Initial Negative Biopsy Research Articles

Abstract 15886: When the Giant is Hidden but Not Dormant

Background: Giant cell myocarditis is a rare etiology of cardiogenic shock, which requires high index of suspicion, rapid immunosuppressive therapy, and sometimes mechanical circulatory supportCase presentation69 year old woman with prior medical history of non-ischemic dilated cardiomyopathy and recovered left ventricular ejection fraction (LVEF) presented with cardiogenic shock complicated by acute renal and liver injury requiring support with Impella 5.5. Suspicion for myocarditis was high and patient underwent endomyocardial biopsy and started on high dose steroids. Biopsy was negative for myocarditis. Despite support, patient had progressive shock and incessant ventricular arrhythmia necessitating IV antiarrhytmics and escalation to VA ECMO in addition to Impella and eventually to central Centrimag BiVAD with drainage cannulas in right atrium and LV apex, and reinfusion catheters in pulmonary artery and ascending aorta. (Figure 1) She was urgently listed for heart transplantation as a status 1 and one day later underwent successful orthotopic heart transplantation. Pathological examination of the explanted heart was consistent with Giant cell Myocarditis (Figure 2) Conclusion: Giant cell myocarditis is a rare etiology of cardiogenic shock. Suggestive features include rapid hemodynamic deterioration and incessant ventricular arrhythmia. Negative initial endomyocardial biopsy is not enough to rule out the disease in high clinical suspicion. Rapid escalation of support is warranted in fulminant cases to preserve end organ function and improve survival.(Figure 1 Created with BioRender.com)

The Problem of Subclinical Antibody-mediated Rejection in Kidney Transplantation.

Defined as histologic evidence of rejection on a protocol biopsy in the absence of kidney dysfunction, subclinical rejection has garnered attention since the 1990s. The major focus of much of this research, however, has been subclinical T cell-mediated rejection (TCMR). Herein, we review the literature on subclinical antibody-mediated rejection (AMR), which may occur with either preexisting donor-specific antibodies (DSA) or upon the development of de novo DSA (dnDSA). In both situations, subsequent kidney function and graft survival are compromised. Thus, we recommend protocol biopsy routinely within the first year with preexisting DSA and at the initial detection of dnDSA. In those with positive biopsies, baseline immunosuppression should be maximized, any associated TCMR treated, and adherence stressed, but it remains uncertain if antibody-reduction treatment should be initiated. Less invasive testing of blood for donor DNA or gene profiling may have a role in follow-up of those with negative initial biopsies. If a protocol biopsy is positive in the absence of detectable HLA-DSA, it also remains to be determined whether non-HLA-DSA should be screened for either in particular or on a genome-wide basis and how these patients should be treated. Randomized controlled trials are clearly needed.

Chronic Baseline Prostate Inflammation is Associated with Lower Tumor Grade in Men with Prostate Cancer on Repeat Biopsy: Results from the REDUCE Study.

We investigated whether baseline acute or chronic prostate inflammation among men with initial negative biopsies for prostate cancer was associated with cancer grade in 2-year repeat biopsies. Retrospective analyses were conducted of 889 men aged 50 to 75 years old with negative baseline prostate biopsy and 2-year repeat biopsy positive for prostate cancer in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study. Acute and chronic prostate inflammation and cancer grade were determined by central pathology during the REDUCE study. The association of inflammation in baseline and 2-year repeat biopsy and prostate cancer grade in 2-year repeat biopsy was evaluated with Student's t-test, chi-squared test and multivariable logistic regression. Chronic, acute inflammation and both were detected in 533 (60%), 12 (1%) and 85 (10%) baseline biopsies, respectively. Presence of acute and chronic inflammation were significantly associated with each other (p <0.001). Both types of inflammation were unrelated to race, body mass index, prostate specific antigen or digital rectal exam. At the 2-year biopsy, 621 (70%) tumors were low grade (Gleason scores 2-6) and 268 (30%) were high grade (Gleason scores 7-10). In univariable and multivariable analyses, men with baseline chronic inflammation had significantly fewer high grade tumors (univariable OR 0.64, 95% CI 0.47-0.87, p=0.004; multivariable OR=0.68, 95% CI0.50-0.93, p=0.016) than those without baseline chronic inflammation. Baseline acute inflammation was not associated with tumor grade (univariable OR 0.74, 95% CI 0.45-1.20, p=0.22; multivariable OR 0.78, 95% CI 0.48-1.29, p=0.34). Chronic inflammation in a negative biopsy was associated with lower prostate cancer grade among men with cancer on follow-up 2-year biopsy.

