Echinacoside attenuates glandular fibrosis in benign prostatic hyperplasia via inhibiting MKK6/MK2 signaling pathway

Background:Lower urinary tract symptoms commonly occur in the elderly population and seriously constrain the quality of life.Glandular fibrosis is an important pathobiological process in benign prostatic hyperplasia and is also a main inducing factor for benign prostatic hyperplasia-associated lower urinary tract symptoms.Cistanches species is an important herbal medicine resource and is traditionally used in ameliorating renal and prostatic defects.Methods:This study was to investigate the potential protective function of echinacoside(a bioactive compound from Cistanches)against prostatic fibrosis in mice and human benign prostatic hyperplasia epithelial-1 cell models.Results:It was found that echinacoside attenuated testosterone-induced prostatic hyperplasia and collagen deposition in mice,relieved prostate local inflammation and oxidative damage,and ameliorated prostatic epithelial-mesenchymal transition.Additionally,echinacoside inhibited the activation of the MKK6/MK2 signaling pathway both in vivo and in vitro.Conclusion:This study added new evidence for the anti-fibrotic function of echinacoside on the prostate and provided new insights for understanding its possible pharmacological mechanisms.

Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Alleviatory effect of isoquercetin on benign prostatic hyperplasia via IGF-1/PI3K/Akt/mTOR pathway

We evaluated the effect of isoquercetin(quercetin-O-3-glucoside-quercetin,IQ)as a functional component of Abeliophyllum disistichum Nakai ethanol extract(ADLE)on prostate cell proliferation and apoptosis and its effects on the IGF-1/PI3K/Akt/mTOR pathway in benign prostatic hyperplasia(BPH).Metabolites in ADLE were analyzed using UHPLC-qTOF-MS and HPLC.IQ was orally administered(1 or 10 mg/kg)to a testosterone propionate-induced BPH rat model,and its effects on the prostate weight were evaluated.The effect of IQ on androgen receptor(AR)signaling was analyzed in LNCaP cells.Whether IGF-1 and IQ affect the IGF-1/PI3K/Akt/mTOR pathway in BPH-1 cells was also examined.The metabolites in ADLE were identified and quantified,which confirmed that ADLE contained abundant IQ(20.88 mg/g).IQ significantly reduced the prostate size in a concentration-dependent manner in a BPH rat model,and significantly decreased the expression of AR signaling factors in the rat prostate tissue and LNCaP cells in a concentration-dependent manner.IQ also inhibited the PI3K/AKT/mTOR pathway activated by IGF-1 treatment in BPH-1 cells.In BPH-1 cells,IQ led to G0/G1 arrest and suppressed the expression of proliferation factors while inducing apoptosis.Thus,IQ shows potential for use as a pharmaceutical and nutraceutical for BPH.

Alterations of gut microbiota diversity, composition and metabonomics in testosterone-induced benign prostatic hyperplasia rats

Background: Studies had shown many diseases affect the stability of human microbiota, but how this relates to benign prostatic hyperplasia(BPH) has not been well understood. Hence, this study aimed to investigate the regulation of BPH on gut microbiota composition and metabonomics.Methods: We analyzed gut samples from rats with BPH and healthy control rats, the gut microbiota composition and metabonomics were detected by 16S rDNA sequencing and liquid chromatography tandem mass spectrometry(LC–MS/MS).Results: High-throughput sequencing results showed that gut microbiota beta-diversity increased(P<0.01) in the BPH group vs. control group. Muribaculaceae(P<0.01), Turicibacteraceae(P<0.05), Turicibacter(P<0.01) and Coprococcus(P<0.01) were significantly decreased in the BPH group, whereas that of Mollicutes(P<0.05) and Prevotella(P<0.05)were significantly increased compared with the control group. Despite profound interindividual variability, the levels of several predominant genera were different. In addition, there were no statistically significant differences in several bacteria. BPH group vs. control group: Firmicutes(52.30% vs. 57.29%, P>0.05), Bacteroidetes(46.54% vs. 41.64%,P>0.05), Clostridia(50.89% vs. 54.66%, P>0.05), Ruminococcaceae(25.67% vs. 20.56%, P>0.05). LC–MS/MS of intestinal contents revealed that differential metabolites were mainly involved in cellular processes, environmental information processing, metabolism and organismal systems. The most important pathways were global and overview maps, lipid metabolism, amino acid metabolism, digestive system and endocrine system. Through enrichment analysis, we found that the differential metabolites were significantly enriched in metabolic pathways, steroid hormone biosynthesis,ovarian steroidogenesis, biosynthesis of unsaturated fatty acids and bile secretion. Pearson correlation analysis(R=0.94) showed that there was a strong correlation between Prevotellaceae, Corynebacteriaceae, Turicibacteraceae,Bifidobacteriaceae and differential metabolites.Conclusions: Our findings suggested an association between the gut microbiota and BPH, but the causal relationship between the two groups is unclear. Thus, further studies are warranted to elucidate the potential mechanisms and causal relationships between BPH and gut microbiota.

