David F Jarrard

University of Wisconsin–Madison, Madison, Wisconsin, United States

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Publications (142)684.53 Total impact


  • No preview · Conference Paper · Dec 2015
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    ABSTRACT: Objective: To evaluate if extreme obesity (BMI ≥ 40) is associated with perioperative outcomes, overall survival (OS), cancer-specific survival (CSS), or recurrence-free survival (RFS) after surgical treatment for RCC. Patients and methods: After IRB approval, an institutional database identified patients treated surgically between January 2000 and December 2014 with pathologic diagnosis of RCC. Comprehensive clinical and pathologic data were reviewed. Kaplan-Meier analyses were used to estimate OS, RFS, and CSS. Univariate and multivariate Cox proportional hazards analysis was used to evaluate for associations with OS, CSS and RFS in patients with extreme obesity among other known predictive variables. Results: A total 100 (11.9%) patients were identified with BMI ≥ 40 and 743 (88.1%) with BMI<40 who were treated surgically for RCC. Morbid obesity was not associated with increased risk of blood transfusion (OR 1, 95% CI 0.587-1.70; p=1.0). Median hospital LOS was 4 days (IQR 3-6). Morbid obesity was not associated with longer LOS (p=0.26) or 30 day hospital readmission rates (p=1.0). Major complications (Clavien ≥3a) were recorded in 67 (7.95%) patients. BMI ≥ 40 was not a predictor of major complications (OR 0.58, 95% (CI 0.227-1.47), p=0.251 or 90 day mortality, p=0.4067. BMI ≥ 40 was not associated with worse OS (p= 0.7) or CSS (p=0.2), or RFS (p=0.5). BMI ≥ 35 was not also not associated with worse OS, CSS or RFS (p=0.3, 0.1, 0.5). Five year OS was 68.9% for the entire cohort including 69% and 70%, for patients with BMI < 40 and BMI ≥ 40 respectively, p=0.69. The 5 year CSS was 79.5% for the entire cohort, including 78.4% and 87.9% (p=0.16) for patients with BMI < 40 and BMI ≥ 40 respectively. The 5-year RFS rates for BMI < 40 and BMI ≥ 40 were 84.1% and 90.6% respectively, p=0.48. Conclusions: Extreme obesity is not associated with worse perioperative or cancer outcomes after surgery for RCC. Surgery should remain a standard treatment option in well selected morbidly obese patients. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2015 · BJU International
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    Preview · Article · Nov 2015

  • No preview · Article · Nov 2015 · International journal of radiation oncology, biology, physics
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    ABSTRACT: Purpose Prior reports suggest that renin-angiotensin system inhibition may decrease nonmuscle invasive bladder cancer recurrence. We evaluated whether angiotensin converting enzyme inhibitor or angiotensin receptor blocker treatment at initial surgery was associated with decreased recurrence or progression in patients with nonmuscle invasive bladder cancer. Materials and Methods Using an institutional bladder cancer database we identified 340 patients with data available on initial transurethral resection of bladder tumor. Progression was defined as an increase to stage T2. Cox proportional hazards models were used to evaluate associations with recurrence-free and progression-free survival. Results Median patient age was 69.6 years. During a median followup of 3 years (IQR 1.3-6.1) 200 patients (59%) had recurrence and 14 (4.1%) had stage progression. Of those patients 143 were receiving angiotensin converting enzyme inhibitor/angiotensin receptor blockers at the time of the first transurethral resection. On univariate analysis factors associated with improved recurrence-free survival included carcinoma in situ (p = 0.040), bacillus Calmette-Guérin therapy (p = 0.003) and angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (p = 0.009). Multivariate analysis demonstrated that patients treated with bacillus Calmette-Guérin therapy (HR 0.68, 95% CI 0.47-0.87, p = 0.002) or angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (HR 0.61, 95% CI 0.45-0.84, p = 0.005) were less likely to experience tumor recurrence. The 5-year recurrence-free survival rate was 45.6% for patients treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers and 28.1% in those not treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers (p = 0.009). Subgroup analysis was performed to evaluate nonmuscle invasive bladder cancer pathology (Ta, T1 and carcinoma in situ) in 85 patients on bacillus Calmette-Guérin therapy alone and in 52 in whom it was combined with angiotensin converting enzyme inhibitor/angiotensin receptor blocker. Multivariate analysis revealed that patients treated with bacillus Calmette-Guérin alone (HR 2.19, 95% CI 1.01-4.77, p = 0.04) showed worse recurrence-free survival compared to patients treated with bacillus Calmette-Guérin and angiotensin converting enzyme inhibitor/angiotensin receptor blocker (stage Ta HR 0.45, 95% CI 0.21-0.98, p = 0.04). Conclusions Pharmacological inhibition of the renin-angiotensin system is associated with improved outcomes in patients with bladder cancer. Renin-angiotensin system inhibitor administration in nonmuscle invasive bladder cancer cases should be studied in a prospective randomized trial. © 2015 American Urological Association Education and Research, Inc.
    No preview · Article · Nov 2015 · The Journal of Urology
  • David F. Jarrard · Wei Huang

