Clinicopathologic Significance of Anterior Prostate Cancer: Comparison With Posterior Prostate Cancer in the Era of Multiparametric Magnetic Resonance Imaging.

Anterior prostate cancer (APC) has been considered an indolent tumor, most commonly arising in the transition zone (TZ). More recently, detection of APC has been facilitated through multiparametric magnetic resonance imaging and improved biopsy techniques, enabling earlier detection. The pathologic features and clinical significance of pure APC in a large contemporary series of well-characterized tumors have, to date, not been elucidated. Cases with APC defined as cancer present anterior to the urethra only were identified from 1761 consecutive radical prostatectomy specimens accessioned between January 2015 and August 2016. The clinicopathologic features of these cases were compared with those of pure posterior prostate cancer (PPC) and the features of anterior peripheral zone (APZ) cancers were compared with those of TZ cancers. In addition, the tumor series from 2015 to 2016 was compared with a cohort of 1054 patients accessioned before the utilization of multiparametric magnetic resonance imaging in the routine workup of patients with prostate cancer. In the 2015-2016 series, there were 188 (10.7%) patients with APC compared with 5.4% in the series from the pre-multiparametric magnetic resonance imaging era. No difference was observed between APC and PPC with regards to patient age or mean serum prostate-specific antigen at presentation. Mean tumor volume and positive surgical margin (PSM) rates were significantly higher in APC. In contrast, PPC was more commonly high grade with more frequent extraprostatic extension (EPE). None of the cases of APC had infiltration of the seminal vesicle or lymph node involvement, in contrast to PPC, with almost 14% of cases in each category. The 3- and 5-year biochemical recurrence-free survival was significantly higher in APC when compared with PPC, although this was not retained on multivariable analysis which included tumor location. On division of APCs according to anatomic zone of origin, 45% were APZ cancer and 37% TZ cancer. On comparison of APZ and TZ cancers, there were no significant differences in mean age and serum prostate-specific antigen at presentation as well as tumor volume, Gleason score, and PSM rate. High-grade malignancy (Gleason score >3 + 4=7) was seen in 26% of TZ cancers which compared with 44% of APZ cancers and 56% of PPC cancers. The rate of EPE was significantly higher in APZ when compared with TZ cancer ( P< 0.0005); however, the biochemical recurrence rate was not significantly different between the groups. The prevalence of APC in radical prostatectomy specimens has increased in recent times, in association with earlier detection at a stage amenable to curative surgical treatment. APC, when compared with PPC, is less commonly high grade with less frequent EPE, despite the APC group having larger tumors and a higher PSM rate at presentation. However, not all anterior cancers are indolent. Anterior cancers are more commonly seen in the APZ than the TZ and APZ cancers appear more locally aggressive than TZ cancers.

Characterizing Lumbar Spine Kinematics and Kinetics During Simulated Low-Speed Rear Impact Collisions.

BACKGROUND: Recent work has demonstrated that low back pain is a common complaint following low-speed collisions. Despite frequent pain reporting, no studies involving human volunteers have been completed to examine the exposures in the lumbar spine during low-speed rear impact collisions. METHODS: Twenty-four participants were recruited and a custom-built crash sled simulated rear impact collisions, with a change in velocity of 8 km/h. Randomized collisions were completed with and without lumbar support. Inverse dynamics analyses were conducted, and outputs were used to generate estimates of peak L4/L5 joint compression and shear. RESULTS: Average (SD) peak L4/L5 compression and shear reaction forces were not significantly different without lumbar support (compression = 498.22 N [178.0 N]; shear = 302.2 N [98.5 N]) compared to with lumbar support (compression = 484.5 N [151.1 N]; shear = 291.3 N [176.8 N]). Lumbar flexion angle at the time of peak shear was 36° (12°) without and 33° (11°) with lumbar support. CONCLUSION: Overall, the estimated reaction forces were 14% and 30% of existing National Institute of Occupational Safety and Health occupational exposure limits for compression and shear during repeated lifting, respectively. Findings also demonstrate that, during a laboratory collision simulation, lumbar support does not significantly influence the total estimated L4/L5 joint reaction force.

