A comparison of prostate health index, total PSA, %free PSA, and proPSA in a contemporary US population-The MiCheck-01 prospective trial.

BACKGROUND: Increasing numbers of patients are presenting with aggressive prostate cancer (CaP); therefore, there exists a need to optimally identify these patients pre-biopsy. OBJECTIVES: To compare the accuracy of total prostate specific antigen (PSA), %free PSA, and prostate health index (PHI) to differentiate between patients without CaP, with non-aggressive (Gleason 3 + 3, non-AgCaP) and with aggressive (Gleason ≥ 3 + 4, AgCaP) in a contemporary US population. DESIGN, SETTINGS, AND PARTICIPANTS: Serum samples were collected from 332 US patients scheduled for biopsy due to an elevated age-adjusted PSA. Site and Central biopsy pathologic assessment were performed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Testing of PSA, free PSA, proPSA, and PHI was performed along with central pathology review. Test performance using logistic regression analysis for differentiating CaP from non-CaP as well as non-AgCaP from AgCaP was evaluated. RESULTS AND LIMITATIONS: Central pathology review resulted in 32 upgrades including 14 Gleason 3 + 3 scores being upgraded to AgCaP with final distribution of 148 no-CaP, 64 non-AgCaP, and 120 AgCaP patients. Receiver operator curve (ROC) analysis of the different tests showed that PHI performed best at differentiating CaP from no-CaP subjects (area under the receiver operator curve 0.79). In contrast, the different tests were essentially equivalent in differentiating AgCaP vs. non-AgCaP. CONCLUSIONS: In this recent US study of prebiopsy patients we observed a high proportion of AgCaP patients consistent with previous studies in contemporary US populations. Central Gleason review is recommended for multi-institutional studies comparing biomarkers. PHI was superior to PSA, free PSA, %free PSA, and proPSA in detecting CaP in this population but was not superior at differentiating AgCaP from non-AgCaP.

Development of a reliable assay to measure glypican-1 in plasma and serum reveals circulating glypican-1 as a novel prostate cancer biomarker.

Prostate cancer is responsible for hundreds of thousands of annual deaths worldwide. The current gold standard in early detection of prostate cancer, the prostate specific antigen test, boasts a high sensitivity but low specificity, resulting in many unnecessary prostate biopsies. Thus, emphasis has been placed on identifying new biomarkers to improve prostate cancer detection. Glypican-1 has recently been proposed as one such biomarker, however further exploration into its predictive power has been hindered by a lack of available, dependable glypican-1 immunoassays. Previously, we identified human glypican-1 as the antigenic target of the MIL-38 monoclonal antibody. Additionally, we have now generated another monoclonal antibody, 3G5, that also recognizes human glypican-1. Here we report the development of a reliable, custom Luminex® assay that enables precise quantitation of circulating human glypican-1 in plasma and serum. Using this assay, we show for the first time that circulating glypican-1 levels can differentiate non-cancer (normal and benign prostatic hyperplasia) patients from prostate cancer patients, as well as benign prostatic hyperplasia patients alone from prostate cancer patients. Our findings strongly promote future investigation into the use of glypican-1 for early detection of prostate cancer.

Comparative Analysis of Prostate Volume as a Predictor of Outcome in Prostate Artery Embolization.

PURPOSE: To determine the role of prostate volume as a predictor of outcome after prostatic artery embolization (PAE). MATERIALS AND METHODS: From January 2012 to September 2014, 78 consecutive patients undergoing PAE were evaluated at baseline and 1, 3, and 6 months. Analysis was performed comparing prostate volume groups (group 1, < 50 cm3; group 2, 50-80 cm(3); group 3, > 80 cm3) at baseline and follow-up to assess for differences in outcomes of American Urological Association (AUA) symptom index, quality of life (QOL)-related symptoms, and International Index of Erectile Function (IIEF). RESULTS: Mean baseline prostate volumes were 37.5 cm(3) in group 1 (n = 16), 65.7 cm3 in group 2 (n = 26), and 139.4 cm3 in group 3 (n = 36). There were no significant differences in baseline age, AUA symptom index, QOL, or IIEF between groups. Bilateral embolization was successful in 75 of 78 patients (96%). Two patients underwent unilateral embolization, and treatment failed in one patient as a result of bilateral atherosclerotic occlusion. A significant reduction in AUA symptom index was achieved within groups from baseline to 1, 3, and 6 months (n = 77): in group 1, from 27.2 to 14.0, 12.9, and 15.9, respectively (P = .002); in group 2, from 25.6 to 17.1, 16.3, and 13.5, respectively (P < .0001); and in group 3, from 26.5 to 15.2, 12.5, and 13.6, respectively (P < .0001). There was also a significant improvement in QOL. Comparative analysis demonstrated no statistically significant differences in AUA symptom index, QOL, or IIEF between groups. Two minor complications occurred: groin hematoma and a urinary tract infection. CONCLUSIONS: PAE offers similar clinical benefits to patients with differing gland sizes and may offer a reasonable alternative for poor candidates for urologic surgery.