    No preview · Article · Nov 2015 · European Urology

  • No preview · Article · Oct 2015 · Journal of the American College of Surgeons

  • No preview · Article · Oct 2015 · Journal of the American College of Surgeons
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    ABSTRACT: Epidemiologic, preclinical, and early phase I studies of the cruciferous vegetable bioactive metabolite, 3,3'-diindolylmethane (DIM), support its potential prostate cancer chemopreventive ability. We performed a multicenter, double-blind, placebo-controlled trial of DIM in patients diagnosed with prostate cancer and scheduled for radical prostatectomy. A total of 45 patients with organ-confined prostate cancer were randomized to 21-28 days of an absorption-enhanced formulation of DIM (BR-DIM) at doses of 100 or 200 mg per os twice daily or to placebo twice daily. Prostate tissue levels of DIM were the primary endpoint, with selected secondary biomarker endpoints including blood levels of DIM, total prostate-specific antigen, testosterone, and the insulin-like growth factor-1: insulin-like growth factor binding protein-3 ratio and the urinary 2-hydroxyestrone/16-hydroxyestrone ratio, obtained at baseline, at day 15, and before surgery, as well as tissue expression of androgen receptor, prostate-specific antigen, Ki67, caspase 3 with cytochrome p450 mRNA expression and genotyping (polymorphisms). DIM was well tolerated with excellent study compliance and relatively rapid accrual of all 45 patients within 1 year. DIM levels were detected in only seven of 28 prostate tissue specimens. There was a statistically significant difference in the change in the urinary 2-hydroxyestrone/16-hydroxyestrone ratio from baseline until before surgery between the placebo and 400 mg DIM groups, with otherwise statistically nonsignificant changes in plasma biomarker expression. The administration of BR-DIM to prostate cancer patients before prostatectomy yields detectable plasma levels but without consistent or significant tissue accumulation or biomarker modulation. This study demonstrates the feasibility of biologic evaluation of relatively nontoxic preventive agents in the preprostatectomy setting with the potential for rapid accrual.
    No preview · Article · Aug 2015 · European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP)
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    ABSTRACT: Background: Androgen-deprivation therapy (ADT) has been the backbone of treatment for metastatic prostate cancer since the 1940s. We assessed whether concomitant treatment with ADT plus docetaxel would result in longer overall survival than that with ADT alone. Methods: We assigned men with metastatic, hormone-sensitive prostate cancer to receive either ADT plus docetaxel (at a dose of 75 mg per square meter of body-surface area every 3 weeks for six cycles) or ADT alone. The primary objective was to test the hypothesis that the median overall survival would be 33.3% longer among patients receiving docetaxel added to ADT early during therapy than among patients receiving ADT alone. Results: A total of 790 patients (median age, 63 years) underwent randomization. After a median follow-up of 28.9 months, the median overall survival was 13.6 months longer with ADT plus docetaxel (combination therapy) than with ADT alone (57.6 months vs. 44.0 months; hazard ratio for death in the combination group, 0.61; 95% confidence interval [CI], 0.47 to 0.80; P<0.001). The median time to biochemical, symptomatic, or radiographic progression was 20.2 months in the combination group, as compared with 11.7 months in the ADT-alone group (hazard ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001). The rate of a prostate-specific antigen level of less than 0.2 ng per milliliter at 12 months was 27.7% in the combination group versus 16.8% in the ADT-alone group (P<0.001). In the combination group, the rate of grade 3 or 4 febrile neutropenia was 6.2%, the rate of grade 3 or 4 infection with neutropenia was 2.3%, and the rate of grade 3 sensory neuropathy and of grade 3 motor neuropathy was 0.5%. Conclusions: Six cycles of docetaxel at the beginning of ADT for metastatic prostate cancer resulted in significantly longer overall survival than that with ADT alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00309985.).
    Full-text · Article · Aug 2015 · New England Journal of Medicine
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    ABSTRACT: No guidelines currently exist that address the need for rebiopsy in patients with a negative diagnosis of prostate cancer on initial biopsy sample analysis. Accurate diagnosis of prostate cancer in these patients is often complicated by continued elevation of serum PSA levels that are suggestive of prostate cancer, resulting in a distinct management challenge. Following negative initial findings of biopsy sample analysis, total serum PSA levels and serum PSA kinetics are ineffective indicators of a need for a repeat biopsy; therefore, patients suspected of having prostate cancer might undergo several unnecessary biopsy procedures. Several alternative strategies exist for identifying men who might be at risk of prostate cancer despite negative findings of biopsy sample analysis. Use of other serum PSA-related measurements enables more sensitive and specific diagnosis and can be combined with knowledge of clinicopathological features to improve outcomes. Other options include the FDA-approved Progensa(®) test and prostate imaging using MRI. Newer tissue-based assays that measure methylation changes in normal prostate tissue are currently being developed. A cost-effective strategy is proposed in order to address this challenging clinical scenario, and potential directions of future studies in this area are also described.
    No preview · Article · Jul 2015 · Nature Reviews Urology
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    ABSTRACT: Purpose: Senescence is a terminal growth arrest that functions as a tumor suppressor in aging and precancerous cells and is a response to selected anticancer compounds. Lysosomal-β-galactosidase (GLB1) hydrolyzes β-galactose from glycoconjugates and is the origin of senescence-associated β-gal activity (SA-β-gal). Using a new GLB1 antibody, senescence biology was investigated in prostate cancer (PCa) tissues. Experimental design: In vitro characterization of GLB1 was determined in primary prostate epithelial cell cultures passaged to replicative senescence and in therapy-induced senescence in PCa lines using chemotherapeutic agents. FFPE tissue microarrays were subjected to immunofluorescent staining for GLB1, Ki67 and HP1γ and automated quantitative imaging initially using AQUA in exploratory samples and Vectra in a validation series. Results: GLB1 expression accumulates in replicative and induced senescence and correlates with senescent morphology and P16 (CDKN2) expression. In tissue arrays, quantitative imaging detects increased GLB1 expression in high-grade prostatic intraepithelial neoplasia (HGPIN), known to contain senescent cells, and cancer compared to benign prostate tissues (p<0.01) and senescent cells contain low Ki67 and elevated HP1γ. Within primary tumors, elevated GLB1 associates with lower T stage (p=0.01), localized versus metastatic disease (p=0.0003) and improved PSA-free survival (p=0.03). Increased GLB1 stratifies better PSA-free survival in intermediate grade PCa (0.01). Tissues that elaborate higher GLB1 display increased uniformity of expression. Conclusion: Increased GLB1 is a valuable marker in formalin-fixed paraffin-embedded (FFPE) tissues for the senescence-like phenotype and associates with improved cancer outcomes. This protein addresses a lack of senescence markers and should be applicable to study the biologic role of senescence in other cancers.
    Full-text · Article · Apr 2015 · PLoS ONE

