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Frontiers in Immunology 2023Prostatitis is an inflammatory disease of the prostate gland, which affects 2-16% of men worldwide and thought to be a cause for prostate cancer (PCa) development....
BACKGROUND
Prostatitis is an inflammatory disease of the prostate gland, which affects 2-16% of men worldwide and thought to be a cause for prostate cancer (PCa) development. Carcinoembryogenic antigen-related cell adhesion molecules (CEACAMs) are deregulated in inflammation and in PCa. The role of CEACAMs in prostate inflammation and their possible contribution to the malignant transformation of prostate epithelial cells is still elusive. In this study, we investigated the expression of CEACAMs in an prostatitis model and their potential role in malignant transformation of prostate epithelial cells.
METHODS
Normal prostate epithelial RWPE-1 cells were treated with pro-inflammatory cytokines to achieve an inflammatory state of the cells. The expression of CEACAMs and their related isoforms were analyzed. Additionally, the expression levels of selected CEACAMs were correlated with the expression of malignancy markers and the migratory properties of the cells.
RESULTS
This study demonstrates that the pro-inflammatory cytokines, tumor necrosis factor alpha (TNFα) and interferon-gamma (IFNγ), induce synergistically an up-regulation of CEACAM1 expression in RWPE-1 cells, specifically favoring the CEACAM1-L isoform. Furthermore, overexpressed CEACAM1-L is associated with the deregulated expression of JAK/STAT, NFκB, and epithelial-mesenchymal transition (EMT) genes, as well as an increased cell migration.
CONCLUSION
We postulate that CEACAM1 isoform CEACAM1-4L may synergistically contribute to inflammation-induced oncogenesis in the prostate.
Topics: Male; Humans; Prostatitis; Prostate; Inflammation; Tumor Necrosis Factor-alpha; Transcription Factors; Cell Transformation, Neoplastic; Cytokines
PubMed: 37691945
DOI: 10.3389/fimmu.2023.1236343 -
Korean Journal of Radiology Nov 2023To elucidate the use of radiological studies, including nuclear medicine, and biopsy for the diagnosis and staging of prostate cancer (PCA) in clinical practice and...
OBJECTIVE
To elucidate the use of radiological studies, including nuclear medicine, and biopsy for the diagnosis and staging of prostate cancer (PCA) in clinical practice and understand the current status of PCA in Asian countries via an international survey.
MATERIALS AND METHODS
The Asian Prostate Imaging Working Group designed a survey questionnaire with four domains focused on prostate magnetic resonance imaging (MRI), other prostate imaging, prostate biopsy, and PCA backgrounds. The questionnaire was sent to 111 members of professional affiliations in Korea, Japan, Singapore, and Taiwan who were representatives of their working hospitals, and their responses were analyzed.
RESULTS
This survey had a response rate of 97.3% (108/111). The rates of using 3T scanners, antispasmodic agents, laxative drugs, and prostate imaging-reporting and data system reporting for prostate MRI were 21.6%-78.9%, 22.2%-84.2%, 2.3%-26.3%, and 59.5%-100%, respectively. Respondents reported using the highest b-values of 800-2000 sec/mm² and fields of view of 9-30 cm. The prostate MRI examinations per month ranged from 1 to 600, and they were most commonly indicated for biopsy-naïve patients suspected of PCA in Japan and Singapore and staging of proven PCA in Korea and Taiwan. The most commonly used radiotracers for prostate positron emission tomography are prostate-specific membrane antigen in Singapore and fluorodeoxyglucose in three other countries. The most common timing for prostate MRI was before biopsy (29.9%). Prostate-targeted biopsies were performed in 63.8% of hospitals, usually by MRI-ultrasound fusion approach. The most common presentation was localized PCA in all four countries, and it was usually treated with radical prostatectomy.
CONCLUSION
This survey showed the diverse technical details and the availability of imaging and biopsy in the evaluation of PCA. This suggests the need for an educational program for Asian radiologists to promote standardized evidence-based imaging approaches for the diagnosis and staging of PCA.
