Prostate Research Articles

Dual targeting of the androgen receptor and PI3K/AKT/mTOR pathways in prostate cancer models improves antitumor efficacy and promotes cell apoptosis.

Prostate cancer is a frequent malignancy in older men and has a very high 5-year survival rate if diagnosed early. The prognosis is much less promising if the tumor has already spread outside the prostate gland. Targeted treatments mainly aim at blocking androgen receptor (AR) signaling and initially show good efficacy. However, tumor progression due to AR-dependent and AR-independent mechanisms is often observed after some time, and novel treatment strategies are urgently needed. Dysregulation of the PI3K/AKT/mTOR pathway in advanced prostate cancer and its implication in treatment resistance has been reported. We compared the impact of PI3K/AKT/mTOR pathway inhibitors with different selectivity profiles on in vitro cell proliferation and on caspase 3/7 activation as a marker for apoptosis induction, and observed the strongest effects in the androgen-sensitive prostate cancer cell lines VCaP and LNCaP. Combination treatment with the AR inhibitor darolutamide led to enhanced apoptosis in these cell lines, the effects being most pronounced upon cotreatment with the pan-PI3K inhibitor copanlisib. A subsequent transcriptomic analysis performed in VCaP cells revealed that combining darolutamide with copanlisib impacted gene expression much more than individual treatment. A comprehensive reversal of the androgen response and the mTORC1 transcriptional programs as well as a marked induction of DNA damage was observed. Next, an in vivo efficacy study was performed using the androgen-sensitive patient-derived prostate cancer (PDX) model LuCaP 35 and a superior efficacy was observed after the combined treatment with copanlisib and darolutamide. Importantly, immunohistochemistry analysis of these treated tumors showed increased apoptosis, as revealed by elevated levels of cleaved caspase 3 and Bcl-2-binding component 3 (BBC3). In conclusion, these data demonstrate that concurrent blockade of the PI3K/AKT/mTOR and AR pathways has superior antitumor efficacy and induces apoptosis in androgen-sensitive prostate cancer cell lines and PDX models.

The Role of Proton Therapy for Prostate Cancer in the Setting of Hip Prosthesis.

Given that the current standard of proton therapy (PT) for prostate cancer is through bilateral beams, this modality is typically avoided when it comes to treatment of patients with hip prosthesis. The purpose of this study was to evaluate whether novel PT methods, i.e., anterior proton beams and proton arc therapy (PArc), could be feasible options to treat this patient subpopulation. We evaluate PT methods in the context of dosimetry and robustness and compare with standard of practice volumetric modulated arc therapy (VMAT) to explore any potential benefits. Two PT and one VMAT treatment plans were retrospectively created for 10 patients who participated in a clinical trial with a weekly repeat CT (rCT) imaging component. All plans were robustly optimized and featured: (1) combination anterior oblique and lateral proton beams (AoL), (2) PArc, and (3) VMAT. All patients had hydrogel spacers in place, which enabled safe application of anterior proton beams. The planned dose was 70 Gy (RBE) to the entire prostate gland and 50 Gy (RBE) to the proximal seminal vesicles in 28 fractions. Along with plan dose-volume metrics, robustness to setup and interfractional variations were evaluated using the weekly rCT images. The linear energy transfer (LET)-weighted dose was evaluated for PArc plans to ensure urethra sparing given the typical high-LET region at the end of range. Both PT methods were dosimetrically feasible and provided reduction of some key OAR metrics compared to VMAT except for penile bulb, while providing equally good target coverage. Significant differences in median rectum V35 (22-25%), penile bulb Dmean (5 Gy), rectum V61 (2%), right femoral head Dmean (5 Gy), and bladder V39 (4%) were found between PT and VMAT. All plans were equally robust to variations. LET-weighted dose in urethra was equivalent to the physical dose for PArc plans and hence no added urethral toxicity was expected. PT for treatment of prostate cancer patients with hip prosthesis is feasible and equivalent or potentially superior to VMAT in quality in some cases. The choice of radiotherapy regimen can be personalized based on patient characteristics to achieve the best treatment outcome.

Creating a 3D-printed pelvic phantom to explore the impact of Magnetic Resonance (MR) scanner noise in radiomics analysis, a technical note.