Management of urethral strictures and stenosis caused by the endo-urological treatment of benign prostatic hyperplasiad-a single-center experience

Objective:Urethral stricture disease after endo-urological treatment of benign prostatic hyperplasia(BPH)is a sparsely described complication.We describe management of five categories of these strictures in this retrospective observational case series.Methods:One hundred and twenty-one patients presenting with symptoms of bladder outflow obstruction after endo-urological intervention for BPH from February 2016 to March 2019 were evaluated.Among them,76 were eligible for this study and underwent reconstructive surgery.Preoperative and postoperative assessments were done with symptom scores,uroflowmetry,ultrasound for post-void residue,and urethrogram.Any intervention during follow-up was classed as a failure.The recurrence and 95%confidence interval for recurrence percentage were calculated.Results:The following five categories of patients were identified:Bulbo-membranous(33[43.4%]),navicular fossa(21[27.6%]),penile/peno-bulbar(8[10.5%]),bladder neck stenosis(6[7.9%]),and multiple locations(8[10.5%]).The average age was 69 years(range:60-84 years).Overall average symptom score,flow rate,and post-void residue changed from 21 to 7,6 mL/s to 19 mL/s,and 210 mL to 20 mL,respectively.The average follow-up was 34 months(range:12-58 months).Overall recurrence and complication rates were 10.5%and 9.2%,respectively.The recurrence in each category was seen in 3,1,2,1,and 1 patient,respectively.Overall 95% confidence interval for recurrence percentage was 4.66-19.69.Conclusion:Urethral stricture disease is a major long-term complication of endo-urological treatment of BPH.The bulbo-membranous strictures need continence preserving approach.Navicular fossa strictures require minimally invasive and cosmetic consideration.Peno-bulbar strictures require judicious use of grafts and flaps.Bladder neck stenosis in this cohort could be treated with endoscopic measures.Multiple locations need treatment based on their sites in single-stage as far as possible.

Fournier’s gangrene after insertion of thermo-expandable prostatic stent for benign prostatic hyperplasia:A case report

BACKGROUND Thermo-expandable urethral stent(Memokath 028)implantation is an alternative treatment for older patients with lower urinary tract symptoms and benign prostatic obstruction.Following prostatic urethral stent implantation,minor complications such as urinary tract infection,irritative symptoms,gross hematuria,and urethral pain have been observed;however,there are no reports of life-threatening events.Herein,we report a critical case of Fournier’s gangrene that occurred 7 years after prostatic stenting.CASE SUMMARY An 81-years-old man with benign prostatic hyperplasia(volume,126 ccs;as measured by transrectal ultrasound)had undergone insertion of a thermoexpandable urethral stent(Memokath 028)as he was unfit for surgery under general anesthesia.However,the patient had undergone a suprapubic cystostomy for recurrent acute urinary retention 4 years after the insertion of prostatic stent(Memokath 028).We had planned to remove the Memokath 028;however,the patient was lost to follow-up.The patient presented to the emergency department 3 years after the suprapubic cystostomy with necrotic changes from the right scrotum to the right inguinal area.In digital rectal examination,tenderness and heat of prostate was identified.Also,the black skin color change with foulsmelling from right scrotum to right inguinal area was identified.In computed tomography finding,subcutaneous emphysema was identified to same area.He was diagnosed with Fournier’s gangrene based on the physical examination and computed tomography findings.In emergency room,Fournier’s gangrene severity index value is seven points.Therefore,he underwent emergent extended surgical debridement and removal of the Memokath 028.Broad-spectrum intravenous antibiotics were administered and additional necrotic tissue debridement was performed.However,the patient died 14 days after surgery due to multiorgan failure.CONCLUSION If Memokath 028 for benign prostatic hyperplasia is not working in older patients,its rapid removal may help prevent severe complications.