Topics: Male; Humans; Prostate; Prostate-Specific Antigen; Image-Guided Biopsy; Prostatic Neoplasms; Biopsy; Magnetic Resonance Imaging; Positron Emission Tomography Computed Tomography
PubMed: 37899520
DOI: 10.3348/kjr.2023.0644 -
Current Urology Reports Oct 2023Prostate ablation is increasingly being utilized for the management of localized prostate cancer. There are several energy modalities with varying mechanism of actions... (Review)
Review
PURPOSE OF REVIEW
Prostate ablation is increasingly being utilized for the management of localized prostate cancer. There are several energy modalities with varying mechanism of actions which are currently used for prostate ablation. Prostate ablations, whether focal or whole gland, are performed under ultrasound and/or MRI guidance for appropriate treatment plan execution and monitoring. A familiarity with different intraoperative imaging findings and expected tissue response to these ablative modalities is paramount. In this review, we discuss the intraoperative, early, and delayed imaging findings in prostate from the effects of prostate ablation.
RECENT FINDINGS
The monitoring of ablation both during and after the therapy became increasingly important due to the precise targeting of the target tissue. Recent findings suggest that real-time imaging techniques such as MRI or ultrasound can provide anatomical and functional information, allowing for precise ablation of the targeted tissue and increasing the effectiveness and precision of prostate cancer treatment. While intraprocedural imaging findings are variable, the follow-up imaging demonstrates similar findings across various energy modalities. MRI and ultrasound are two of the frequently used imaging techniques for intraoperative monitoring and temperature mapping of important surrounding structures. Follow-up imaging can provide valuable information about ablated tissue, including the success of the ablation, presence of residual cancer or recurrence after the ablation. It is critical and helpful to understand the imaging findings during the procedure and at different follow-up time periods to evaluate the procedure and its outcome.
Topics: Humans; Male; Magnetic Resonance Imaging; Prostate; Prostatic Neoplasms; Ultrasonography; Ablation Techniques
PubMed: 37421582
DOI: 10.1007/s11934-023-01175-4 -
Phytomedicine : International Journal... Jan 2024Astaxanthin (AST) is a natural compound with anti-inflammatory/immunomodulatory properties that has been found to have probiotic properties. However, the role and...
BACKGROUND
Astaxanthin (AST) is a natural compound with anti-inflammatory/immunomodulatory properties that has been found to have probiotic properties. However, the role and mechanism of AST in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still not fully understood.
PURPOSE
The aim of this study was to evaluate the effect of AST on CP/CPPS and elucidate the mediating role of the gut microbiota.
MATERIALS AND METHODS
An experimental autoimmune prostatitis (EAP) mouse model was utilized to test the potential role of AST on CP/CPPS. Antibiotic cocktail (ABX) treatment and fecal microbiota transplantation (FMT) were used to elucidate the gut microbiota-mediated effects on AST. In addition, 16S rRNA gene sequencing and qRT-PCR analyses were used to analyze changes in the gut microbiota of EAP mice and CP/CPPS patients. Finally, the mechanism by which AST exerts a protective effect on CP/CPPS was explored by untargeted metabolomics and gut barrier function assays.
RESULTS
Oral administration of AST reduced prostate inflammation scores, alleviated tactile sensitization of the pelvic region in EAP mice, reduced CD4+ T cell and CD68+ macrophage infiltration in the prostatic interstitium, and inhibited the up-regulation of systemic and localized pain/pro-inflammatory mediators in the prostate. After ABX, the protective effect of AST against CP/CPPS was attenuated, whereas colonization with fecal bacteria from AST-treated EAP mice alleviated CP/CPPS. 16S rRNA gene sequencing and qRT-PCR analyses showed that Akkermansia muciniphila in the feces of EAP mice and CP/CPPS patients showed a trend toward a decrease, which was associated with poor progression of CP/CPPS. In contrast, oral administration of AST increased the relative abundance of A. muciniphila, and oral supplementation with A. muciniphila also alleviated inflammation and pain in EAP mice. Finally, we demonstrated that both AST and A. muciniphila interventions increased serum levels of SCFAs acetate, up-regulated expression of colonic tight junction markers, and decreased serum lipopolysaccharide levels in EAP mice.