Rebiopsy rate after transperineal or transrectal prostate biopsy.

BackgroundIn recent years, transperineal biopsies gained popularity for prostate cancer diagnosis; lower infective complications and improved sampling of the prostate are the main advantages of this technique. One question that remains unclear is whether an initial transperineal biopsy confers a lower risk for rebiopsy compared with the transrectal approach.MethodsSix hundred seventy-one men were prospectively followed after an initial negative prostate biopsy for a median period of 49.50 (IQR: 37.62–61.17) months. Rebiopsy rate was analyzed attending to first biopsy approach (transrectal versus transperineal systematic) and clinical variables.ResultsDiagnostic rate was similar for transrectal and transperineal systematic biopsies. Targeted biopsies outperformed any systematic approach, and transperineal targeted in particular was superior to transrectal targeted. Rebiopsy rates were 15.4% and 5.26% for the transrectal and transperineal systematic groups, respectively. Prostate-specific antigen density and type of first biopsy were identified as rebiopsy predictors.ConclusionMen undergoing transperineal systematic biopsies had a three times lower rate of rebiopsy over the study period compared with the traditional transrectal approach. This advantage could be added to the already described potential benefits of transperineal biopsies. Targeted biopsies had lower rebiopsy rate over the study period. Further innovations that decreased the cost of transperineal biopsies could favor this approach in the future.

Biomarkers in previous histologically negative prostate biopsies can be helpful in repeat biopsy decision-making processes.

To evaluate whether the addition of biomarkers to traditional clinicopathological parameters may help to increase the accurate prediction of prostate re‐biopsy outcome. A training cohort with 98 patients and a validation cohort with 72 patients were retrospectively recruited into our study. Immunohistochemical analysis was used to evaluate the immunoreactivity of a group of biomarkers in the initial negative biopsy normal‐looking tissues of the training and validation cohorts. p‐STAT3, Mcm2, and/or MSR1 were selected out of 10 biomarkers to construct a biomarker index for predicting cancer and high‐grade prostate cancer (HGPCa) in the training cohort based on the stepwise logistic regression analysis; these biomarkers were then validated in the validation cohort. In the training cohort study, we found that the biomarker index was independently associated with the re‐biopsy outcomes of cancer and HGPCa. Moreover supplementing the biomarker index with traditional clinical‐pathological parameters can improve the area under the receiver operating characteristic curve of the model from 0.722 to 0.842 and from 0.735 to 0.842, respectively, for predicting cancer and HGPCa at re‐biopsy. In the decision‐making analysis, we found the model supplemented with the biomarker index can improve patients’ net benefit. The application of the model to clinical practice, at a 10% risk threshold, would reduce the number of biopsies by 34.7% while delaying the diagnosis of 7.8% cancers and would reduce the number of biopsies by 73.5% while delaying the diagnosis of 17.8% HGPCas. Taken together, supplementing the biomarker index with clinicopathological parameters may help urologists in re‐biopsy decision‐making processes.

Detection of prostate cancer using prostate imaging reporting and data system score and prostate-specific antigen density in biopsy-naive and prior biopsy-negative patients.

BackgroundFew studies report on indications for prostate biopsy using Prostate Imaging–Reporting and Data System (PI-RADS) score and prostate-specific antigen density (PSAD). No study to date has included biopsy-naïve and prior biopsy-negative patients. Therefore, we evaluated the predictive values of the PI-RADS, version 2 (v2) score combined with PSAD to decrease unnecessary biopsies in biopsy-naïve and prior biopsy-negative patients.Materials and methodsA total of 1,098 patients who underwent multiparametric magnetic resonance imaging at our hospital before a prostate biopsy and who underwent their second prostate biopsy with an initial benign negative prostatic biopsy were included. We found factors associated with clinically significant prostate cancer (csPca). We assessed negative predictive values by stratifying biopsy outcomes by prior biopsy history and PI-RADS score combined with PSAD.ResultsThe median age was 65 years (interquartile range: 59-70), and the median PSA was 5.1 ng/mL (interquartile range: 3.8-7.1). Multivariate logistic regression analysis revealed that age, prostate volume, PSAD, and PI-RADS score were independent predictors of csPca. In a biopsy-naïve group, 4% with PI-RADS score 1 or 2 had csPca; in a prior biopsy-negative group, 3% with PI-RADS score 1 or 2 had csPca. The csPca detection rate was 2.0% for PSA density <0.15 ng/mL/mL and 4.0% for PSA density 0.15-0.3 ng/mL/mL among patients with PI-RADS score 3 in a biopsy-naïve group. The csPca detection rate was 1.8% for PSA density <0.15 ng/mL/mL and 0.15-0.3 ng/mL/mL among patients with PI-RADS score 3 in a prior biopsy-negative group.ConclusionPatients with PI-RADS v2 score ≤2, regardless of PSA density, may avoid unnecessary biopsy. Patients with PI-RADS score 3 may avoid unnecessary biopsy through PSA density results.

