Multi-quadrant biopsy technique improves diagnostic ability in large heterogeneous renal masses. Abel EJ, Heckman JE, Hinshaw L, Best S, Lubner M, Jarrard DF, Downs TM, Nakada SY, Lee FT Jr, Huang W, Ziemlewicz T.J Urol. 2015 Oct;194(4):886-91. [Epub 2015 Mar 30]. doi: 10.1016/j.juro.2015.03.106.

PURPOSE: Percutaneous biopsy obtained from a single location is prone to sampling error in large heterogeneous renal masses, leading to nondiagnostic results or failure to detect poor prognostic features. We evaluated the accuracy of percutaneous biopsy for large renal masses using a modified multi-quadrant technique vs. a standard biopsy technique. MATERIALS AND METHODS: Clinical and pathological data for all patients with cT2 or greater renal masses who underwent percutaneous biopsy from 2009 to 2014 were reviewed. The multi-quadrant technique was defined as multiple core biopsies from at least 4 separate solid enhancing areas in the tumor. The incidence of nondiagnostic findings, sarcomatoid features and procedural complications was recorded, and concordance between biopsy specimens and nephrectomy pathology was compared. RESULTS: A total of 122 biopsies were performed for 117 tumors in 116 patients (46 using the standard biopsy technique and 76 using the multi-quadrant technique). Median tumor size was 10cm (IQR: 8-12). Biopsy was nondiagnostic in 5 of 46 (10.9%) standard and 0 of 76 (0%) multi-quadrant biopsies (P = 0.007). Renal cell carcinoma was identified in 96 of 115 (82.0%) tumors and nonrenal cell carcinoma tumors were identified in 21 (18.0%). One complication occurred using the standard biopsy technique and no complications were reported using the multi-quadrant technique. Sarcomatoid features were present in 23 of 96 (23.9%) large renal cell carcinomas studied. Sensitivity for identifying sarcomatoid features was higher using the multi-quadrant technique compared to the standard biopsy technique at 13 of 15 (86.7%) vs. 2 of 8 (25.0%) (P = 0.0062). CONCLUSIONS: The multi-quadrant percutaneous biopsy technique increases the ability to identify aggressive pathological features in large renal tumors and decreases nondiagnostic biopsy rates.

A biopsy-integrated algorithm for determining Gleason 6 upgrading risk stratifies risk of active surveillance failure in prostate cancer.

INTRODUCTION: A significant proportion of patients that fail active surveillance (AS) for prostate cancer management do so because of cancer upgrading. A previously validated upgrading nomogram generates a score that predicts risk of biopsy Gleason 6 upgrading following radical prostatectomy in lower-risk populations that are candidates for Active Surveillance (Cancer, 2013). OBJECTIVES: We hypothesize that the upgrading risk (UR) score generated by this nomogram at diagnosis improves the ability to predict patients that will subsequently fail AS. METHODS: To evaluate the nomogram, retrospective data from several institutional cohorts of patients who met AS criteria, group 1 (n = 75) and group 2 (n = 1230), were independently examined. A UR score was generated using the coefficients from the nomogram consisting of PSA density (PSAD), BMI, maximum % core involvement (MCI), and number of positive cores. AS failure was defined as Gleason score (GS) >6, >50 % maximum core involvement, or >2 positive cores on biopsy. Univariate and multivariate Cox proportional-hazards regression models, upgrading risk score, and other clinicopathologic features were each assessed for their ability to predict AS failure. RESULTS: Clinicopathologic parameters were similar in both groups with the exception of mean PSAD (0.13 vs. 0.11, p < 0.01) and follow-up (2.1 vs. 3.2 years, p = 0.2). Most common cause of AS failure was GS > 6 (group 1) compared to >2 positive cores (group 2). On univariate analysis in both populations, features at diagnosis including PSAD and the UR score were significant in predicting AS failure by upgrading (Gleason > 6) and any failure. Multivariate analysis revealed the UR score predicts AS failure by GS upgrading (HR 1.8, 95 % CI 1.12-2.93; p = 0.01) and any failure criteria (HR 1.7, 95 % CI 1.06-2.65); p = 0.02) for group 1. Likewise, the UR score in group 2 predicts AS failure with GS upgrading (HR 1.3, 95 % CI 1.15-1.42; p < 0.0001) and any failure criteria (HR 1.18, 95 % CI 1.18-1.38; p < 0.0001). An ROC generated an AUC of 0.66. Decision curve analysis demonstrated a high net benefit for the UR score across a range of threshold probabilities. Based on these outcomes, at 3 years, patients in the lowest risk quartile have a 15 % risk of AS failure versus a 46 % risk in the highest quartile (p < 0.0001). CONCLUSIONS: The UR score was predictive of pathologic AS failure on multivariate analysis in several AS cohorts. It outperformed single clinicopathologic criteria and may provide a useful adjunct using clinicopathologic data to stratify patients considering AS.

Primary cutaneous adenosquamous carcinoma of the penis: the first characterization of HPV status in this rare and diagnostically challenging entity with review of glandular carcinomas of the penis.

