Gut microbiome: a novel preventive and therapeutic target for prostatic disease.

The human gut microbiome (GM) impacts various physiological processes and can lead to pathological conditions and even carcinogenesis if homeostasis is disrupted. Recent studies have indicated a connection between the GM and prostatic disease. However, the underlying mechanisms are still unclear. This review aims to provide a summary of the existing information regarding the connection between the GM and various prostatic conditions such as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), benign prostatic hyperplasia (BPH), and prostate cancer (PCa). Furthermore, the review aims to identify possible pathogenic mechanisms and suggest potential ways of targeting GM to prevent and treat prostatic disease. Due to the complexity of the mechanism between GM and prostatic diseases, additional research is required to comprehend the association between the two. This will lead to more effective treatment options for prostatic disease.

Association between cathepsins and benign prostate diseases: a bidirectional two-sample Mendelian randomization study.

Objectives: The relationship between cathepsins and prostate cancer (PCa) has been reported. However, there is a lack of research on cathepsins and benign prostate diseases (BPDs). This study investigated the potential genetic link between cathepsins and BPDs through the utilization of Mendelian randomization (MR) analysis to determine if a causal relationship exists. Methods: Publicly accessible summary statistics on BPDs were obtained from FinnGen Biobank. The data comprised 149,363 individuals, with 30,066 cases and 119,297 controls for BPH, and 123,057 individuals, with 3,760 cases and 119,297 controls for prostatitis. The IEU OpenGWAS provided the Genome-wide association data on ten cathepsins. To evaluate the causal relationship between BPDs and cathepsins, five distinct MR analyses were employed, with the primary method being the inverse variance weighted (IVW) approach. Additionally, sensitivity analyses were conducted to examine the horizontal pleiotropy and heterogeneity of the findings. Results: The examination of IVW MR findings showed that cathepsin O had a beneficial effect on BPH (IVW OR=0.94, 95% CI 0.89-0.98, P=0.0055), while cathepsin X posed a threat to prostatitis (IVW OR=1.08, 95% CI 1.00-1.16, P=0.047). Through reverse MR analysis, it was revealed that prostatitis had an adverse impact on cathepsin V (IVW OR=0.89, 95% CI 0.80-0.99, P=0.035), while no favorable association was observed between BPH and cathepsins. The results obtained from MR-Egger, weighted median, simple mode, and weighted mode methods were consistent with the findings of the IVW approach. Based on sensitivity analyses, heterogeneity, and horizontal pleiotropy are unlikely to distort the results. Conclusion: This study offers the initial evidence of a genetic causal link between cathepsins and BPDs. Our findings revealed that cathepsin O was beneficial in preventing BPH, whereas cathepsin X posed a potential threat to prostatitis. Additionally, prostatitis negatively affected cathepsin V level. These three cathepsins could be targets of diagnosis and treatment for BPDs, which need further research.

Multidrug-resistant Escherichia coli causing canine pyometra and urinary tract infections are genetically related but distinct from those causing prostatic abscesses.

Despite extensive characterisation of uropathogenic Escherichia coli (UPEC) causing urinary tract infections (UTIs), the genetic background of non-urinary extraintestinal pathogenic E. coli (ExPEC) in companion animals remains inadequately understood. In this study, we characterised virulence traits of 104 E. coli isolated from canine pyometra (n = 61) and prostatic abscesses (PAs) (n = 38), and bloodstream infections (BSIs) in dogs (n = 2), and cats (n = 3). A stronger association with UPEC of pyometra strains in comparison to PA strains was revealed. Notably, 44 isolates exhibited resistance to third-generation cephalosporins and/or fluoroquinolones, 15 were extended-spectrum ß-lactamase-producers. Twelve multidrug-resistant (MDR) strains, isolated from pyometra (n = 4), PAs (n = 5), and BSIs (n = 3), along with 7 previously characterised UPEC strains from dogs and cats, were sequenced. Genomic characteristics revealed that MDR E. coli associated with UTIs, pyometra, and BSIs belonged to international high-risk E. coli clones, including sequence type (ST) 38, ST131, ST617, ST648, and ST1193. However, PA strains belonged to distinct lineages, including ST12, ST44, ST457, ST744, and ST13037. The coreSNPs, cgMLST, and pan-genome illustrated intra-clonal variations within the same ST from different sources. The high-risk ST131 and ST1193 (phylogroup B2) contained high numbers of ExPEC virulence genes on pathogenicity islands, predominating in pyometra and UTI. Hybrid MDR/virulence IncF multi-replicon plasmids, containing aerobactin genes, were commonly found in non-B2 phylogroups from all sources. These findings offer genomic insights into non-urinary ExPEC, highlighting its potential for invasive infections in pets beyond UTIs, particularly with regards to high-risk global clones.

