Review article: MRI-targeted biopsies for prostate cancer diagnosis and management.

PURPOSE: Transrectal ultrasound (TRUS)-guided biopsy has been the traditional biopsy route in the detection of prostate cancer. However, due to concern regarding overdetection of low-risk cancer and missed clinically significant cancers as well as risk of sepsis, alternative approaches have been explored. Transperineal template biopsy-sampling the gland every 5 m to 10 mm-reduces error by sampling the whole prostate but increases risk of detecting clinically insignificant cancers as well as conferring risks of side effects such as urinary retention and bleeding. METHODS: There are various targeted biopsy techniques, each with different cancer detection rates, costs and learning curves. Current research focuses on refining biopsy methodology to maximize detection of significant cancers, whilst minimising invasiveness and complications. In this article, the up-to-date research data about MRI-targeted prostate biopsy were reviewed to show its utilization in prostate cancer management and diagnosis. RESULTS AND CONCLUSION: Prostate multiparametric MRI has become an effective tool in the detection of significant cancers and an essential component of the prostate cancer diagnostic pathway incorporating MRI-guided biopsy decisions.

Intraprostatic Cancer Recurrence following Radical Radiotherapy on Transperineal Template Mapping Biopsy: Implications for Focal Ablative Salvage Therapy.

PURPOSE: Men in whom external beam radiotherapy fails are usually placed on delayed hormone therapy. Some of these men have localized recurrence that might be suitable for further local therapy. We describe patterns of recurrence and suitability for focal ablative therapy in those undergoing transperineal template prostate mapping biopsies. MATERIALS AND METHODS: The study included 145 consecutive patients (December 2007 to May 2014) referred with suspicion of recurrence due to rising prostate specific antigen after external beam radiotherapy or brachytherapy who underwent transperineal template prostate mapping biopsies. Suitability for focal ablative therapy required the cancer to be unifocal or unilateral, or bilateral/multifocal with 1 dominant index lesion and secondary lesions with Gleason score 3+3=6 with no more than 3 mm cancer core involvement. RESULTS: Mean patient age was 70.7 (SD 5.8) years. Median prostate specific antigen at time of transperineal template prostate mapping biopsy was 4.5 ng/ml (IQR 2.5-7.7). Overall 75.9% (110) were suitable for a form of focal salvage treatment, 40.7% (59) were suitable for quadrant ablation, 14.5% (21) hemiablation, 14.5% (21) bilateral focal ablation and 6.2% (9) for index lesion ablation. CONCLUSIONS: Three-quarters of patients who have localized radiorecurrent prostate cancer may be suitable for focal ablative therapy to the prostate based on transperineal template prostate mapping biopsies.

A Multicenter Study of the Clinical Utility of Nontargeted Systematic Transperineal Prostate Biopsies in Patients Undergoing Pre-Biopsy Multiparametric Magnetic Resonance Imaging.

PURPOSE: The added value of nontargeted systematic prostate biopsies when performed alongside magnetic resonance imaging targeted biopsies in men referred with a suspicion of prostate cancer is unclear. We aimed to determine the clinical utility of transperineal nontargeted systematic prostate biopsies, when performed alongside targeted systematic prostate biopsies, using pre-biopsy multiparametric magnetic resonance imaging. MATERIALS AND METHODS: Consecutive patients referred with a suspicion of prostate cancer (April 2017 to October 2019) underwent pre-biopsy multiparametric magnetic resonance imaging. A transperineal biopsy was advised if multiparametric magnetic resonance imaging PI-RADS® (v.2.0) score was 4 or 5, and score 3 required a prostate specific antigen density 0.12 ng/ml or greater. Primary threshold for clinically significant prostate cancer was defined as any Gleason 3+4 or greater. Multivariable logistic regression analysis identified pre-biopsy predictors of clinically significant prostate cancer in nontargeted systematic prostate biopsies, regardless of targeted pathology (p <0.05, R, version 3.5.1). RESULTS: A total of 1,719 men underwent a pre-biopsy multiparametric magnetic resonance imaging, with 679 (39.5%) proceeding to combined targeted systematic prostate biopsies and nontargeted systematic prostate biopsies. In these men clinically significant prostate cancer was detected in 333 (49%) and 139 (20.5%) with targeted systematic prostate biopsies and nontargeted systematic prostate biopsies, respectively. In those men with clinically significant prostate cancer in targeted systematic prostate biopsies, clinically significant prostate cancer was also present in nontargeted systematic prostate biopsies in 117 (17.2%); Gleason 3+3 was present in 50 (7.4%). In 287 men without any cancer in the targeted systematic prostate biopsies, 13 (1.9%) had clinically significant prostate cancer in nontargeted systematic prostate biopsies. In addition 18/679 (2.7%) had Gleason 3+3 disease and no Gleason greater than 4+3 was detected. Predictors associated with clinically significant prostate cancer in nontargeted systematic prostate biopsies were prostate specific antigen 5 ng/ml or greater (OR 2.05, 95% CI 1.13-3.73, p=0.02), PI-RADS score 5 (OR 2.26, 95% CI 1.51-3.38, p <0.001) and prostate volume less than 50 cc (OR 2.47, 95% CI 1.57-3.87, p <0.001). CONCLUSIONS: Detection of clinically significant prostate cancer in exclusively nontargeted transperineal systematic biopsies in a pre-biopsy multiparametric magnetic resonance imaging pathway was low (1.9%).

