Comparative Effectiveness of Targeted Prostate Biopsy Using Magnetic Resonance Imaging Ultrasound Fusion Software and Visual Targeting: a Prospective Study.

PURPOSE: We compared the diagnostic outcomes of magnetic resonance-ultrasound fusion and visually targeted biopsy for targeting regions of interest on prostate multiparametric magnetic resonance imaging. MATERIALS AND METHODS: Patients presenting for prostate biopsy with regions of interest on multiparametric magnetic resonance imaging underwent magnetic resonance imaging targeted biopsy. For each region of interest 2 visually targeted cores were obtained, followed by 2 cores using a magnetic resonance-ultrasound fusion device. Our primary end point was the difference in the detection of high grade (Gleason 7 or greater) and any grade cancer between visually targeted and magnetic resonance-ultrasound fusion, investigated using McNemar's method. Secondary end points were the difference in detection rate by biopsy location using a logistic regression model and the difference in median cancer length using the Wilcoxon signed rank test. RESULTS: We identified 396 regions of interest in 286 men. The difference in the detection of high grade cancer between magnetic resonance-ultrasound fusion biopsy and visually targeted biopsy was -1.4% (95% CI -6.4 to 3.6, p=0.6) and for any grade cancer the difference was 3.5% (95% CI -1.9 to 8.9, p=0.2). Median cancer length detected by magnetic resonance-ultrasound fusion and visually targeted biopsy was 5.5 vs 5.8 mm, respectively (p=0.8). Magnetic resonance-ultrasound fusion biopsy detected 15% more cancers in the transition zone (p=0.046) and visually targeted biopsy detected 11% more high grade cancer at the prostate base (p=0.005). Only 52% of all high grade cancers were detected by both techniques. CONCLUSIONS: We found no evidence of a significant difference in the detection of high grade or any grade cancer between visually targeted and magnetic resonance-ultrasound fusion biopsy. However, the performance of each technique varied in specific biopsy locations and the outcomes of both techniques were complementary. Combining visually targeted biopsy and magnetic resonance-ultrasound fusion biopsy may optimize the detection of prostate cancer.

The Prognostic Impact of a Positive Vascular Margin on pT3 Clear Cell Renal Cell Carcinoma.

PURPOSE: We examined the impact of positive vascular margins in patients with pT3 clear cell renal cell carcinoma. MATERIALS AND METHODS: After excluding patients with nonvascular positive margins, metastasis, lymph node involvement, neoadjuvant therapy or nonclear cell histology, we identified 224 patients with venous tumor invasion through our institutional database from 1999 to 2013. Kaplan-Meier analysis and log rank tests were used to evaluate whether positive vascular margins were associated with progression-free survival or cancer specific survival. RESULTS: There were 41 patients (18%) with a positive vascular margin. Margin status was directly related to the level of invasion (p <0.0001). Compared to the negative vascular margin group the positive group had a significantly worse progression-free survival (p=0.01) but not cancer specific survival (p=0.3). Similarly the level of vascular thrombus invasion was significantly associated with worse progression-free survival (p=0.02) but not cancer specific survival (p=0.4). The 3-year progression-free survival was worst with inferior vena cava invasion and best with segmental/muscular venous branch invasion (54%, 95% CI 34-70 vs 76%, 95% CI 64-85). Among patients with only main renal vein thrombus, vascular margin status was not associated with progression-free survival (p=0.5) or cancer specific survival (p=0.2). CONCLUSIONS: In patients with pT3N0/XM0 clear cell renal cell carcinoma positive vascular margins are associated with risk of disease progression. However, the risk of relapse associated with positive vascular margins is driven by the extent of vascular thrombus invasion. These findings suggest that the clinical significance of vascular margin status as currently defined in pT3 clear cell renal cell carcinoma is minimal.

Twenty-year prevalence of diabetes mellitus and hypertension in patients receiving shock-wave lithotripsy for urolithiasis.

