Therapy For Benign Prostatic Hyperplasia Research Articles

Editorial Comment to "One hundred cases of Rezum water vapor thermal therapy for benign prostatic hyperplasia: Real-world data at a single institution in Japan".

Editorial Comment to "One hundred cases of Rezum water vapor thermal therapy for benign prostatic hyperplasia: Real-world data at a single institution in Japan".

Diterpene glycosides from Fructus Rubi ameliorates benign prostatic hyperplasia in rats through the androgen and TGF-β/Smad signaling pathway

Fructus Rubi (FR), a food material with medicinal value, is used in traditional Chinese medicine (TCM) for treatment of various kidney-related problems, such as impotence, spermatorrhea, and frequent urination. It is also frequently used to produce diverse functional foods in China. The purpose of this research was to assess the therapeutic effects of FR diterpene glycosides on RWPE-1 epithelial cell (RWPE-1), a human normal prostatic epithelial cell, and benign prostate hyperplasia (BPH) rats, both of which had been exposed to dihydrotestosterone (DHT) and testosterone propionate (TP), respectively, and to investigate the mechanism of action. Target proteins that could stably bind to certain diterpene glycosides were screened through drug affinity responsive target stability combined with mass spectrometry (DARTS/MS). DHT-induced RWPE-1cells were used to detect drug activity. TP was subcutaneously injected to induce BPH in rats. The extract of diterpene glycosides from FR (FDS) was orally administered for 28 days. The DHT levels in the serum and prostate tissue of the rats were measured through enzyme-linked immunosorbent assay (ELISA), and to analyze cell proliferation and epithelial-mesenchymal transition (EMT), the protein expression of prostate-specific antigen (PSA), androgen receptor (AR), steroid 5α-reductase type 2 (SRD5A2), proliferating cell nuclear antigen (PCNA), S100 calcium-binding protein A2 (S100A2), transforming growth factor-β1 (TGF-β1), E-cadherin, vimentin, and Smad4 was determined through western blotting (WB), immunohistochemistry (IHC), or immunofluorescence (IF). FDS reduced the proliferation of DHT-induced RWPE-1cells. It also significantly inhibited rat prostate enlargement; decreased DHT levels in the serum and prostate tissue; inhibited the protein expression of AR, PSA, PCNA, S100A2, TGF-β1, E-cadherin, and Smad4; and increased the protein expression of E-cadherin. The present study is the first to report that diterpene glycosides isolated from FR inhibited BPH at the cellular level, regulated the proliferation of prostate cells through the androgen signaling pathway, and prevented EMT in the prostate through the S100A2-mediated TGF-β/Smad signaling pathway. These results indicate that FDS is a promising multitarget therapy for BPH.

5α-reductase inhibitors with or without alpha-blockers and risk of incident upper tract urothelial carcinoma in men with benign prostatic hyperplasia: Analysis of US insurance claims data

BackgroundIncreasing data suggests that androgen receptor signaling may play an important role in the carcinogenesis of urothelial cancers. While the chemoprotective effect of 5-alpha reductase inhibitors (5-ARi) on bladder cancer risk in men with Benign Prostatic Hyperplasia (BPH) has been explored with conflicting results, the evidence regarding 5-ARi treatment, and the risk of incident Upper Tract Urothelial Carcinoma (UTUC) development is lacking. Therefore, our objective was to investigate the impact of the 5-ARi administration on the incidence of new UTUC cases using a large US database. MethodsThe MerativeTM Marketscan® database was used to identify men ≥ 50 years old with a diagnosis of BPH and an active 5-ARi prescription between 2007 and 2021 and were subsequently matched with paired controls. A multivariable Cox regression model was implemented to ascertain the association of 5-ARi and/or alpha-blocker (α-B) medications on the incidence of UTUC. Additional subgroup analyses were conducted based on exposure risk (with a 2-year threshold) to investigate the relationship between 5-ARi and UTUC over time. ResultsOverall, n=1,103,743 men BPH without prescriptions for BPH, n=31,142 men on 5-ARi, and n=160,049 using 5-ARi + α-B were identified. Over the follow-up period, a total of n=4,761 patients were diagnosed with UTUC. After matching, UTUC incidence ranged from 0.36% to 0.41% in men without active BPH therapy vs. 0.30% and 0.52% for the 5-ARi and 5-ARi + α-B groups, respectively. In multivariable analysis, the chemoprotective effect on UTUC risk was not observed for either 5-ARi monotherapy (adjusted hazard ratio [aHR]: 0.91, 95% CI: 0.58–1.44) or 5-ARi + α-B combination (aHR: 1.02, 95% CI: 0.87–1.19). This remained true for both short-term (≤ 2 years) and long-term (> 2 years) follow-up periods. ConclusionsThe use of 5-ARi for BPH, whether used alone or in combination with α-B, is not associated with incident UTUC.