Giant Midline Prostatic Cyst: An Unusual Cause of Acute Urinary Retention.

Midline prostatic cysts are infrequent and mostly asymptomatic. We presented a striking case of a giant midline cyst and detailed its diagnosis, evolution, and treatment. From this case, we offered a comparison of congenital intraprostatic midline cysts, namely, Müller's cysts and utricle cysts. A 40-year-old male experienced recurrent urinary retention. A 10 × 11 mm2 cyst in the mid-prostatic region was diagnosed through transrectal ultrasound, leading to a transperineal puncture as a minimally invasive intervention. Seven years later, the cyst recurred, manifesting obstructive symptoms such as a weak urinary stream, frequent urination, and residual urine sensation. Laparoscopic surgery was then performed for the confirmed 98 × 13 mm2 cystic recurrence. The postoperative course was favourable with no complications. Symptoms were completely resolved, which was maintained over a three-year follow-up period. The therapeutic approach to midline cysts targets symptomatic cases or infertility, ranging from cyst puncture to transurethral endoscopic treatment. Recurrence after minimally invasive interventions is a challenge, with laparoscopic surgery as an alternative post-failed conservative approach. Although total cyst removal risks adjacent structure damage, marsupialisation improves the clinical outcomes. In summary, symptomatic midline prostatic cysts present challenges owing to recurrences after minimally invasive approaches. Enhanced laparoscopic techniques offer a solution, particularly in highly symptomatic cases requiring definitive treatment, as illustrated by this outstanding case report.

Feasibility of outpatient daycase local anaesthestic Rezum™ without sedation.

BACKGROUND: Rezum™ is a relatively new bladder outflow obstruction (BOO) procedure that uses thermal energy through water vapour to cause necrosis of prostatic tissue. The standard delivery of this treatment is in an operating theatre under a general or spinal anaesthetic, or under local anaesthetic with sedation that requires patient monitoring. METHODS: We propose an outpatient daycase method of delivering Rezum™ under local anaesthetic without sedation, using a prostatic local anaesthetic block and cold local anaesthetic gel instillation into the urethra. RESULTS: Preliminary results of our first thirteen patients demonstrate the feasibility of this new technique, with a mean pain score of 2.1 out of 10 on a visual analogue scale, a successful trial without catheter in all 13 patients (one patient voided successfully on second trial), a reduction in mean International Prostate Symptom Score (IPSS) from 20.6 to 5.4, and improvement in maximum flow from 8.8 ml/s to 14.4 ml/s. The complications were minor (Clavien-Dindo less than III) and included a UTI, minor bleeding not requiring admission, and retrograde ejaculation. CONCLUSIONS: We demonstrate that an outpatient local anaesthetic daycase service without sedation is feasible. This can be delivered in a clinic setting, reduce waiting times for BOO surgery, and increase availability of operating theatre for other general anaesthetic urological procedures.

Maternal malnutrition associated with postnatal sugar consumption increases inflammatory response and prostate disorders in rat offspring.

Maternal malnutrition can alter developmental biology, programming health and disease in offspring. The increase in sugar consumption during the peripubertal period, a worldwide concern, also affects health through adulthood. Studies have shown that maternal exposure to a low protein diet (LPD) is associated with an increase in prostate disease with aging. However, the combined effects of maternal LPD and early postnatal sugar consumption on offspring prostate disorders were not investigated. The effects on aging were evaluated using a maternal gestational model with lactational LPD (6% protein) and sugar consumption (10%) from postnatal day (PND) 21-90, associating the consequences on ventral prostate (VP) rats morphophysiology on PND540. An increase was shown in mast cells and in the VP of the CTR + SUG and Gestational and Lactational Low Protein (GLLP) groups. In GLLP + SUG, a significant increase was shown in TGF-ß1 expression in both the systemic and intra-prostatic forms, and SMAD2/3p had increased. The study identified maternal LPD and sugar consumption as risk factors for prostatic homeostasis in senility, activating the TGFß1-SMAD2/3 pathway, a signaling pathway with potential markers for prostatic disorders.

Multispecies comparative prostate anatomy by imaging: Implications for experimental models of prostatic disease.