OBJECTIVES: To compare the prevalence of hypertension and diabetes mellitus (DM) in patients treated with an unmodified HM-3 lithotripter (USWL) and a second-generation modified HM-3 lithotripter (MSWL) 20 years ago at our Centre with that in the provincial population. To determine whether the type of lithotripter was differentially associated with the development of these sequelae. PATIENTS AND METHODS: Retrospective review of 727 patients at Vancouver General Hospital who underwent shock-wave lithotripsy (SWL) between 1985 and 1989. Our study group was compared with Statistics Canada data describing the provincial prevalence of these diseases. Multivariate analysis was performed. RESULTS: The response rate was 37.3%. There was a greater proportion of overweight and obese individuals in the study group compared with the provincial average. In univariate analysis, lithotripsy with an unmodified HM-3 (USWL) was associated with a higher rate of DM than the provincial rate, whereas lithotripsy with the modified HM-3 (MSWL) was not. Hypertension was more prevalent in all lithotripsy subjects. On multivariate analysis the type of lithotripter was not associated with the development of either sequela. CONCLUSIONS: No association between lithotripsy and the development of either DM or hypertension in a multivariate analysis Metabolic syndrome may have elevated the prevalence of DM and hypertension observed in our subjects on univariate analysis, which is in keeping with the fact that our study population had statistically higher body mass indices than the provincial rate. Lithotripsy using the HM-3 was not associated with increased DM or hypertension.

Case series and review of Ayurvedic medication induced liver injury.

BACKGROUND: Complementary and alternative medicine use among Americans is prevalent. Originating in India, Ayurvedic medicine use in the United States has grown 57% since 2002. CAM accounts for a significant proportion of drug induced liver injury in India and China, but there have been only three reports of drug induced liver injury from Ayurvedic medications in the U.S. We report three cases of suspected Ayurvedic medication associated liver injury seen at a Southern California community hospital and review literature of Ayurvedic medication induced liver injury. CASE PRESENTATIONS: Three patients presented with acute hepatocellular injury and jaundice after taking Ayurvedic supplements for 90-120 days. First patient took Giloy Kwath consisting solely of Tinospora cordifolia. Second patient took Manjishthadi Kwatham and Aragwadhi Kwatham, which contained 52 and 10 individual plant extracts, respectively. Third patient took Kanchnar Guggulu, containing 10 individual plant extracts. Aminotransferase activities decreased 50% in < 30 days and all 3 patients made a full recovery. Roussel Uclaf Causality Assessment Method (RUCAM) scores were 7-8, indicating probable causality. These products all contained ingredients in other Ayurvedic and traditional Chinese medicines with previously reported associations with drug induced liver injury. CONCLUSIONS: These patients highlight the risk of drug induced liver injury from Ayurvedic medications and the complexity of determining causality. There is a need for a platform like LiverTox.gov to catalog Ayurvedic ingredients causing liver damage.

Improved Recovery of Erectile Function in Younger Men after Radical Prostatectomy: Does it Justify Immediate Surgery in Low-risk Patients?

BACKGROUND: Although active surveillance is increasingly used for the management of low-risk prostate cancer, many eligible patients are still nonetheless subject to curative treatment. One argument for considering surgery rather than active surveillance is that the probability of postoperative recovery of erectile function is age dependent, that is, patients who delay surgery may lose the window of opportunity to recover erectile function after surgery. OBJECTIVE: To model erectile function over a 10-yr period for immediate surgery versus active surveillance. DESIGN, SETTING, AND PARTICIPANTS: Data from 1103 men who underwent radical prostatectomy at a tertiary referral center were used. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients completed the International Index of Erectile Function (IIEF-6) pre- and postoperatively as a routine part of clinical care. Preoperative IIEF-6 scores were plotted against age to assess the natural rate of functional decline due to aging. Reported erectile scores in the 2-yr period following surgery were used to assess post-surgical recovery. RESULTS AND LIMITATIONS: Each year increase in patient age resulted in a 0.27 reduction in IIEF scores. In addition to IIEF reducing with increased age, the amount of erectile function that is recovered from presurgery to 12-mo postsurgery also decreases (-0.16 IIF points/yr, 95% confidence interval -0.27, -0.05, p=0.006). However, delayed radical prostatectomy increased the mean IIEF-6 score over a 10-yr period compared with immediate surgery (p=0.001), even under the assumption that all men placed on active surveillance are treated within 5 yr. CONCLUSIONS: Small differences in erectile function recovery in younger men are offset by a longer period of time living with decreased postoperative function. Better erectile recovery in younger men should not be a factor used to recommend immediate surgery in patients suitable for active surveillance, even if crossover to surgery is predicted within a short period of time. PATIENT SUMMARY: Younger men have better recovery of erectile function after surgery for prostate cancer. This has led to the suggestion that delaying surgery for low-risk disease may lead patients to miss a window of opportunity to recover erectile function postoperatively. We conducted a modeling study and found that predicted erectile recovery was far superior on delayed treatment because slightly better recovery in younger men is offset by a longer period of time living with poorer postoperative function in those choosing immediate surgery.