Simultaneous Management of Inguinal Hernia and Benign Prostatic Hypertrophy in a Single Operation at the Chu D’abeche/Chad

Introduction: Benign prostatic hypertrophy and inguinal hernia are related and frequent pathologies in people over 50 years old. Their incidence is 15% to 25% according to the literature. The occurrence of hernia during benign prostatic hyperplasia is favored by disorders of the lower urinary tract. Simultaneous single-stage treatment of these two pathologies makes it possible to obtain satisfactory results that can reduce the cost of hospital stay and the multiple risk of anesthesia. The aim of our study was to: 1) Report the epidemiological, anatomo-clinical and para-clinical aspects of hernias during benign prostatic hypertrophy;2) Evaluate the feasibility and the results of the combined treatment of inguinal hernia and prostatic adenectomy in a single operation. Patients and Method: This was a retrospective descriptive study over a period of 7 years from March 2014 to February 2021, including patients operated on simultaneously at the University Hospital of Abeche for inguinal hernia and benign prostatic hypertrophy. The variables studied were: age, antecedents, favouring factors, clinical symptomatology, para-clinical elements, treatments and results: Results: 356 patients underwent surgery for benign prostatic hyperplasia, 36 of whom had an associated inguinal hernia. The mean age was 65.5 years, ranging from 50 to 93 years. The main reason for consultation was chronic urinary retention. The average consultation time was 10.2 months. The inguinal hernia was located on the right in 51% of cases and on the left in 18.4%. The mean prostatic volume measured by suprapubic ultrasound was 60.5 ± 25 cc. 14% and 10.2% of patients respectively were found to have struggle bladder and bilateral ureterohydronephrosis. Transvesical suprapubic adenectomy of the prostate was performed in all patients. The Bassini technique was the most commonly used (91%) for hernia repair. The average hospital stay was 7.5 days. Conclusion: Simultaneous treatment of benign prostatic hypertrophy and inguinal hernia reduces the number of hospital admissions in elderly patients, as well as the length of hospital stay.

Top 50 most cited articles on prostatic artery embolization for benign prostatic hyperplasia:A bibliometric review

BACKGROUND Bibliometric analysis can be used to assess the current state of the literature and publication trends on a given topic.There has not been a review of this kind on prostatic artery embolization(PAE)for benign prostatic hyperplasia(BPH).PAE is a relatively new and somewhat controversial treatment option for BPH.Given the novelty and controversy,there has been much research published on the topic recently.AIM To survey the current state of research on PAE for BPH by using bibliometric analysis to analyze the top 50 most highly cited articles.METHODS A cross-sectional study was performed using the Web of Science database to identify the most cited articles published on PAE for BPH as of June 2022.Articles that did not primarily focus on PAE or BPH as an indication were eliminated.The 50 most cited articles were carried forward for analysis.RESULTS All but 6 articles were published in the last decade with contributions from 15 countries.Fifty-two percent of the studies had a C level of evidence.The majority were published in the Journal of Vascular and Interventional Radiology and Cardiovascular and Interventional Radiology.Twenty percent(n=10)of the articles were published in urologic journals.On average,articles published in urologic journals tended to be more recent.The mean year of publication for an article in a urological journal was 2016.6 compared to 2013.9 in a non-urologic journal(P=0.02).Seventy percent of the articles focused on clinical outcomes,while only 2%focused on practice guidelines.Self-citations accounted for 11.4 citations perarticle on average,corresponding to 14.7%of all citations analyzed.CONCLUSION The most influential papers on this topic represent a fairly recent body of work with contributions from a wide variety of countries and journals.The fact that articles in urologic journals were published significantly more recently than articles on the list in non-urologic journals may suggest that the field of urology is starting to accept PAE for a wider range of indications.Finally,while there has been much high-quality research published,more influential studies on practice guidelines and technique may be beneficial.