  • No preview · Article · Apr 2015 · The Journal of Urology
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    ABSTRACT: Prior reports have suggested that inhibition of the renin-angiotensin system (RAS) may decrease recurrence of non-muscle invasive bladder cancer (NMIBC). The purpose of this study was to evaluate if treatment with ACE-inhibitors (ACE-I) or angiotensin receptor blockers (ARBs) at initial surgery was associated with decreased recurrence or progression in NMIBC patients. An institutional bladder cancer database identified 340 patients with data available for initial TURBT. Progression was defined increase to stage T2. Cox proportional hazards models were used to evaluate associations with recurrence-free (RFS) and progression-free survival (PFS). Median patient age was 69.6. During a median follow-up of 3 years (IQR 1.3-6.1), 200 (59%) patients had recurrence and 14 (4.1%) had stage progression. Of those, 143 patients were taking ACE-I/ARBs at the time of their first TUR. On univariate analysis, factors associated with improved RFS included presence of CIS (p=0.040), bacillus Calmette-Guerin (BCG) therapy (p=0.003), and ACE-I/ARB therapy (p=0.009). Multivariate analysis demonstrated that patients treated with BCG therapy (HR 0.68, 95% CI 0.47-0.87; p=0.002) or ACE-I/ARB therapy (HR 0.61, 95% CI 0.45-0.84; p=0.005), were less likely to experience tumor recurrence. The 5-year RFS rate was 45.6% for patients treated with ACE-I/ARBs and 28.1% for patients not treated with ACE-I/ARBs (p=0.009). Subgroup analysis was performed evaluating patients on BCG therapy alone (n=85) and combined with ACE-I/ARB therapy (n=52) on NMIBC pathology (Ta, T1, CIS). Multivariate analysis revealed that patients treated with BCG alone (HR 2.19, 95% CI 1.01-4.77; p=0.04) were associated with a worse RFS compared to patients treated with BCG and ACE-I/ARB therapy (HR 0.45, 95% CI 0.21-0.98; p=0.04) for stage Ta. Pharmacologic inhibition of RAS is associated with improved outcomes in bladder cancer patients. RAS inhibitor administration in NMIBC should be studied in a prospective randomized trial. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
    Preview · Article · Apr 2015 · The Journal of Urology