BACKGROUND: There is an increasing interest in using preclinical models for development and assessment of medical devices and imaging techniques for prostatic disease care. Still, a comprehensive assessment of the prostate's radiological anatomy in primary preclinical models such as dogs, rabbits, and mice utilizing human anatomy as a reference point remains necessary with no optimal model for each purpose being clearly defined in the literature. Therefore, this study compares the anatomical characteristics of different animal models to the human prostatic gland from the imaging perspective. METHODS: We imaged five Beagle laboratory dogs, five New Zealand White rabbits, and five mice, all sexually mature males, under Institutional Animal Care and Use Committee (IACUC) approval. Ultrasonography (US) was performed using the Vevo® F2 for mice (57 MHz probe). Rabbits and dogs were imaged using the Siemens® Acuson S3000 (17 MHz probe) and endocavitary (8 MHz) probes, respectively. Magnetic resonance imaging (MRI) was also conducted with a 7T scanner in mice and 3T scanner in rabbits and dogs. RESULTS: Canine transrectal US emerged as the optimal method for US imaging, depicting a morphologically similar gland to humans but lacking echoic zonal differentiation. MRI findings in canines indicated a homogeneously structured gland similar to the human peripheral zone on T2-weighted images (T2W) and apparent diffusion coefficient (ADC). In rabbits, US imaging faced challenges due to the pubic symphysis, whereas MRI effectively visualized all structures with the prostate presenting a similar aspect to the human peripheral gland on T2W and ADC maps. Murine prostate assessment revealed poor visualization of the prostate glands in ultrasound due to its small size, while 7T MRI delineated the distinct prostates and its lobes, with the lateral and dorsal prostate resembling the peripheral zone and the anterior prostate the central zone of the human gland. CONCLUSION: Dogs stand out as superior models for advanced preclinical studies in prostatic disease research. However, mice present as a good model for early stage studies and rabbits are a cost-effective alternative and serve as valuable tools in specific research domains when canine research is not feasible.

Associations between gut microbiota and three prostate diseases: a bidirectional two-sample Mendelian randomization study.

According to previous observational researches and clinical trials, the gut microbiota is related to prostate diseases. However, the potential association between gut microbiota and prostate disorders is still uncertain. We first identified groups of gut microbiota based on the phylum, class, order, family, and genus levels from consortium MiBioGen. And we acquired prostate diseases statistics from the FINNGEN study and PRACTICAL consortium. Next, two-sample Mendelian randomization was used to investigate the potential associations between three prevalent prostate disease and gut microbiota. In addition, we performed a reverse MR analysis and Benjamini-Hochberg (BH) test for further research. We investigated the connection between 196 gut microbiota and three prevalent prostate diseases. We identified 42 nominally significant associations and 2 robust causative links. Upon correction for multiple comparisons using the Benjamini-Hochberg procedure, our analysis revealed a positive correlation between the risk of prostatitis and the presence of the taxonomic order Gastranaerophilales. Conversely, the risk of prostate cancer exhibited an inverse correlation with the presence of the taxonomic class Alphaproteobacteria. Our study revealed the potential association between gut microbiota and prostate diseases. The results may be useful in providing new insights for further mechanistic and clinical studies of prostate diseases.

The role of autophagy in prostate cancer and prostatic diseases: a new therapeutic strategy.

BACKGROUND: Autophagy is a well-conserved catabolic process that plays a key role in cell homeostasis. In the prostate, defective autophagy has been implicated in the genesis and progression of several pathological conditions. AIM: The present review explored the autophagy pathway in prostate-related dysfunctions, focusing on prostate cancer (PCa), benign prostatic hyperplasia (BPH) and prostatitis. RESULTS: Impaired autophagy activity has been shown in animal models of BPH and prostatitis. Moreover, autophagy activation by specific and non-specific drugs improved both conditions in pre-clinical studies. Conversely, the efficacy of autophagy inducers in PCa remains controversial, depending on intrinsic PCa characteristics and stage of progression. Intriguingly, autophagy inhibitors have shown beneficial effects in PCa suppression or even to overcome chemotherapy resistance. However, there are still open questions regarding the upstream mechanisms by which autophagy is deregulated in the prostate and the exact role of autophagy in PCa. The lack of specificity and increased toxicity associated with the currently autophagy inhibitors limits its use clinically, reflecting in reduced number of clinical data. CONCLUSION: New therapeutic strategies to treat prostatic diseases involving new autophagy modulators, combination therapy and new drug formulations should be explored. Understanding the autophagy signaling in each prostatic disease is crucial to determine the best pharmacological approach.

Is imaging accurate enough to detect index lesion in prostate cancer? Analysis of the performance of MRI and other imaging modalities.