Primary tumour PSMA intensity is an independent prognostic biomarker for biochemical recurrence-free survival following radical prostatectomy.

PURPOSE: The prognostic value of PSMA intensity on PSMA PET/CT due to underlying biology and subsequent clinical implications is an emerging topic of interest. We sought to investigate whether primary tumour PSMA PET intensity contributes to pre- and post-operative prediction of oncological outcomes following radical prostatectomy. METHODS: We performed a retrospective cohort study of 848 men who underwent all of multiparametric MRI (mpMRI), transperineal prostate biopsy, and 68 Ga-PSMA PET/CT prior to radical prostatectomy. PSMA intensity, quantified as maximum standard uptake value (SUVmax), and other clinical variables were considered relative to post-operative biochemical recurrence-free survival (BRFS) using Cox regression and Kaplan-Meier analysis. RESULTS: After a median follow-up of 41 months, 219 events occurred; the estimated 3-year BRFS was 79% and the 5-year BRFS was 70%. Increasing PSMA intensity was associated with less favourable BRFS overall (Log rank p < 0.001), and within subgroups of Gleason score category (Log rank p < 0.03). PSMA intensity was significantly associated with shorter time to biochemical recurrence, after adjusting for pre-operative (HR per 5-unit SUVmax increase = 1.15) and post-operative (HR per 5-unit SUVmax increase = 1.10) parameters. CONCLUSION: These results in a large series of patients confirm PSMA intensity to be a novel, independent prognostic factor for BRFS.

Partitioning the total seatback reaction force amongst the lumbar spine motion segments during simulated rear-impact collisions.

Purpose. This study aimed to determine how the seatback force is distributed across lumbar spine motion segments during a simulated low-velocity rear-impact collision with and without the application of mechanical lumbar support. Methods. A ferroresistive pressure-sensing system was used during simulated rear-impact collisions (ΔV = 7.66 km/h). Total seatback reaction force was derived from pressure recordings as the product of calibrated pressure outputs and sensel areas. The three-dimensional position of the pressure mat and the lumbar spinous processes were tracked and then used to extract the seatback force that was applied to the lumbar motion segments. Results. On average, 77% (637 N) and 53% (430 N) of the total seatback force was applied directly to the lumbar spine with and without lumbar support, respectively (p < 0.001). In addition to four of five individual motion segments bearing a greater force with lumbar support (p < 0.029), the distribution of the total lumbar force was found to be significantly different between support type conditions. Conclusions. Although lumbar supports can alter the magnitude and distribution of shear force applied to the lumbar spine during low-velocity rear-impact collisions, they do not appear to elevate the injury risk.

Histological findings of totally embedded robot assisted laparoscopic radical prostatectomy (RALP) specimens in 1197 men with a negative (low risk) preoperative multiparametric magnetic resonance imaging (mpMRI) prostate lobe and clinical implications.

BACKGROUND: Prostate multiparametric magnetic resonance imaging (mpMRI) has become a popular initial investigation of an elevated PSA and is being incorporated into active surveillance protocols. Decisions on prostate cancer investigation and management based solely on a normal mpMRI remains controversial. Histopathological findings of a totally embedded normal mpMRI lobe are rarely described. METHODS: A retrospective review of the histological findings of negative preoperative mpMRI lobes in men treated by robot assisted laparoscopic radical prostatectomy (RALP). Inclusion criteria included a preoperative low risk mpMRI for both lobes (Prostate Imaging-Reporting and Data System (PIRADS) ≤ 2) or one negative lobe (with a PIRADS 3-5 in the opposite lobe). RESULTS: A single normal mpMRI lobe was identified in 1018 men (PIRADS 3-5 group). Both lobes were normal in 179 men (PIRADS ≤ 2 group). Prostate cancer was identified in 47.6% (485/1018) of the normal mpMRI lobe opposite a PIRADS 3-5 lesion, including 13.2% (134/1018) with >0.5 cc of International Society of Urologic Pathologists (ISUP) grade 2, or a higher grade cancer. ISUP grade 4-5 was only identified in 2% (20/1018). Compared to RALP histology of the PIRADS 3-5 mpMRI tumour, a pathological ISUP upgrade in the normal mpMRI lobe was identified in 58/1018 men (5.7%). In the PIRADS ≤ 2 group extraprostatic extension occurred in 19% (34/179) and seminal vesicle invasion (pT3b) in 3.9% (7/179). There was no difference in margin status between the PIRADS 3-5 and ≤2 groups (p = 0.247). CONCLUSIONS: mpMRI underestimates tumour grade and volume compared to totally embedded histopathological analysis of RALP specimens, although ISUP grade 4-5 cancer is uncommon. Our analysis provides useful insight into the multifocality of prostate cancers, and highlights the utility of systematic biopsy, in addition to targeted biopsies. These results have ramifications for clinical decisions on prostate cancer management based solely on the mpMRI appearance, including active surveillance.