One hundred cases of Rezum water vapor thermal therapy for benign prostatic hyperplasia: Real-world data at a single institution in Japan.

The objective of our study was to assess the efficacy of Rezum, a minimally invasive surgical treatment, for patients with lower urinary tract symptoms related to benign prostatic hyperplasia (BPH) in real-world clinical practice at a single institution in Japan. We conducted a prospective study involving 100 patients who underwent the Rezum procedure between October 2022 and February 2024. We analyzed patient backgrounds that are compliant with Japanese regulations and assessed descriptive outcomes such as symptom scores, peak flow in uroflowmetry, post-void residual (PVR) volume, and prostate volume (PVol). These data were collected at 1 and/or 3 months postoperatively. On average, 4.7 water vapor injections were administered during the Rezum procedures, with a mean operative time of 6.3 min. Patients experienced significant relief in symptoms, with reductions of 55% in International Prostate Symptom Score, 53% in quality of life score, and 30% in Overactive Bladder Symptom Score. There was also a significant decrease in mean PVR volume (50% reduction) and PVol (27% reduction). Among the subgroup of 23 pre-interventional catheter-dependent patients, 91% achieved catheter independence. Our single-center analysis demonstrates that Rezum is an effective and safe minimally invasive therapeutic option for patients with BPH. This promising novel technique can be particularly beneficial for patients at an augmented risk of bleeding or those considered high risk for anesthesia.

The risk of psychiatric disorders in finasteride users with benign prostatic hyperplasia and androgenetic alopecia: A population-based case-control study.

There is a long-standing debate if finasteride, a medication used to treat benign prostatic hyperplasia (BPH) and androgenetic alopecia (AGA), can cause psychiatric side effects. The goal of this large-scale population-based study was to determine whether finasteride therapy for BPH and AGA is associated with the emergence of mental health conditions. This observational case-control study compared the data from patients with BPH who received finasteride 5 mg daily and patients with AGA who received finasteride 1 mg daily with age- and gender-matched controls. The incidence of psychological health outcomes such as depression, anxiety, neuroses, bipolar disorder, schizophrenia, psychoses and alcohol abuse within 2 years of the initiation of finasteride therapy has been evaluated and compared between the finasteride groups and controls. The BPH group included 307 men with a mean age of 61.5 (±17.4) years and 1218 controls. Mental health outcomes recorded in 2.3% of the patients, with no significant increase in rate when compared to controls. The AGA group consisted of 23,227 men with a mean age of 31.4 (±10.3) years and 39,444 controls. Only One percent of AGA patients developed psychiatric disorders. In comparison to controls, patients with AGA had higher rates of anxiety and depression (0.6% vs. 0.4%, p = 0.04, and 0.5% vs. 0.4%, p = 0.007, respectively). In multivariate regression models, finasteride was found as one of the risk factors for anxiety (OR 1.449, p = 0.002) and depression (OR 1.439, p = 0.003) when stratified to age, sector, socioeconomic status and comorbidities. According to our research, finasteride users had a very low rate of adverse mental health effects, with no increase in psychological sequelae in BPH patients and a slight increase in anxiety and depression in AGA patients.

Thulium laser enucleation of the prostate plus thulium fiber laser therapy for benign prostatic hyperplasia combined with bladder stones

Thulium laser enucleation of the prostate plus thulium fiber laser therapy for benign prostatic hyperplasia combined with bladder stones

Four years of real-world sexual function outcomes after Rezum therapy in men with and without baseline erectile dysfunction.