Reproducibility of radiomics features necessitates that scanner noise be considered prior to feature extraction. Phantom research provides the opportunity for such ‘ground truth’ measurements, without the additional complication of patient-related factors. The aim of this technical note was to create a 3D printed Magnetic Resonance Imaging (MRI)-compatible pelvic phantom that can be used for subsequent analysis of the impact of scanner noise on the reproducibility of radiomics features.A 3D printed phantom of a male pelvis was created using fused deposition modelling technology. It was 3D printed using the high density MRI-compatible acrylonitrile butadiene styrene (ABS). The ‘negative’ mould created was then filled with silicone, and the prostate gland and femoral heads were also simulated.We successfully created an MRI-compatible 3D printed pelvic phantom, with a test scan. The phantom will subsequently be utilised to determine the impact of MRI scanner noise on radiomics feature reproducibility.

Evaluation of the anti-androgenic and cytotoxic effects of benzophenone-3 in male Sprague-Dawley rats

ABSTRACT Benzophenone-3 (BP-3, 2-hydroxy-4-methoxybenzophenone, oxybenzone) is one of the most widely used types of benzophenone organic sunscreen. However, this compound is a potentially harmful toxicant. The aim of this study was 2-fold to: (1) utilize a Hershberger bioassay in vivo in castrated male Sprague-Dawley rats to investigate the anti-androgenic activities of BP-3, and (2) use in vitro a methyl tetrazolium assay to compare the toxicity between Leydig cells (TM3 cells) and mouse fibroblast (NIH-3T3) cell lines. In the Hershberger assay, rats were divided into 6 groups (each of n = 7): a vehicle control, negative control, positive control, PB-3 low (40 mg/kg), BP-3 intermediate (200 mg/kg), and BP-3 high (1000 mg/kg)-dose. The weight of the ventral prostate was significantly decreased at BP-3 doses of 200 or 1,000 mg/kg/day. In addition, the levator anibulbocavernosus muscle weights were also significantly reduced at BP-3 doses of 40, 200, or 1,000 mg/kg/day. In the MTT assay, the viability of NIH-3T3 mouse fibroblast cells was within the normal range. However, the TM3 mouse testis Leydig cell viability was significantly lowered in a concentration-dependent manner. Therefore, data indicate that BP-3 might exert in vivo anti-androgenic and in vitro cytotoxic effects in cells associated with the male reproductive system compared to normal non-reproductive cells. Abbreviation: BP-3: benzophenone-3; CG: Cowper’s gland; DMEM: Dulbecco’s modified Eagle’s medium; DMSO: dimethyl sulfoxide; GP: glans penis; LABC: levator anibulbocavernosus muscle; MTT: methyl tetrazolium; NC: negative control; PC: positive control; SV: seminal vesicle; TP: testosterone propionate; VC: vehicle control; VP: ventral prostate

3D convolutional network with edge detection for prostate gland and tumor segmentation on T2WI and ADC

Prostate cancer (PCa) ranks as the third most prevalent cancer globally. Accurate segmentation of the prostate and tumor in magnetic resonance image (MRI) has vital importance for supporting auxiliary diagnosis and subsequent research on prostate diseases. Specifically, T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) sequences serve as crucial references for identifying the prostate boundaries and locating the lesion areas. In this study, we propose a multi-segmentation model that takes T2WI and ADC and outputs the corresponding prostate gland and tumor segmentations. In the network, we introduced SE-Net to enhance feature processing with the combination of Cased Pyramid Convolution and Attention Gate. We utilized convolutions with different scales to implement residual connections for dealing with the inconsistent spatial information of the features and optimizing the training process. One major challenge in prostate segmentation arises from the blurred image of the tissue edge regions. To overcome this difficulty, we designed a pure convolution-based edge detection block in the model's architecture to constrain edge regions simultaneously. This approach improved the segmentation accuracy of the indistinct boundaries between the prostate gland, tumor, and surrounding anatomical structures. Upon evaluating with magnetic resonance images from Guizhou Provincial People's Hospital, we achieved the best scores in two metrics: Average boundary distance, and Hausdorff distance for both the prostate gland and the tumor segmentation results. The external validation results demonstrated the model's generalization ability, substantiating its efficacy when applied to data from other sources.

Distribution of neurovascular structures within the prostate gland and their relationship to complications after radical prostatectomy.