Focal laser ablation as clinical treatment of prostate cancer: report from a Delphi consensus project.

PURPOSE: To define the role of focal laser ablation (FLA) as clinical treatment of prostate cancer (PCa) using the Delphi consensus method. METHODS: A panel of international experts in the field of focal therapy (FT) in PCa conducted a collaborative consensus project using the Delphi method. Experts were invited to online questionnaires focusing on patient selection and treatment of PCa with FLA during four subsequent rounds. After each round, outcomes were displayed, and questionnaires were modified based on the comments provided by panelists. Results were finalized and discussed during face-to-face meetings. RESULTS: Thirty-seven experts agreed to participate, and consensus was achieved on 39/43 topics. Clinically significant PCa (csPCa) was defined as any volume Grade Group 2 [Gleason score (GS) 3+4]. Focal therapy was specified as treatment of all csPCa and can be considered primary treatment as an alternative to radical treatment in carefully selected patients. In patients with intermediate-risk PCa (GS 3+4) as well as patients with MRI-visible and biopsy-confirmed local recurrence, FLA is optimal for targeted ablation of a specific magnetic resonance imaging (MRI)-visible focus. However, FLA should not be applied to candidates for active surveillance and close follow-up is required. Suitability for FLA is based on tumor volume, location to vital structures, GS, MRI-visibility, and biopsy confirmation. CONCLUSION: Focal laser ablation is a promising technique for treatment of clinically localized PCa and should ideally be performed within approved clinical trials. So far, only few studies have reported on FLA and further validation with longer follow-up is mandatory before widespread clinical implementation is justified.

Prevalence and correlates of depressive disorders in people with Type 2 diabetes: results from the International Prevalence and Treatment of Diabetes and Depression (INTERPRET-DD) study, a collaborative study carried out in 14 countries.

AIMS: To assess the prevalence and management of depressive disorders in people with Type 2 diabetes in different countries. METHODS: People with diabetes aged 18-65 years and treated in outpatient settings were recruited in 14 countries and underwent a psychiatric interview. Participants completed the Patient Health Questionnaire and the Problem Areas in Diabetes scale. Demographic and medical record data were collected. RESULTS: A total of 2783 people with Type 2 diabetes (45.3% men, mean duration of diabetes 8.8 years) participated. Overall, 10.6% were diagnosed with current major depressive disorder and 17.0% reported moderate to severe levels of depressive symptomatology (Patient Health Questionnaire scores >9). Multivariable analyses showed that, after controlling for country, current major depressive disorder was significantly associated with gender (women) (P<0.0001), a lower level of education (P<0.05), doing less exercise (P<0.01), higher levels of diabetes distress (P<0.0001) and a previous diagnosis of major depressive disorder (P<0.0001). The proportion of those with either current major depressive disorder or moderate to severe levels of depressive symptomatology who had a diagnosis or any treatment for their depression recorded in their medical records was extremely low and non-existent in many countries (0-29.6%). CONCLUSIONS: Our international study, the largest of this type ever undertaken, shows that people with diabetes frequently have depressive disorders and also significant levels of depressive symptoms. Our findings indicate that the identification and appropriate care for psychological and psychiatric problems is not the norm and suggest a lack of the comprehensive approach to diabetes management that is needed to improve clinical outcomes.