Rezum alleviates lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH) while preserving sexual function, but long-term sexual function outcomes are lacking in patients with baseline erectile dysfunction (ED). The study sought to analyze 4years of real-world sexual function outcomes of Rezum using the International Index of Erectile Function (IIEF) questionnaire, stratified by baseline ED status. Participants included multiethnic Rezum-treated patients from a single outpatient office. IIEF domains and BPH medication usage were compared at baseline and 6, 12, and 48months using t tests, Mann-Whitney U tests, chi-square tests, and Wilcoxon signed rank tests. Primary outcomes over 4years included the IIEF functional domains (erectile function [EF], orgasmic function [OF], sexual desire [SD], intercourse satisfaction [IS], overall satisfaction [OS]) and BPH medication usage. A total of 91 patients were included: 40 (44%) in the ED cohort and 51 (56%) in the no ED cohort. History of diabetes was more prevalent in the ED cohort (35% vs 15.7%; P = .048). Baseline scores in the EF, OF, IS, and OS domains were lower in the ED cohort. Compared with baseline, there were no significant changes in any IIEF domains in either cohort at 6months. At 12months, the ED cohort had significant percent decreases in OF (-25%; P = .02), SD (-22.2%; P = .04), and OS (-33.3%; P = .004); the no ED cohort had a significant percent increase in EF (5%; P = .04). At 48months, the no ED cohort had no significant changes in any IIEF domains, while the ED cohort had significant percent increases in EF (30%; P = .01), SD (22.5%; P = .02), IS (20%; P = .01), and OS (58.3%; P = .008). Both cohorts significantly discontinued BPH medications at all follow-ups. At 48months, there were no cases of de novo ED in the no ED cohort. As modern BPH therapies continue to demonstrate efficacy in alleviating lower urinary tract symptoms, the preservation or improvement of sexual function emerges as an increasingly important consideration for patients, with our study suggesting Rezum as a compelling option. Our study has the strength of long-term Rezum outcomes in an ethnically diverse patient population, stratified by the presence of baseline ED, but is limited by retrospective design, single-center nature, and small sample sizes at long-term follow-ups. Rezum preserved long-term sexual function in patients without baseline ED and improved sexual function in those with baseline ED; however, individuals with ED may experience temporary decreases in sexual function at 12months.

Enhancing the Management of Benign Prostatic Hyperplasia: The Role of Electronic Health Record Patient Portal Distribution of the International Prostate Symptom Score.

Recent AUA guidelines for the management of benign prostatic hyperplasia (BPH) recommend routine collection of the International Prostate Symptom Score (IPSS) data, but routine collection can be challenging to fully implement. We investigated the impact of distributing the IPSS by electronic patient portal (EPP) on IPSS completion and its impact on BPH management. We performed a retrospective, longitudinal study of men undergoing a new patient visit (NPV) for BPH at our academic medical center. From September 2019 to November 2022, we identified patients undergoing an NPV for BPH. Prior to January 2021, the IPSS was collected in person at NPVs via paper forms; afterwards, the IPSS was distributed before the NPV using the EPP. Our primary outcome was IPSS completion; secondary outcomes were new BPH medications and BPH surgery ordered within 6 months. We identified 485 patients who underwent an NPV for BPH. EPP implementation significantly increased IPSS questionnaire completion (36.5% vs 56.9%, P < .0001). Following EPP implementation, we found that new BPH medications ordered at time of NPV decreased (10.4% vs 4.7%, P = .02). Although BPH surgery ordered within 6 months was similar, patients following EPP implementation had shorter time to BPH surgery compared to prior. Our study revealed that EPP distribution of the IPSS improves IPSS collection compliance, aligning our practice closer with AUA guidelines. Routine collection of the IPSS may impact clinical practice through the detection of more severe BPH, which reduces medical BPH management and time to definitive BPH therapy. Further work is needed to confirm findings.

Chronic inflammation in benign prostatic hyperplasia: Pathophysiology and treatment options.

Benign prostatic hyperplasia, a prevalent condition in aging men, is characterized by the proliferation of prostatic epithelial and stromal cells, which leads to bladder outlet obstruction and the exacerbation of lower urinary tract symptoms. There is increasing evidence that chronic prostatic inflammation contributes to the pathogenesis and progression of benign prostatic hyperplasia. This review explores the complex relationship between chronic inflammation and benign prostatic hyperplasia, focusing on the underlying mechanisms, clinical implications, and current therapeutic approaches. The pathophysiology of benign prostatic hyperplasia is multifaceted, involving factors such as hormonal changes, hypoxia, urine reflux into prostatic ducts and stroma, autoimmune responses, and infection-induced inflammation. Inflammatory cytokines, particularly interleukin-17 and interleukin-8, may play key roles in tissue remodeling and smooth muscle contraction within the prostate, thereby influencing benign prostatic hyperplasia progression. Current therapies for benign prostatic hyperplasia include α1-blockers, phosphodiesterase 5 inhibitors, 5α-reductase inhibitors, and plant-based treatments (e.g., pollen extract). These therapies aim to alleviate symptoms by reducing prostatic inflammation, improving blood flow, and inhibiting hormonal pathways involved in prostatic enlargement. However, patients with chronic prostatic inflammation often experience more severe lower urinary tract symptoms and may be resistant to conventional treatments. This resistance has prompted the exploration of alternative therapies targeting inflammation. Chronic prostatic inflammation plays a central role in the pathogenesis and severity of benign prostatic hyperplasia. An understanding of its mechanisms will enable the development of more effective treatments to improve the quality of life among patients with benign prostatic hyperplasia.