Radical prostatectomy remains the main choice of treatment for prostate cancer. However, despite improvements in surgical techniques and neurovascular sparing procedures, rates of erectile dysfunction, and urinary incontinence remain variable. This is due, at least in part, to an incomplete understanding of neurovascular structures associated with the prostate. The objective of this study was to provide a comprehensive, detailed histological overview of the distribution of nerves and blood vessels within the prostate, facilitating subsequent correlation of prostatic neurovascular structures with patients' clinical outcomes after radical prostatectomy. Neurovascular structures within the prostate were investigated in a total of 309 slides obtained from 15 patients who underwent non-nerve-sparing radical prostatectomy. Immunohistochemical staining was performed to identify and distinguish between parasympathetic and sympathetic nerves, whereas hematoxylin and eosin staining was used to identify blood vessels. The total number, density, and relative position of nerves and blood vessels were established using quantitative morphometry and illustrated using visualization approaches. Patient-specific outcome data were then used to establish whether the internal distribution of nerves and blood vessels within the prostate correlated with the nature and extent of complications after surgery. One-way analysis of variance tests and unpaired ttests were applied to establish statistically significant differences across the measured variables. Nerves and blood vessels were present across all prostatic levels and regions. However, their number and density varied considerably between regions. Assessment of the precise positioning of neurovascular structures revealed that the majority of nerve fibers were located within the dorsal and peripheral aspects of the gland. In contrast, blood vessels were predominantly located within ventral and dorsal midline regions. The number of intraprostatic nerves was found to be significantly lower in patients who recovered their continence within 12 months of surgery, compared to those whose recovery took 12 months or longer. We report an unexpected disconnect between the localization and positioning of nerve fibers and blood vessels within the prostate. Moreover, individual variability in the density of intraprostatic neurovascular structures appears to correlate with the successful recovery of urinary continence after radical prostatectomy, suggesting that differences in intrinsic neurovascular arrangements of the prostate influence postoperative outcomes.

Manual prostate MRI segmentation by readers with different experience: a study of the learning progress

ObjectiveTo evaluate the learning progress of less experienced readers in prostate MRI segmentation.Materials and methodsOne hundred bi-parametric prostate MRI scans were retrospectively selected from the Göteborg Prostate Cancer Screening 2 Trial (single center). Nine readers with varying degrees of segmentation experience were involved: one expert radiologist, two experienced radiology residents, two inexperienced radiology residents, and four novices. The task was to segment the whole prostate gland. The expert’s segmentations were used as reference. For all other readers except three novices, the 100 MRI scans were divided into five rounds (cases 1–10, 11–25, 26–50, 51–76, 76–100). Three novices segmented only 50 cases (three rounds). After each round, a one-on-one feedback session between the expert and the reader was held, with feedback on systematic errors and potential improvements for the next round. Dice similarity coefficient (DSC) > 0.8 was considered accurate.ResultsUsing DSC > 0.8 as the threshold, the novices had a total of 194 accurate segmentations out of 250 (77.6%). The residents had a total of 397/400 (99.2%) accurate segmentations. In round 1, the novices had 19/40 (47.5%) accurate segmentations, in round 2 41/60 (68.3%), and in round 3 84/100 (84.0%) indicating learning progress.ConclusionsRadiology residents, regardless of prior experience, showed high segmentation accuracy. Novices showed larger interindividual variation and lower segmentation accuracy than radiology residents. To prepare datasets for artificial intelligence (AI) development, employing radiology residents seems safe and provides a good balance between cost-effectiveness and segmentation accuracy. Employing novices should only be considered on an individual basis.Clinical relevance statementEmploying radiology residents for prostate MRI segmentation seems safe and can potentially reduce the workload of expert radiologists. Employing novices should only be considered on an individual basis.Key Points• Using less experienced readers for prostate MRI segmentation is cost-effective but may reduce quality. • Radiology residents provided high accuracy segmentations while novices showed large inter-reader variability. • To prepare datasets for AI development, employing radiology residents seems safe and might provide a good balance between cost-effectiveness and segmentation accuracy while novices should only be employed on an individual basis. Graphical abstract

Disseminated cryptococcosis in a patient with idiopathic CD4 + T lymphocytopenia presenting as prostate and adrenal nodules: diagnosis from pathology and mNGS, a case report