Concordance between patient-reported and physician-reported sexual function after radical prostatectomy.

PURPOSE: Accurately tracking health-related quality-of-life after radical prostatectomy is critical to counseling patients and improving technique. Physicians consistently overestimate functional recovery. We measured concordance between surgeon-assessed and patient-reported outcomes and evaluated a novel method to provide feedback to surgeons. MATERIALS AND METHODS: Men treated with radical prostatectomy self-completed the International Index of Erectile Function-6 questionnaire at each postoperative visit. Separately, physicians graded sexual function on a 5-point scale. International Index of Erectile Function -6 score<22 and grade ≥3 defined patient-reported and physician-assessed erectile dysfunction (ED), respectively. Feedback on concordance was given to physicians starting in May 2013 with the implementation of the Amplio feedback system. Chi-square tests were used to assess agreement proportions and linear regression to evaluate changes in agreement after implementation. RESULTS: From 2009 to 2015, 3,053 men completed at least 1 postprostatectomy questionnaire and had a concurrent independent physician-reported outcome. Prior to implementation of feedback in 2013, patients and physicians were consistent as to ED 83% of the time; in 10% of cases, physicians overestimated function; in 7% of cases, physicians, but not patients reported ED. Agreement increased after implementation of feedback but this was not statistically significant, likely owing to a ceiling effect. Supporting this hypothesis, increase in agreement postfeedback was greater during late follow-up (≥12mo), where baseline agreement was lower compared to earlier follow-up. CONCLUSIONS: Agreement was higher than expected at baseline; implementation of feedback regarding discrepancies between patient-reported and physician-assessed outcomes did not further improve agreement significantly. Our observed high rate of agreement may be partly attributed to our institutional practice of systematically capturing patient-reported outcomes as part of normal clinical care.

Contemporary Management of Prostate Cancer Patients Suitable for Active Surveillance: A North American Population-based Study.

BACKGROUND: Active surveillance (AS) is increasingly recognized as a recommended treatment option for prostate cancer (PCa) patients with clinically localized, low-risk disease; however, previous studies suggested that its utilization is uncommon in the United States. OBJECTIVE: We evaluated the nationwide utilization rate of AS in the contemporary era. DESIGN, SETTING, AND PARTICIPANTS: We relied on the 2010-2011 Surveillance Epidemiology and End Results (SEER) database using all 18 SEER-based registries. We identified 9049 patients that fulfilled the University of California, San Francisco AS criteria (prostate-specific antigen level <10ng/ml, clinical T stage ≤2a, Gleason score ≤6 [no pattern 4 or 5], and percentage of positive biopsy cores <33%). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression analysis tested the relationship between receiving local treatment and all available predictors. RESULTS AND LIMITATIONS: Only 32% of AS candidates did not receive any active local treatment. This proportion varied widely among the SEER-based registries, ranging from 13% to 49% (p<0.001). In multivariable analyses, clinical stage T2a (odds ratio [OR]: 1.23; p=0.04) and percentage of positive cores (OR: 1.10 for each 2% increase; p<0.001) were associated with a higher probability of receiving local treatment. Conversely, older age (OR: 0.89 for each 2-yr increase; p<0.001), not being married (OR: 0.64; p<0.001), and uninsured status (OR: 0.55; p=0.008) were associated with a lower probability of receiving active local treatment. The study is limited by the fact that SEER does not distinguish among patients undergoing observation, AS, watchful waiting, or initial hormonal therapy. CONCLUSIONS: In the United States, a considerable proportion of patients suitable for AS receive local treatment for PCa. Proportions differ significantly among SEER registries. PATIENT SUMMARY: Having more extensive and palpable disease, having medical insurance, being married, and being younger are associated with an increased probability of receiving local treatment for low-risk prostate cancer.