  • No preview · Article · Apr 2015 · The Journal of Urology
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    Preview · Article · Apr 2015 · The Journal of Urology
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    Full-text · Article · Apr 2015 · The Journal of Urology
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    ABSTRACT: Percutaneous biopsy obtained from a single location is prone to sampling error in large heterogeneous renal masses, leading to non-diagnostic results or failure to detect poor prognostic features. The purpose of this study was to evaluate the accuracy of percutaneous biopsy for large renal masses using a modified multi-quadrant technique (quadBX) compared to standard biopsy technique (sBX). Clinical and pathologic data for all patients with ≥ cT2 renal masses who underwent percutaneous biopsy from 2009 - 2014 were reviewed. The quadBX technique was defined as multiple core biopsies from at least four separate solid enhancing areas within the tumor. The incidence of non-diagnostic findings, sarcomatoid features, and procedural complications was recorded and concordance between biopsy specimens and nephrectomy pathology was compared. A total of 122 biopsies were performed for 117 tumors in 116 patients (46 using sBX technique and 76 quadBX technique). Median tumor size was 10 cm (IQR 8-12). Biopsy was non-diagnostic in 5/46 (10.9%) sBX and 0/76 (0%) quadBX, p=0.007. RCC was identified in 96/115 (82.0%) tumors and non-RCC tumors were identified in 21 (18.0%). One complication occurred using the sBX technique;, no complications reported using quadBX technique. Sarcomatoid features were present in 23/96 (23.9%) of large RCC tumors studied. Sensitivity for identifying sarcomatoid features was higher using quadBX technique compared to the sBX technique, 13/15 (86.7%) vs. 2/8 (25.0%), p= 0.0062. Multi-quadrant percutaneous biopsy technique increases the ability to identify aggressive pathologic features in large renal tumors and decreases non-diagnostic biopsy rates. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Mar 2015 · The Journal of urology
  • Michael L Blute · Nathan A Damaschke · David F Jarrard
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    ABSTRACT: There is a major deficit in our ability to detect and predict the clinical behavior of prostate cancer (PCa). Epigenetic changes are associated with PCa development and progression. This review will focus on recent results in the clinical application of diagnostic and prognostic epigenetic markers. The development of high throughput technology has seen an enormous increase in the discovery of new markers that encompass epigenetic changes including those in DNA methylation and histone modifications. Application of these findings to urine and other biofluids, but also cancer and noncancerous prostate tissue, has resulted in new biomarkers. There has been a recent commercial development of a DNA methylation-based assay for identifying PCa risk from normal biopsy tissue. Other biomarkers are currently in the validation phase and encompass combinations of multiple genes. Epigenetic changes improve the specificity and sensitivity of PCa diagnosis and have the potential to help determine clinical prognosis. Additional studies will not only provide new and better biomarker candidates, but also have the potential to inform new therapeutic strategies given the reversibility of these processes.
    No preview · Article · Jan 2015 · Current Opinion in Urology
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    ABSTRACT: Genomic imprinting is an epigenetic mechanism that restricts gene expression to one inherited allele. Improper maintenance of imprinting has been implicated in a number of human diseases and developmental syndromes. Assays are needed that can quantify the contribution of each paternal allele to a gene expression profile. We have developed a rapid, sensitive quantitative assay for the measurement of individual allelic ratios termed Pyrosequencing for Imprinted Expression (PIE). Advantages of PIE over other approaches include shorter experimental time, decreased labor, avoiding the need for restriction endonuclease enzymes at polymorphic sites, and prevent heteroduplex formation which is problematic in quantitative PCR-based methods. We demonstrate the improved sensitivity of PIE including the ability to detect differences in allelic expression down to 1%. The assay is capable of measuring genomic heterozygosity as well as imprinting in a single run. PIE is applied to determine the status of Insulin-like Growth Factor-2 (IGF2) imprinting in human and mouse tissues. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · Jan 2015 · Journal of Cellular Biochemistry

Publication Stats

4k Citations
684.53 Total Impact Points

Institutions

  • 1998-2015
    • University of Wisconsin–Madison
      • • Department of Urology
      • • Molecular and Environmental Toxicology Center
      • • Department of Surgery
      Madison, Wisconsin, United States
  • 2012-2013
    • James Madison University
      Harisonburg, Virginia, United States
  • 2003-2005
    • University of Wisconsin - Stout
      Menominee, Wisconsin, United States
  • 2002
    • Stanford University
      Palo Alto, California, United States
  • 1995-1997
    • Johns Hopkins University
      • Department of Medicine
      Baltimore, Maryland, United States
  • 1996
    • Johns Hopkins Medicine
      • Department of Urology
      Baltimore, Maryland, United States