Scrotal calcinosis cutis an unrelated finding in benign prostatic hyperplasia patient, is treatment sine qua non? A case report

Calcinosis cutis is a reactive and nonmalignant lesion characterized by solitary or multiple cutaneous nodules that can affect different parts of the body including the scrotum among other structures. Treatment is often sought because of cosmesis, itching, or pain. Despite this, it remains unclear or unimaginable why patients will be reluctant to accept treatment in the face of disfigurement. Several reasons have been documented, but the fear of genital mutilation from open surgical intervention is an unfamiliar reason advanced by the index case for declining open surgical intervention. Its diagnosis requires careful clinical evaluation and is confirmed by lesional biopsy for histological confirmation. This is a case of a 50-year-old trader who presented to our facility with a 35-year history of multiple, painless scrotal nodules and difficulty in passing urine for six months’ duration. He was diagnosed with benign prostatic hyperplasia (BPH) with the indication for surgical therapy and idiopathic scrotal calcinosis cutis. He consented and had endoscopic therapy for benign prostatic hyperplasia (BPH) but was reluctant to open surgical intervention for idiopathic scrotal calcinosis cutis despite disfigurement because of the fear of genital mutilation. The current treatment options include follow-up observation, medications, cryotherapy, laser, and surgical excision, depending on the patient’s choice, availability, and surgical expertise. The surgical option is often favored and encouraged due to its associated reduced chances of recurrence. Therefore, it is pertinent to respect the patient’s opinion and should override other considerations in clinical practice. The lesson herein can assist other clinicians in avoiding justifiable medical litigations, hence, the need for this case report and a review of the literature.

The oxytocin antagonist cligosiban reduces human prostate contractility: Implications for the treatment of benign prostatic hyperplasia.

With increasing life expectancy, benign prostatic hyperplasia (BPH) consequently affects more ageing men, illustrating the urgent need for advancements in BPH therapy. One emerging possibility may be the use of oxytocin antagonists to relax smooth muscle cells in the prostate, similar to the currently used (although often associated with side effects) α1-adrenoceptor blockers. For the first time we used live-imaging, combined with a novel image analysis method, to investigate the multidirectional contractions of the human prostate and determine their changes in response to oxytocin and the oxytocin antagonists atosiban and cligosiban. Human prostate samples were obtained and compared from patients undergoing prostatectomy due to prostate cancer as well as from patients with transurethral resection of prostate tissue due to severe BPH. The two cohorts of tissue samples showed spontaneous multidirectional contractions, which significantly increased after the addition of oxytocin. Different to atosiban, which showed ambiguous effects of short duration, only long-acting cligosiban reliably prevented, as well as counteracted, any contractile oxytocin effect. Furthermore, cligosiban visibly reduced not only oxytocin-induced contractions, but also showed intrinsic activity to relax prostatic tissue. Thus, the oxytocin antagonist cligosiban could be an interesting candidate in the search for novel BPH treatment options.

Minimally invasive surgical therapies for benign prostatic hyperplasia in the geriatric population: A systematic review.

Geriatric patients, prone to adverse events (AEs) and low compliance with drugs, may benefit from minimally invasive surgical therapies (MISTs) for managing benign prostatic hyperplasia (BPH). We evaluated the efficacy, safety, and procedural characteristics of MISTs in geriatric patients with BPH. PubMed/MEDLINE database was systematically searched for relevant articles through October 1, 2023. Eligible studies focused on geriatric patients (≥65 years) with BPH who were treated with MISTs and evaluated follow-up surgical, micturition, and/or sexual outcomes. Studies were included if there was separate reporting for age subgroups ≥65 years, or if the mean age minus standard deviation was ≥65 years, or if the first quartile was ≥65 years. Out of 292 screened studies, 32 (N = 3972 patients) met inclusion criteria and assessed prostatic artery embolization (PAE), Rezum, GreenLight, holmium laser enucleation of the prostate (HoLEP), thulium laser enucleation of the prostate (ThuLEP), diode laser enucleation of the prostate (DiLEP), and Aquablation. Except for Rezum, all MISTs required a planned overnight stay. While PAE and Rezum could be performed under local anesthesia, the other MISTs needed general or spinal anesthesia. Postoperative catheterization duration was longest for PAE (median 14 days) and Rezum (21 days) and shortest for GreenLight (1.9 days). At 12 months postoperatively, all MISTs exhibited significant percent changes in International Prostate Symptom Score (median -69.9%) and quality of life (median -72.5%). Clavien-Dindo Grade 1 AEs ranged widely, with PAE (5.8%-36.8%), Rezum (0%-62.1%), and GreenLight (0%-67.6%) having the largest range, and HoLEP (0%-9.5%), ThuLEP (2%-6.9%), and DiLEP (5%-17.5%) having the smallest. PAE, Rezum, DiLEP, and Aquablation reported no significant changes in the International Index of Erectile Function. Although all the MISTs reviewed in this study effectively treat BPH in geriatric patients, differences in procedural characteristics and safety profiles across MISTs were considerable. Physicians should use shared decision-making processes, considering risks and patient characteristics, when choosing a suitable treatment option for their patients.

