Integrating MRI for the diagnosis of prostate cancer

Purpose of review We review recent developments in prostate MRI for prostate cancer diagnosis. Recent findings Large series have strengthened the case for the use of MRI prior to subsequent biopsy to maximize the detection of clinically significant disease, and reduce the detection of clinically insignificant disease. This has effectively moved the discussion on from whether MRI is useful in prostate cancer detection to how best to use it, and at which time point. The Prostate Imaging- Reporting And Data System (PIRADS) group have published a second version of the PIRADS criteria for prostate MRI, covering acquisition, interpretation, and reporting both for clinical practice and data collection for research. There is debate about the commonly used and more prescriptive PIRADS system versus the less prescriptive systems based on overall clinical impression of clinically significant disease (e.g. Likert or simplified quantum scoring). Studies suggest that the Likert or simplified quantum scoring approach may outperform PIRADSv2. Published data are conflicting on whether software-assisted fusion of MRI lesions to ultrasound used at biopsy is more effective than visual registration by a trained operator. Summary The use of prostate MRI is increasing worldwide, and the debate now focuses on how best to use it to optimize the detection of clinically significant disease

Impact of Educational Intervention Measures on Knowledge regarding HIV/ Occupational Exposure and Post Exposure Prophylaxis among Final Year Nursing Students of a Tertiary Care Hospital in Central India

Amongst the different Health Care Personnel nurses are at a greater risk of being accidentally exposed to HIV and other Blood Borne Pathogens. The present study was conducted among 50 final year nursing students of a Medical College Hospital to assess the knowledge regarding HIV, occupational exposure and Post Exposure Prophylaxis (PEP) among the students and analyses the impact of educational intervention measures on the issues amongst the study subjects. A Pre-designed and Pre-tested semi-structured questionnaire was used to evaluate the level of knowledge before and after educational intervention sessions. Knowledge regarding risk of transmission of HIV by needle-stick injury and body fluids against which universal precautions were mandatory increased by 72% following the intervention sessions (χ2 = 53.202, p <0.001). 72% and 36% respondents correctly knew the duration within which to start PEP and the drugs available for PEP, post educational sessions 98% and 96% students were aware of it: the difference being statistically significant (χ2 = 11.294, p <0.001) and (χ2 = 37.748, p <0.001) respectively. The mean pre-intervention score was 8.32; mean post-intervention score was 14.40: statistical analysis showed the results to be significant (t= 13.857, p< 0.001). The study reflects that there is a dearth of knowledge among the study group. Incorporating the concerned issues in the academic curriculum to provide the students with adequate knowledge and information during their formative years is needed

HistoScanningTM to Detect and Characterize Prostate Cancer—a Review of Existing Literature

Purpose of Review: The widely acknowledged limitations of the standard prostate cancer (PCa) diagnostic paradigm have provided an impetus to explore novel imaging modalities to diagnose, localize, and risk stratify PCa. As the body of literature focused on HistoScanning™(HS) grows, there is need for a comprehensive review of the clinical efficacy of this technology. Recent Findings: Eighteen original, English language articles were found to adequately study the use of HistoScanning™ for prostate cancer diagnosis in the clinical setting. The articles were found by conducting a bibliographic search of PubMed in April 2017 in addition to utilizing references. The studies are divided into four groups based on study design. Study methods and quantitative data are summarized for each of the relevant articles. The results are synthesized to evaluate the utility of HistoScanning™ for the purpose of diagnosing PCa. Summary: Despite the promise of early pilot studies, there is a lack of consistent results across a number of further investigations of HistoScanning™. This becomes increasingly evident as study size increases. As various other modern diagnostic modalities continue to develop, the future of HistoScanning™, both alone and in conjunction with these technologies, remains unclear

A multicentre randomised controlled trial assessing whether MRI-targeted biopsy is non-inferior to standard transrectal ultrasound guided biopsy for the diagnosis of clinically significant prostate cancer in men without prior biopsy: a study protocol

