. At presentation, follow-up urine cytology and UroVysion studies were negative. Cxbladder test was also initially negative. However, during close clinical monitoring, the Cxbladder test became positive. Cystoscopy was once more performed, which was unremarkable. Bilateral ureteroscopy was performed, revealing high-grade upper tract renal papillary carcinoma (UTUC) in the left renal pelvis. The patient declined a nephroureterectomy. She was treated with two sessions of holmium laser ablation of the left renal pelvis tumor and underwent 6 weekly courses of BCG + interferon instilled into her left renal pelvis using a 5F open-ended catheter. Repeat urine cytology, UroVysion, and Cxbladder tests were negative after completion of upper tract BCG therapy. Cxbladder test may be useful and an adjunct to urine cytology and the UroVysion FISH assay to evaluate patients at high risk for recurrent UTUC.
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http://dx.doi.org/10.1089/cren.2016.0124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5178002PMC
December 2016

Robotic assisted laparoscopic radical cystectomy with stentless intracorporeal modified Ves.Pa neobladder: early experience.

J Robot Surg 2017 Dec 9;11(4):423-431. Epub 2017 Jan 9.

Rush University Medical Center, Chicago, IL, USA.

This study aimed at demonstrating the feasibility of robotic assisted laparoscopic radical cystectomy with pure intracorporeal modified Ves.Pa neobladder with stentless ureteroileal anastomosis. Pure intracorporeal robotic assisted laparoscopic technique has been recently developed with a select number of high-volume centers utilizing various operative and neobladder techniques. We reviewed the patient characteristics, operative details and perioperative courses in the two patients who have undergone robotic assisted laparoscopic radical cystectomy with pure intracorporeal modified Ves.Pa neobladder and one who has undergone the Hautmann W neobladder. These results were compared to other contemporary robotic neobladder series. We demonstrate technical success with similar operative and perioperative results with the modified Ves.Pa neobladder. The robotic pure intracorporeal modified Ves.Pa neobladder is a technically feasible operation and may be easier to perform compared to other neobladders. Initial experience suggests operative time and perioperative outcomes are similar to other robotic techniques.
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http://dx.doi.org/10.1007/s11701-017-0673-5DOI Listing
December 2017

Robotic Assisted Radical Cystectomy with Extracorporeal Urinary Diversion Does Not Show a Benefit over Open Radical Cystectomy: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

PLoS One 2016 7;11(11):e0166221. Epub 2016 Nov 7.

Division of Surgery and Interventional Science, University College London, London, United Kingdom.

Background: The number of robotic assisted radical cystectomy (RARC) procedures is increasing despite the lack of Level I evidence showing any advantages over open radical cystectomy (ORC). However, several systematic reviews with meta-analyses including non-randomised studies, suggest an overall benefit for RARC compared to ORC. We performed a systematic review with meta-analysis of randomised controlled trials (RCTs) to evaluate the perioperative morbidity and efficacy of RARC compared to ORC in patients with bladder cancer.

Methods: Literature searches of Medline/Pubmed, Embase, Web of Science and clinicaltrials.gov databases up to 10th March 2016 were performed. The inclusion criteria for eligible studies were RCTs which compared perioperative outcomes of ORC and RARC for bladder cancer. Primary objective was perioperative and histopathological outcomes of RARC versus ORC while the secondary objective was quality of life assessment (QoL), oncological outcomes and cost analysis.

Results: Four RCTs (from 5 articles) met the inclusion criteria, with a total of 239 patients all with extracorporeal urinary diversion. Patient demographics and clinical characteristics of RARC and ORC patients were evenly matched. There was no significant difference between groups in perioperative morbidity, length of stay, positive surgical margin, lymph node yield and positive lymph node status. RARC group had significantly lower estimated blood loss (p<0.001) and wound complications (p = 0.03) but required significantly longer operating time (p<0.001). QoL was not measured uniformly across trials and cost analysis was reported in one RCTs. A test for heterogeneity did highlight differences across operating time of trials suggesting that surgeon experience may influence outcomes.

Conclusions: This study does not provide evidence to support a benefit for RARC compared to ORC. These results may not have inference for RARC with intracorporeal urinary diversion. Well-designed trials with appropriate endpoints conducted by equally experienced ORC and RARC surgeons will be needed to address this.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0166221PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098822PMC
June 2017

Renal fungus ball: a challenging clinical problem.

