Jennifer Ahn

Ureterorenoscopy for Upper Tract Urothelial Carcinoma: How Often Are We Missing Lesions?

OBJECTIVE To determine the ability of ureterorenoscopy (URS) to identify the precise number and location of all lesions as compared with pathologic review of nephroureterectomy specimens, which have not been previously determined. Upper tract urothelial carcinoma (UTUC) comprises 5% of all urothelial malignancies in the United States. With advances in endoscopic equipment, there has been a move toward using flexible ureteroscopes to perform URS as part of the diagnostic evaluation and management. METHODS We identified patients who had undergone URS with biopsy before radical nephroureterectomy for UTUC. Operative reports for each procedure were reviewed and compared with the surgical pathology reports. RESULTS URS correctly identified the number and location of lesions in 57 of 76 patients (75%). The most common locations for missed lesions were in the ureter (9 patients) and renal pelvis (8 patients). Carcinoma in situ was missed on the initial biopsy for 9 patients. Three of 11 patients (27%) with a solitary lesion in the distal ureter visualized by URS had a missed lesion in the renal pelvis. URS with biopsy accurately predicted the grade of UTUC lesions in 79% of cases, whereas 65% of patients were upstaged on final pathology. CONCLUSION URS with biopsy can accurately map UTUC in the majority of patients. However, up to 25% of patients will have missed lesions, and nearly 50% of these patients will have a missed carcinoma in situ lesion. Undergrading and understaging of UTUC lesions remain shortcomings with potentially severe consequences.

Urine Exosomes for Non-Invasive Assessment of Gene Expression and Mutations of Prostate Cancer.

Purpose The analysis of exosome/microvesicle (extracellular vesicles (EVs)) and the RNA packaged within them (exoRNA) has the potential to provide a non-invasive platform to detect and monitor disease related gene expression potentially in lieu of more invasive procedures such as biopsy. However, few studies have tested the diagnostic potential of EV analysis in humans. Experimental Design The ability of EV analysis to accurately reflect prostate tissue mRNA expression was examined by comparing urinary EV TMPRSS2:ERG exoRNA from pre-radical prostatectomy (RP) patients versus corresponding RP tissue in 21 patients. To examine the differential expression of TMPRSS2:ERG across patient groups a random urine sample was taken without prostate massage from a cohort of 207 men including prostate biopsy negative (Bx Neg, n = 39), prostate biopsy positive (Bx Pos, n = 47), post-radical prostatectomy (post-RP, n = 37), un-biopsied healthy age-matched men (No Bx, n = 44), and young male controls (Cont, n = 40). The use of EVs was also examined as a potential platform to non-invasively differentiate Bx Pos versus Bx Neg patients via the detection of known prostate cancer genes TMPRSS2:ERG, BIRC5, ERG, PCA3 and TMPRSS2. Results In this technical pilot study urinary EVs had a sensitivity: 81% (13/16), specificity: 80% (4/5) and an overall accuracy: 81% (17/21) for non-invasive detection of TMPRSS2:ERG versus RP tissue. The rate of TMPRSS2:ERG exoRNA detection was found to increase with age and the expression level correlated with Bx Pos status. Receiver operator characteristic analyses demonstrated that various cancer-related genes could differentiate Bx Pos from Bx Neg patients using exoRNA isolated from urinary EVs: BIRC5 (AUC 0.674 (CI:0.560–0.788), ERG (AUC 0.785 (CI:0.680–0.890), PCA3 (AUC 0.681 (CI:0.567–0.795), TMPRSS2:ERG (AUC 0.744 (CI:0.600–0.888), and TMPRSS2 (AUC 0.637 (CI:0.519–0.754). Conclusion This pilot study suggests that urinary EVs have the potential to be used as a platform to non-invasively differentiate patients with prostate cancer with very good accuracy. Larger studies are needed to confirm the potential for clinical utility.

New agents for bacillus Calmette-Guérin-refractory nonmuscle invasive bladder cancer.