Disseminated Cryptococcosis infection typically occurs in immunocompromised patients, often manifested as pneumonia or meningoencephalitis. Cases with involvement of either prostate or adrenal glands are less frequent. We describe a case of an immunocompromised 62-year-old man with new-found Idiopathic CD4 + T lymphocytopenia who presented with urinary irritation symptoms followed by headache. The patient was finally diagnosed as disseminated cryptococcosis of prostate, adrenal gland involvement with the help of combining histopathology of formalin-fixed, paraffin-embedded tissue with metagenomic next-generation sequencing technique to identify C neoformans sensu stricto in prostate, adrenal gland tissues. Clinicians should be aware of atypical presentations of cryptococcal disease. In this case of cryptococcosis in immunocompromised patients, we find that cryptococcosis can affect varied organs simultaneously and should be considered in the differential of infectious diseases. And mNGS technology helps to confirm the diagnosis.

The Effects of High Fat Diet on the Incidence of Obesity and Monocyte Chemoattractant Protein-1 Levels on Histological Changes in Prostate Wistar Rats.

Benign prostatic hyperplasia (BPH) is a histopathological diagnosis characterized by the increase in stromal cells and epithelial cells of the prostate gland in the transitional zone surrounding the urethra. Obesity is the risk factor of BPH. The most frequent cause of obesity is a high-fat diet (HFD). Obesity and HFD lead to pro-inflammatory conditions. One of the pathomechanisms for the occurrence of BPH is a low-degree inflammatory factor, one of which is the level of monocyte chemoattractant protein-1/MCP-1. This study aims to determine the influence of HFD on the incidence of obesity and inflammatory factors (monocyte chemoattractant protein-1/MCP-1 levels) on the histopathological picture of the prostate. Experimental research was performed on male Wistar rats with each of the 6 rats given normal fat (ND) and HFD intake and terminated at 8 weeks and 6 rats given each ND and HFD were terminated at 16 weeks. The determination of obesity was determined based on Lee's criteria which were categorized as obese if the Lee index >0.3 and non-obese if ≤0.3. Examination of circulating MCP-1 was carried out by the ELISA method and determination of prostatic hyperplasia was done by calculating the percentage of prostate glands that had a large per-field cystic dilatation on light microscopy examination. All data are analyzed statistically with the Fisher Exact Test and Spearman Correlation Test. Of the 12 rats that were given ND, none of them became obese according to Lee's criteria, on the other hand, of the 12 rats that were given HFD 8 became obese (66.7%, p = 0.001). Serum MCP-1 levels and the percentage of prostate glands that had cystic dilatation were significantly higher in mice receiving HFD than ND; both at week-8 (MCP-1; 18.87 vs 15.66) and (prostate gland experiencing cystic dilatation; 63.46% vs 47.24%) and week-16 (MCP-1; 21.27 vs 21.27) and (prostate gland experiencing cystic dilatation; 67.79% vs 56.39%). Spearman correlation analysis showed that only circulating MCP-1 levels were significantly correlated (p < 0.05) to the percentage of the prostate gland that had cystic dilatation; especially in week 16 (r = 0.713 and p < 0.001). At 8 weeks, it was not statistically significant (r = 0.406 and p = 0.095). High fat intake has been shown to increase the risk of obesity, but obesity does not increase inflammatory status and the incidence of prostate glands with cystic dilatation. On the other hand, high-fat intake increases inflammatory status which in turn causes prostate glands to develop cystic dilatation.

Роль цинка в здоровой предстательной железе и при хроническом простатите

The review article discusses modern aspects of the physiological role of zinc in the prostate gland, as well as the consequences for the prostate gland of deficiency of this one of the most important vital trace elements. The mechanisms of intracellular zinc transport, as well as various physiological processes in prostate tissue requiring the mandatory presence of zinc, are covered in more detail. In a separate section of the literature review, the modern evidence base of the relationship of zinc deficiency in the prostate gland with chronic prostatitis is presented and the results of modern studies showing the need for zinc replacement therapy in the framework of complex pharmacotherapy of chronic prostatitis occurring against the background of zinc deficiency are summarized.

