Do commonly used prostate medications alter prostate MRI and fusion biopsy performance?

AIMS: To determine whether phosphodiesterase inhibitors (PDEi) or α-antagonists (AA) were associated with differences in region of interest (ROI) characteristics or prostate cancer detection on fusion biopsy (FB). MATERIALS AND METHODS: Records from 847 consecutive patients undergoing FB at three separate institutions over a period of 2 years were retrospectively reviewed. Associations between medication use, Prostate Imaging Reporting & Data System (PIRADS) scores, and ROI locations were assessed with ordinal logistic regression. Associations with lesion size and International Society of Urologic Pathology (ISUP) grade group (GG) on biopsy were tested using multivariate regression. RESULTS: Medication use included PDEi in 14.2% and AA in 23.0%. PDEi use was associated with 19.3% smaller lesion diameter (-2.8 mm; CI from -4.8 to -0.7; p < 0.01) and lower PIRADS scores on MRI (OR 0.60; CI 0.40 - 1.00; p = 0.05). AA use was associated with higher PIRADS scores (OR 1.43; CI 0.97 - 2.11; p = 0.06), fewer positive fusion-directed biopsy cores (-28.6%, CI from -57.9 to 0.01%, p = 0.05), and downgrading on final pathology (-19%; CI from -40 to 2%; p = 0.06). CONCLUSION: For PIRADS scores ≥ 3, PDEi use is associated with smaller ROI and lower PIRADS scores, while AA use is associated with higher PIRADS scores. Neither medication was associated with differences in biopsy GG. Prospective studies are needed to investigate the discordance between multi-parametric magnetic resonance imaging (mpMRI) results and oncologic outcomes associated with PDEi and AA use.

Initial Experience of Magnetic Resonance Imaging Fusion Biopsy in the Community Setting.

INTRODUCTION: Magnetic resonance imaging fusion biopsy is diagnostically superior to transrectal ultrasound guided biopsy for detecting clinically significant prostate cancer. Fusion biopsy has an expanding role at major academic centers. However, the reproducibility of outcomes in the community setting is unknown. Our goal was to determine if there are significant differences in the yield of clinically significant prostate cancer upon implementation of fusion biopsy in the community setting. METHODS: We compared biopsy results from the first consecutive 175 patients undergoing fusion biopsy at an academic setting to the first 175 patients undergoing fusion biopsy at a community practice. Patients treated at an academic setting were matched to nonacademic setting treated patients using Mahalonobis distance matching. A treatment effects model was used to evaluate the effect of practice setting on the rate of clinically significant prostate cancer detection. RESULTS: The matching model resulted in 160 community based patients matched to 150 academic based patients. Balance was verified by reduction in standardized differences and variances ratios between samples. Standard errors and the 95% CI were calculated from 3,000 bootstrap samples. Practice setting had no significant effect on clinically significant prostate cancer detection, clinically significant prostate cancer detection by fusion biopsy, upgrading by fusion cores, upgrading by template cores, clinically significant prostate cancer missed by template cores or clinically significant prostate cancer missed by fusion cores. CONCLUSIONS: A sample-matched analysis of the first consecutive patients enrolled in fusion biopsy at an academic versus a community setting indicates that practice setting did not have a significant effect on the overall detection of clinically significant prostate cancer. This lends support to the use of fusion biopsy outside of academic centers.

Primary myxoid and epithelioid mesenchymal tumor of the kidney with a novel GLI1-FOXO4 fusion.

To our knowledge, we describe the first mesenchymal tumor with a novel GLI1-FOXO4 fusion gene. This well-circumscribed kidney tumor displayed variably myxoid and epithelioid histologic features with a focally nodular growth pattern. The tumor cells showed bland, round to ovoid nuclei, with no overt high-grade features. The tumor showed focal immunopositivity for smooth muscle actin and Melan-A, which raised the possibility of a relationship with a perivascular epithelioid cell tumor. The clinical and morphologic features appear distinct from other reported neoplasms harboring GLI1 or FOXO4 gene rearrangements. The patient underwent radical nephrectomy and is without evidence of disease during a relatively short clinical follow-up period. However, the features of this tumor likely warrant long-term follow-up to monitor for the possibility of a late recurrence or metastasis. In addition to reporting this novel fusion-positive tumor, we also provide a brief review of GLI1 and FOXO4 gene functions in both normal and neoplastic contexts.