Intratumoural evolutionary landscape of high-risk prostate cancer: the PROGENY study of genomic and immune parameters.

BACKGROUND: Intratumoural heterogeneity (ITH) is well recognised in prostate cancer (PC), but its role in high-risk disease is uncertain. A prospective, single-arm, translational study using targeted multiregion prostate biopsies was carried out to study genomic and T-cell ITH in clinically high-risk PC aiming to identify drivers and potential therapeutic strategies. PATIENTS AND METHODS: Forty-nine men with elevated prostate-specific antigen and multiparametric-magnetic resonance imaging detected PC underwent image-guided multiregion transperineal biopsy. Seventy-nine tumour regions from 25 patients with PC underwent sequencing, analysis of mutations, copy number and neoepitopes combined with tumour infiltrating T-cell subset quantification. RESULTS: We demonstrated extensive somatic nucleotide variation and somatic copy number alteration heterogeneity in high-risk PC. Overall, the mutational burden was low (0.93/Megabase), but two patients had hypermutation, with loss of mismatch repair (MMR) proteins, MSH2 and MSH6. Somatic copy number alteration burden was higher in patients with metastatic hormone-naive PC (mHNPC) than in those with high-risk localised PC (hrlPC), independent of Gleason grade. Mutations were rarely ubiquitous and mutational frequencies were similar for mHNPC and hrlPC patients. Enrichment of focal 3q26.2 and 3q21.3, regions containing putative metastasis drivers, was seen in mHNPC patients. We found evidence of parallel evolution with three separate clones containing activating mutations of ß-catenin in a single patient. We demonstrated extensive intratumoural and intertumoural T-cell heterogeneity and high inflammatory infiltrate in the MMR-deficient (MMRD) patients and the patient with parallel evolution of ß-catenin. Analysis of all patients with activating Wnt/ß-catenin mutations demonstrated a low CD8+/FOXP3+ ratio, a potential surrogate marker of immune evasion. CONCLUSIONS: The PROGENY (PROstate cancer GENomic heterogeneitY) study provides a diagnostic platform suitable for studying tumour ITH. Genetic aberrations in clinically high-risk PC are associated with altered patterns of immune infiltrate in tumours. Activating mutations of Wnt/ß-catenin signalling pathway or MMRD could be considered as potential biomarkers for immunomodulation therapies. CLINICAL TRIALS.GOV IDENTIFIER: NCT02022371.

The Prevalence of Clinically Significant Prostate Cancer According to Commonly Used Histological Thresholds in Men Undergoing Template Prostate Mapping Biopsies.

PURPOSE: Transrectal prostate biopsies are inaccurate and, thus, the prevalence of clinically significant prostate cancer in men undergoing biopsy is unknown. We determined the ability of different histological thresholds to denote clinically significant cancer in men undergoing a more accurate biopsy, that of transperineal template prostate mapping. MATERIALS AND METHODS: In this multicenter, cross-sectional cohort of men who underwent template prostate mapping biopsies between May 2006 and January 2012, 4 different thresholds of significance combining tumor grade and burden were used to measure the consequent variation with respect to the prevalence of clinically significant disease. RESULTS: Of 1,203 men 17% (199) had no previous biopsy, 38% (455) had a prior negative transrectal ultrasound biopsy, 24% (289) were on active surveillance and 21% (260) were seeking risk stratification. Mean patient age was 63.5 years (SD 7.6) and median prostate specific antigen was 7.4 ng/ml (IQR 5.3-10.5). Overall 35% of the patients (424) had no cancer detected. The prevalence of clinically significant cancer varied between 14% and 83% according to the histological threshold used, in particular between 30% and 51% among men who had no previous biopsy, between 14% and 27% among men who had a prior negative biopsy, between 36% and 74% among men on active surveillance, and between 47% and 83% among men seeking risk stratification. CONCLUSIONS: According to template prostate mapping biopsy between 1 in 2 and 1 in 3 men have prostate cancer that is histologically defined as clinically significant. This suggests that the commonly used thresholds may be set too low.