Prostate imaging techniques have progressed across the years allowing for a better detection and characterization of prostate cancer (PCa) lesions. These advancements have led to the possibility to also improve and tailor the treatments on the most aggressive lesion, defined as Index Lesion (IL), to reduce morbidity. The IL is, indeed, considered as the entity which encompass the most aggressive features in prostate cancer disease. Multiparametric magnetic resonance imaging (mpMRI) has emerged as the suggested tool to detect the disease and plan treatments, including those under investigation such as focal therapy (FT). Our review aimed to query the literature on the ability of mpMRI in IL detection and to explore the future perspectives in PCa IL diagnosis. A review of the literature was performed from January 2010 to July 2023. All studies investigating the performance of mpMRI and other main imaging techniques able to detect the IL were assessed and evaluated. mpMRI performs well in the detection of IL with a sensitivity which reaches 71% to 94% among the different studies. However, mpMRI seems to have limited sensitivity in the detection of small tumours (<0.5 mL) and low-grade histology lesions. To overcome these limitations other diagnostic imaging techniques have been proposed. Multiparametric Ultrasound has shown results comparable to mpMRI while detecting 4.3% fewer clinically significant PCa (P=0.042). Positron emission tomography-based modalities using PSMA seems to have higher sensitivity than mpMRI, being able to yield from 13.5% to 18.2% additional cancers. MRI has emerged as the recommended tool since most of the IL can be easily identified, and is the imaging of choice while selecting patients for FT. Other imaging modalities has been proposed to improve PCa lesions detection, but results need to be confirmed by ongoing randomized controlled trial.

A novel strategy for the study on molecular mechanism of prostate injury induced by 4,4'-sulfonyldiphenol based on network toxicology analysis.

The study aimed to investigate the underlying molecular mechanisms of prostate injury induced by 4,4'-sulfonyldiphenol (BPS) exposure and propose a novel research strategy to systematically explore the molecular mechanisms of toxicant-induced adverse health effects. By utilizing the ChEMBL, STITCH, and GeneCards databases, a total of 208 potential targets associated with BPS exposure and prostate injury were identified. Through screening the potential target network in the STRING database and Cytoscape software, we determined 21 core targets including AKT1, EGFR, and MAPK3. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses conducted through the DAVID database illustrated that the potential targets of BPS in prostatic toxicity were primarily enriched in cancer signaling pathways and calcium signaling pathways. These findings suggest that BPS may actively participate in the occurrence and development of prostate inflammation, prostatic hyperplasia, prostate cancer, and other aspects of prostate injury by regulating prostate cancer cell apoptosis and proliferation, activating inflammatory signaling pathways, and modulating prostate adipocytes and fibroblasts. This research provides a theoretical basis for understanding the molecular mechanism of underlying BPS-induced prostatic toxicity and establishes a foundation for the prevention and treatment of prostatic diseases associated with exposure to plastic products containing BPS and certain BPS-overwhelmed environments.

Prostatic abscess due to carbapenem-resistant K. pneumonia: A case report.

RATIONALE: Due to the widespread use of broad-spectrum antibiotics, the morbidity of prostate abscesses (PA) has declined dramatically. However, under special circumstances, such as invasive procedures and immunosuppressive conditions, some patients are more likely to develop this disease. Here, we present the case of a 21-year-old man, diagnosed with PA, with a history of chronic steroid use and a long-term indwelling urinary catheter. The pathogen was confirmed as carbapenem-resistant Klebsiella pneumoniae, a rare bacterium. This case indicates that immunodeficiency and invasive catheter use may be risk factors for PA and opportunistic bacterial infections. PATIENT CONCERNS: A 21-year-old young man presented with sudden onset of high fever (39.7°C). The patient had a history of long-term use of steroids and long-term indwelling urinary catheter. Digital rectal examination revealed obvious swelling and tenderness of the prostate. Subsequent pelvic magnetic resonance imaging showed a high signal lesion measuring 2.1 × 2.9 × 2.8 cm with T1 enhancement and T2 enhancement. DIAGNOSES: On the 8th day of hospitalization, the patient underwent a PA drainage procedure and a pus culture was conducted. Subsequent pus and urine cultures showed the presence of Klebsiella pneumoniae, which exhibited resistance to all injectable carbapenems, cephalosporins, aminoglycosides, piperacillin-tazobactam, and quinolone drugs. INTERVENTIONS: On the 8th day of hospitalization, the patient underwent PA drainage surgery under general anesthesia to drain the abscess and relieve obstruction. After the surgery, the patient received a 2-week treatment of doxycycline. OUTCOMES: Finally, the patient was discharged after recovery and did not experience recurrence during the 6-month follow-up period. LESSONS: PA is not commonly found, but some patients are more susceptible to this disease under certain host conditions. Immunodeficiency and invasive catheter use may be risk factors for PA and opportunistic bacterial infections. The use of omadacycline for the treatment of carbapenem-resistant Klebsiella pneumoniae infections appears to be effective.