INTRODUCTION: The classical pathway for the diagnosis of prostate cancer is transrectal ultrasound-guided (TRUS) biopsy of the prostate initiated on the basis of a raised prostate-specific antigen (PSA). An alternative pathway is to perform multi-parametricMRI (MPMRI) to localise cancer and to use this information to influence the decision for, and conduct of, a subsequent biopsy, known as an MPMRI-targeted biopsy. An MPMRI pathway has been shown to detect a similar or greater amount of clinically significant cancer as TRUS biopsy but has several advantages, including the potential to biopsy fewer men with fewer cores. METHODS: This is a pragmatic, international, multicentre, parallel group randomised study in which men are allocated in a 1:1 ratio to an MPMRI or TRUS biopsy pathway. This study will assess whether an MPMRI-targeted biopsy approach is non-inferior to a standard TRUS biopsy approach in the diagnosis of clinically significant cancer.Men in the MRI arm will undergo targeted biopsy of suspicious areas only and no biopsy will be carried out if the MRI is non-suspicious. Men in the TRUS biopsy will undergo a standard 10-12-core TRUS biopsy. The main inclusion criteria are a serum PSA ≤20 ng/mL, a digital rectal examination finding of T2 or less and no prior prostate biopsy.The primary outcome is the proportion of men with clinically significant cancer detected. A sample size of at least 470 patients is required. Key secondary outcomes include the proportion of clinically insignificant cancer detected. ETHICS AND DISSEMINATION: Ethical approval was obtained from the National Research Ethics Committee East Midlands, Leicester (15/EM/0188). Results of this study will be disseminated through national and international papers. The participants and relevant patient support groups will be informed about the results of the study. REGISTRATION DETAILS: NCT02380027; Pre-results

Association Between Multiparametric Magnetic Resonance Imaging of the Prostate and Oncological Outcomes after Primary Treatment for Prostate Cancer: A Systematic Review and Meta-analysis

CONTEXT: The diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) for prostate cancer (PCa) diagnosis has been extensively explored. Little is known about the prognostic value of mpMRI suspicion scores and other quantitative mpMRI information. OBJECTIVE: To systematically review the current literature assessing the relationship between pretreatment mpMRI and oncological outcomes after primary treatment for PCa to assess the role of mpMRI as a prognostic tool. EVIDENCE ACQUISITION: A computerized bibliographic search of MEDLINE/PubMed, EMBASE, Scopus, and the Cochrane Library CENTRAL databases was performed for all studies assessing the relationship between mpMRI and oncological outcomes after primary treatment for PCa. The review protocol is registered in the PROSPERO database (CRD42020209899). EVIDENCE SYNTHESIS: A total of six studies were included. Reliable evidence is still limited in this field. The Prostate Imaging-Reporting and Data System (PI-RADS) score was an independent predictor of biochemical recurrence (BCR) after radical prostatectomy (RP) in the majority of the studies included. The tumor volume at mpMRI was not significantly associated with BCR after RP for PCa. Data on disease progression and PCa-specific mortality are limited. Heterogeneity among the studies was substantial. CONCLUSIONS: The review shows that PI-RADS scores provide information on the future likelihood of cancer recurrence or progression, at least for men undergoing RP. We are of the view that this information should be taken into account to identify men at higher risk of unfavorable outcomes. PATIENT SUMMARY: A higher Prostate Imaging-Reporting and Data System score for magnetic resonance imaging of the prostate seems to be positively associated with oncological failure in prostate cancer and should be incorporated into future risk models

Final Results of a Phase I/II Multicenter Trial of WST11 Vascular Targeted Photodynamic Therapy for Hemi-Ablation of the Prostate in Men with Unilateral Low Risk Prostate Cancer Performed in the United States