Mental Health Assessment of Health Care Providers of Bangladesh during Covid-19 Pandemic: A Cross-Sectional Web-Based Study.

SARS COV 2 raised immense agony to everyone. As health care workers remains direct contact with patients, they are vulnerable to mental health disorder. The study was done to identify mental health status of health care providers of Bangladesh. It was a cross sectional web based survey among health care providers of bangladesh. A structured web based questionnaire was prepared both in Bangla and English version for better understanding. Total 2594 health care workers responded to online survey. Male were 1303(50.2%) and female were 1291(49.8%). Occupational demography shows 98.5% were physicians. Mean value of patient health questionnaire 9 (PHQ9) and generalized anxiety disorder (GAD) were 8.43±6.082 and 8.27±5.234 respectively among healthcare providers. To overcome anxiety and depression, 93.4% of HCW didn't receive any psychological material and 85.6% HCW didn't find physiological resources even through media. Despite many lacking, healthcare workers were resilient in our study.

Role of focal salvage ablative therapy in localised radiorecurrent prostate cancer.

Up to one-third of men can fail radical external beam radiotherapy for primary prostate cancer. Most of these men have expectant management with delayed hormones. However, around half of these men have localised recurrence. Challenges remain in identifying such men accurately, in order to enable them to undergo local salvage therapy which is potentially curative. Currently, this includes radical prostatectomy, brachytherapy and ablative whole-gland therapies, such as cryotherapy and high intensity focused ultrasound, all of which can carry significant morbidity. New approaches may involve targeting the area of recurrence alone--focal salvage therapy--in order to reduce tissue damage and thus reduce morbidity. This requires accurate localisation of intraprostatic recurrent disease and precision targeted ablation.

Fine mapping of QTLs for rice grain yield under drought reveals sub-QTLs conferring a response to variable drought severities.

Fine-mapping studies on four QTLs, qDTY(2.1), qDTY(2.2), qDTY(9.1) and qDTY(12.1), for grain yield (GY) under drought were conducted using four different backcross-derived populations screened in 16 experiments from 2006 to 2010. Composite and bayesian interval mapping analyses resolved the originally identified qDTY(2.1) region of 42.3 cM into a segment of 1.6 cM, the qDTY(2.2) region of 31.0 cM into a segment of 6.7 cM, the qDTY(9.1) region of 32.1 cM into two segments of 9.4 and 2.4 cM and the qDTY(12.1) region of 10.6 cM into two segments of 3.1 and 0.4 cM. Two of the four QTLs (qDTY(9.1) and qDTY(12.1)) having effects under varying degrees of stress severity showed the presence of more than one region within the original QTL. The study found the presence of a donor allele at RM262 within qDTY(2.1) and RM24334 within qDTY(9.1) showing a negative effect on GY under drought, indicating the necessity of precise fine mapping of QTL regions before using them in marker-assisted selection (MAS). However, the presence of sub-QTLs together in close vicinity to each other provides a unique opportunity to breeders to introgress such regions together as a unit into high-yielding drought-susceptible varieties through MAS.

Emotional and Behavioural Changes in Children and Adolescents and Their Association With Parental Depression During COVID-19 Pandemic: a Pilot Study in Bangladesh.