Evaluation of greenlight photoselective vaporization of the prostate for the treatment of high-risk patients with benign prostatic hyperplasia

Aim： To explore the feasibility and safety of greenlight photoselective vaporization of the prostate （PVP） on high-risk patients presenting with lower urinary tract symptoms suggestive of benign prostatic hyperplasia （BPH） and to evaluate their clinical and voiding outcome. Methods： A total of 85 high-risk patients with obstructive BPH underwent PVP with an 80 W potassium-titanyl-phosphate laser, which was delivered through a side-deflecting fiber with a 23 Fr continuous flow cystoscope. Operative time, blood loss, indwelling catheterzation, international prostate symptom score （IPSS）, quality of life score （QoL）, uroflowmetry, postvoid residual urine volume and short-term complication rates were evaluated for all patients. Results： All patients got through the perioperative period safely. The chief advantages of PVP were： short operative time （25.6 ± 7.6 min）, little bleeding loss （56.8 ± 14.3 mL） and short indwelling catheterization （1.6 ± 0.8 d）. The IPSS and QoL decreased from （29.6 ± 5.4） and （5.4 ± 0.6） to （9.5 ± 2.6） and （1.3 ± 0.6）, respectively. The vast majority of patients were satisfied with voiding outcome. The mean maximal urinary flow rate increased to 17.8 mL/s and postvoid residual urine volume decreased to 55.6 mL. These results are significantly different from preoperative data （P 〈 0.05）. No patient required blood transfusion or fluid absorption. There were few complications and very high patient satisfaction after operation. Conclusion： PVP has a short operative time and high tolerance, and is safe, effective and minimally invasive for high-risk patients, therefore it might be considered as a good alternative treatment for high-risk patients with obstructive urinary symptoms as a result of BPH.

The role of photovaporization of the prostate in small volume benign prostatic hyperplasia and review of the literature

Objective:Our objective was to characterize the safety and efficacy of the 180 W XPS-GreenLight laser in men with lower urinary tract symptoms secondary to a small volume benign prostatic hyperplasia(BPH).Methods:A retrospective analysis was performed for all patients who underwent 180 W XPSlaser photoselective vaporization of the prostate(PVP)vaporization of the prostate between 2012 and 2016 at two-tertiary medical centers.Data collection included baseline comorbidities,disease-specific quality of life scores,maximum urinary flow rate(Qmax),postvoid residual(PVR),complications,prostate volume and prostate-specific antigen(PSA).The secondary endpoints were the incidence of intraoperative and postoperative adverse events.Complications were stratified using the Clavien-Dindo grading system up to 90 days after surgery.Results:Mean age of men was 67.8 years old,with a mean body mass index of 29.7 kg/m2.Mean prostate volume as measured by transrectal ultrasound was 29 mL.Anticoagulation use was 47%and urinary retention with catheter at time of surgery was 17%.Mean hospital stay and catheter time were 0.5 days.Median follow-up time was 6 months with the longest duration of follow-up being 22.5 months(interquartile range,3-22.5 months).The International Prostate Symptom Score improved from 22.8±7.0 at baseline to 10.7±7.4(p<0.01)and 6.3±4.4(p<0.01)at 1 and 6 months,respectively.The Qmax improved from 7.70±4.46 mL/s at baseline to 17.25±9.30 mL/s(p<0.01)and 19.14±7.19 mL/s(p<0.001)at 1 and 6 months,respectively,while the PVR improved from 216.0±271.0 mL preoperatively to 32.8±45.3 mL(p<0.01)and 26.2±46.0 mL(p<0.01)at 1 and 6 months,respectively.The PSA dropped from 1.97±1.76 ng/mL preoperatively to 0.71±0.61 ng/mL(p<0.01)and 0.74±0.63 ng/mL at 1 and 6 months,respectively.No patient had a bladder neck contracture postoperatively and no capsular perforations were noted intraoperatively.Conclusion:The 180 W GreenLight XPS system is safe and effective for men with small volume BPH.PVP produced improvements in symptomatic and clinical parameters without any safety concern.It represents a safe surgical option in this under studied population.

Nitric oxide synthase 2 gene polymorphisms are associated with prostatic volume in Korean men with benign prostatic hyperplasia