Clinical Outcomes of Patients With T1 Nested Variant of Urothelial Carcinoma Compared to Pure Urothelial Carcinoma of the Bladder.

PURPOSE: Evaluate oncologic outcomes of patients with cT1 nested variant (NV) of urothelial carcinoma (UC) and compare with cases of pure UC of the bladder. MATERIALS AND METHODS: We retrospectively identified 30 patients with NV who, between 1997 and 2012, underwent transurethral resection with T1 tumor stage, followed by restaging transurethral resection within 3 months confirming non-muscle-invasive disease. Radical cystectomy within 3 months of restaging transurethral resection was considered "early" treatment. We matched 3 patients with pure UC to each nested patient. RESULTS: Median follow-up for survivors was 4.3 years from T1-staged transurethral resection. Patients with NV had no statistically significant difference in metastasis-free survival (P = .2) and cancer-specific survival (P = .2) compared with patients with pure UC. However, it is concerning that the rate of upstaging to bladder and/or lymph nodes was 54% in patients with NV who underwent early radical cystectomy, even after rigorous restaging. CONCLUSIONS: Although NV UC may be diagnosed at a higher stage, when stage matched we have not seen any statistical evidence that it is more aggressive than typical UC. Because patients with NV UC who are cT1 on restaging transurethral resection appear to have a higher propensity to develop nodal metastatic disease and a higher rate of upstaging, patients with cT1 NV UC on restaging biopsy may benefit from "early" radical cystectomy, whereas patients with 

Unexpected Long-term Improvements in Urinary and Erectile Function in a Large Cohort of Men with Self-reported Outcomes Following Radical Prostatectomy.

BACKGROUND: It is generally assumed that if a man does not regain urinary continence or erectile function within 12 mo of radical prostatectomy (RP), then the chance of subsequent recovery is low. OBJECTIVE: To determine the probability of achieving good urinary function (UF) or erectile function (EF) up to 48 mo postoperatively in men who reported poor UF or EF at 12 mo after RP. DESIGN, SETTING, AND PARTICIPANTS: We identified 3187 patients who underwent RP from 2007 through 2013 at a tertiary institution and had extended multidisciplinary follow-up with patient-reported UF and EF scores at ≥12 mo. INTERVENTION: Open or minimally invasive RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome was good UF as defined by a urinary score ≥17 (range: 0-21) or good EF as defined by a modified International Index of Erectile Function-6 score ≥22 (range: 1-30). The probability of functional recovery beyond 12 mo was determined by Kaplan-Meier analyses. RESULTS AND LIMITATIONS: Among patients incontinent at 12 mo, the probability of achieving good UF at 24, 36, and 48 mo was 30%, 49%, and 59%. In patients experiencing erectile dysfunction at 12 mo, the probability of recovering EF at 24, 36, and 48 mo was 22%, 32%, and 40%. On multivariable analyses, 12-mo functional score and age were associated with recovery, but only score was consistently significant. CONCLUSIONS: Men with incontinence or erectile dysfunction at 12 mo have higher than anticipated rates of subsequent functional improvement. Probability of recovery is strongly influenced by score at 12 mo. Further research should address the impact of ongoing multidisciplinary follow-up care on our observed rates of recovery. PATIENT SUMMARY: Many prostate cancer patients continue to recover urinary and erectile function after 12 mo. The level of functional recovery by 12 mo is associated with long-term recovery and should be discussed by the physician and patient when deciding on rehabilitative interventions.