OBJECTIVE: The COVID-19 pandemic has affected the mental health of children, adolescents, and their parents. This study aimed to assess the emotional and behavioural changes in children and adolescents and their association with parental depression during the COVID-19 pandemic in Bangladesh. METHODS: On 7 May 2020 during COVID-19 lockdown, an online questionnaire was distributed through social media and made available for 10 days. Data were collected from parents of children aged 4 to 17 years. The Bangla version of the parent-rated version of the Strengths and Difficulties Questionnaire (SDQ) was used to determine the behavioural and emotional disturbances of the children and adolescents. The Bangla version of the Patient Health Questionnaire (PHQ-9) was used to assess the depression status of parents. RESULTS: There were 512 participants. 21.5% of children and adolescents had emotional and behavioural problems. More boys than girls had abnormal peer relationship problems (21.1% vs 15.4%, p = 0.03). Of the parents, 16.2% had moderate depression, 5.5% moderately severe depression, and 2.9% severe depression. 8.2% and 2.9% of parents reported that it was very difficult and extremely difficult, respectively, to do work, take care of things at home, or get along with other people; the proportion was higher in mothers than fathers (χ2 = 11.4, df = 3, p = 0.01). The PHQ-9 total score of parents mildly correlated with the SDQ score of children and adolescents (r = 0.51, p = 0.01). In multiple linear regression, a combination of parent sex (ß = 0.08, p < 0.001), child's history of developmental/psychiatric problems (ß = 0.02, p = 0.67), and the SDQ total score of children and adolescents (ß = 0.52, p = 0.03) accounted for 27% of the variability in PHQ total score of parents. CONCLUSION: During lockdown, the prevalence of psychiatric disorder among children and adolescents and their parents increased. The depression status of parents mildly correlated with the behavioural and emotional disturbances of children and adolescents. We recommend opening the schools as soon as the situation improves and developing interventions such as virtual mental health assessment for children and adolescents and their parents.

Diagnostic accuracy of magnetic resonance imaging targeted biopsy techniques compared to transrectal ultrasound guided biopsy of the prostate: a systematic review and meta-analysis.

BACKGROUND: Multiparametric MRI localizes cancer in the prostate, allowing for MRI guided biopsy (MRI-GB) 43 alongside transrectal ultrasound-guided systematic biopsy (TRUS-GB). Three MRI-GB approaches exist; visual estimation (COG-TB); fusion software-assisted (FUS-TB) and MRI 'in-bore' biopsy (IB-TB). It is unknown whether any of these are superior. We conducted a systematic review and meta-analysis to address three questions. First, whether MRI-GB is superior to TRUS-GB at detecting clinically significant PCa (csPCa). Second, whether MRI-GB is superior to TRUS-GB at avoiding detection of insignificant PCa. Third, whether any MRI-GB strategy is superior at detecting csPCa. METHODS: A systematic literature review from 2015 to 2019 was performed in accordance with the START recommendations. Studies reporting PCa detection rates, employing MRI-GB and TRUS-GB were included and evaluated using the QUADAS-2 checklist. 1553 studies were found, of which 43 were included in the meta-analysis. RESULTS: For csPCa, MRI-GB was superior in detection to TRUS-GB (0.83 vs. 0.63 [p = 0.02]). MRI-GB was superior in detection to TRUS-GB at avoiding detection of insignificant PCa. No MRI-GB technique was superior at detecting csPCa (IB-TB 0.87; COG TB 0.81; FUS-TB 0.81, [p = 0.55]). There was significant heterogeneity observed between the included studies. CONCLUSIONS: In patients with suspected PCa on MRI, MRI-GB offers superior rates of csPCa detection and reduces detection of insignificant PCa compared to TRUS-GB. No individual MRI-GB technique was found to be better in csPCa detection. Prospective adequately powered randomized controlled trials are required.

Meta-analysis of grain yield QTL identified during agricultural drought in grasses showed consensus.

BACKGROUND: In the last few years, efforts have been made to identify large effect QTL for grain yield under drought in rice. However, identification of most precise and consistent QTL across the environments and genetics backgrounds is essential for their successful use in Marker-assisted Selection. In this study, an attempt was made to locate consistent QTL regions associated with yield increase under drought by applying a genome-wide QTL meta-analysis approach. RESULTS: The integration of 15 maps resulted in a consensus map with 531 markers and a total map length of 1821 cM. Fifty-three yield QTL reported in 15 studies were projected on a consensus map and meta-analysis was performed. Fourteen meta-QTL were obtained on seven chromosomes. MQTL1.2, MQTL1.3, MQTL1.4, and MQTL12.1 were around 700 kb and corresponded to a reasonably small genetic distance of 1.8 to 5 cM and they are suitable for use in marker-assisted selection (MAS). The meta-QTL for grain yield under drought coincided with at least one of the meta-QTL identified for root and leaf morphology traits under drought in earlier reports. Validation of major-effect QTL on a panel of random drought-tolerant lines revealed the presence of at least one major QTL in each line. DTY12.1 was present in 85% of the lines, followed by DTY4.1 in 79% and DTY1.1 in 64% of the lines. Comparative genomics of meta-QTL with other cereals revealed that the homologous regions of MQTL1.4 and MQTL3.2 had QTL for grain yield under drought in maize, wheat, and barley respectively. The genes in the meta-QTL regions were analyzed by a comparative genomics approach and candidate genes were deduced for grain yield under drought. Three groups of genes such as stress-inducible genes, growth and development-related genes, and sugar transport-related genes were found in clusters in most of the meta-QTL. CONCLUSIONS: Meta-QTL with small genetic and physical intervals could be useful in Marker-assisted selection individually and in combinations. Validation and comparative genomics of the major-effect QTL confirmed their consistency within and across the species. The shortlisted candidate genes can be cloned to unravel the molecular mechanism regulating grain yield under drought.