Detection of clinically significant prostate cancer after negative fusion and systematic biopsy.

288 Background: MRI/Ultrasound fusion biopsy of the prostate has enhanced the detection of clinically significant prostate cancer (csPCa). Detection of csPCa is greatest when fusion and systematic biopsies are combined. However, the finding of a negative fusion and negative systematic biopsy in patients with suspicious lesion on imaging raises the question of either falsely positive imaging or a false negative biopsy. Methods: We retrospectively reviewed our database of patients undergoing MRI/transrectal US-guided fusion biopsy. All images were graded according to the Prostate Imaging Reporting and Data System version (PIRADS) 2.0. Patients underwent targeted biopsy followed by systematic 12-core double sextant biopsy within the same session. csPCa was defined as Grade Group (GG) ≥2 PCa. Patients with no prostate cancer (PCa) found on biopsies were followed. MRI studies with PIRADS v2 score ≤ 2 were considered to have no MRI evidence of PCa. Results: A total of 400 patients had at least one PIRADS ≥3 lesion and underwent fusion/systematic biopsy. Of these, 113 (28.3%) patients had no evidence of PCa on either fusion or systematic biopsy. Median follow-up was 32.5 months. 44 (39%) patients underwent repeat MRI and of these, 24 (54%) had no evidence of PCa on repeat MRI. PIRADS lesion disappearance was associated with lower PSA Density (PSAd) (0.12 vs 0.20; P = 0.0319) and decreased progression to repeat biopsy (8.33% vs 95%; P &lt; 0.0001). Patients who had a repeat biopsy had a greater PSAd ( 0.21 vs 0.12; P = 0.0054). Of 113 patients with negative initial biopsy, 23 (20.4 %) underwent repeat biopsy: 16 (14.2 %) had PCa and 11 (9.7%) had csPCa. Thus, 48% of patients who underwent repeat biopsy had csPCa. Among patients with a PCa on repeat biopsy, cancer was sampled by MRI targeted cores in 80% of patients. Conclusions: Despite a negative initial fusion/systematic biopsy, at least 10% of patients were subsequently diagnosed with clinically significant PCa. The combination of elevated PSAd and the persistence of a suspicious lesion on repeat MRI appears selective for previously missed PCa. However, after negative fusion biopsy, repeat MRI yields a high rate of PIRADS lesion disappearance in patients with low PSAd.

MP24-02 CLINICAL UTILITY OF CONFIRMMDX FOR PROSTATE CANCER IN A COMMUNITY UROLOGY PRACTICE

INTRODUCTION AND OBJECTIVES:There is an unmet need for methods to better identify patients most likely to benefit from repeat prostate biopsy after an initial negative biopsy. ConfirmMDx is a molec...

Clinical utility study of confirms mdx for prostate cancer in a community urology practice.