Purpose of review Radical cystectomy is the standard of care for patients who fail intravesical bacillus Calmette–Guérin (BCG) for nonmuscle invasive bladder cancer (NMIBC). For patients unwilling or unable to undergo cystectomy, numerous local therapies exist, although few are approved by the Food and Drug Administration. This review describes available therapies for this challenging clinical entity. Recent findings Combination intravesical chemotherapy, targeted therapy, and drug delivery enhancement have all been under recent investigation and are promising, although none has proven superior as of yet. Summary While BCG is standard treatment for intermediate and high-risk NMIBC, many patients fail therapy with recurrence or progression. Early cystectomy is the standard of care for BCG failure; however, many patients are unwilling or unable to undergo cystectomy. Multiple intravesical therapies have been used in this BCG failure population with moderate success, and, recently, technologies to improve drug delivery or create novel drugs have also been applied. Comparing efficacy of these therapies remain challenging as study cohorts are heterogeneous and study designs are variable. However, there are an increasing number of novel treatment options that can be offered to patients faced with recurrent NMIBC after BCG who seek bladder-sparing therapy.

New Agents for Bacillus Calmette-Guérin–Refractory Bladder Cancer

Bacillus Calmette-Guérin has been established as the primary treatment of high-risk non-muscle invasive bladder cancer. If patients do not respond or later recur, the most reliable treatment option is cystectomy. For those who are unwilling or unable to undergo this significant procedure, there is a multitude of alternative intravesical therapies. This article provides an overview of treatment options for patients with non-muscle invasive bladder cancer who have failed intravesical bacillus Calmette-Guérin therapy. It includes information on recent and ongoing trials and serves as a guide for clinicians regarding available therapies and a reference for researchers in this field.

Endoscopic Management of Intraluminal Ureteral Endometriosis

OBJECTIVE To present the largest experience on the ureteroscopic management of ureteral obstruction secondary to intraluminal endometrial implantation. MATERIALS AND METHODS We retrospectively evaluated patients who underwent ureteroscopic management of intraluminal endometriosis from 1996 to 2012. All patients were diagnosed with ureteroscopic biopsy and underwent at least 1 ureteroscopic ablation with a holmium YAG (Ho:Yag) laser. Patients were monitored for evidence of disease persistence, recurrence, or progression with computed tomography, sonography, renal scan, ureteroscopy, and retrograde urography. Success was defined as the complete eradication of ureteral endometriosis, resolution of symptoms, and maintenance of renal function. RESULTS Five patients were identified. Mean age was 37.5 years. All patients had hydroureteronephrosis at presentation whereas 2 had severely impaired renal function. Three patients were successfully treated with a single ablative procedure, whereas 2 had persistent symptomatic hydroureteronephrosis and underwent repeat ablation. Of those requiring repeat ablation, 1 became disease-free after the second ablation, whereas the other had persistence of disease, requiring nephroureterectomy. Three patients developed ureteral strictures, requiring balloon dilation and serial stent exchanges. At a median follow-up of 35 months (16-84), overall success rate was observed in 4 of 5 patients (80%). CONCLUSION Endometriosis affects approximately 15% of premenopausal women and can present anywhere along the urinary tract including the ureters, which might result in urinary obstruction and impaired renal function. Although surgical resection is the conventional treatment option for intraluminal endometriosis, ureteroscopic management is a viable nephron-sparing alternative. Follow-up imaging, including ureteroscopic surveillance and retrograde urography is recommended to detect disease recurrence or progression, or both.

Serum Cystatin C as a Novel Marker to Differentiate Pseudoazotemia in the Setting of Intraperitoneal Urine Extravasation

Urinary ascites results in pseudoazotemia due to urinary creatinine reabsorption across the peritoneum. We report a case of a pyeloplasty complicated by urine extravasation, in which the diagnosis was aided by discrepant findings of an elevated serum creatinine level but a stable cystatin C level. Cystatin C is a marker of renal function but is not typically excreted into the urine and therefore can be used to differentiate pseudoazotemia from true azotemia and is a better marker of renal function in the setting of known urinary ascites. These findings are relevant for patients with potential traumatic or nontraumatic sources of urine extravasation.