CONCLUSION
Our results showed that AST improved CP/CPPS by up-regulating A. muciniphila, which provides new potentially effective strategies and ideas for CP/CPPS management.
Topics: Humans; Male; Mice; Animals; Prostatitis; RNA, Ribosomal, 16S; Inflammation; Pelvic Pain; Intestines; Chronic Pain; Akkermansia; Xanthophylls
PubMed: 38056144
DOI: 10.1016/j.phymed.2023.155249 -
Prostate Cancer and Prostatic Diseases Jun 2024
Review
Topics: Humans; Prostatitis; Pelvic Pain; Male; Chronic Pain; Chronic Disease; Syndrome
PubMed: 36631538
DOI: 10.1038/s41391-023-00645-7 -
Radiotherapy and Oncology : Journal of... Dec 2023Prostate cancer patients treated with radiotherapy are susceptible to acute gastrointestinal (GI) toxicity due to substantial overlap of the intestines with the...
BACKGROUND
Prostate cancer patients treated with radiotherapy are susceptible to acute gastrointestinal (GI) toxicity due to substantial overlap of the intestines with the radiation volume. Due to their intimate relationship with GI toxicity, faecal microbiome and metabolome dynamics during radiotherapy were investigated.
MATERIAL & METHODS
This prospective study included 50 prostate cancer patients treated with prostate (bed) only radiotherapy (PBRT) (n = 28) or whole pelvis radiotherapy (WPRT) (n = 22) (NCT04638049). Longitudinal sampling was performed prior to radiotherapy, after 10 fractions, near the end of radiotherapy and at follow-up. Patient symptoms were dichotomized into a single toxicity score. Microbiome and metabolome fingerprints were analyzed by 16S rRNA gene sequencing and ultra-high-performance liquid chromatography hybrid high-resolution mass spectrometry, respectively.
RESULTS
The individual α-diversity did not significantly change over time. Microbiota composition (β-diversity) changed significantly over treatment (PERMANOVA p-value = 0.03), but there was no significant difference in stability when comparing PBRT versus WPRT. Levels of various metabolites were significantly altered during radiotherapy. Baseline α-diversity was not associated with any toxicity outcome. Based on the metabolic fingerprint, no natural clustering according to toxicity profile could be achieved.
CONCLUSIONS
Radiation dose and treatment volume demonstrated limited effects on microbiome and metabolome fingerprints. In addition, no distinctive signature for toxicity status could be established. There is an ongoing need for toxicity risk stratification tools for diagnostic and therapeutic purposes, but the current evidence implies that the translation of metabolic and microbial biomarkers into routine clinical practice remains challenging.
Topics: Male; Humans; Prospective Studies; RNA, Ribosomal, 16S; Prostatic Neoplasms; Prostate; Metabolome
PubMed: 37827280
DOI: 10.1016/j.radonc.2023.109950 -
Radiology Dec 2023
Topics: Male; Humans; Prostate; Prostatic Hyperplasia; Cost-Benefit Analysis; Embolization, Therapeutic; Arteries; Treatment Outcome; Lower Urinary Tract Symptoms
PubMed: 38085086
DOI: 10.1148/radiol.233162 -
European Urology Oncology Dec 2023It is unclear whether a magnetic resonance imaging (MRI)-targeted transperineal (TP) biopsy can improve the detection of clinically significant prostate cancer (csPCa). (Meta-Analysis)
Meta-Analysis Review
Is There an Impact of Transperineal Versus Transrectal Magnetic Resonance Imaging-targeted Biopsy in Clinically Significant Prostate Cancer Detection Rate? A Systematic Review and Meta-analysis.