Mischievous malakoplakia: A potential pitfall of mpMRI of the prostate?

Interpretation of multiparametric magnetic resonance imaging (mpMRI) for prostate cancer diagnosis and staging can be challenging and, in some cases, benign prostate disease can mimic locally advanced malignancy. We present the case of a 57 year-old male with biopsy-proven Gleason 3 + 4 prostate cancer and a preoperative mpMRI showing extraprostatic extension who was later found to have infiltrating malakoplakia on final surgical pathology. This case highlights the importance of recognizing that malakoplakia of the prostate can present as a PI-RADS 5 lesion with extracapsular extension on mpMRI. Such cases can result in wide-excision, non-nerve sparing radical prostatectomies that may be unwarranted.

A case of contralateral superficial inguinal recurrence of testicular embryonal carcinoma.

Metastatic embyronal carcinoma to the subcutaneous tissues is rare. Prior cases have occurred in the setting of undiagnosed widely metastatic disease. Here we present the first case of metastatic embyronal cancer to the contralateral subcutaneous inguinal region in the absence of any other sites of metastatic disease.

'Dr Google': trends in online interest in prostate cancer screening, diagnosis and treatment.

OBJECTIVES: To examine trends in online search behaviours related to prostate cancer on a national and regional scale using a dominant major search engine. MATERIALS AND METHODS: Google Trends was queried using the terms 'prostate cancer', 'prostate-specific antigen' (PSA), and 'prostate biopsy' between January 2004 and January 2019. Search volume index (SVI), a measure of relative search volume on Google, was obtained for all terms and examined by region and time period: pre-US Preventive Services Task Force (USPSTF) Grade D draft recommendation on PSA screening; during the active Grade D recommendation; and after publication of the recent Grade C draft recommendation. RESULTS: Online interest in PSA screening differed by time period (P < 0.01). The SVI for PSA screening was greater pre-Grade D draft recommendation (82.7) compared to during the recommendation (74.5), while the SVI for PSA screening was higher post-Grade C draft recommendation (90.4) compared to both prior time periods. Similar results were observed for prostate biopsy and prostate cancer searches. At the US state level, online interest in prostate cancer was highest in South Carolina (SVI 100) and lowest in Hawaii (SVI 64). For prostate cancer treatment options, online interest in cryotherapy, prostatectomy and prostate cancer surgery overall increased, while searches for active surveillance, external beam radiation, brachytherapy and high-intensity focused ultrasonography remained stable. CONCLUSION: Online interest in prostate cancer has changed over time, particularly in accordance with USPSTF screening guidelines. Google Trends may be a useful tool in tracking public interest in prostate cancer screening, diagnosis, and treatment, especially as it relates to major shifts in practice guidelines.

Brief report: Impact of healthcare quality on prostate specific antigen screening for the early detection of prostate cancer.

With recent guidelines emphasizing patient values, patient preferences and shared decision-making in regards to prostate specific antigen (PSA) screening it is important for primary care providers and urologists to identify factors that influence men's decisions to undergo PSA screening. We sought to evaluate the impact of men's perceptions of healthcare quality on obtaining a screening PSA for the early detection of prostate cancer. A retrospective secondary data analysis was conducted of men ages 55-69 without a history of prostate cancer using 2015 Medical Expenditure Panel Survey (MEPS) data. The relationship between Consumer Assessment of Healthcare Providers and Systems (CAHPS) questions captured in MEPS and PSA screening in the last two years were assessed using multiple logistic regression. The analysis was carried out in October 2018 at Dartmouth-Hitchcock Medical Center. The final survey sample consisted of 1249 men that equated to 15,313,605.5 once weighted; 69.5% underwent PSA screening. Men who were offered help with filling out forms in the office (OR: 1.86, 95% CI: 1.14-3.01) or rated the quality of healthcare from their doctors ≥7 (OR: 1.63, 95% CI: 1.10-2.44) on a scale from 0 (worst healthcare) to 10 (best health care) had significantly greater adjusted odds of undergoing PSA screening. Men who rated the quality of healthcare delivered to them as high had significantly greater odds of undergoing PSA screening compared to those who rated it lower. Our results may suggest that improvements in healthcare quality and patient experience of care have the potential to positively influence PSA screening.