Comparison of Robot-Assisted and Open Retropubic Radical Prostatectomy for Risk of Biochemical Progression in Men with Positive Surgical Margins

OBJECTIVE Robot-assisted radical prostatectomy (RARP) is a minimally invasive alternative to open retropubic radical prostatectomy (RP), and is reported to offer equivalent oncologic outcomes while reducing perioperative morbidity. However, the technique of extirpation can differ based on the usage of thermal energy and coagulation during RARP, which may alter the risk of finding a positive surgical margin (PSM) as cautery may destroy residual cancer cells. We sought to evaluate whether the method of surgery (RP vs RARP) affects the rate of biochemical recurrence (BCR) in patients with PSMs. MATERIALS & METHODS The Columbia University Urologic Oncology Database was reviewed to identify patients who underwent RP and RARP from 2000 to 2010 and had a PSM on final pathology. BCR was defined as a postoperative prostate-specific antigen (PSA) ≥0.2 ng/mL. The Kaplan-Meier analysis was utilized to calculate BCR rates based on the method of surgery. Cox regression analysis was performed to determine if the method of surgery was associated with BCR. RESULTS We identified 3267 patients who underwent prostatectomy, of which 910 (28%) had a PSM. Of those with a PSM, 337 patients had available follow-up data, including 229 who underwent RP (68%) and 108 who underwent RARP (32%). At a mean follow-up time of 37 months for the RP group, 103 (46%) patients demonstrated BCR; at a mean follow-up time of 44 months for the RARP group, 62 (57%) patients had a BCR (p=0.140). Two-year BCR-free rates for RP vs RARP were 65% and 49%, respectively (log-rank p<0.001). However, after controlling for age, PSA, grade, and year of surgery, the surgical method was not significantly associated with increased risk of BCR (HR 1.25; p=0.29). CONCLUSION Our results confirm the noninferiority of RARP to RP with regard to patients with PSMs. As such, all patients with a PSM at RP are at high risk for BCR and should be followed in the same manner regardless of the surgical approach.

Comparison of Original and Internal Pathology Reports Referred for UrothelialCarcinoma to Determine Rate of Discrepancies and the Impact on Treatment Decisions

Objective: The purpose of the current study is to perform a standardized comparison of original and internal repeat pathology reviews of identical bladder specimens to identify discrepancies and characterize the impact of repeat review on treatment decisions as well as identify patients most likely to benefit from this practice. Materials/Methods: Ninety-one patients with an outside diagnosis of urothelial cancer of the bladder were referred to our institution for repeat review of 91 bladder resection specimens and biopsies. A discrepancy in either the presence or absence of muscularis propria and presence of invasive disease in the muscularis propria was deemed a “treatment-altering” characteristic, while presence of carcinoma in situ, lymphovascular invasion, or micropapillary features was deemed a “clinically-significant” characteristic. Results: After repeat review at our institution, 29.7% (27) specimens had treatment altering discrepancies, and 61.5% (56) specimens had at least one clinically-significant discrepancy. Conclusion: Repeat review of referred bladder specimens frequently impacts treatment decisions in patients with urothelial carcinoma.

HIV and Prostate Cancer

Highly active antiretroviral therapy (HAART) for the treatment of HIV-positive patients has delayed progression of HIV to AIDS and promoted immune system restoration thereby reducing AIDS-related mortality. Non-AIDS-defining malignancies such as prostate cancer (PCa) have been diagnosed more frequently given such extended survival. However, the actual incidence of prostate cancer in the HIV population remains ambiguous. This chapter includes search of all English-language articles describing HIV and prostate cancer between 1975 and 2011. A total of 1,178 patients with HIV and PCa were identified from the literature (87 patients from case reports, 1,091 from population-based studies). Prostate cancer incidence in HIV patients is different than the general population in multiple studies, and in the largest and most recent PSA-era population studies, incidence is typically decreased compared with the general population. During the HAART era, differences in PSA kinetics and prostate cancer behavior between HIV-positive and HIV-negative patients have not been apparent. HIV-infected patients should be managed in accordance with the most recent American Urological Association (AUA) guidelines which recommend screening of all men with age ≥40 years and a life expectancy of >10 years. All treatment options offered to the general population with prostate cancer should be available to the HIV-positive population with prostate cancer. Although long-term outcomes are still being accrued, initial results indicate response rates which are similar to HIV-negative patients.