Botanical Sources, Pharmacokinetics, and Therapeutic Efficacy of Palmatine and Its Derivatives in the Management of Cancer: A Comprehensive Mechanistic Analysis

Natural compounds and their derivatives have been identified as valuable sources of therapeutic ingredients for cancer treatment. The naturally occurring phytochemical palmatine (isoquinoline alkaloid) is extracted from plant parts (rhizomes, roots, stems, stem barks, and others) and has protective effects including antioxidant, anti‐inflammatory, and anticancer. This study aims to summarize the anticancer potential of palmatine and its derivatives in the treatment of numerous types of cancer with molecular mechanisms. We also include the pharmacokinetic features, botanical origin, and toxicological characteristics of palmatine and its derivatives. For this, data have been collected from plausible different electronic databases, including PubMed, Google Scholar, PubChem, Science Direct, Web of Science, Scopus, Springer Link, and Wiley Online. The findings demonstrate that palmatine and its derivatives have a protective anticancer effect against a variety of cancers, including breast, colorectal, gastric, ovarian, prostate, pancreatic, skin, hepatocellular cancer, and mammary gland tumors. They provoke their anticancer properties against various cancer cell lines via modifying molecular mechanisms like induction of oxidative stress, cytotoxicity, apoptosis, inhibition of cell invasion and migration, arresting the cell cycle at the S phase, antiproliferative, and antiangiogenic effects. It is suggested that palmatine and its derivatives may be a good option in the development of novel drugs for cancer therapy in the future.

Efecto del extracto de Boswellia serrata sobre el daño testicular inducido por Metotrexato

This study aimed to determine the effect of Boswellia serrata extract on Methotrexate– induced testicular damage by evaluating antioxidant system, reproductive organ weights, some spermatological parametres and serum Testesterone levels. For this purpose, 40 Sprague Dawley rats were divided into 4 groups. 1. Control Group (n=10): No treatment was given for 10 days. 2. B. serrata Group (n=10): B. serrata was given by gavage at a dose of 500 mg·kg-1 for 10 days. 3. Methotrexate Group (n=10): Methotrexate was given intraperitoneally as a single dose of 20 mg·kg-1. 4. Methotrexate + B. serrata Group (n=10): After methotrexate was given intraperitoneally as a single dose of 20 mg·kg-1, 500 mg·kg-1 B. serrata was given by gavage for 10 days. It was determined that B. serrata significantly increased serum Testosterone levels (P&lt;0.001), testicular GSH levels (P&lt;0.001), motility of sperm (P&lt;0.001), concentration of sperm (P&lt;0.001), absolute ventral prostate (P&lt;0.001) and absolute seminal vesicles (P&lt;0.05) organ weight in Methotrexate + B. serrata group. The decrease in testicular MDA levels (P&gt;0.05) and the increase in GSH–Px enzyme activity of testes (P&gt;0.05) and final body weight (P&gt;0.05) were not significant in Methotrexate + B. serrata group compared to the Methotrexate group. In conclusion, the negative effects of Methotrexate on the male reproductive system can be reduced by administering B. serrata extract.

Correlation of Intravesical Prostatic Protrusion with Severity of Lower Urinary Tract Symptoms in Men With Symptomatic Benign Prostatic Hyperplasia at University of Nigeria Teaching Hospital, Ituku-Ozalla Enugu

Abstract Background: Benign prostatic hyperplasia (BPH) is one of the causes of lower urinary tract symptoms (LUTS) in men above 50 years of age. It is known that the severity of LUTS (degree of bladder outlet obstruction) does not correlate with the size of the prostate gland in BPH. Severity of LUTS due to BPH can be assessed using the internationally validated international prostate symptom score (IPSS). There are some concerns that the IPSS is subjective and may pose some challenges to the poorly educated patients in our environment during administration. Intravesical prostatic protrusion may be an objective index of degree of bladder outlet obstruction in men with BPH measured using abdominopelvic ultrasound. So the objective of this study is to evaluate for any correlation between IPP and IPSS in men with symptomatic BPH. Objective: The objective of the study is to assess the correlation between IPP and IPSS. Patients and Methods: A hospital based cross-sectional study of new patients with symptomatic LUTS of BPH, who presented to the Urology clinics of University of Nigeria Teaching Hospital Ituku-Ozalla Enugu. Ethical approval was obtained from the ethical committee of the hospital and informed consent from patients. After evaluation (including IPSS, PSA, and FBC, S/E/Ur/Cr, Urinalysis and M/C/S), participants had abdominopelvic ultrasonography measurement of IPP and midline sagittal image of the prostate (at bladder Volume of &gt; 100mls) using Prosound model SSD 3500 with an abdominal probe frequency of 3.5MHz (Versana Essentials) IPP was divided into three grades (Grade I: 0-4.9mm; Grade II: 5.0-9.9mm; Grade III: 10.0mm and above). Data was analyzed using SPSS Version 20 (IBM, SPSS, Chicago, IL, USA). The Pearson correlation was used to assess correlation where necessary. P- value &lt;0.005 was considered significant. Results: Two hundred and seventy four men with a mean age of 64.76+/- 9.04 years were included in the study. Most of the participants had highest educational level of primary education 145 (52.9 %). The average IPSS, IPP, PSA Total were 15.90+/- 4.74 SD, 9.49+/- 2.98 SD, 6.13+/- 1.83 respectively. There is significant positive correlation between IPP and IPSS (r = 0.451; P &lt; 0.001), and a statistically significant negative correlation between IPP, IPSS (r = - 0.742; P &lt; 0.001), (r = - 0.500; P &lt; 0.001) respectively and Qmax. Conclusion: There was a significant positive correlation between IPP and IPSS. Intravesical prostatic protrusion may be used to help assess severity of lower urinary tract symptoms in men with BPH.