Systematic review and network meta-analysis of re-intervention rates of new surgical interventions for benign prostatic hyperplasia.

To assess the re-intervention rates of new surgical benign prostatic hyperplasia (BPH) interventions, as the clinical durability of new surgical interventions for BPH is not widely known. A critical review of new surgical BPH therapies namely 'UroLift®', 'Aquablation', 'Rezum', 'prostatic artery embolisation (PAE)' and 'temporary implantable nitinol device (iTIND)' was performed on PubMed, the Cochrane Library, and Embase databases between May 2010 and December 2022 according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statement. All relevant articles were reviewed, and the risk of bias was evaluated using the Cochrane risk assessment tool and Newcastle-Ottawa Scale. Of the 32 studies included, there were 10 randomised controlled trials and 22 prospective observational cohorts. A total of 2400 participants were studied with a median patient age of 66 years, a median prostate volume of 51.9 mL, and a median International Prostate Symptom Score of 22. The lowest re-intervention rate at 12 months was for Aquablation at 0.01%, followed by Rezum at 0.02%, iTIND at 0.03%, and PAE at 0.05%. Network meta-analysis (NMA) showed that the best-ranked treatment at 12 months was transurethral resection of the prostate (TURP), followed by Aquablation, iTIND, Rezum, and UroLift. Re-intervention rates with these new BPH interventions are comparable, although some interventions reported better outcomes than TURP in the shorter term. While this systematic review and NMA showed that the re-intervention rate with these new surgical BPH interventions appears to be comparable to TURP in the short term, further studies are required to directly compare these various BPH procedures.

Antegrade ejaculation preservation in surgical treatment for benign prostatic hyperplasia: quest for balance between voiding and sexual function.

Surgical treatment of benign prostatic hyperplasia (BPH) carries a significant risk of ejaculation dysfunction. Preservation of antegrade ejaculation while providing effective, well tolerated, and durable treatment of BPH is a paramount component of physical and sexual well being for significant number of men. We reviewed available literature with an aim of providing status on antegrade ejaculation preserving BPH surgical therapies. Minimally invasive surgical therapies for BPH have been developed over the last decade, with significant marketing emphasis on their potential for preservation of antegrade ejaculation. However, the question about durability of relief of bladder outlet obstruction remains. Parallel to this technological development, the understanding of anatomical structures involved in ejaculation have resulted in technical modifications of well established surgical treatments modalities like transurethral resection of prostate, endoscopic enucleation of prostate and simple prostatectomy, thereby providing safe and durable relief of bladder outlet obstruction secondary to BPH with a satisfactory preservation of antegrade ejaculation. Preservation of antegrade ejaculation is an important goal for significant number of men needing BPH surgery. Novel minimally invasive surgical technologies have been developed for this purpose; but understanding of the anatomical structures essential for antegrade ejaculation have allowed technical modification of existing surgical techniques with excellent preservation of antegrade ejaculation.

An analysis of benign prostatic hyperplasia surgical treatment reimbursement trends across Canada Examining provincial changes over the recent decade with comparison to cost of living changes.

A variety of procedures for the endoscopic surgical treatment of symptomatic benign prostatic hyperplasia (BPH) refractory to medical therapy have existed for decades. The present study examined trends in surgeon compensation for these treatments within Canada. The physician fee schedule for BPH surgery across 10 Canadian provinces for the years 2010 and 2023 were obtained. A descriptive study examined first the provincial reimbursement for transurethral resection of prostate (TURP) and laser ablative/enucleation surgery; second, the difference in TURP reimbursement between 2010 and 2023; and third, the annual change in TURP reimbursement juxtaposed with the annual change in the provincial Consumer Price Index (CPI) and annual salary for the working population aged 35-44. Seven of 10 Canadian provinces reimburse laser BPH surgery equally to TURP. The average provincial TURP reimbursement is $545, ranging from $451 in Ontario to $688 in Saskatchewan. Since 2010, TURP reimbursement has varied by province from a 0% net change in Ontario to an increase of 21% in Nova Scotia. Reimbursement for TURP has increased at a slower pace than the local CPI, and for half of the provinces at a slower pace than the annual salary for people aged 35-44. The compensation model for endoscopic BPH surgery does not have a unified structure in Canada that is consistent across provinces, nor does it keep up with inflation, possibly impacting future recruitment, increasing geographic disparities, and most importantly, limiting the adoption of new BPH therapies.