The precise aetiology of benign prostatic hyperplasia （BPH） remains unclear; however, it is known that immunological inflammatory processes have a role in the pathogenesis of BPH initiation and progression. Nitric oxide synthase 2 （NOS2） inducible expression is closely correlated with prostatic disease, including prostate cancer and BPH. The aim of this study was to investigate the relationship between NOS2 polymorphisms and BPH. With a cohort of 205 controls and 229 BPH subjects, we genotyped three single nucleotide polymorphisms （SNPs） in the NOS2 gene, including rs2779248 （promoter, -278 T/C）, rs 10459953 （5＇-untranslated region） and rs2297518 （exon 16, missense, Ser608Leu）, using direct sequencing and restriction fragment length polymorphism. The genotypic and allelic frequencies between control and BPH subjects were compared, and the associations among the BPH subjects were analyzed. SNPStats, SNPAnalyzer and HelixTree programmes were used to analyze SNPs. There was no association on SNPs between control and BPH subjects. When BPH subjects were analyzed, there was no association on SNPs between the low and high prostate-specific antigen groups. However, one SNP （rs 10459953, odds ratio [OR] = 0.44, 95% confidence interval [CI] = 0.29-0.65, P 〈 0.0001, in codominant model; OR = 0.23, 95% CI = 0.12-0.46, P 〈 0.0001, in dominant model; and OR = 0.46, 95% CI = 0.24-0.86, P = 0.015, in recessive model） was associated with prostatic volume in BPH. We detected a strong association in genotype frequencies of NOS2 SNP （rs10459953） between subjects with small and large prostatic volume in BPH. The result suggests that NOS2 may be associated with prostatic volume in BPH.

The use of 5-alpha reductase inhibitors in the treatment of benign prostatic hyperplasia

Benign prostatic hyperplasia(BPH)is characterized by an enlarged prostate,lower urinary tract symptoms(LUTS),and a decreased urinary flow rate.Common in older men,BPH is a progressive disease that can eventually lead to complications including acute urinary retention(AUR)and the need for BPH-related surgery.Both normal and abnormal prostate growth is driven by the androgen dihydrotestosterone(DHT),which is formed from testosterone under the influence of 5-alpha reductase.Thus,5-alpha reductase inhibitors(5-ARIs)effectively reduce the serum and intraprostatic concentration of DHT,causing an involution of prostate tissue.Two 5-ARIs are currently available for the treatment of BPHdfinasteride and dutasteride.Both have been demonstrated to decrease prostate volume,improve LUTS and urinary flow rates,which ultimately reduces the risk of AUR and BPH-related surgery.Therefore,either alone or in combination with other BPH medications,5-ARIs are a mainstay of BPH management.

Benign prostatic hyperplasia and male lower urinary symptoms:A guide for family physicians

Male patients with lower urinary tract symptoms(LUTS)and benign prostatic hyperplasia(BPH)are increasingly seen by family physicians worldwide due to ageing demographics.A systematic way to stratify patients who can be managed in the community and those who need to be referred to the urologist is thus very useful.Good history taking,physical examination,targeted blood or urine tests,and knowing the red flags for referral are the mainstay of stratifying these patients.Case selection is always key in clinical practice and in the setting of the family physician.The best patient to manage is one above 40 years of age,symptomatic with nocturia,slower stream and sensation of incomplete voiding,has a normal prostatespecific antigen level,no palpable bladder,and no haematuria or pyuria on the labstix.The roles of α blockers,5-α reductase inhibitors,and antibiotics in a primary care setting to manage this condition are also discussed.

Pathophysiology of clinical benign prostatic hyperplasia

A disease can be defined as an abnormal anatomy(pathology)and/or function(physiology)that may cause harm to the body.In clinical benign prostatic hyperplasis(BPH),the abnormal anatomy is prostate adenoma/adenomata,resulting in a varying degree of benign prostatic obstruction(BPO)that may cause harm to the bladder or kidneys.Thus clinical BPH can be defined as such and be differentiated from other less common causes of male lower urinary tract symptoms.Diagnosis of the prostate adenoma/adenomata(PA)can be made by measuring the intravesical prostatic protrusion(IPP)and prostate volume(PV)with non-invasive transabdominal ultrasound(TAUS)in the clinic.The PA can then be graded(phenotyped)according to IPP and PV.Multiple studies have shown a good correlation between IPP/PV and BPO,and therefore progression of the disease.The severity of the disease clinical BPH can be classified into stages from stage Ⅰ to Ⅳ for further management.The classification is based on the effect of BPO on bladder functions,namely that of emptying,normal if postvoid residual urine(PVRU)<100 mL;and bladder storage,normal if maximum voided volume(MVV)>100 mL.The effect of BPO on quality of life(QoL)can be assessed by the QoL index,with a score≥3 considered bothersome.Patients with no significant obstruction and no bothersome symptoms would be stage Ⅰ;those with no significant obstruction but has bothersome symptoms(QoL≥3)would be stage Ⅱ;those with significant obstruction(PVRU>100 mL;or MVV<100 mL),irrespective of symptoms would be stage Ⅲ;those with complications of the disease clinical BPH such as retention of urine,bladder stones,recurrent bleeding or infections would be stage Ⅳ.After assessment,further management can then be individualised.A low grade and stage disease can generally be watched(active surveillance)while a high grade and stage disease would need more invasive management with an option for surgery.The final decision making would take into account the patient’s age,co-morbidity,social economic background and his preferences/values. Proper understanding of pathophysiology of clinical BPH would lead to better selection of patients for individualised and personalised care andmore cost effective management.

