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

Tan, Wei Shen; Tan, Wei Phin; Tan, Mae-Yen; Khetrapal, Pramit; Dong, Liqin; deWinter, Patricia; Feber, Andrew; Kelly, John D
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/CONCLUSIONS: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.
PMID: 29902678
ISSN: 1532-1967
CID: 5149602

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

Deane, Leslie A; Tan, Wei Phin; Strong, Andrea; Lowe, Megan; Antoine, Nency; Ghai, Ritu; Ekbal, Shahid
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/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/CONCLUSIONS: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.
PMCID:6442172
PMID: 30044594
ISSN: 1677-6119
CID: 5149612

Robot-Assisted Laparoscopic Radical Cystectomy with Stentless Intracorporeal Modified Ves.Pa Neobladder: Early Experience

Whelan, Patrick; Tan, Wei Phin; Papagiannopoulos, Dimitri; Omotosho, Philip; Deane, Leslie A
ORIGINAL:0015715
ISSN: 2151-1136
CID: 5285232

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

Whelan, Patrick; Tan, Wei Phin; Papagiannopoulos, Dimitri; Omotosho, Philip; Deane, Leslie
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.
PMID: 28070738
ISSN: 1863-2491
CID: 5149502

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

Tan, Wei Phin; Whelan, Patrick; Deane, Leslie A
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.
PMID: 28111222
ISSN: 1527-9995
CID: 5149522

Schistosoma haematobium: A Delayed Cause of Hematuria [Case Report]

Tan, Wei Phin; Hwang, Thomas; Park, Ji-Weon; Elterman, Lev
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.
PMID: 28652164
ISSN: 1527-9995
CID: 5149532

An Atypical Presentation of Retroperitoneal Fibrosis [Case Report]

Tan, Wei Phin; Hwang, Thomas; Medairos, Robert; Pessis, Dennis A
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.
PMCID:5582446
PMID: 28878601
ISSN: 1661-7649
CID: 5149552

What Can We Do for Chronic Scrotal Content Pain?

Tan, Wei Phin; Levine, Laurence A
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.
PMCID:5746485
PMID: 29282906
ISSN: 2287-4208
CID: 5149562

Genital Dermatillomania [Case Report]

Alexandrov, Philip; Tan, Wei Phin; Elterman, Lev
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.
PMCID:5814777
PMID: 29463978
ISSN: 1661-7649
CID: 5149582

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

Tan, Wei Phin; Mazzone, Andrew; Shors, Stephanie; Antoine, Nency; Ekbal, Shahid; Khare, Narendra; McKiel, Charles; Pessis, Dennis; Deane, Leslie
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.
PMID: 27692837
ISSN: 1873-2496
CID: 5149462