Effects of Protoves-M1® and IPB-tre® on the prevention and the treatment of irritative symptoms after REZUM therapy of benign prostatic hyperplasia (BPH)

Effects of Protoves-M1® and IPB-tre® on the prevention and the treatment of irritative symptoms after REZUM therapy of benign prostatic hyperplasia (BPH)

Elucidation of active components and target mechanism in Jinqiancao granules for the treatment of prostatitis and benign prostatic hyperplasia

Ethnopharmacological relevanceProstatitis and benign prostatic hyperplasia (BPH) are inflammations of the prostate gland, which surrounds the urethra in males. Jinqiancao granules are a traditional Chinese medicine used to treat kidney stones and this medicine consists of four herbs: Desmodium styracifolium (Osbeck) Merr., Pyrrosia calvata (Baker) Ching, Plantago asiatica L. and stigma of Zea mays L. Aim of the studyWe hypothesized that Jinqiancao granules could be a potential therapy for prostatitis and BPH, and this work aimed to elucidate active compounds in Jinqiancao granules and their target mechanisms for the potential treatment of the two diseases. Materials and methodsJinqiancao granules were commercially available and purchased. Database-driven data mining and networking were utilized to establish a general correlation between Jinqiancao granules and the two diseases above. Ultra-performance liquid chromatography-mass spectrometry was used for compound separation and characterization. The characterized compounds were evaluated on four G-protein coupled receptors (GPCRs: GPR35, muscarinic acetylcholine receptor M3, alpha-1A adrenergic receptor α1A and cannabinoid receptor CB2). A dynamic mass redistribution technique was applied to evaluate compounds on four GPCRs. Nitric acid (NO) inhibition was tested on the macrophage cell line RAW264.7. Molecular docking was conducted on GPR35-active compounds and GPR35 crystal structure. Statistical analysis using GEO datasets was conducted. ResultsSeventy compounds were isolated and twelve showed GPCR activity. Three compounds showed potent GPR35 agonistic activity (EC50 < 10 μM) and the GPR35 agonism action of PAL-21 (Scutellarein) was reported for the first time. Docking results revealed that the GPR35-targeting compounds interacted at the key residues for the agonist-initiated activation of GPR35. Five compounds showed weak antagonistic activity on M3, which was confirmed to be a disease target by statistical analysis. Seventeen compounds showed NO inhibitory activity. Several compounds showed multi-target properties. An experiment-based network reflected a pharmacological relationship between Jinqiancao granules and the two diseases. ConclusionsThis study identified active compounds in Jinqiancao granules that have synergistic mechanisms, contributing to anti-inflammatory effects. The findings provide scientific evidence for the potential use of Jinqiancao granules as a treatment for prostatitis and BPH.

(212) Minimally Invasive Surgical Therapies for Benign Prostatic Hyperplasia in the Geriatric Population: A Systematic Review