Giant Prostate Abscess: A Case Report and Literature Review.

Prostate abscess, a rare condition often associated with prostate bacterial infections, often occurs in immunosuppressive individuals and manifests as fever and lower urinary tract symptoms. Clinical practice lacks standardized diagnostic and treatment protocols for prostate abscesses, resulting in predominantly empirical approaches with uncertain outcomes. This study presents a case of a giant prostate abscess, diagnosed in a patient exhibiting fever, lower urinary tract symptoms (including dysuria, urinary frequency, urgency, and weakness), and anal pain. The diagnosis was confirmed through prostate magnetic resonance imaging and transrectal color ultrasound examinations. Treatment included targeted anti-infective therapy (based on the urine culture results), urine flow diversion (suprapubic bladder puncture stomy), ultrasound-guided perineal puncture drainage of the prostatic abscess, intermittent abscess cavity irrigation, and urethral electroprostatectomy. The patient experienced a complete recovery and significantly improved quality of life. This successful case underscores several key points: (1) the importance of targeted anti-infective therapy based on etiological findings in prostate abscess treatment; (2) early urine flow diversion, precise puncture drainage, and intermittent abscess cavity irrigation may be one of crucial elements in abscess management; (3) the potential significance of transurethral prostate resection following abscess resolution in preventing recurrence. It is hoped that this case report offers new valuable insights for diagnosing and treating prostate abscesses. Slightly different from previous treatment experience, we extra used early urine diversion, intermittent abscess cavity irrigation, and etiological electroprostatectomy, which might also hold promise as potential therapies.

A Rare Case of Prostatic Malakoplakia Associated with Prostate Adenocarcinoma: A Case Report and Review of Literature.

Malakoplakia is a chronic granulomatous condition that has been rarely seen affecting the prostate. Isolated malakoplakia of the prostate occurring together with prostatic adenocarcinoma is rarer still with only 9 previously recorded cases. We present a case diagnosed through needle biopsy with prostatic adenocarcinoma and then on subsequent prostatectomy was diagnosed with extensive malakoplakia occurring with the carcinoma. Patient was noted to have a urinary tract infection (UTI) 2 weeks after needle biopsy and notably, 4 of the 9 previously reported cases also presented with UTI following their biopsies. The theory that prostatic malakoplakia may be a complication of the prostate needle biopsy is logically possible, but due to the paucity in cases, it is difficult to infer causality.

Unveiling prostatic inflammation to optimize management of lower urinary tract symptoms: a discussion with experts.

Benign prostatic obstruction (BPO) and associated lower urinary tract symptoms (LUTS) are common conditions in men, which increase in frequency and severity with age, and have a significant impact on quality of life. Chronic prostatic inflammation is increasingly being recognized as a key component of BPO. This may lead to new targets for the management of BPO/LUTS. This podcast is based on presentations from a symposium titled 'Unveiling prostatic inflammation to optimize LUTS management' held at the European Association of Urology 2023 Congress. The presenters outline evidence of a role for prostatic inflammation in the development and progression of BPO/LUTS, approaches to the identification of biomarkers of inflammation, and the implications of prostatic inflammation for the optimal management of BPO/LUTS.

Melioidosis of the Female Genitourinary Tract.

Prostatic abscess is a common manifestation of melioidosis in men, but the characteristics of female genitourinary melioidosis are incompletely defined. There were 453 cases of melioidosis in Far North Queensland, tropical Australia, between January 1998 and April 2023; genitourinary involvement was less common in women than in men (13/140 [9%] versus 76/313 [24%], odds ratio [95% confidence interval]: 0.32 [0.17-0.60], P = 0.0004). In 11 of these 13 (85%) women, other organs were also affected. The two women with disease involving only the genitourinary tract had underlying anatomical abnormalities: one had an ovarian malignancy, the only case to involve the female reproductive system in the cohort, while the other had a urethral diverticulum. In 3 of 13 (23%) women, genitourinary involvement was identified only with computed tomography, emphasizing the importance of early imaging of patients with melioidosis to identify unexpected foci of disease and to inform the optimal duration of antibiotic therapy.

Benign prostatic obstruction (BPO) as a possible risk factor for Peyronie's disease (PD). The influence of BPO and PD on mental health.

Not available.