CONTEXT
It is unclear whether a magnetic resonance imaging (MRI)-targeted transperineal (TP) biopsy can improve the detection of clinically significant prostate cancer (csPCa).
OBJECTIVE
To compare the MRI-targeted TP and transrectal (TR) approaches for csPCa detection.
EVIDENCE ACQUISITION
A literature search was conducted using the PubMed/Medline, Embase, and Web of Science databases to identify reports published until February 2023. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed to identify eligible studies. The primary outcome was the detection of csPCa (Gleason grade group ≥2). Sensitivity analyses were performed to investigate csPCa detection rates according to tumor location, Prostate Imaging Reporting and Data System (PI-RADS) score, and type of fusion (cognitive or software based).
EVIDENCE SYNTHESIS
Eleven studies met our inclusion criteria, and data from 3522 and 5140 patients who underwent, respectively, TR and TP MRI-targeted biopsies were reviewed. No statistically significant difference in the detection of csPCa was observed between the TR and TP approaches (odds ratio [OR] 1.11, 95% confidence interval [CI] 0.98-1.25; p = 0.1). When stratifying patients according to lesion location, the TP approach was associated with higher csPCa detection in case of anterior (OR 2.17, 95% CI 1.46-3.22; p < 0.001) and apical (OR 1.86, 95% CI 1.14-3.03; p = 0.01) lesions. In the subgroup analysis based on PI-RADS score, the TP approach was associated with higher csPCa detection (OR 1.57, 95% CI 1.07-2.29; p = 0.02) in PI-RADS 4 lesions. Conversely, no difference was found in PI-RADS 3 and 5 lesions (p > 0.05). The main limitation was the retrospective design of most included studies.
CONCLUSIONS
No significant association was found between the prostate biopsy approach and csPCa detection rate when we considered all biopsy indications. The TP approach provides a detection advantage in anterior and apical tumors, arguing for a preferred use of the TP approach in these lesion locations.
PATIENT SUMMARY
The transperineal magnetic resonance imaging-targeted prostate biopsy approach appears to be more effective only for selected lesions. No clear benefit was seen for the transperineal approach in the overall population.
Topics: Male; Humans; Prostatic Neoplasms; Prostate; Magnetic Resonance Imaging; Retrospective Studies; Biopsy
PubMed: 37634971
DOI: 10.1016/j.euo.2023.08.001 -
JAMA Network Open Mar 2024Multiple strategies integrating magnetic resonance imaging (MRI) and clinical data have been proposed to determine the need for a prostate biopsy in men with suspected... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Multiple strategies integrating magnetic resonance imaging (MRI) and clinical data have been proposed to determine the need for a prostate biopsy in men with suspected clinically significant prostate cancer (csPCa) (Gleason score ≥3 + 4). However, inconsistencies across different strategies create challenges for drawing a definitive conclusion.
OBJECTIVE
To determine the optimal prostate biopsy decision-making strategy for avoiding unnecessary biopsies and minimizing the risk of missing csPCa by combining MRI Prostate Imaging Reporting & Data System (PI-RADS) and clinical data.
DATA SOURCES
PubMed, Ovid MEDLINE, Embase, Web of Science, and Cochrane Library from inception to July 1, 2022.
STUDY SELECTION
English-language studies that evaluated men with suspected but not confirmed csPCa who underwent MRI PI-RADS followed by prostate biopsy were included. Each study had proposed a biopsy plan by combining PI-RADS and clinical data.
DATA EXTRACTION AND SYNTHESIS
Studies were independently assessed for eligibility for inclusion. Quality of studies was appraised using the Quality Assessment of Diagnostic Accuracy Studies 2 tool and the Newcastle-Ottawa Scale. Mixed-effects meta-analyses and meta-regression models with multimodel inference were performed. Reporting of this study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline.