Abstract Introduction Benign prostatic hyperplasia (BPH) is an extremely common disease in aging men and can lead to lower urinary tract symptoms (LUTS) and complications. While the initial management of BPH includes behavioral modifications and pharmacologic therapies, older patients have increased susceptibility to adverse events (AEs) and therefore have decreased compliance. Consequently, geriatric patients may benefit from minimally invasive surgical therapies (MISTs) as treatment alternatives for BPH. Currently, there is no systematic review describing MISTs outcomes in specifically older populations. Objective To evaluate the efficacy and safety profile of MISTs in geriatric patients with BPH. Methods PubMed/MEDLINE database was systematically searched for relevant articles in the English language through June 24, 2023. Studies that evaluated surgical and/or urinary outcomes of MISTs in geriatric patients (≥65 years of age) were deemed eligible. Studies were included if there was separate reporting for age subgroups ≥65 years, if mean age minus SD was ≥65 years, or if median age minus Q1 was ≥65 years. Studies with patients with catheter dependent urinary retention were not excluded. Results A total of 263 studies were screened, of which 22 (N=2,911 patients) met inclusion. Of the 22 studies, 3 evaluated PAE, 1 evaluated Rezum, 7 evaluated GreenLight, 4 evaluated HoLEP, 4 evaluated ThuLEP, 1 evaluated DiLEP, 1 evaluated Aquablation, and 1 evaluated both PAE + Rezum. The Rezum study and the PAE + Rezum study only included patients with an indwelling catheter at baseline. Follow-up ranged between 1 and 36 months (median 12 months). All the MISTs were performed inpatient and required hospitalization. Hospitalization times ranged between 0.9 and 7.6 days (median 3 days) and was the longest for DiLEP (median 7.6 days) and PAE (median 5.1 days) and the shortest for Rezum (median 1 day). Procedure time ranged between 4.8 and 148 minutes (median 70.6 minutes), with PAE having the longest time (median 102 minutes) and Rezum having the shortest time (median 6.4 minutes). When compared to baseline, PAE, GreenLight, HoLEP, ThuLEP, DiLEP, and Aquablation showed significant percent changes in international prostate symptom score (median -69.6%), quality of life (-72.7%), maximum urinary flow (113.1%), and postvoid residual (-80.1%) at a median of 12 months postoperatively. The studies assessing catheter independence in patients with chronic urinary retention reported a catheter-free rate of 100% for Rezum and 45.5% for PAE at 12 months postoperatively. Occurrence of AEs ranged between 0 and 67.5% (median 12.2%). AEs were lowest for HoLEP (median 4.6%) and Rezum (median 8.8%) and highest for PAE (33.1%) and Aquablation (34%). Reoperation rates across all MISTs ranged between 0 and 5% (median 1.5%) at a median of 12 months postoperatively. Conclusions Although all the MISTs reviewed in this study resulted in durable improvements in LUTS secondary to BPH in the geriatric population, differences in procedural characteristics and safety profiles across MISTs were considerable. Rezum had the shortest procedure and hospitalization time and lowest occurrence of AEs, while PAE had the longest procedure and hospitalization time and highest occurrence of AEs. Additional studies evaluating Rezum in elderly patients without urinary retention are warranted. Disclosure No.

Transcriptomic analysis of benign prostatic hyperplasia identifies critical pathways in prostatic overgrowth and 5-alpha reductase inhibitor resistance.

The medical therapy of prostatic symptoms (MTOPS) trial randomized men with symptoms of benign prostatic hyperplasia (BPH) and followed response of treatment with a 5α-reductase inhibitor (5ARI), an alpha-adrenergic receptor antagonist (α-blocker), the combination of 5ARI and α-blocker or no medical therapy (none). Medical therapy reduced risk of clinical progression by 66% but the reasons for nonresponse or loss of therapeutic response in some patients remains unresolved. Our previous work showed that prostatic glucocorticoid levels are increased in 5ARI-treated patients and that glucocorticoids can increased branching of prostate epithelia in vitro. To understand the transcriptomic changes associated with 5ARI treatment, we performed bulk RNA sequencing of BPH and control samples from patients who received 5ARI versus those that did not. Deconvolution analysis was performed to estimate cellular composition. Bulk RNA sequencing was also performed on control versus glucocorticoid-treated prostate epithelia in 3D culture to determine underlying transcriptomic changes associated with branching morphogenesis. Surgical BPH (S-BPH) tissue was defined as benign prostatic tissue collected from the transition zone (TZ) of patients who failed medical therapy while control tissue termed Incidental BPH (I-BPH) was obtained from the TZ of men undergoing radical prostatectomy for low-volume/grade prostatic adenocarcinoma confined to the peripheral zone. S-BPH patients were divided into four subgroups: men on no medical therapy (none: n = 7), α-blocker alone (n = 10), 5ARI alone (n = 6) or combination therapy (α-blocker and 5ARI: n = 7). Control I-BPH tissue was from men on no medical therapy (none: n = 8) or on α-blocker (n = 6). A human prostatic cell line in 3D culture that buds and branches was used to identify genes involved in early prostatic growth. Snap-frozen prostatic tissue taken at the time of surgery and 3D organoids were used for RNA-seq analysis. Bulk RNAseq data were deconvoluted using CIBERSORTx. Differentially expressed genes (DEG) that were statistically significant among S-BPH, I-BPH, and during budding and branching of organoids were used for pathway analysis. Transcriptomic analysis between S-BPH (n = 30) and I-BPH (n = 14) using a twofold cutoff (p < 0.05) identified 377 DEG (termed BPH377) and a cutoff < 0.05 identified 3377 DEG (termed BPH3377). Within the S-BPH, the subgroups none and α-blocker were compared to patients on 5ARI to reveal 361 DEG (termed 5ARI361) that were significantly changed. Deconvolution analysis of bulk RNA seq data with a human prostate single cell data set demonstrated increased levels of mast cells, NK cells, interstitial fibroblasts, and prostate luminal cells in S-BPH versus I-BPH. Glucocorticoid (GC)-induced budding and branching of benign prostatic cells in 3D culture was compared to control organoids to identify early events in prostatic morphogenesis. GC induced 369 DEG (termed GC359) in 3D culture. STRING analysis divided the large datasets into 20-80 genes centered around a hub. In general, biological processes induced in BPH supported growth and differentiation such as chromatin modification and DNA repair, transcription, cytoskeleton, mitochondrial electron transport, ubiquitination, protein folding, and cholesterol synthesis. Identified signaling pathways were pooled to create a list of DEG that fell into seven hubs/clusters. The hub gene centrality was used to name the network including AP-1, interleukin (IL)-6, NOTCH1 and NOTCH3, NEO1, IL-13, and HDAC/KDM. All hubs showed connections to inflammation, chromatin structure, and development. The same approach was applied to 5ARI361 giving multiple networks, but the EGF and sonic hedgehog (SHH) hub was of particular interest as a developmental pathway. The BPH3377, 5ARI363, and GC359 lists were compared and 67 significantly changed DEG were identified. Common genes to the 3D culture included an IL-6 hub that connected to genes identified in BPH hubs that defined AP1, IL-6, NOTCH, NEO1, IL-13, and HDAC/KDM. Reduction analysis of BPH and 3D organoid culture uncovered networks previously identified in prostatic development as being reinitiated in BPH. Identification of these pathways provides insight into the failure of medical therapy for BPH and new therapeutic targets for BPH/LUTS.