Low-velocity motor vehicle collision characteristics associated with claimed low back pain.

Objective: Up to 50% of individuals involved in low-velocity motor vehicle collisions report low back pain (LBP). A major limitation in such cases is the lack of knowledge of injury mechanisms linking the collision characteristics to the pain and pathology associated with LBP reporting. Thus, the objective of this investigation was to characterize the physical circumstances of low-velocity motor vehicle collisions that resulted in claims of LBP. Methods: Eighty-three forensically assessed cases were analyzed to identify specific collision and claimant characteristics. Results: Seventy-seven percent of reviewed cases involved a claim of LBP. Of these LBP claim cases, 70% of cases involved a rear-end collision configuration, and 40% of all cases were low-velocity collisions, with severities ranging between 10 and 12 km/h. The most common pre-existing medical condition was prior LBP or evidence of disc degeneration. Conclusions: The results of this investigation provide knowledge of collision characteristics that can be employed in future studies on the mechanisms of low back injury in low-speed motor vehicle collisions.

Characterizing trunk muscle activations during simulated low-speed rear impact collisions.

Objective: The purpose of this study was to evaluate the activation profiles of muscles surrounding the lumbar spine during unanticipated and braced simulated rear-end collisions. Methods: Twenty-two low-speed sled tests were performed on 11 human volunteers ( △ V = 4 km/h). Each volunteer was exposed to one unanticipated impact and one braced impact. Accelerometers were mounted on the test sled and participants' low back. Six bilateral channels of surface electromyography (EMG) were collected from the trunk during impact trials. Peak lumbar accelerations, peak muscle activation delay, muscle onset time, and peak EMG magnitudes, normalized to maximum voluntary contractions (MVCs), were examined across test conditions. Results: Though not statistically significant, bracing for impact tended to reduce peak lumbar acceleration in the initial rearward impact phase of the occupant's motion by approximately 15%. The only trunk muscles with peak activations exceeding 10% MVC during the unanticipated impact were the thoracic erector spinae. Time of peak muscle activation was slightly longer for the unanticipated condition (unanticipated = 296 ms; braced = 241 ms). Conclusions: Results from this investigation demonstrate that during an unanticipated low-speed rear-end collision, the peak activation of muscles in the lumbar spine are low in magnitude. As such, muscle activation likely has minimal contribution to the internal joint loads that are experienced in the lumbar intervertebral joints during low-speed rear impact collisions. These findings justify the use of simplified joint models in estimating the joint loads in the lumbar spine during low-speed rear impact collisions and support the application of cadaveric and anthropomorphic test device (ATD) testing in understanding the resultant joint loads in the lumbar spine associated with rear-end collisions.

Prospective study of diagnostic accuracy comparing prostate cancer detection by transrectal ultrasound-guided biopsy versus magnetic resonance (MR) imaging with subsequent MR-guided biopsy in men without previous prostate biopsies.