94 Background: There is an unmet need for methods to better identify patients most likely to benefit from repeat prostate biopsy after an initial negative biopsy. ConfirmMDx is a molecular test clinically validated for detection of prostate cancer (PCa) in tissue from PCa-negative biopsies. In this clinical utility study, we evaluated the impact of ConfirmMDx on the management of patients being considered for repeat prostate biopsy in a community urology practice. Methods: The study population consisted of 605 men with a prior PCa-negative prostate biopsy, who were counseled on the need to undergo repeat biopsy at a large community urology practice due to persistent elevated risk of PCa. All tissue cores from each PCa-negative patient were tested with the ConfirmMDx methylation-specific PCR test, and positive or negative ConfirmMDx results based on the presence or absence of GSTP1, APC or RASSF1 methylation in the biopsy tissue. ConfirmMDx results were provided to the physician for use in repeat biopsy decision-making. Medical record review was conducted at a minimum of nine months after ConfirmMDx results were reported. Results: Of the 605 subjects enrolled, 308 (51%) had a negative ConfirmMDx test result and 297 (49%) were positive. For the entire study population, average age was 64 (median 64, interquartile range 59 to 69), average serum PSA level 6.8 ng/mL (5.7, 4.3 to 8.1). The median follow-up for both Confirm positives and negatives was 10 months post-testing. Repeat biopsy rates for ConfirmMDx positive and negative men were 32.3% (96/297) and 5.8% (15/308), respectively (P &lt; 0.001). For patients who received a biopsy during the follow-up period, the time between ConfirmMDx and repeat biopsy was shorter for ConfirmMDx positive men versus ConfirmMDx negatives (median 4 vs. 8 months, P = 0.007). Conclusions: In this utility study, ConfirmMDx had a significant impact on repeat prostate biopsy decision-making in a U.S. community urology setting. Repeat biopsy rates in ConfirmMDx positive men were six-fold higher than in ConfirmMDx negatives. These results reflect the clinical utility of ConfirmMDx for biopsy decision-making in real world clinical practice.

Population-based outcomes of men with a single negative prostate biopsy: Importance of continued follow-up among older patients

PurposeTo determine in Ontario-based men with a single negative transrectal ultrasound-guided prostate biopsy the long-term rates of prostate cancer-specific mortality, diagnosis, and treatment; number of repeat biopsies; and predictors of prostate cancer diagnosis and mortality. Materials and methodsThis was a population-based cohort study, using data from linked, validated health administrative databases, of all Ontario-based men with a negative first biopsy between January 1994 and October 2014. Patients were followed from time of first biopsy till death, administrative censoring, or end of study period. Cumulative incidence functions were used to calculate the study outcomes’ cumulative incidences. Univariable and multivariable regression analyses using Fine and Gray's semiparametric proportional hazards model were used to assess predictors of prostate cancer diagnosis and mortality. ResultsThe study cohort included 95,675 men with a median age of 63.0years. Median follow-up was 8.1years. The 20-year cumulative rates of prostate cancer-specific mortality and diagnosis were 1.8% and 23.7%, respectively. Men ages 70 to 79 and 80 to 84 at initial biopsy had 20-year prostate cancer-specific mortality cumulative rates of 3.2% and 6.4% respectively. The 20-year cumulative rate of receiving radical prostatectomy was 7.6%. Higher socioeconomic status and urban residence were associated with higher diagnosis risks yet lower prostate cancer-specific mortality risks. ConclusionsThis is the first population-based study assessing long-term cancer outcomes in North American men with a single negative transrectal ultrasound-guided prostate biopsy. Following a negative initial biopsy, 23.7% of men are still diagnosed with and 1.8% die of prostate cancer within 20years. Cancer-specific mortality outcomes are significantly worse in older men, with prostate cancer mortality rates several times higher than the rest of the population.

Clinical significance of the De Ritis ratio for detecting prostate cancer in a repeat prostate biopsy.

PurposeWe evaluated factors predicting a positive repeat biopsy result in patients with an initial negative prostate biopsy result.Materials and MethodsThis study included 124 patients in whom prostate cancer (PCa) was not detected in the initial transrectal ultrasound-guided prostate biopsy and who underwent repeat biopsy from January 2011 to December 2017. Patients without PCa in both initial and repeat prostate biopsies were designated as group 1 (n=82), and those in whom PCa was detected on a repeat prostate biopsy were designated as group 2 (n=42). Among group 2 patients, 6 had insignificant PCa according to the Epstein criteria and were combined with group 1 patients to make up group A (n=88). Patients with significant PCa were categorized as group B (n=36). We compared clinicopathologic characteristics between the groups.ResultsMultivariate analysis showed that age (p=0.018) and detection of atypical small acinar proliferation (ASAP) or ≥3 cores of high-grade prostatic intraepithelial neoplasia (HGPIN) (p=0.011) on the initial biopsy were predictive factors for a positive result on a repeat biopsy. When we compared group A and group B, age (p=0.004) and the De Ritis ratio (p=0.024) were significantly higher in group B in the multivariate analysis.ConclusionsAge and the detection of ASAP or ≥3 cores of HGPIN on the initial biopsy were associated with detection of PCa on a repeat biopsy. Age and the De Ritis ratio were found to be predictive factors for the detection of clinically significant PCa on a repeat biopsy.