Ultrasound organometry of the human prostate in the age aspect and its changes in chronic alcoholism

The article presents the results of a study on age-related ultrasound morphometry of the biometric parameters of the human prostate and its changes during chronic alcohol exposure. Age-related changes in the prostate are uneven, which is due to the morphofunctional characteristics of the organ in different age periods. The greatest increase in prostate length was revealed in adolescence (34.0%), in adolescence the thickness increases by 38.5%, the width by 2.0 times, the volume of the gland by 3.4 times. The smallest increase in the volume-linear parameters of the gland was found in men of senile age. In men suffering from chronic alcoholism, there is an increase in the organometric parameters of the prostate gland.

Prevalence of Bladder Cancers Incidentally Detected During Multiparametric MRI Scans of the Prostate Gland and the Clinical Significance of Scoring Them According to VI-RADS: A Pictorial Single-Centre Study.

To determine the prevalence of incidentally detected bladder cancers (BCs) on multiparametric magnetic resonance imaging (mpMRI) of the prostate and to highlight the clinical importance of scoring them according to the Vesical Imaging-Reporting and Data System (VI-RADS). VI-RADS scores for incidental bladder lesions on mpMRI of the prostate were collected in 1693 patients with elevated prostate-specific antigen but no hematuria. The study included 19 patients with 28 incidental bladder lesions. During this period, 39 incidental bladder lesions were found in 30 patients, representing 1.7% of cases. Of the 28 lesions, 11 were categorized by VI-RADS as VI-RADS 1, 14 as VI-RADS 2, 1 as VI-RADS 3, 1 as VI-RADS 4, and 1 as VI-RADS 5. Histopathological examination revealed 1 benign lesion, 24 non-muscle invasive BCs, and 3 muscle-invasive BCs in the 19 patients. Impressively, 97% of the incidental lesions detected by prostate mpMRI and categorized by VI-RADS were BCs without apparent prostate cancer invasion. Notably, 93% of these lesions were consistent with histopathological findings of muscle invasion and extravesical spread. Our study concludes the prevalence 1% incidental BC in prostate mpMRI. The research underscores a thorough bladder examination during prostate MRI scans. Utilizing mpMRI assists in distinguishing varying BC stages, aiding treatment decisions, and patient outcomes. VI-RADS categorization aligns with histopathological results, enhancing diagnosis, and healthcare communication. Early detection significantly influences patient care by enabling timely interventions and suitable treatment strategies, particularly for low-stage BCs linked to reduced progression and recurrence rates.

Innervation density and types of nerves in prostate cancer.