BACKGROUND: The current diagnosis of prostate cancer (PCa) uses transrectal ultrasound-guided biopsy (TRUSGB). TRUSGB leads to sampling errors causing delayed diagnosis, overdetection of indolent PCa, and misclassification. Advances in multiparametric magnetic resonance imaging (mpMRI) suggest that imaging and selective magnetic resonance (MR)-guided biopsy (MRGB) may be superior to TRUSGB. OBJECTIVE: To compare the diagnostic efficacy of the magnetic resonance imaging (MRI) pathway with TRUSGB. DESIGN, SETTING, AND PARTICIPANTS: A total of 223 consecutive biopsy-naive men referred to a urologist with elevated prostate-specific antigen participated in a single-institution, prospective, investigator-blinded, diagnostic study from July 2012 through January 2013. INTERVENTION: All participants had mpMRI and TRUSGB. Men with equivocal or suspicious lesions on mpMRI also underwent MRGB. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was PCa detection. Secondary outcomes were histopathologic details of biopsy and radical prostatectomy specimens, adverse events, and MRI reader performance. Sensitivity, specificity, negative predictive values (NPVs), and positive predictive values were estimated and basic statistics presented by number (percentage) or median (interquartile range). RESULTS AND LIMITATIONS: Of 223 men, 142 (63.7%) had PCa. TRUSGB detected 126 cases of PCa in 223 men (56.5%) including 47 (37.3%) classed as low risk. MRGB detected 99 cases of PCa in 142 men (69.7%) with equivocal or suspicious mpMRI, of which 6 (6.1%) were low risk. The MRGB pathway reduced the need for biopsy by 51%, decreased the diagnosis of low-risk PCa by 89.4%, and increased the detection of intermediate/high-risk PCa by 17.7%. The estimated NPVs of TRUSGB and MRGB for intermediate/high-risk disease were 71.9% and 96.9%, respectively. The main limitation is the lack of long follow-up. CONCLUSIONS: We found that mpMRI/MRGB reduces the detection of low-risk PCa and reduces the number of men requiring biopsy while improving the overall rate of detection of intermediate/high-risk PCa. PATIENT SUMMARY: We compared the results of standard prostate biopsies with a magnetic resonance (MR) image-based targeted biopsy diagnostic pathway in men with elevated prostate-specific antigen. Our results suggest patient benefits of the MR pathway. Follow-up of negative investigations is required.

Ammonia emissions during vermicomposting of sheep manure.

The effect of C:N ratio, temperature and water content on ammonia volatilization during two-phase composting of sheep manure was evaluated. The aerobic phase was conducted under field conditions. This was followed by Phase II, vermicomposting, conducted in the laboratory under controlled conditions of water content (70% and 80%) and temperature (15 and 22 °C). The addition of extra straw lead to a 10% reduction in NH3 volatilization compared to sheep manure composted without extra straw. Temperature and water content significantly effected ammonia volatilization at 0 day in Phase II, with a water content of 70% and temperature of 22 °C leading to greater losses of ammonia. Nitrogen loss by ammonia volatilization during vermicomposting ranged from 8% to 15% of the initial N content. The addition of extra straw did not result in significant differences in total carbon content following vermicomposting.

The use of artificial neural networks to reduce data collection demands in determining spine loading: a laboratory based analysis.

The extensive data requirements of three-dimensional inverse dynamics and joint modelling to estimate spinal loading prevent the implementation of these models in industry and may hinder development of advanced injury prevention standards. This work examines the potential of feed forward artificial neural networks (ANNs) as a data reduction approach and compared predictions to rigid link and EMG-assisted models. Ten males and ten females performed dynamic lifts, all approaches were applied and comparisons of predicted joint moments and joint forces were evaluated. While the ANN under- predicted peak extension moments (p = 0.0261) and joint compression (p < 0.0001), predictions of cumulative extension moments (p = 0.8293) and cumulative joint compression (p = 0.9557) were not different. Therefore, the ANNs proposed may be used to obtain estimates of cumulative exposure variables with reduced input demands; however they should not be applied to determine peak demands of a worker's exposure.

The role of dynamic flexion in spine injury is altered by increasing dynamic load magnitude.