Developing a Chinese PI-RADS v2-based nomogram for predicting clinically significant prostate cancer in patients with a prior negative biopsy

Objective: To develop a nomogram based on prostate imaging reporting and data system version 2 (PI-RADS v2) to predict clinically significant prostate cancer in patients with a prior negative prostate biopsy. Methods: The clinical and pathological data of 231 patients who underwent repeat prostate biopsy and multiparametric MRI (mpMRI) were reviewed. Based on PI-RADS v2, the mpMRI results were assigned as PI-RADS grade from 0 to 2. A Logistic regression nomogram for predicting the probabilities of clinically significant prostate cancer were constructed. The performances of the nomogram were assessed using area under the receiver operating characteristic (ROC) curve, calibrations and decision curve analysis. Results: Of the total 231 repeat prostate biopsy patients, clinically significant prostate cancer was detected in 59 cases(25.5%). In multivariate Logistic regression analysis, age, prostate specific antigen (PSA), prostate volume (PV), digital rectal examination (DRE) and mpMRI results were significant independent predictors of the diagnosis of clinically significant prostate cancer (P<0.05). The nomogram with super predictive accuracy were constructed (AUC=0.927, P<0.001), and exhibited excellent calibration. Decision curve analysis also demonstrated a high net benefit across a wide range of threshold probabilities . Conclusions: PI-RADS v2 combined with age, PSA, PV and DRE can predict the probability of clinically significant prostate cancer in patients with negative initial biopsies. The nomogram generated may help the decision-making process in patients with prior benign histology before the performance of repeat biopsy.

A narrative review and update on management following negative prostate biopsy.

Prostate cancer has traditionally been diagnosed using systematic transrectal ultrasound-guided biopsy. However, given the inherent nature of sampling, a negative biopsy does not exclude clinically significant prostate cancer (csPCa), and continued controversy exists in the optimal management following initial biopsy. Numerous avenues for evaluation include multiparametric MRI (mpMRI), use of molecular biomarkers, repeat biopsy, and observation. mpMRI has shown promise in guiding further biopsy management: for individuals with identified target lesions, increased accuracy and detection using combination targeted and systematic sampling has been repeatedly demonstrated in the literature as an effective strategy. For those with negative MRIs and/or negative biomarker (blood, urinary, tissue) studies, increasing evidence has suggested that these individuals may be able to avoid biopsy altogether, albeit at a small risk of missing csPCa. Observation should be based on an individual's risk of csPCa versus their competing health risks, and saturation biopsy reserved for rare cases with high clinical suspicion. Management following an initial negative prostate biopsy requires careful discussion with the patient, their risk tolerance, and threshold for intervention. Although subject to availability, mpMRI and molecular biomarkers may better risk stratify patients, identify target lesions, and in certain cases, spare biopsy altogether.

The role of mpMRI and PSA density in patients with an initial negative prostatic biopsy.

While an elevated PSA significantly increases the risk of men harboring prostate cancer, many men with a persistently elevated PSA have negative prostate biopsies. More recently, multiparametric MRI (mpMRI) has had promising implications for the diagnosis of prostate cancer. We aim to investigate the diagnostic role of mpMRI in predicting the future diagnosis of prostate cancer in patients with an initial negative biopsy. This study included all men with negative biopsies, elevated PSA and mpMRI. All patients had their age, PSA, and PSAd recorded. mpMRI lesions were classified using the PI-RADS 2 scoring system. mpMRI imaging was performed in 336 men with an initial negative biopsy, of whom 108, 111, 76 and 41 men underwent single, two, three and four biopsies, respectively. Of the 228 men with more than one biopsy, 115 patients were diagnosed with prostate cancer on further biopsies. Older patients and men with higher PSA, PSAd and PIRADS score had a significant risk to progress to cancer but only higher PSAd and higher PI-RADS score were significantly associated with clinically significant cancers. For clinically significant cancer; sensitivity and specificity of PI-RADS scoring was 86 and 45%, respectively, and a NPV of 87.6%. When combined with PSAd, NPV was 93%. Men with benign prostatic biopsy and both PSAd < 0.15 and low PI-RADS score may avoid second biopsy. PI-RADS scoring system has a high sensitivity to diagnose clinically significant prostate cancer and repeat biopsy should be recommended in men with benign biopsy and high score.