PURPOSE: Vascular targeted photodynamic therapy with WST11 (TOOKAD® Soluble) is a form of tissue ablation that may be used therapeutically for localized prostate cancer. To study dosing parameters and associated treatment effects we performed a prospective, multicenter, phase I/II trial of WST11 vascular targeted photodynamic therapy of prostate cancer. MATERIALS AND METHODS: A total of 30 men with unilateral, low volume, Gleason 3 + 3 prostate cancer were enrolled at 5 centers after local institutional review board approval. Light energy, fiber number and WST11 dose were escalated to identify optimal dosing parameters for vascular targeted photodynamic therapy hemi-ablation. Men were treated with photodynamic therapy and evaluated by posttreatment magnetic resonance imaging and biopsy. Prostate specific antigen, light dose index (defined as fiber length/desired treatment volume), toxicity and quality of life parameters were recorded. RESULTS: After dose escalation 21 men received optimized dosing of 4 mg/kg WST11 at 200 J energy. On posttreatment biopsy residual prostate cancer was found in the treated lobe in 10 men, the untreated lobe in 4 and both lobes in 1. At a light dose index of 1 or greater with optimal dosing in 15 men 73.3% had a negative biopsy in the treated lobe. Six men undergoing retreatment with the optimal dose and a light dose index of 1 or greater had a negative posttreatment biopsy. Minimal effects were observed on urinary and sexual function, and overall quality of life. CONCLUSIONS: Hemi-ablation of the prostate with WST11 vascular targeted photodynamic therapy was well tolerated and resulted in a negative biopsy in the treated lobe in the majority of men. Dosing parameters and the light dose index appear related to tissue response as determined by magnetic resonance imaging and biopsy. These parameters may serve as the basis for further prospective studies

The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

Peer reviewedPublisher PD

Chemoprevention of Prostate Cancer with the Polyamine Synthesis Inhibitor Difluoromethylornithine

In vitro and in vivo preclinical results suggest that inhibition of polyamine synthesis inhibits the progression of prostate cancer. These findings has led to two clinical trials in patients at risk for invasive prostate cancer with difluoromethylornithine which specifically and irreversibly inhibits ornithine decarboxylase which catalyses the conversion of ornithine to putrescine the rate limiting step in polyamines synthesis. We have conducted a phase IIa one month and placebo randomized phase IIb 12 months trials in patients at increased risk for invasive prostate cancer. Favorable reduction in prostate polyamine levels and prostate volume was documented with no difference in clinical hearing changes. Patients with Gleason's VI lesions in a surveillance cohort would be appropriate candidates for a definitive risk reduction trial although the unavailability of validated biomarkers for invasive progression would require a large and lengthy study

5-α reductase inhibitors and prostate cancer prevention: where do we turn now?

With the lifetime risk of being diagnosed with prostate cancer so great, an effective chemopreventive agent could have a profound impact on the lives of men. Despite decades of searching for such an agent, physicians still do not have an approved drug to offer their patients. In this article, we outline current strategies for preventing prostate cancer in general, with a focus on the 5-α-reductase inhibitors (5-ARIs) finasteride and dutasteride. We discuss the two landmark randomized, controlled trials of finasteride and dutasteride, highlighting the controversies stemming from the results, and address the issue of 5-ARI use, including reasons why providers may be hesitant to use these agents for chemoprevention. We further discuss the recent US Food and Drug Administration ruling against the proposed new indication for dutasteride and the change to the labeling of finasteride, both of which were intended to permit physicians to use the drugs for chemoprevention. Finally, we discuss future directions for 5-ARI research

Mycobacterium tuberculosis acg Gene Is Required for Growth and Virulence In Vivo

Mycobacterium tuberculosis dosRS two-component regulatory system controls transcription of approximately 50 genes including hspX, acg and Rv2030c, in response to hypoxia and nitric oxide conditions and within macrophages and mice. The hspX lies between acg and Rv2030c. However, the functions of the dosR regulated genes in vitro and in vivo are largely unknown. Previously, we demonstrated that deletion of hspX gene produced a mutant which grew faster in macrophages and in mice. In this study, we attempted to determine the functions of acg and Rv2030c by gene inactivation. We demonstrate that Rv2030c is dispensable for virulence and growth. However, deletion of acg produced a mutant which is attenuated in both resting and activated macrophages and in acute and persistent murine infection models. Surprisingly, deletion of acg did not compromise the viability of the mutant to nitrosative and oxidative stresses in vitro and in vivo. In addition, when the WT and the acg mutants were treated with antibiotics such as the prodrugs nitrofurantoin and nitrofuran, the acg mutant became more sensitive than the WT strain to these drugs. This suggests that Acg may not function as a nitroreductase. These data indicate that acg encodes an essential virulence factor for M. tuberculosis and enables it to grow and survive in macrophages and in mouse organs