BACKGROUND: Evidence indicates that loads and postures that an individual is exposed to alter their risk of reporting low back pain or incurring a spine injury. In vitro research indicates cyclic flexion under static compressive loads can lead to disc herniation, while repetitive compression in neutral or flexed postures leads to vertebral failure. However, no research has examined the likelihood of altering injury site (disc vs. bone) when dynamic load exposures are varied concurrently with cyclic flexion. METHODS: Fifty porcine cervical spinal units were assigned to one of five groups based on peak normalized loads of 10%, 30%, 50%, 70% and 90% of the unit's predicted tolerance. Specimens underwent passive range of motion tests to determine individualized range of motion. Once individualized loads and angles were determined, specimens were cyclically compressed and flexed based on profiles obtained from a floor to waist height lift until failure occurred or 12h elapsed. After testing specimens were dissected to identify injury site, and cumulative exposures sustained to failure were calculated. FINDINGS: Disc injury was not observed when peak loads exceeded 30% of the tolerance, while they comprised a higher percentage of the total injuries incurred when decreasing from the 30% to 10% groups. Those specimens exhibiting disc injury tolerated significantly greater: cycles to failure (9000 vs. 930, P<0.0001), cumulative compression (10872.7 vs. 1089.5MNs, P<0.001), shear (1822.1 vs. 150.6MNs, P<0.001) and angular excursion (130809.7 degrees vs. 12714.7 degrees , P<0.001). INTERPRETATION: If the spine is exposed to greater levels of load, in the presence of repetitive flexion, it is more likely to experience vertebral fracture. However, if the spine is exposed to many cycles of low peak loads, injury is more likely to occur to the intervertebral disc than to the vertebral bone or endplate.

Can periods of static loading be used to enhance the resistance of the spine to cumulative compression?

Results of in vitro studies conducted on isolated bone specimens have indicated a higher tolerance to static load than exists when exposed to cyclic loading, when controlled for creep rate. If this difference in load tolerance exists, it may be exploited to extend the life of vertebral bone exposed to repetitive compression, and potentially alter the development of spinal injury. However, little work has been conducted on functional spinal units to determine if bone displays this characteristic within an intact joint. Additionally, static loading may result in load redistribution within the intervertebral disc forcing more of the compressive load towards the periphery of the endplate away from the nucleus. In order to examine these potential mechanisms, 218 osteoligamentous porcine functional spinal units were assigned to one of 15 loading scenarios. This involved one of three normalized peak load magnitudes (50%, 70% and 90% of estimated compressive tolerance) and one of five normalized static load applications (0%, 50%, 100%, 200% and 1000% of the total dynamic work duration). Load magnitude significantly altered the resistance to cumulative compression with decreased peak magnitudes corresponding to both increased cumulative load tolerance and increased height loss. Static load periods did not alter the resistance of the spinal unit to cumulative compression or impact the number of cycles tolerated to failure. The insertion of static load periods impacted the total survival time to failure, but only for the 1000% static load group, an exposure unlikely to occur for most in vivo exposures. The insertion of static load periods decreased the amount of height loss during testing which may play a protective role by allowing load redistribution within the vertebral bone and intervertebral disc.

Estimating the compressive strength of the porcine cervical spine: an examination of the utility of DXA.

STUDY DESIGN: The failure strength of porcine spinal units was correlated with vertebral size and bone mineralization. The accuracy of the resulting predictive equations was tested with an independent sample of spinal units. OBJECTIVES: To determine if dual energy x-ray absorptiometry (DXA)-obtained measures of bone mineralization can be used to accurately predict the compressive tolerance of porcine spinal units. SUMMARY OF BACKGROUND DATA: Porcine spinal units are often used in place of cadaveric tissues, and normalization is used to improve the transferability of model results. In compressive testing, normalization can be performed to the estimated compressive strength. Bone mineralization measures have been shown to be positively correlated with compressive tolerance and have been used to predict the tolerance of human spinal units. However, the accuracy of these predictive equations has not been assessed with an independent sample. METHODS: Twenty porcine cervical spinal units were scanned (DXA) to obtain measures of bone mineral content (BMC) and bone mineral density (BMD). The units were compressed to failure, and the failure loads were correlated with the measured bone mineralization and endplate area of the spinal unit. The regression equations were used to predict the compressive tolerance of an independent sample of spinal units. RESULTS: BMC (P = 0.078) and BMD (P = 0.2834) were not significantly correlated to compressive strength. Endplate area was the most highly correlated variable, with an r of 0.5329. The use of a predictive equation including BMC on the second independent sample resulted in errors of estimation of 1.4 +/- 1.2 kN, corresponding to 13% of the average compressive strength. In comparison, the use of an equation employing endplate area alone resulted in estimation errors of 11%. CONCLUSIONS: Measures of BMC/BMD did not enhance predictions of compressive strength and will not reduce errors in compressive load normalization in a porcine model. The poor correlations found between BMC and compressive strength may be due to the non-load-bearing anterior processes of the porcine cervical spine.