Application of transperineal prostate projection supersaturated needle in prostate biopsy

Objective To explore diagnostic value of transperineal prostate projection supersaturated needle (TPPSN) after initial negative biopsy result and to assess the efficacy and safety. Methods A total of 218 patients were enrolled in this study. These patients were diagnosed with benign prostatic hyperplasia by transperineal template biopsy but were suspected to have prostate cancer through the abnormal prostate specific antigen(PSA) and digital rectal examination (DRE). All patients were divided into the observation group (TPPSN) and the control group (traditional transperineal template saturated biopsies) according to different way of puncture. According to the prostate volume different interval ( 80 mL), the positive rates of two groups were contrasted. The incidence of postoperative complications such as gross hematuria, fever, retention of urine and perineum discomfort of two groups were compared. Results The total cancer detection rate of the observation group was higher than that of the control group (P=0.044), the improvement of cancer detection rate was higher only when the prostate volume was greater than 80 mL (P=0.041). Compared to the control group, the incidence of complication such as gross hematuria, fever, retention of urine and perineum discomfort by TPPSN was low, but there was no significant difference (P>0.05 ). Conclusions For the patients who are initial negative biopsy but highly suspected with prostate cancer, the TPPSN can improve the positive rate of prostate biopsy. It can more accurate positioning the prostate cancer and is a safe and effective diagnostic method for prostate cancer. TPPSN can be a safe and reliable way to prostate biopsy. Key words: Prostate; Biopsy, Needle; Perineum

BIOMARKERS FOR DIAGNOSING OF PROSTATE CANCER: THE PRESENT AND THE FUTURE

This review analyze data of clinical trials, systematic reviews and meta-analyses, which evaluated the sensitivity and specificity of any biomarkers using for diagnostics of prostate cancer before an initial prostate biopsy or after a negative initial biopsy.

Non-invasive early detection of malignant pulmonary nodules by FISH-based sputum test

BackgroundEarly detection decreases lung cancer mortality. The Target-FISH Lung Cancer Detection (LCD) Test is a non-invasive test designed to detect chromosomal changes (deletion or amplification) via Fluorescence in situ Hybridization (FISH) in sputum specimens from persons suspected of having lung cancer. We evaluated the performance of the LCD test in patients with highly suspicious pulmonary nodules who were scheduled for a biopsy procedure. MethodsInduced sputum was collected from patients who were scheduled for biopsy of a solitary pulmonary nodule (0.8–3 cm) in one of 6 tertiary medical centers in the US and Israel. The lung cancer detection (LCD) Test combined sputum cytology and Target-FISH analysis on the same target cells and the results were compared to the pathology. Participants with non-surgical negative biopsy results were followed for 2 years to determine their final diagnosis. ResultsOf the 173 participants who were evaluated, 112 were available for analysis. Overall, the LCD test had a sensitivity of 85.5% (95% CI, 76.1–92.3), specificity of 69% (95% CI, 49.2–84.7) and an accuracy of 81.3% (95% CI, 72.8–88). The positive and negative predictive values (PPV, NPV) were 88.8% and 62.5%, respectively. The LCD test was positive in 9 of 11 lung cancer patients who had an initial negative biopsy. ConclusionsIn a cohort of patients with highly suspicious lung nodules, the LCD test is a non-invasive option with good sensitivity and a high positive predictive value. A positive LCD test reinforces the need to aggressively pursue a definitive diagnosis of suspicious nodules.