Glandular and pseudoglandular tumors of the penile skin are extremely uncommon and can present diagnostic challenges. Primary adenosquamous carcinoma of the penis is an extremely rare tumor, composed of distinct areas of malignant squamous and glandular cells, making it a diagnostically challenging entity. The World Health Organization (WHO) recognizes several subtypes of squamous cell carcinoma (SCC), each with its own distinctive pathologic appearance, clinical associations and prognosis. Among these variants is the exceedingly uncommon adenosquamous carcinoma (ASC), representing 1%-2% of all SCC of the penis. Recent large studies have interrogated the presence of human papillomavirus (HPV) in malignant penile tumors and have shown specific morphologic patterns and clinical presentations to associate with HPV status. However, given the rarity of the adenosquamous variant of SCC, it has largely been excluded from these studies. The glandular components of these lesions can present a confusing appearance, particularly when a large tumor is represented on a small biopsy. Here we describe a difficult histologic presentation of this rare tumor, with the first published characterization of the HPV status of this subtype. This case represents a distinctly unusual case of metastatic HPV-positive primary cutaneous adenosquamous carcinoma of the penis.

Neoadjuvant chemotherapy use in bladder cancer: a survey of current practice and opinions.

Objectives. Level 1 evidence supports the use of neoadjuvant chemotherapy (NAC) to improve overall survival in muscle invasive bladder cancer; however utilization rates remain low. The aims of our study were to determine factors associated with NAC use, to more clearly define reasons for low utilization, and to determine the current rate of NAC use among urologic oncologists. Materials and Methods. Active members of the Society for Urologic Oncology were provided a 20-question survey. Descriptive statistical analysis was conducted for each question and univariate analysis was performed. Results. We achieved a response rate of 21%. Clinical T3/T4 disease was the most often selected reason for recommending NAC (87%). Concerns with recommending NAC were age and comorbidities (54%) followed by delay in surgery (35%). An association was identified between urologic oncologists who discussed NAC with >90% of their patients and medical oncologists "always" recommending NAC (P = 0.0009). NAC utilization rate was between 30 and 57%. Conclusions. Amongst this highly specialized group of respondents, clinical T3-T4 disease was the most common reason for implementation of NAC. Respondents who frequently discussed NAC were more likely to report their medical oncologist always recommending NAC. Reported NAC use was higher in this surveyed group (30-57%) compared with recently published rates.

Robot-assisted laparoscopic radical prostatectomy in men with human immunodeficiency virus.

The aim of this study is to evaluate the outcomes of robot-assisted laparoscopic prostatectomy (RALP) in prostate cancer (PCa) patients with human immunodeficiency virus (HIV). This is a prospective cohort study of HIV patients undergoing RALP, comparing the demographics, tumor characteristics, complications, and short-term oncological outcomes of HIV-positive men to HIV-negative men using univariate (χ(2), Mann-Whitney test) and multivariable (logistic regression) analyses. From 2007 to 2010, 298 men underwent RALP, 8 of whom were known to be HIV positive. Preoperatively, all eight were taking highly active antiretroviral therapy (HAART) and had undetectable viral loads (<50); mean CD4 count was 634 cells per mm(3). HIV-positive men were younger (54 versus 62 years, P=0.010) and less likely to be white (P=0.007). There were no significant differences between groups with respect to clinical staging, pathological and oncological outcomes or most complication rates. However, the prevalence of perioperative transfusions (P=0.031) and ileus (P=0.021) were higher in HIV-positive patients. HIV remained significantly associated with risk of transfusion after adjustment for age, race, Gleason sum and clinical T stage (P=0.002). After a median of 2.6 (range 0.03-19.2) months of follow-up, PSA remained undetectable in all eight HIV patients. These data suggest that RALP is safe for, and demonstrates short-term oncological efficacy in, HIV-positive patients with PCa.

De novo calcification of liver and nodal metastases in prostate carcinoma.

Prostate cancer has a distinctly recognized pattern of metastases: multifocal and osteoblastic lesions involving the axial skeleton and non-calcified lymph nodes in the pelvic and lumbar aortic groups. Most adenocarcinomas are capable of producing macrocalcification. We report a case of prostate cancer with de novo calcified metastases to the liver and retroperitoneal lymph nodes mimicking the pattern usually seen in mucin-producing adenocarcinomas arising from the gastrointestinal tract. To our knowledge, this is the first such case to be reported in the literature. We propose a multifactorial mechanism that supports dystrophic calcification in this case. The knowledge of atypical presentation of metastatic disease can prevent diagnostic delay and prompt initiation of therapy.

IFN-alpha 2B enhances Th1 cytokine responses in bladder cancer patients receiving Mycobacterium bovis bacillus Calmette-Guérin immunotherapy.