Innervation of cancerous tissue represents an important pathway enabling the nervous system to influence the processes associated with the initiation, progression, and metastasis of a neoplastic process. In the context of prostate cancer, several papers report the presence of innervation and its modulating effect on the cancer prognosis. However, most of the data are experimental, with limited information on human prostate cancer innervation. Morphometric analysis of archival prostate specimen immunohistochemistry with neural markers PGP9.5 and S100 showed a significant decrease of nerve density in the prostate cancer (n=44) compared to the normal prostate tissue (n=18) and benign prostatic hyperplasia (n=28). Sympathetic nerves were detected with TH, parasympathetic with VAChT, and sensory nerves with SP and CGRP protein detection. Dual immunofluorescence revealed numerous sympathetic nerves in normal prostate and benign prostatic hyperplasia, especially in the peripheral parts. Only a few parasympathetic nerves were found between the glands and in the peripheral parts of the prostate and benign hyperplasia. Sporadic positivity for sensory innervation was present only in approximately 1/10 of nerve fibers, especially in the larger nerves. The pattern of innervation in prostate cancer was analogous to that in normal prostate gland and benign prostatic hyperplasia but there was a significantly lower amount of all nerve types, especially in high-grade carcinoma cases. Although not significant, there was a tendency of decreasing innervation density with increasing Gleason score. Regarding the low density of nerves in prostate carcinoma, the significantly lower PCNA counts in nerves of the cancer specimens cannot be ascribed to lower proliferation activity. Our data confirmed the lower nerve density in the prostate cancer compared to the benign prostate tissue. We could not approve an increased nerve proliferation activity in prostate cancer. All nerve types, most the sympathetic, less the parasympathetic, and the sensory nerves, are present in prostate cancer. The highest nerve density at the periphery of the cancer tissue implies this to be the result of an expansive tumor growth. It is evident that the results of experimental prostate cancer models can be applied to human pathology only to a certain extent. The relation between the range of innervation and the biology of prostate cancer is very complex and will require more detailed information to be applied in therapeutic solutions.

Хронический простатит, ассоциированный с герпесвирусами

The most common microorganisms are herpesviruses, which are capable of infecting many organs and systems, including reproductive organs (due to their biological properties) causing in some cases the occurrence of infertility and life-threatening generalized infections. Among the many herpesviruses, there are 9 that are transmitted from humans: herpes simplex viruses types 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, herpes viruses types 6, 7, 8, as well as macacine herpesvirus 1. In recent decades, there has been intensive research into their role in damage to the male reproductive system, including the prostate gland. The authors attempted to assess the possible association of herpesviruses with symptoms of chronic prostatitis and infertility, for which a search was conducted in the Pubmed database for the following search query: human papillomavirus, Epstein-Barr virus, cytomegalovirus, herpes virus 1, 2, 6, sexual transmission, sperm, prostatitis. Epidemiological studies concerning the possible association of herpesviruses with chronic prostatitis (CP) / chronic pelvic pain syndrome (CPPS) symptoms in young men have shown that viruses can enter the genital organs through sexual contact or a systemic route. However, some of them do not damage the male reproductive system organs, but rather affect sperm cells, leading to infertility. Despite the contradictory isolated studies, most of them indicated the role of herpesviruses in the damage to the male reproductive system, including the prostate gland, with spermatogenesis disorder and infertility occurrence. Thus, patients with CP/CPPS should be examined for the herpesvirus detection, since atypical, uncultivated, intracellular, as well as viral pathogens (along with typical pathogens) can play a role in the prostatitis progression. KEYWORDS: herpesviruses, Epstein-Barr virus, cytomegalovirus, herpes simplex virus type 1, herpes simplex virus type 2, human herpesvirus type 6, human papillomavirus, chronic prostatitis, infertility. FOR CITATION: Kadyrov Z.A., Ramishvili Sh.V., Stepanov V.S., Ignatiev A.V., Mashaneishvili Sh.G. Chronic prostatitis associated with herpesviruses. Russian Medical Inquiry. 2024;8(4):221–227 (in Russ.). DOI: 10.32364/2587-6821-2024-8-4-6.

Современные возможности лечения доброкачественной гиперплазии предстательной железы и симптомов нижних мочевыводящих путей: новые данные и опыт клинического применения гексанового экстракта плодов Serenoa repens