Exploring the potential mechanism of Xiaojin Pill therapy for benign prostatic hyperplasia through metabolomics and gut microbiota analysis.

Xiaojin Pill (XJP) is a traditional Chinese medicine prescribed for treating benign prostatic hyperplasia (BPH). It has been proven to have multiple effects, such as regulating sex hormone levels, exhibiting anti-tumor, anti-inflammatory, analgesic, and anti-platelet aggregation properties, and improving immunity. However, the material basis of XJP's therapeutic effect on BPH and its metabolic process in vivo remains to be clarified. At the same time, many microorganisms that exist in the urogenital tract, including those related to BPH, can also affect the health of the host. Using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), the chemical components of XJP were identified. A BPH model was created through bilateral testicular ablation and injections of testosterone propionate. A comprehensive evaluation of XJP efficacy was conducted using pathological ELISA, TUNEL, and immunohistochemical techniques. In addition, UPLC-MS metabolomics and 16S rRNA sequencing revealed the serum metabolic profile and intestinal microbiota composition. We performed a Spearman correlation coefficient analysis to highlight the interactions between "intestinal microbiota-serum factors" and "intestinal microbiota-metabolites." XJP contains 91 compounds that alleviate pathologies of BPH in rats, decreasing prostate weight, index, and serum levels of Dihydrotestosterone (DHT), Prostate-Specific Antigen (PSA), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) levels. It inhibits prostatic epithelial cell apoptosis and downregulates Bax, TGF-β1, and IGF-1 proteins in the caspase-3 pathway. Metabolomics studies have revealed 10 upregulated and 10 downregulated metabolites in treated rats, with 5-methylcytosine, uracil, and cytosine enriched in pyrimidine metabolism. L-arginine plays a pivotal role in metabolic pathways encompassing pyrimidine metabolism, arginine biosynthesis, and the mammalian target of rapamycin (mTOR) signaling pathway. 16S rRNA sequencing revealed that XJP optimized the diversity and balance of intestinal flora in BPH rats by decreasing the Bacteroidetes/Firmicutes (B/F) ratio, enhancing the beneficial bacteria, such as Eggerthellaceae, Anaerovoracaceae, and Romboutsia, and suppressing the dysfunctional bacteria, such as Atopobiaceae, Prevotellaceae_NK3B31_group, Dorea, and Frisingicoccus. According to the Spearman correlation coefficient analysis, Lactobacillus was found to be most associated with serum factors, whereas Romboutsia showed the highest correlation with metabolites. This finding suggests that XJP modulates pyrimidine metabolism disorders in BPH rats, a regulation that aligns closely with Romboutsia, Prevotellaceae_NK3B31_group, Lactobacillus, Chujaibacter, and Enterorhabdus, thereby providing valuable biological insights. In summary, these findings indicate that XJP possesses a synergistic anti-BHP effect through its multi-component, multi-target, multi-gut microbiota, and multi-metabolic pathway properties. The effect involves the regulation of sex hormone levels, growth factors, and the anti-epithelial cell apoptosis process. The modulation of specific gut microbiota by the host and the involvement of multiple metabolic pathways are likely one of the significant mechanisms of XJP in treating BPH. Notably, pyrimidine metabolism and the intestinal microbial ecosystem are closely intertwined in this process.