Ultrasound-accelerated catheter-directed thrombolysis for acute submassive pulmonary embolism.

PURPOSE: To evaluate the safety and efficacy of ultrasound-accelerated catheter-directed thrombolysis (USAT) in patients with submassive pulmonary embolism (PE). MATERIALS AND METHODS: This retrospective study comprised 45 consecutive patients (15 prospective, 30 retrospective) who underwent USAT for submassive PE from June 2012-May 2014. Inclusion criteria were right ventricular dysfunction (RVD) as indicated by right ventricle-to-left ventricle (RV:LV) ratio > 0.9, symptoms of < 2 weeks' duration, and absence of absolute contraindication to thrombolysis. All patients underwent pulmonary artery catheterization with a standardized protocol (24 mg recombinant tissue plasminogen activator). Hemodynamic evaluation immediately after USAT, RV:LV ratio evaluation at 48-72 hours after USAT by computed tomography angiography and echocardiography, and adverse event reporting for a minimum of 30 days were performed. Outcomes and complications are reported as per the Society of Interventional Radiology Reporting Standards for Endovascular Treatment of Pulmonary Embolism. RESULTS: USAT was technically successful in 100% (n = 45) of patients. Main pulmonary artery pressure significantly decreased from 49.8 mm Hg to 31.1 mm Hg (P < .0001). RVD significantly improved with mean RV:LV ratios decreasing from 1.59 to 0.93 (P < .0001). There were 6 complications: 4 minor bleeding episodes at access sites and 2 major bleeding complications (flank and arm hematoma). All-cause mortality at 30 days was 0%. There were no readmissions for PE at 30 days after discharge. CONCLUSIONS: Ultrasound-accelerated catheter-directed thrombolysis using a standardized low-dose protocol is a safe and efficacious method of treatment of submassive PE to reduce acute pulmonary hypertension and RVD.

Clinical utility of a biopsy-based cell cycle gene expression assay in localized prostate cancer.

OBJECTIVE: The CCP signature test (Prolaris) quantifies a patient's risk of disease progression and prostate cancer specific mortality using a gene-expression-based cell cycle progression (CCP) score. This study evaluated the potential clinical utility of the CCP test in a US-based clinical setting. METHODS: Urologists who participated in a prospective clinical study were sent a retrospective questionnaire to assess the value of the CCP test result. Fifteen board-certified urologists participated in the study, representing 15 distinct community urology group practices. Questionnaires were received for 294 evaluable patients. All patients had localized prostate cancer (T1-T3b, N0, M0). RESULTS: Physicians found the CCP score valuable and indicated that 55% of tests generated a mortality risk that was either higher or lower than expected. Physicians also indicated that 32% of test results would lead to a definite or possible change in treatment. The data suggest that the test would have the net effect of shifting patients from more aggressive treatment to more conservative treatment. This was evidenced by the significant association between change in treatment and lower CCP scores (p < 0.002) and by the fact that 62% of tests likely to lead to a definite or possible change in treatment had mortality risks lower than the physician expected versus only 10% with risks higher than expected. STUDY LIMITATIONS: This study measured the retrospectively assessed likelihood of change in treatment as estimated by the physician, not the actual change in treatment. CONCLUSIONS: The CCP score adds meaningful new information to risk assessment for localized prostate cancer patients. Real-world use of the test is likely to lead to a change in treatment in a significant portion of tested patients, particularly by shifting patients towards more conservative management. This could reduce overtreatment of patients with less aggressive disease, decreasing patient morbidity and costs for payers and the healthcare system.