Acquired hemophilia presenting as gross hematuria following kidney stone - a case report and review of the literature

ABSTRACT A rare condition in itself, acquired hemophilia A, seldom presents as isolated gross hematuria. It is a serious condition with a high mortality rate and thus clinical suspicion followed by prompt diagnosis is imperative (1). In fact, only 8 cases of such presentation of this condition have been reported thus far in the literature. Of these, none describe the initial presentation of hematuria with the inciting event of a kidney stone. We present a case of a 67-year-old man with signs and symptoms of nephrolithiasis accompanied by profuse hematuria, who was subsequently found to have developed expression of factor VIII inhibitor leading to acquired hemophilia A.

Acquired Hemophilia presenting as Gross Hematuria following Kidney Stone - A Case Report and Review of the Literature.

A rare condition in itself, acquired hemophilia A, seldom presents as isolated gross hematuria. It is a serious condition with a high mortality rate and thus clinical suspicion followed by prompt diagnosis is imperative (1). In fact, only 8 cases of such presentation of this condition have been reported thus far in the literature. Of these, none describe the initial presentation of hematuria with the inciting event of a kidney stone. We present a case of a 67-year-old man with signs and symptoms of nephrolithiasis accompanied by profuse hematuria, who was subsequently found to have developed expression of factor VIII inhibitor leading to acquired hemophilia A.

Primary renal lymphoma: an unusual finding following radical nephrectomy.

Secondary kidney involvement by disseminated non-Hodgkin's lymphoma (NHL) is quite common and is estimated to approach 30 - 60% in NHL patients. However, primary renal lymphoma is exceedingly rare and estimated to make up less than 1% of all kidney masses. We report a case of primary renal NHL presenting with profound hypercalcemia and renal failure recalcitrant to medical management, ultimately treated with urgent radical nephrectomy. To our knowledge, this is the first report of primary renal lymphoma presenting in this acute fashion.

Clinical Outcomes After Neoadjuvant Chemotherapy and Radical Cystectomy in the Presence of Urothelial Carcinoma of the Bladder With Squamous or Glandular Differentiation.

UNLABELLED: We assessed 126 patients with cT1-4, N0-2 urothelial carcinoma of the bladder who were treated with neoadjuvant chemotherapy followed by radical cystectomy. Twenty patients (16%) had squamous or glandular histological variation (HV). Significant pathologic downstaging (pT<2, N0) was seen in the HV patients (60% vs. 32%; P [ .02) and this difference remained significant after controlling for other clinical and pathological confounders. BACKGROUND: To assess the pathological response rates and survival outcomes in patients with squamous or glandular histological variation (HV) treated with neoadjuvant chemotherapy (nCT) and radical cystectomy (RC), and compare these with patients with pure urothelial carcinoma of the bladder (PUCB). PATIENTS AND METHODS: We performed a retrospective review of patients with clinical stage T1-4, N0-2 urothelial cancer treated with cisplatin-based nCT and RC in a single institution setting. Patients who received neoadjuvant carboplatin-based regimens were excluded. The primary end point was pathological response. Overall survival (OS) was a secondary end point. Logistic regression and Cox proportional hazard models were used for multivariate analyses. RESULTS: We evaluated 126 patients, including 20 (16%) with HV. Median estimated glomerular filtration rate (79.6 vs. 73.6 mL/min; P = .07) and the rate of complete endoscopic resection (75% vs. 40%; P = .01) were higher in the HV patients. Complete pathological response was similar between the groups (21% PUCB vs. 25% HV; P = .77). However, a significantly higher rate of pathologic downstaging (pT<2, N0 [pDS]) was seen in the HV patients (60% vs. 32%; P = .02). In a logistic regression model to predict pDS, in which clinically relevant confounding variables were included, HV (odds ratio, 4.01; 95% confidence interval, 1.16-13.9) remained an independent predictor of pDS. OS was similar between the 2 groups (HV: 45.7 vs. PUCB: 48.3 months; P = .73). CONCLUSION: When controlling for confounding factors, improved pDS rates were seen in the HV patients although there were no significant differences in the OS stratified according to histology. These results support the continued use of systemic nCT for this subgroup of patients.

Minimally invasive post-chemotherapy retroperitoneal lymph node dissection for nonseminoma.