Effects of prolonged sitting on the passive flexion stiffness of the in vivo lumbar spine.

BACKGROUND CONTEXT: Prolonged sitting may alter the passive stiffness of the lumbar spine. Consequently, performing full lumbar flexion movements after extended periods of sitting may increase the risk of low back injury. PURPOSE: The purpose was to quantify time-varying changes in the passive flexion stiffness of the lumbar spine with exposure to prolonged sitting and to link these changes to lumbar postures and trunk extensor muscle activation while sitting. A secondary objective was to determine whether men and women responded differently to prolonged sitting. STUDY DESIGN: Passive lumbar flexion moment-angle curves were generated before, during and after 2 hours of sitting. Lumbar flexion/extension postures and extensor muscle activation levels were measured while sitting. SAMPLE: Twelve (6 men, 6 women) university students with no recent low back pain were studied. OUTCOME MEASURES: Quantified changes in the shapes of the passive flexion moment-angle curves (slopes, breakpoints and maximum lumbar flexion angles) were the outcome measures. While sitting, average lumbar flexion/extension angles, the distribution of lumbar flexion/extension postures, average electromyogram (EMG) amplitude, the number and average length of EMG gaps, and trunk extensor muscle rest levels were measured. METHODS: Participants performed deskwork for 2 hours while sitting on the seat pan of an office chair. Moment-angle relationships for the lumbar spine were derived by pulling participants through their full voluntary range of lumbar flexion on a customized frictionless table. RESULTS: Lumbar spine stiffness increased in men after only 1 hour of sitting, whereas the responses of women were variable over the 2-hour trial. Men appeared to compensate for this increase in stiffness by assuming less lumbar flexion in the second hour of sitting. CONCLUSIONS: Changes in the passive flexion stiffness of the lumbar spine may increase the risk of low back injury after prolonged sitting and may contribute to low back pain in sitting.

The time-varying response of the in vivo lumbar spine to dynamic repetitive flexion.

OBJECTIVE: To quantify the time-varying stiffness and kinematic responses of the in vivo lumbar spine exposed to dynamic repetitive flexion movements. DESIGN: Changes in in vivo passive lumbar moment-angle relationships were monitored in response to dynamic repetitive flexion. BACKGROUND: While previous in vitro studies have provided conflicting evidence on the effects of repetitive flexion movements on the stiffness of the lumbar spine, no previous studies have quantified the time-varying changes of the in vivo lumbar spine to dynamic repetitive flexion. METHODS: Subjects lifted and lowered a 4.5 kg load over two barriers at a rate of 7 lifts per minute for 1.5 h inducing at least 80% of the lumbar flexion range of motion. Prior to lifting and at 30 min intervals passive moment-angle relationships were obtained by pulling the subject into flexion on a customized frictionless table. RESULTS: Repetitive lifting induced a decreasing stiffness trend after 30 min, followed by a recovery towards initial stiffness levels with further loading. The trends were non-significant for all measures studied. CONCLUSIONS: The results indicate that after 30 min of lifting, creep within the passive tissues may allow workers to exceed their initial range of motion, altering joint mechanics and loading patterns potentially leading to an increased risk of developing low back pain. RELEVANCE: Given the potential for time-varying changes to alter the spine's risk of injury and injury mechanisms, knowledge regarding the stiffness response of the in vivo lumbar spine exposed to repetitive flexion may lead to improved understanding and prevention of work related back pain.

Investigation of an anthrax outbreak in Alberta in 1999 using a geographic information system.

A Geographic Information System was used to document an anthrax outbreak in Alberta in 1999 and to describe the physical and environmental conditions of the area. The majority of infected farms were located on poorly drained organic soils. Regulatory agencies should consider adopting this tool for animal disease outbreak investigations.