Early results from a United States trial of prostatic artery embolization in the treatment of benign prostatic hyperplasia.

PURPOSE: To report early findings from a prospective United States clinical trial to evaluate the efficacy and safety of prostatic artery embolization (PAE) for benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: From January 2012 to March 2013, 72 patients were screened and 20 patients underwent treatment. Patients were evaluated at baseline and selected intervals (1, 3, and 6 mo) for the following efficacy variables: American Urological Association (AUA) symptom score, quality of life (QOL)-related symptoms, International Index of Erectile Function score, peak urine flow rate, and prostate volume (on magnetic resonance imaging at 6 mo). Complications were monitored and reported per Society of Interventional Radiology guidelines. RESULTS: Embolization was technically successful in 18 of 20 patients (90%); bilateral PAE was successful in 18 of 19 (95%). Unsuccessful embolizations were secondary to atherosclerotic occlusion of prostatic arteries. Clinical success was seen in 95% of patients (19 of 20) at 1 month, with average AUA symptom score improvements of 10.8 points at 1 month (P < .0001), 12.1 points at 3 months (P = .0003), and 9.8 points at 6 months (P = .06). QOL improved at 1 month (1.9 points; P = .0002), 3 months (1.9 points; P = .003), and 6 months (2.6 points; P = .007). Sexual function improved by 34% at 1 month (P = .11), 5% at 3 months (P = .72), and 16% at 6 months (P = .19). Prostate volume at 6 months had decreased 18% (n = 5; P = .05). No minor or major complications were reported. CONCLUSIONS: Early results from this clinical trial indicate that PAE offers a safe and efficacious treatment option for men with BPH.

Utility of cone-beam CT imaging in prostatic artery embolization.

PURPOSE: To evaluate the utility of cone-beam computed tomography (CT) in patients undergoing prostatic artery (PA) embolization (PAE) for benign prostatic hyperplasia. MATERIALS AND METHODS: From January 2012 to January 2013, 15 patients (age range, 59-81 y; mean, 68 y) with moderate- or severe-grade lower urinary tract symptoms, in whom medical management had failed were enrolled in a prospective United States trial to evaluate PAE. During pelvic angiography, 15 cone-beam CT acquisitions were performed in 11 patients, and digital subtraction angiography was performed in all patients. Cone-beam CT images were reviewed to assess for sites of potential nontarget embolization that impacted therapy, a pattern of enhancement on cone-beam CT suggesting additional PAs, confirmation of prostatic parenchymal perfusion before embolization, and contralateral prostatic parenchymal enhancement. RESULTS: Cone-beam CT was successful in 14 of 15 acquisitions, and PAE was successful in 14 of 15 patients (92%). Cone-beam CT provided information that impacted treatment in five of 11 patients (46%) by allowing for identification of sites of potential nontarget embolization. Duplicated prostatic arterial supply and contralateral perfusion were each identified in 21% of patients (three of 11). Prostatic perfusion was confirmed before embolization in 50% of acquisitions (seven of 14). CONCLUSIONS: Cone-beam CT is a useful technique that can potentially mitigate the risk of nontarget embolization. During treatment, it can allow for the interventionalist to identify duplicated prostatic arterial supply or contralateral perfusion, which may be useful when evaluating a treatment failure.