MAIN OUTCOMES AND MEASURES
Independent risk factors of csPCa were determined by performing meta-regression between the rate of csPCa and PI-RADS and clinical parameters. Yields of different biopsy strategies were assessed by performing diagnostic meta-analysis.
RESULTS
The analyses included 72 studies comprising 36 366 patients. Univariable meta-regression showed that PI-RADS 4 (β-coefficient [SE], 7.82 [3.85]; P = .045) and PI-RADS 5 (β-coefficient [SE], 23.18 [4.46]; P < .001) lesions, but not PI-RADS 3 lesions (β-coefficient [SE], -4.08 [3.06]; P = .19), were significantly associated with a higher risk of csPCa. When considered jointly in a multivariable model, prostate-specific antigen density (PSAD) was the only clinical variable significantly associated with csPCa (β-coefficient [SE], 15.50 [5.14]; P < .001) besides PI-RADS 5 (β-coefficient [SE], 9.19 [3.33]; P < .001). Avoiding biopsy in patients with lesions with PI-RADS category of 3 or less and PSAD less than 0.10 (vs <0.15) ng/mL2 resulted in reducing 30% (vs 48%) of unnecessary biopsies (compared with performing biopsy in all suspected patients), with an estimated sensitivity of 97% (vs 95%) and number needed to harm of 17 (vs 15).
CONCLUSIONS AND RELEVANCE
These findings suggest that in patients with suspected csPCa, patient-tailored prostate biopsy decisions based on PI-RADS and PSAD could prevent unnecessary procedures while maintaining high sensitivity.
Topics: Male; Humans; Magnetic Resonance Imaging; Prostatic Neoplasms; Prostate-Specific Antigen; Prostate; Biopsy
PubMed: 38551559
DOI: 10.1001/jamanetworkopen.2024.4258 -
Urology Oct 2023To identify a subgroup of patients with mast cell dysfunction in chronic prostatitis/chronic pelvic pain syndrome and evaluate efficacy of mast cell-directed therapy.
OBJECTIVE
To identify a subgroup of patients with mast cell dysfunction in chronic prostatitis/chronic pelvic pain syndrome and evaluate efficacy of mast cell-directed therapy.
MATERIALS AND METHODS
Men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) were recruited and evaluated in an open-label, interventional uncontrolled trial after therapy with cromolyn sodium and cetirizine hydrochloride. The primary endpoint was a change in mast cell tryptase concentrations after treatment while secondary endpoints were changes in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and AUA-SI. Isolated cells from postprostatic massage urine were evaluated for immune changes using mRNA expression analysis.
RESULTS
31 patients with a diagnoses of Category III CP/CPPS were consented, 25 patients qualified and 20 completed the study after meeting a prespecified threshold for active tryptase in expressed prostatic secretions. After treatment with cromolyn sodium and cetirizine dihydrochloride for 3-week, active tryptase concentrations were significantly reduced from 49.03±14.05 ug/mL to 25.49±5.48 ug/mL (P<.05). The NIH-CPSI total score was reduced with a mean difference of 5.2±1 along with reduction in the pain, urinary and quality of life subscores (P<.001). A reduction in the AUA-SI was observed following treatment (P<.05). NanoString mRNA analysis of isolated cells revealed downregulation of immune-related pathways including Th1 and Th17 T cell differentiation and TLR signaling. Marked reduction in CD45+ cells and specifically macrophages and neutrophil abundance was observed.
CONCLUSION
Identification of CP/CPPS patients with mast cell dysfunction may be achieved using tryptase as a discriminating biomarker. Mast cell-directed therapy in this targeted subgroup may be effective in reducing symptoms and modulating the immune inflammatory environment.
Topics: Male; Humans; Chronic Pain; Prostatitis; Quality of Life; Mast Cells; Tryptases; Cromolyn Sodium; Th17 Cells; Chronic Disease; Pelvic Pain; RNA, Messenger
PubMed: 37442295
DOI: 10.1016/j.urology.2023.05.047