CT-guided biopsy in suspected spondylodiscitis: microbiological yield, impact on antimicrobial treatment, and relationship with outcome

PurposeTo investigate the clinical impact of CT-guided biopsy, as performed in routine clinical practice, in patients with suspected spondylodiscitis on MRI in terms of culture yield, impact on antimicrobial treatment, and outcome.MethodsThis study included 64 patients with MRI findings compatible with spondylodiscitis who underwent CT-guided biopsy.ResultsInitial CT-guided biopsies were culture-positive in 20/64 (31.3%, 95% confidence interval [CI] 21.2–43.3%). Repeat CT-guided biopsies (after initial negative biopsy) were culture-positive in an additional 5/15 (33.3%, 95% CI 15.2–58.3%). Serum leukocytes, C-reactive protein, pre-biopsy use of antibiotics, neurological symptoms, MRI findings, vertebral height loss, and hyperkyphosis were not significantly different between culture-positive and culture-negative cases (P = 0.214–1.000); 75% (15/20) of initial CT-guided biopsies that were culture-positive provided additional information to clinicians for guiding antibiotic treatment. Sixty-two of 64 patients (96.9%, 95% CI 89.3–99.1%) would have been adequately treated if a strategy was followed that would subject all patients without clinical findings suspicious for “atypical” microorganisms and negative blood cultures to empirical antibiotics (i.e., clindamycin for coverage of Gram-positive bacteria) without using biopsy results to determine the optimal antibiotic regimen. Outcome within 6 months (development of neurologic or orthopedic complications, surgery, and death) was not significantly different (P = 0.751) between culture-positive and culture-negative patients.ConclusionsAlthough CT-guided biopsies are culture-positive in a minority of cases, the majority of positive cultures are useful to tailor antibiotic treatment. Empirical treatment with clindamycin may cover almost all micro-organisms in positive biopsy specimens, provided patients are not immunocompromised. Outcome appears similar between culture-positive and culture-negative patients.

Evaluation of an Epigenetic Assay for Predicting Repeat Prostate Biopsy Outcome in African American Men

To evaluate an epigenetic assay performed on tissue from negative prostate biopsies in a group of African American (AA) men undergoing repeat biopsy, and to compare accuracy for predicting repeat biopsy outcome to prior studies conducted in predominantly Caucasian populations. The study population consisted of 211 AA men from 7 urology centers across the United States; all of whom were undergoing 12-core transrectal ultrasound-guided repeat biopsy within 30 months from a negative index biopsy. All biopsy cores from the negative index biopsy were profiled for the epigenetic biomarkers GSTP1, APC, and RASSF1 using ConfirmMDx for Prostate Cancer (MDxHealth, Irvine, CA). Upon repeat biopsy, 130 of 211 subjects (62%) had no prostate cancer (PCa) detected and 81 of 211 (38%) were diagnosed with PCa. Of the subjects with PCa, 54 (67%) were diagnosed with Gleason score (GS) ≤6 PCa and 27 (33%) with GS ≥7 disease. For detection of PCa at repeat biopsy, ConfirmMDx sensitivity was 74.1% and specificity was 60.0%, equivalent to prior studies (P = .235 and .697, respectively). For detection of GS ≥7 PCa, sensitivity was 78% and specificity was 53%. The negative predictive values for detection of all PCa and GS ≥7 PCa were 78.8% and 94.2%, respectively. In this group of AA men, we successfully validated an epigenetic assay to assess the need for repeat biopsy. Results were consistent with previous studies from predominantly Caucasian populations. Therefore, the ConfirmMDx assay is a useful tool for risk stratification of AA men who had an initial negative biopsy.

The use of transrectal ultrasound-guided biopsy following the introduction of prostate-specific antigen testing in Denmark: a population-based analysis

Objective: Incidence rates of prostate cancer in Denmark resemble those of countries that endorse prostate-specific antigen (PSA) screening. So far, no studies have described the consequences of PSA testing on diagnostic activity on a population level. The aim of this study was to describe the frequency of systematic transrectal ultrasound-guided biopsy (TRUS-gb) activity, including rebiopsy rates, in Denmark between 1995 and 2011.Materials and methods: All men who underwent TRUS-gb during the period were identified in the Danish Prostate Cancer Registry. In total, 83,041 biopsy sets from 64,430 individuals were identified. The diagnostic rate and the frequency of rebiopsy were analyzed. Age, histology and PSA were compared at the time of biopsy.Results: The number of TRUS-gb per 100,000 men per year increased 4.6-fold. The mean number of TRUS-gb procedures per individual increased from 1.08 in 1995 to 1.46 in 2011 (p = .0001), and the proportion of men with negative initial biopsy sets who underwent rebiopsy increased from 22% in 1995 to 41% in 2004, later decreasing to 31% in 2009.Conclusions: The diagnostic activity in Denmark and the rebiopsy rates in men with initial negative TRUS-gb have increased substantially, and guidelines for the management of men with a negative initial biopsy are highly warranted.