Staff time and motion assessment for administration of erythropoiesis-stimulating agents: a two-phase pilot study in clinical oncology practices.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are used for the management of anaemia in patients with non-myeloid malignancies where anaemia is due to the effect of concomitant myelosuppressive chemotherapy. Assessing the impact of different ESA dosing regimens on office staff time and projected labour costs is an important component of understanding the potential for optimization of oncology practice efficiencies. OBJECTIVES: A two-phase study was conducted to evaluate staff time and labour costs directly associated with ESA administration in real-world oncology practice settings among cancer patients undergoing chemotherapy. The objective of Phase 1 was to determine the mean staff time required for the process of ESA administration in patients with anaemia due to concomitantly administered chemotherapy. The objective of Phase 2 was to quantify and compare the mean staff time and mean labour costs of ESA administered once weekly (qw) with ESA once every 3 weeks (q3w) over an entire course of chemotherapy. METHODS: Phase 1 was a prospective, cross-sectional time and motion study conducted in six private oncology practices in the US based on nine steps associated with ESA administration. Using findings from Phase 1, Phase 2 was conducted as a retrospective chart review to collect data on the number and types of visits in two private oncology practices for patients receiving a complete course of myelosuppressive chemotherapy. RESULTS: In Phase 1, the mean total time that clinic staff spent on ESA administration was 23.2 min for patient visits that included chemotherapy administration (n(chemo) = 37) and 21.5 min when only ESA was administered (n(ESAonly) = 36). In Phase 2, the mean duration of treatment was significantly longer for q3w than qw (53.84 days for qw vs. 113.38 for q3w, p < 0.0001); thus, analyses were adjusted using analysis of covariance (ANCOVA) for episode duration for between-group comparisons. Following adjustment by ANCOVA, qw darbepoetin alfa (DA) patients (n(qw) = 83) required more staff time for ESA + chemotherapy visits and ESA-only visits than q3w patients (n(q3w) = 118) over a course of chemotherapy. Overall, mean total staff time expended per chemotherapy course was greater for patients receiving qw versus q3w DA. Weekly DA dosing was associated with greater projected mean labour costs ($US38.16 vs. $US31.20 [average for 2007-2010]). CONCLUSIONS: The results from this real-world study demonstrate that oncology practices can attain staff time and labour costs savings through the use of q3w ESA. The degree of savings depends on the individual oncology practice's staffing model and ESA administration processes, including those that allow for optimized synchronization of patient visits for ESA and chemotherapy administration. These findings indicate that additional research using standard ESA administration protocols for longer periods of time with a larger number of oncology practices and patients should be conducted to confirm these findings.

The burden of blood transfusion: a utilization and economic analysis--a pilot study in patients with chemotherapy-induced anemia (CIA).

OBJECTIVE: The objective is to measure the burden of blood transfusion of Packed Red Blood Cells (PRBCs) in patients with chemotherapy-induced anemia (CIA) on the institutional outpatient transfusion center. METHODS: This is a retrospective chart review (starting July 1, 2010, working backwards until 120 evaluable patients are accrued) at a single institutional transfusion center in the US. The mean and standard deviation (SD) were calculated for patient's age, pre-transfusion Hgb level, and other transfusion-related activities. RESULTS: One hundred and twenty records were reviewed. The majority included patients who were female (71%), African American (61%), and had either Medicare (48%) or private insurance (39%). The mean patient age was 59 years and the average pre-transfusion Hgb was 7.9 g/dL. The average patient visit to facility ranged from 213 min for one PRBC unit to 411 minutes for three PRBC units. The mean staff time for patient evaluation was 66 minutes. Actual time for transfusion was ∼100 min for each PRBC unit; 90% of patients received two PRBC units. Staff was engaged in direct patient care for an average of 322 min for two PRBC units. The labor cost of transfusion (in 2011 $US) ranged from $46.13-$49.33 per PRBC unit. The estimated fully loaded bundled cost was $596.49 for transfusion of one unit of PRBC. Limitations of the study include: the site included in this study may not be applicable to all sites in practice and the evaluated patient population was varied, with the exception that all patients were treated for some type of malignancy; and the review of blood bank records for 120 patients was not 120 independent events and, as such, may not have adequately captured actual variability. CONCLUSIONS: This analysis quantifies expense in terms of time for administration of the transfusion, as well as costs associated with outpatient blood transfusions.

Geniculate artery embolization in the management of spontaneous recurrent hemarthrosis of the knee: case series.

Spontaneous recurrent hemarthrosis after knee arthroplasty is reported to occur in 0.3%-1% of patients, likely secondary to hypertrophic vascular synovium. Five patients who underwent previous arthroplasty presented with spontaneous hemarthrosis. Selective arterial embolization was performed with spherical embolic particles (diameter range, 100-700 µm). Angiography demonstrated synovial hypervascularity with geniculate artery "tumor blush" appearance in all patients. Average time to resolution of effusion was 2.6 weeks, with no recurrences reported during follow-up (mean, 25.4 mo; range, 16-48 mo). Two patients experienced transient cutaneous ischemia. Selective geniculate artery embolization with spherical embolic particles is an effective treatment for spontaneous recurrent hemarthrosis of the knee.