Urologia 2017 Apr 15;84(2):113-115. Epub 2016 Oct 15.

Department of Urology, Rush University Medical Center, Chicago, Illinois - USA.

Introduction: We describe a case of renal pelvi-ureteric fungus ball managed with placement of two nephrostomy tubes and amphotericin B irrigation through a nephrostomy tube with the other to free drain.

Case Report: A 46-year-old man with uncontrolled Type 2 diabetes mellitus was referred to the urology clinic for workup of recurrent urinary tract infection. Urine culture grew Candida albicans. The patient was started on oral fluconazole therapy. Cystoscopy and cystogram revealed a grade 3 left vesicoureteral reflux and right retrograde pyelogram revealed a filling defect in the right renal pelvis extending into the proximal ureter with severe hydroureteronephrosis. Two nephrostomy tubes were placed (mid-pole and lower pole) to ensure that the system was not obstructed. Amphotericin B (50 mg/1000 ml normal saline) irrigation was then instilled through the mid-pole nephrostomy tube at a rate of 30 ml/h with the lower pole nephrostomy tube to free drain. An antegrade nephrostogram was performed after 5 days of amphotericin B instillation, showing complete resolution of the fungus ball. The patient is awaiting definitive minimally invasive management of the distal ureteral narrowing.

Comments: Renal and pelvi-ureteric fungus ball is a challenging clinical entity. It must be addressed promptly and efficiently to be successful. We describe a minimally invasive approach that was tolerated well and resulted in complete clearance of the fungus ball in a relatively short time frame.
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http://dx.doi.org/10.5301/uro.5000201DOI Listing
April 2017

Author Reply.

Urology 2016 Dec 7;98:111-112. Epub 2016 Oct 7.

Department of Urology, Rush University Medical Center, Chicago, IL.

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http://dx.doi.org/10.1016/j.urology.2016.07.044DOI Listing
December 2016

Central zone lesions on magnetic resonance imaging: Should we be concerned?

Urol Oncol 2017 01 28;35(1):31.e7-31.e12. Epub 2016 Sep 28.

Department of Urology, Rush University Medical Center, Chicago, IL.

Introduction And Objective: The Prostate Imaging Reporting and Data System (PI-RADS) score was developed to evaluate lesions in the peripheral and transition zone on multiparametric magnetic resonance imaging (mpMRI) of the prostate. We aim to determine if the PI-RADS scoring system can be used to evaluate central zone lesions on mpMRI.

Materials And Methods: A retrospective review of 73 patients who underwent mpMRI/ultrasound (US) fusion-guided biopsy of 143 suspicious lesions between February 2014 and October 2015 was performed. All patients underwent a 3T mpMRI. Indications for mpMRI included an abnormal digital rectal examination, PSA velocity >0.75ng/dl/y, and patients on active surveillance. The mpMRI sequence involved T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast enhancement. Using 3-dimensional model software (Invivo Corporation, Gainesville, FL, USA), a minimum of 3 magnetic resonance imaging (MRI)/US fusion-guided biopsy samples were taken from each prostate lesion seen on mpMRI irrespective of PI-RADS score, using local anesthesia in an outpatient clinic setting.

Results: A total of 73 patients underwent MRI/US fusion-guided biopsy of 85 peripheral zone lesions, 31 transitional zone lesions, and 27 central zone lesions. Only 2 (7%) of central zone lesions were positive for prostate cancer. Both patients had lesions which were graded as PI-RADS 3. Both the patients had multifocal lesions that encompassed≥50% of the central and transition zones on the sagittal view MRI images. Both patients previously had transrectal US-guided biopsy of the prostate which was negative for cancer. Both patients underwent a robotic-assisted laparoscopic prostatectomy, each revealing high-grade cancer.

Conclusions: Lesions involving only the central gland/zone seen on MRI are less concerning for malignancy and should not be given equal weight as peripheral zone lesions. In this series, no lesions involving solely the central gland/zone, regardless of PI-RADS score, was positive for malignancy on MRI/US fusion-guided biopsy. Consideration of a modified PI-RADS scoring system should be given to help identify central zone lesions with malignant potential.
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http://dx.doi.org/10.1016/j.urolonc.2016.08.006DOI Listing
January 2017