INTRODUCTION: We present our experience with minimally-invasive retroperitoneal lymph node dissection (MI-RPLND) in the post-chemotherapy (PC) setting for residual masses in patients with nonseminoma. MATERIALS AND METHODS: Nineteen men who underwent PC MI-RPLND (14--laparoscopic, 5--robotic) for low-volume residual disease (no more than 5 clinically enlarged retroperitoneal masses, size < 5 cm, no adjacent organ or vascular invasion) between 2006 and 2011 were identified. Clinicodemographic information and pathological outcomes were reported. RESULTS: Median age of our study population was 32 (interquartile range [IQR]: 28-39). Most patients presented with clinical stage II disease (63%) and were categorized as good risk (90%) by the International Germ Cell Consensus Classification. Median size of residual masses on PC imaging was 2.1 cm (IQR: 1.7-3). Full-template bilateral RPLND was completed in 53% of cases, and modified left-sided RPLND in 47%. Median operative time was 370 minutes (IQR: 320-420), and median estimated blood loss was 300 cc (IQR: 150-450). Median length of stay was 3 days (IQR: 2-3). Five patients (26%) experienced a postoperative 30 day complication, but none were higher than Clavien grade II. On final pathology, median number of lymph nodes removed was 12 (IQR: 8-23), and 8 patients (42%) had residual teratoma. No patient experienced a recurrence at median follow up of 24 months (IQR: 5-76). CONCLUSIONS: PC MI-RPLND is a feasible option in a select group of patients with acceptable patient morbidity and short-term outcomes. Longer follow up is required to determine the oncologic efficacy of this approach.

Using percentage of sarcomatoid differentiation as a prognostic factor in renal cell carcinoma.

BACKGROUND: The objective of this study was to determine if the percentage of sarcomatoid differentiation (%Sarc) in renal cell carcinoma (RCC) can be used for prognostic risk stratification, because sarcomatoid RCC (sRCC) is an aggressive variant of kidney cancer. PATIENTS AND METHODS: We performed a retrospective analysis of patients who underwent surgery for RCC at our institution between 1999 and 2012. Pathology slides for all sRCC cases were reexamined by a single pathologist and %Sarc was calculated. %Sarc was analyzed as a continuous variable and as a categorical variable at cut points of 5%, 10%, and 25%. Potential prognostic factors associated with overall survival (OS) were determined using the Cox regression model. OS curves were generated using Kaplan-Meier methods and survival differences compared using the log-rank test. RESULTS: One thousand three hundred seven consecutive cases of RCC were identified, of which 59 patients had sRCC (4.5%). As a continuous variable %Sarc was inversely associated with OS (P = .023). Predictors of survival on multivariable analysis included pathologic (p) T status, tumor size, clinical (c) M status and %Sarc at the 25% level. OS was most dependent on the presence of metastatic disease (4 months vs. 21.2 months; P = .001). In cM0 patients with locally advanced (≥ pT3) tumors, OS was significantly diminished in patients with > 25 %Sarc (P = .045). However, %Sarc did not influence OS in patients with cM1 disease. CONCLUSION: Patients with sRCC have a poor overall outcome as evidenced by high rates of recurrence and death, indicating the need for more effective systemic therapies. In nonmetastatic patients, the incorporation of %Sarc in predictive nomograms might further improve risk stratification.

Clinicopathological correlates of Gli1 expression in a population-based cohort of patients with newly diagnosed bladder cancer.

INTRODUCTION: Dysregulation of the hedgehog signaling pathway has been linked to the development and progression of a variety of different human tumors including cancers of the skin, brain, colon, prostate, blood, and pancreas. We assessed the clinicopathological factors that are potentially related to expression of Gli1, the transcription factor that is thought to be the most reliable marker of hedgehog pathway activation in bladder cancer. METHODS: Bladder cancer cases were identified from the New Hampshire State Cancer Registry as histologically confirmed primary bladder cancer diagnosed between January 1, 2002, and July 31, 2004. Immunohistochemical analysis was performed on a tissue microarray to detect Gli1 and p53 expression in these bladder tumors. We computed odds ratios (ORs) and their 95% CIs for Gli1 positivity for pathological category using T category (from TNM), invasiveness, and grade with both the World Health Organization 1973 and World Health Organization International Society of Urological Pathology criteria. We calculated hazard ratios and their 95% CI for Gli1 positivity and recurrence for both Ta-category and invasive bladder tumors (T1+). RESULTS: A total of 194 men and 67 women, whose tumors were assessable for Gli1 staining, were included in the study. No appreciable differences in Gli1 staining were noted by sex, age, smoking status, or high-risk occupation. Ta-category tumors were more likely to stain for Gli1 as compared with T1-category tumors (adjusted OR = 0.38, CI: 0.17-0.87). Similarly, low-grade (grades 1-2) tumors were more likely to stain for Gli1 as compared with high-grade tumors (grade 3) (adjusted OR = 0.44, CI: 0.21-0.93). In a Cox proportional hazards regression analysis, non-muscle-invasive bladder tumors expressing Gli1 were less likely to recur (adjusted hazard ratio = 0.48; CI: 0.28-0.82; P<0.05) than those in which Gli1 was absent. CONCLUSION: Our findings indicate that Gli1 expression may be a marker of low-stage, low-grade bladder tumors and an indicator of a reduced risk of recurrence in this group.