Focal therapy for localized prostate cancer: a phase I/II trial.

PURPOSE: Men with localized prostate cancer currently face a number of treatment options that treat the entire prostate. These can cause significant sexual and urinary side effects. Focal therapy offers a novel strategy that targets the cancer rather than the prostate in an attempt to preserve tissue and function. MATERIALS AND METHODS: A prospective, ethics committee approved trial was conducted to determine the side effects of focal therapy using high intensity focused ultrasound. Multiparametric magnetic resonance imaging (T2-weighted, dynamic contrast enhanced, diffusion-weighted) and template transperineal prostate mapping biopsies were used to identify unilateral disease. Genitourinary side effects and quality of life outcomes were assessed using validated questionnaires. Posttreatment biopsies were performed at 6 months and followup was completed to 12 months. RESULTS: A total of 20 men underwent high intensity focused ultrasound hemiablation. Mean age was 60.4 years (SD 5.4, range 50 to 70) with mean prostate specific antigen 7.3 ng/ml (SD 2.8, range 3.4 to 11.8). Of the men 25% had low risk and 75% had intermediate risk cancer. Return of erections sufficient for penetrative sex occurred in 95% of men (19 of 20). In addition, 90% of men (18 of 20) were pad-free, leak-free continent while 95% were pad-free. Mean prostate specific antigen decreased 80% to 1.5 ng/ml (SD 1.3) at 12 months. Of the men 89% (17 of 19, 1 refused biopsy) had no histological evidence of any cancer, and none had histological evidence of high volume or Gleason 7 or greater cancer in the treated lobe. In addition, 89% of men achieved the trifecta status of pad-free, leak-free continence, erections sufficient for intercourse and cancer control at 12 months. CONCLUSIONS: Our results appear sufficiently promising to support the further evaluation of focal therapy as a strategy to decrease some of the harms and costs associated with standard whole gland treatments.

A systematic review and meta-analysis of the diagnostic accuracy of biparametric prostate MRI for prostate cancer in men at risk.

INTRODUCTION: Multiparametric magnetic resonance imaging (mpMRI), the use of three multiple imaging sequences, typically T2-weighted, diffusion weighted (DWI) and dynamic contrast enhanced (DCE) images, has a high sensitivity and specificity for detecting significant cancer. Current guidance now recommends its use prior to biopsy. However, the impact of DCE is currently under debate regarding test accuracy. Biparametric MRI (bpMRI), using only T2 and DWI has been proposed as a viable alternative. We conducted a contemporary systematic review and meta-analysis to further examine the diagnostic performance of bpMRI in the diagnosis of any and clinically significant prostate cancer. METHODS: A systematic review of the literature from 01/01/2017 to 06/07/2019 was performed by two independent reviewers using predefined search criteria. The index test was biparametric MRI and the reference standard whole-mount prostatectomy or prostate biopsy. Quality of included studies was assessed by the QUADAS-2 tool. Statistical analysis included pooled diagnostic performance (sensitivity; specificity; AUC), meta-regression of possible covariates and head-to-head comparisons of bpMRI and mpMRI where both were performed in the same study. RESULTS: Forty-four articles were included in the analysis. The pooled sensitivity for any cancer detection was 0.84 (95% CI, 0.80-0.88), specificity 0.75 (95% CI, 0.68-0.81) for bpMRI. The summary ROC curve yielded a high AUC value (AUC = 0.86). The pooled sensitivity for clinically significant prostate cancer was 0.87 (95% CI, 0.78-0.93), specificity 0.72 (95% CI, 0.56-0.84) and the AUC value was 0.87. Meta-regression analysis revealed no difference in the pooled diagnostic estimates between bpMRI and mpMRI. CONCLUSIONS: This meta-analysis on contemporary studies shows that bpMRI offers comparable test accuracies to mpMRI in detecting prostate cancer. These data are broadly supportive of the bpMRI approach but heterogeneity does not allow definitive recommendations to be made. There is a need for prospective multicentre studies of bpMRI in biopsy naïve men.