Combination therapy with intravesical bacillus Calmette-Guérin (BCG) plus IFN-alpha for superficial bladder cancer has been demonstrated to be more effective than either single agent alone in animal studies and of suggested greater efficacy in clinical studies. However, the mechanism by which IFN-alpha enhances BCG-mediated antitumor activity is poorly understood. Using PBMCs from bladder cancer patients, IFN-alpha was found to substantially enhance the efficacy of BCG to induce IFN-gamma production. Among 34 patients tested, 80% showed >4-fold increase. This effect of IFN-alpha was observed in both initial and memory responses to BCG. In addition, IFN-alpha up-regulated BCG-induced IL-12 and TNF-alpha and down-regulated BCG-induced IL-10. Neutralizing endogenous IL-10 or adding exogenous IL-12 provided further synergy for IFN-gamma production. In clinical practice, intravesical IFN-alpha 2B (50 million units (MU)/dose) was observed to accelerate urinary IFN-gamma production to low-dose BCG (one-tenth or one-third of a full dose) in patients treated with combination therapy compared with BCG alone. These results suggest that IFN-alpha is a potent BCG enhancer that polarizes the BCG-induced immune response toward the cellular immune pathway by promoting Th1 cytokine expression and reducing Th2 cytokine expression. This study provides an immunological basis for future rational use of IFN-alpha in conjunction with intravesical BCG for bladder cancer immunotherapy.

Sexual dysfunction in patients with benign prostatic hyperplasia.

Two of the most common problems presenting to urologists are benign prostatic hyperplasia and sexual dysfunction, with an increasing number of patients presenting for treatment as a result of the proliferation of less invasive therapies. How such therapies for lower urinary tract symptoms affect sexual function in men is important to both urologists and their patients, and is the focus of this review.

Pharmacological biocompatibility between intravesical preparations of BCG and interferon-alpha 2B.

PURPOSE: To determine if BCG and interferon alpha-2B are mutually compatible as mixed intravesical agents for clinical bladder cancer therapy. MATERIALS AND METHODS: Mutual compatibility was assessed by measuring IFN-alpha's effect on BCG metabolic activity, growth rate, and clumping tendency and conversely by observing BCG's effect on IFN-alpha's anti-viral activity. Optical density at 600 nm. (OD600) was used to estimate the number of colony forming units of BCG in suspension during 3 hours measurements of clumping and 8 days measurements of BCG proliferation. BCG viability was evaluated using a substrate marker, MTT, which correlates with BCG density and metabolic activity. The anti-viral activity of IFN-alpha was determined in a cytopathic protection bioassay using the encephalomyocarditis virus/FS-4 cell system. RESULTS: Continuous shaking of reconstituted BCG for 3 hours at 37C resulted in a marginal (11.3%) drop in OD600 which was minimally altered by inclusion of IFN-alpha at 2 million units (MU)/ml. (12.7% drop). Metabolic activity and growth rate of BCG alone or BCG with IFN-alpha were essentially identical. IFN-alpha's antiviral activity was not affected by incubation with BCG. CONCLUSIONS: The inclusion of IFN-alpha into the usual BCG formulation for intravesical administration has no apparent effect on BCG's viability or tendency to form clumps in suspension. Similarly, the physical mixing of IFN-alpha with BCG does not impair its biological activity. Thus, both agents are pharmacologically compatible for future clinical studies involving combination intravesical therapy.

Primary lymphoma of the bladder: a unique cystoscopic appearance.

Primary lymphoma of the bladder is a rare disorder that occurs in the fifth to seventh decades, with a female preponderance. Although computed tomographic scanning is the best diagnostic imaging study, cystoscopic biopsy and immunoperoxidase staining are needed to make the diagnosis. Primary lymphoma of the bladder has a good prognosis and responds to a variety of therapeutic modalities. Throughout the literature, authors have described primary lymphoma of the bladder as a submucosal tumor, smooth, nonulcerative, edematous, friable, or even hemorrhagic. We present what we believe to be the first photographic image of the cystoscopic appearance of primary lymphoma of the bladder.

The selective use of dimercaptosuccinic acid renal scans in children with vesicoureteral reflux.

Dimercaptosuccinic acid (DMSA) renal scans were performed on 75 children (115 refluxing renal units) to determine the efficacy of routine scanning in patients with various grades of vesicoureteral reflux. Cystourethrography demonstrated grades I and II reflux in 75 renal units and grades III to V in 40. Of the patients 51 presented with febrile urinary tract infection and 24 were asymptomatic (patients presenting with nonfebrile urinary tract infections or those undergoing sibling screening). Renal ultrasounds were performed in 60 patients. All patients were initially managed with medical therapy and 19 (25%) ultimately underwent antireflux surgery. DMSA scans demonstrated scarring in 17 of 40 renal units (43%) of patients with high grade vesicoureteral reflux and 6 of 75 renal units (8%) of those with low grade reflux. Renal ultrasounds that were interpreted as normal always correlated to a normal DMSA scan in asymptomatic patients. In patients presenting with febrile urinary tract infections the correlation between ultrasound and DMSA scan was inconsistent. We advocate a tailored approach in the evaluation of patients with vesicoureteral reflux. Renal sonography may be sufficient in the assessment of renal scarring in asymptomatic patients with reflux and those with low grade reflux. Conversely, in patients with high grade vesicoureteral reflux, a history of febrile urinary tract infections and abnormal renal ultrasound DMSA renal scans appear to be most useful.