Effect of tumor size on recurrence-free survival of upper tract urothelial carcinoma following surgical resection.

OBJECTIVE: To identify predictors of recurrence-free survival (RFS) based on the clinicopathological features of patients with upper tract urothelial carcinoma (UTUC) who have undergone radical nephroureterectomy (RNU) with bladder cuff resection. MATERIALS AND METHODS: We retrospectively reviewed the records of patients from October 1998 to July 2012 at our tertiary institution and identified 120 patients with sufficient data who underwent RNU for UTUC. We recorded various clinical and histopathological parameters as potential predictors of outcome. Recurrence was defined as any occurrence of urothelial carcinoma after RNU either intravesically, local/regionally, or at distant sites. Univariate, multivariate, and RFS analyses were conducted using the Cox regression and Kaplan-Meier methods. RESULTS: The median age of our cohort was 71 years (interquartile range: 64-78). Median RNU-specimen tumor size was 3.0 cm (interquartile range: 2.0-5.0 cm). Fifty-four patients (45%) had a tumor<3.0 cm and 66 (55%) had a tumor≥3.0 cm. Eighty patients (66.7%) had organ-confined UTUC (≤pT2) and 40 (33.3%) had non-organ-confined UTUC (≥pT3). Sixty-five patients (54.2%) experienced at least 1 recurrence. Forty-three patients (35.8%) had at least 1 episode of intravesical recurrence and 28 (23.3%) had distant recurrence. A multivariate analysis revealed non-organ-confined disease (hazard ratio [HR] = 3.62, P<0.001), tumor diameter≥3 cm (HR = 1.97, P = 0.011), and male gender (HR = 1.81, P = 0.047) to be significant independent predictors of disease recurrence. The 5-year RFS rate was 46.9% and 25.8% for patients with tumor size<3 and ≥3 cm, respectively. CONCLUSIONS: Following RNU, the incidence of recurrence remains high among patients with UTUC. In our cohort of patients, tumor diameter≥3.0 cm, non-organ-confined UTUC, and male gender constitute important risk factors for poor RFS outcomes following RNU. These patients require diligent postoperative surveillance and may potentially benefit from perioperative systemic therapy.

New therapeutic targets in the management of urothelial carcinoma of the bladder.

Urothelial carcinoma of the bladder, despite the myriad of treatment approaches and our progressively increasing knowledge into its disease processes, remains one of the most clinically challenging problems in modern urological clinical practice. New therapies target biomolecular pathways and cellular mediators responsible for regulating cell growth and metabolism, both of which are frequently overexpressed in malignant urothelial cells, with the intent of inducing cell death by limiting cellular metabolism and growth, creating an immune response, or selectively delivering or activating a cytotoxic agent. These new and novel therapies may offer a potential for reduced toxicity and an encouraging hope for better treatment outcomes, particularly for a disease often refractory or not amenable to the current therapeutic approaches.

Urinary tract infections in children: recommendations for antibiotic prophylaxis and evaluation. An evidence-based approach.

Urinary tract infections (UTIs) are common in children, but the routine work-up and treatment recommendations are still controversial. Long-term complications, including renal scarring, hypertension, and renal failure, have been the main concern and the reason for use of antibiotic prophylaxis and invasive imaging techniques. In the past several years, numerous studies have been published comparing different imaging protocols and questioning the use of antibiotic prophylaxis. The latest guidelines from the United Kingdom, published in 2007, recommend more selective approach based on evidence. In this review, we critically appraise the literature published in the past 5 years. The risk of developing long-term complications after a UTI is extremely low, and the evidence suggests selective imaging to a select group of children at risk. Finding those at risk for long-term complications is yet to be determined.