The article discusses the pharmacological properties and results concerning the clinical use of a medicinal herbal preparation — hexane extract of Serenoa repens (HESr) (creeping palm fruit). In recent years, quite a lot of research data has been accumulated indicating a multicomponent mechanism of drug action. It has been found to have antiandrogenic, antiproliferative and anti-inflammatory effects in the tissues of the prostate gland (pancreas). Studies have been published describing a new mechanism of action of HESr — antineurogenic, the implementation of which helps to reduce infravesical obstruction, leads to inhibition of α1-adrenergic, thromboxane-induced and cholinergic contraction of the pancreatic and detrusor smooth muscles, and also inhibits the growth of pancreatic stromal cells. At present, there is evidence proving the highest clinical efficacy level of the HESr (data from several meta-analyses). The listed effects and patterns of HESr are illustrated by clinical examples of prescribing this drug to patients with lower urinary tract symptoms and benign pancreatic hyperplasia. The safety of use in conditions of polypragmasy in a comorbid patient, the possibility of long-term use without the adverse events occurrence and ensuring a higher life quality while maintaining full sexual function are also particularly noted. KEYWORDS: lower urinary tract symptoms, benign prostatic hyperplasia, chronic bacterial prostatitis, hexane extract of Serenoa repens fruit, ejaculation, life quality. FOR CITATION: Amdiy R.E., Simanov R.N. Modern treatment options for benign prostatic hyperplasia and lower urinary tract symptoms: new data and clinical picture of the hexane extract of Serenoa repens fruit. Russian Medical Inquiry. 2024;8(4):228–234 (in Russ.). DOI: 10.32364/2587-6821-2024-8-4-7.

The natural history of benign prostatic hyperplasia-related voiding symptoms following penile prosthesis implantation.

There is a rising prevalence of benign prostatic hyperplasia (BPH)-related urinary symptoms along with erectile dysfunction in the aging male population. Therefore, assessment of lower urinary tract symptoms (LUTS) is advised before penile prosthesis surgery with some men requiring preoperative transurethral surgical management to reduce the risk of post-procedure complications. However, less is known about the natural history of men with uncomplicated LUTS who do not require surgical management for BPH before penile prosthesis. We sought to assess the natural history of BPH-related uncomplicated LUTS in men following penile prosthesis surgery. Single institution retrospective review. Following institutional review board approval, we performed a retrospective review of all adult males with a preoperative diagnosis of LUTS undergoing penile prosthesis surgery at our institution from January 2017 to November 2022. The primary outcome was progression to transurethral surgery. From 2017 to 2022, 211 patients with preexisting LUTS underwent penile prosthesis surgery and met all criteria for inclusion including no history of transurethral surgery. The median (interquartile range, IQR) AUA symptom score (AUA-SS) was 12 (12). Post-void residual was below 200 cc in 96.2% of patients preoperatively and 99.1% of patients after surgery. At a median (IQR) follow-up duration of 9 (23) months after surgery, 5.7% (12/211) of patients had progressed to bladder outlet surgery and 35.5% of patients endorsed LUTS bother with a median (IQR) AUA-SS of 14.5 (11.8). The majority of patients with uncomplicated LUTS did not require bladder outlet surgery following penile prosthesis implantation and could be managed with conservative or pharmacologic measures alone. Prostate gland size was significantly larger in patients who progressed to bladder outlet surgery. While the results are overall reassuring, further study is needed to identify specific factors associated with pursuing bladder outlet surgery in this small subset of patients.

Complex Anterior Supralevator Anal Fistula With Prostatic Abscess Treated With Ksharasutra: A Case Report

Anorectal diseases are a major health threat in the field of health sciences. Fistula‐in‐ano is one of the treatable complex benign lesions of the rectum and anal canal. Complex high anal fistulas can reoccur even after surgical treatment. Establishing a cure for cryptoglandular fistula‐in‐ano is problematic, as a significant percentage of these diseases persist or recur if the internal opening of the anal fistula is left untreated. Here, we report a case of complex left anterolateral supralevator anal fistula with communication to the prostate gland that forms a prostatic abscess, as it is very rare. After following Ksharasutra (Ayurvedic medicated seton) treatment with regular wound care, significant regression in the condition was observed. A follow‐up scan showed no evidence of fistula‐in‐ano. A 50‐year‐old businessman presented with complaints of discomfort deep inside the rectum and perineum associated with pain at the base of the scrotum and pus discharge from the perianal region for 1 year. He was diagnosed to have a complex left anterolateral supralevator anal fistula with communication to the prostate substance after a thorough clinical examination and transrectal ultrasonography. After undergoing Ksharasutra treatment for 4 months, pus discharge completely stopped, and sonofistulogram report showed no evidence of fistula‐in‐ano. Images of the sonofistulogram report were documented before and after the treatment. This article highlights the unique feature of Ksharasutra therapy where the fistula extending to the prostate was treated with no loss of function of the anal sphincter.