Erythropoiesis-Stimulating Agent (ESA) Practice Patterns in Patients With Chemotherapy-Induced Anemia (CIA) Treated at Hospital Oncology Clinics.

OBJECTIVES: To characterize erythropoiesis-stimulating agent (ESA) usage initiated in hospital outpatient oncology centers that employ weekly (QW) and every-3-week (Q3W) ESA dosing regimens; describe the frequency of ESA dosing, transfusions, hemoglobin determinations, and anemia-related visits between these 2 regimens; and compare the rates at which inpatient ESA doses are administered on QW versus Q3W schedules. METHODS: This was a retrospective, observational record review evaluating ESA usage in 641 patients from 8 outpatient oncology clinics throughout the United States. Adult patients who initiated myelosuppressive chemotherapy for a documented solid tumor between August 1, 2007 and June 30, 2009 and received their first 3 consecutive outpatient ESA doses on a QW or Q3W schedule were eligible for study inclusion. During a single course of chemotherapy, ESA administrations were recorded as long as ESA therapy was continued on the initial regimen. ESA doses were captured until termination of ESA therapy, until 9 months had elapsed since the first ESA dose, until the patient was switched to another ESA regimen, or until death. ESA administration during inpatient admissions was also recorded. RESULTS: ESA utilization varied between the dosing groups, with fewer ESA doses administered per follow-up month in patients receiving Q3W versus QW ESA therapy (mean, 1 vs 2 doses). Compared to weekly administration, extended-dose ESA therapy also reduced the number of hemoglobin determinations and anemia-related visits without chemotherapy required per follow-up month. Neither the number of transfusions nor the number of packed red blood cell units administered per follow-up month differed between treatment groups. Compared to weekly ESA therapy, Q3W administration reduced costs associated with ESA prescribing and utilization. CONCLUSION: Extended-dose ESA therapy (Q3W dosing) may improve practice efficiency and may be associated with reduced frequencies of hemoglobin determinations and ESA doses required. Q3W dosing may also reduce inpatient ESA utilization by reducing the number of ESA doses required for previously maintained outpatients.

Clinical staff resource use with intravenous patient-controlled analgesia in acute postoperative pain management: results from a multicenter, prospective, observational study.

The purpose of this study was to evaluate hospital resource utilization associated with intravenous patient-controlled analgesia (IV-PCA), with a focus on nursing, pharmacy, and central supply/engineering time spent from a hospital perspective. Data were collected during a multicenter (29 sites), prospective observational study in the United States of subjects who underwent total knee replacement (TKR), total hip replacement (THR), or abdominal hysterectomy (AH) and were administered analgesia through IV PCA for the management of acute postoperative pain. Nursing staff recorded the IV PCA-related tasks they performed for a subject and the duration of time required to perform each task from initial IV PCA set-up to discontinuation. Hospital administrators, nursing managers, central supply/engineering staff, and pharmacy directors were interviewed to obtain data regarding other IV PCA labor resource use. The distribution of surgery type among the 457 subjects was 31.1% THR, 35.9% TKR, and 33.0% AH. The average duration of IV PCA use was 32.6 hours. Nurses reported having to perform an average of 39.6 IV PCA-related tasks, which required an average of 67.4 minutes. The most common IV PCA-related tasks were evaluating pump use and settings, assessing the IV site, evaluating and addressing analgesia side effects, instructing/reinstructing the subject on use, administering supplemental pain medications, assisting with self-care or moving the subject, and assisting the subject with use of the button. Pharmacists reported that they spend approximately 7.9 minutes and pharmacy technicians spend approximately 9.8 minutes, per subject daily course of IV PCA therapy, on the following tasks: checking and verifying the order, doing inventory of the analgesia, preparing the analgesia (ie, filling reservoirs), checking the analgesia, and delivering the analgesia to the nursing units. In addition, pharmacists and RNs spend an average of 47.3 and 40.7 minutes per year in IV PCA-related training. Intravenous patient-controlled analgesia postoperative care requires coordination and involvement of numerous hospital departments. It is labor intensive and involves numerous time-consuming tasks, oversight of IV PCA, and ongoing training. Alternative methods of patient-controlled pain management with similar efficacy that reduces labor resource utilization may be warranted.