Nobiletin attenuates VLDL overproduction, dyslipidemia, and atherosclerosis in mice with diet-induced insulin resistance.

OBJECTIVE: Increased plasma concentrations of apolipoprotein B100 often present in patients with insulin resistance and confer increased risk for the development of atherosclerosis. Naturally occurring polyphenolic compounds including flavonoids have antiatherogenic properties. The aim of the current study was to evaluate the effect of the polymethoxylated flavonoid nobiletin on lipoprotein secretion in cultured human hepatoma cells (HepG2) and in a mouse model of insulin resistance and atherosclerosis. RESEARCH DESIGN AND METHODS: Lipoprotein secretion was determined in HepG2 cells incubated with nobiletin or insulin. mRNA abundance was evaluated by quantitative real-time PCR, and Western blotting was used to demonstrate activation of cell signaling pathways. In LDL receptor-deficient mice (Ldlr(-/-)) fed a Western diet supplemented with nobiletin, metabolic parameters, gene expression, fatty acid oxidation, glucose homeostasis, and energy expenditure were documented. Atherosclerosis was quantitated by histological analysis. RESULTS: In HepG2 cells, activation of mitogen-activated protein kinase-extracellular signal-related kinase signaling by nobiletin or insulin increased LDLR and decreased MTP and DGAT1/2 mRNA, resulting in marked inhibition of apoB100 secretion. Nobiletin, unlike insulin, did not induce phosphorylation of the insulin receptor or insulin receptor substrate-1 and did not stimulate lipogenesis. In fat-fed Ldlr(-/-) mice, nobiletin attenuated dyslipidemia through a reduction in VLDL-triglyceride (TG) secretion. Nobiletin prevented hepatic TG accumulation, increased expression of Pgc1α and Cpt1α, and enhanced fatty acid ß-oxidation. Nobiletin did not activate any peroxisome proliferator-activated receptor (PPAR), indicating that the metabolic effects were PPAR independent. Nobiletin increased hepatic and peripheral insulin sensitivity and glucose tolerance and dramatically attenuated atherosclerosis in the aortic sinus. CONCLUSIONS: Nobiletin provides insight into treatments for dyslipidemia and atherosclerosis associated with insulin-resistant states.

Pediatric thyroid fine-needle aspiration cytology: a meta-analysis.

BACKGROUND: There is conflicting evidence in the current literature regarding the use of fine-needle aspiration (FNA) biopsy in the diagnosis of a thyroid nodule in the pediatric population. There are numerous studies that look at the sensitivity and specificity of this test with varying results. A meta-analysis will provide further insight into this topic. PURPOSE: Our objective was to investigate the diagnostic parameters of FNA biopsy in the diagnosis of a thyroid nodule in the pediatric population, specifically, to determine the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of the test in differentiating malignant vs benign tumors. MATERIAL AND METHODS: We performed a literature search of Medline, Embase, and evidence based medicine (EBM) reviews for English studies that looked at FNA biopsy in thyroid nodules in the pediatric population, in which diagnostic values were present or could be calculated and where FNA results were compared to an acceptable reference standard. Two reviewers independently selected all abstracts, and from these, studies to review. Two reviewers also independently checked diagnostic values in the studies or calculated them from data available. A meta-analysis was performed, and pooled diagnostic test values were calculated using a random-effects, bivariate meta-regression model. Studies were also assessed for quality using the quality assessment for diagnostic accuracy studies tool. RESULTS: Twelve studies were included for review. The quality of the studies in general was good. The pooled estimate of sensitivity and specificity were 94% (95% confidence interval [CI], 86%-100%) and 81% (95% CI, 72%-91%), respectively. Assuming 20% of nodules are malignant, the accuracy, PPV, and NPV were 83.6%, 55.3%, and 98.2%, respectively. CONCLUSION: This meta-analysis provides good evidence that FNA biopsy of thyroid nodules is a sensitive test in the pediatric population and may be a useful tool for excluding malignancy in young patients. Future prospective studies are needed to evaluate this further.