PROState Pathway Embedded Comparative Trial: The IP3-PROSPECT study.

INTRODUCTION: The traditional double blind RCT is the 'gold standard' trial design. For a variety of reasons, these designs often fail to accrue enough participants to conclude. This is particularly challenging in localized prostate cancer. The cohort multiple randomised controlled trial (cmRCT) trial design may represent an alternative approach to delivering robust comparative data in prostate cancer. PATIENTS AND METHODS: IP3-PROSPECT is a cmRCT designed to test multiple prostate cancer interventions from eligible men in one cohort. Key to the design is two points of consent. First, at point of consent one, men referred for prostate cancer investigations are invited to join the cohort. They may then be randomly invited at a later date to consider an intervention at point of consent two. In the pilot phase we will test the acceptability and feasibility of developing the cohort. RESULTS: Acceptability and feasibility of the study will be measured by a combination of quantitative and qualitative methods. The primary outcome measure is the rate of consent to inclusion to the IP3-PROSPECT cohort. Secondary outcome measures include the completeness of data collection at sites and return rates of patient questionnaires. We will also interview patients and healthcare professionals to explore their thoughts on the implementation, practicality and efficiency of IP3-PROSPECT. CONCLUSION: The IP3-PROSPECT study will evaluate the cmRCT design in prostate cancer. Initially we will pilot the design, assessing for acceptability and feasibility. The cmRCT is an innovative design that offers potential for building a modern comparative evidence base for prostate cancer.

Relatedness of Macrophomina phaseolina isolates from tallgrass prairie, maize, soybean and sorghum.

Agricultural and wild ecosystems may interact through shared pathogens such as Macrophomina phaseolina, a generalist clonal fungus with more than 284 plant hosts that is likely to become more important under climate change scenarios of increased heat and drought stress. To evaluate the degree of subdivision in populations of M. phaseolina in Kansas agriculture and wildlands, we compared 143 isolates from maize fields adjacent to tallgrass prairie, nearby sorghum fields, widely dispersed soybean fields and isolates from eight plant species in tallgrass prairie. Isolate growth phenotypes were evaluated on a medium containing chlorate. Genetic characteristics were analysed based on amplified fragment length polymorphisms and the sequence of the rDNA-internal transcribed spacer (ITS) region. The average genetic similarity was 58% among isolates in the tallgrass prairie, 71% in the maize fields, 75% in the sorghum fields and 80% in the dispersed soybean fields. The isolates were divided into four clusters: one containing most of the isolates from maize and soybean, two others containing isolates from wild plants and sorghum, and a fourth containing a single isolate recovered from Solidago canadensis in the tallgrass prairie. Most of the sorghum isolates had the dense phenotype on media containing chlorate, while those from other hosts had either feathery or restricted phenotypes. These results suggest that the tallgrass prairie supports a more diverse population of M. phaseolina per area than do any of the crop species. Subpopulations show incomplete specialization by host. These results also suggest that inoculum produced in agriculture may influence tallgrass prairie communities, and conversely that different pathogen subpopulations in tallgrass prairie can interact there to generate 'hybrids' with novel genetic profiles and pathogenic capabilities.

Targeted and Systematic Biopsy for the Diagnosis and Management of Prostate Cancer - A Case for Lesion Targeted-Only Biopsies.

For much of the 1990s, transrectal ultrasound systematic biopsy was the standard approach for prostate cancer diagnosis. However, in the past decade multiparametric magnetic resonance imaging, multiparametric ultrasound and image fusion targeting have come to the fore. Here we present the state-of-the-art diagnostic strategies in prostate cancer detection and examine the case for target-only biopsy, as well as the benefits and limitations.