Intravesical Prostate Protrusion (IPP) versus Middle Lobe Volume on Ultrasonography in Assessing the Impact of Benign Prostatic Hyperplasia

Background: Ultrasound is the main method of exploring the prostate. In benign prostatic hyperplasia (BPH), it provides important morphological information and assesses its impact, helping to guide the treatment. Objective: To compare intravesical prostatic protrusion (IPP) and middle lobe volume by ultrasound in BPH. Method: This was a single center prospective, descriptive and analytical study, over a period of 6 months, including 95 patients, undergoing prostatic trans-abdominal ultrasound. Patients were selected by a single urologist for clinical suspicion of benign prostatic hypertrophy. The ultrasound examination was done by a single senior radiologist. Results: The mean age of the patients was 66.63 ± 11.55 years with ranges from 38 to 98 years. The prevalence of BPH was 76.84%. The rate of patient with middle lobe protrusion was 48.42%. The mean middle lobe volume was 11.29 ± 12.90 ml. More than half of the patients (50.91%) had an IPP stage 3 of. The mean bladder wall thickness was 6.08 ± 2.58 mm, with 50.53% being pathological. The post-voiding residue (PVR) was significant in 38.75% of patients. Renal repercussions were present in 17.89%. The correlation analysis did not note a statistical link between prostate volume and quality of life score (p > 0.05). There was a statistically significant correlation between IPP values and quality of life score (p = 00461), IPSS score (p = 0.0424) and PVR (p = 0.0395). For middle lobe volume, there was a correlation with PVR (p = 0.0018). There was no correlation with clinical impact (quality of life score and IPSS score). Conclusion: The IPP appears to be an easy element to measure and better than the volume of the prostate and the middle lobe in assessing the impact of BPH.

Efficacy of Bladder Neck Incision (BNI) Versus Transurethral Resection of Prostate (TURP) in Management of Benign Prostatic Hyperplasia (BPH) Causing Obstruction: A Randomised Controlled Study

Objective: To compare the efficacy of bladder neck incision (BNI) with transurethral resection of prostate (TURP) in the treatment of patients with urinary obstruction caused by benign prostatic hyperplasia (BPH) on the basis of short term follow up of 4 months. Patient and Methods: The study was conducted in Department of General Surgery in Maulana Azad Medical College, New Delhi. 60 men with proven clinical diagnosis of BPH of size 30 grams and less presenting with symptoms of bladder outlet obstruction (BOO) were randomised prospectively to undergo either of the two operative modalities. Preoperatively size of the prostate, symptom scoring (IPSS), peak flow rate (Qmax) were assessed. Postoperatively and during 4 months follow up the following data were collected—operative time, catheterisation period, hospital stay, blood loss, Qmax and IPSS. Results: Preoperative parameters in both the groups showed no statistically significant differences with respect to prostate size, Qmax and IPSS Scoring. At 4 months follow up Qmax increased from (6.35 ± 4.49) to (16.41 ± 2.28) in TURP group and (4.51 ± 3.57) to (15.95 ± 2.58) in BNI group. IPSS decreased from 18.70 to 5.7 in TURP group and 18.90 to 6.00 in BNI group. All differences were statistically significant. There was a statistically significant difference in operative time, blood loss, hospital stay, catheterisation timing favouring BNI. Conclusion: TURP and BNI are equally effective in providing symptomatic improvement. BNI has an upper hand in reference to operative time, hospital stay, duration of catheterisation and blood loss.

Association of Increased Urine Brain Derived Neurotrophic Factor with Lower Urinary Tract Symptoms in Men with Benign Prostatic Hyperplasia

Urinary brain-derived neurotrophic factor（BDNF）, an ubiquitous neurotrophin, was found to rise in patients with benign prostatic hyperplasia（BPH）. We hypothesized that the urinary level of BDNF could be a potential biomarker for lower urinary tract symptoms（LUTS） in patients with BPH. Totally, 76 patients with BPH-caused LUTS and 32 male control subjects without BPH were enrolled. International Prostate Symptom Score（IPSS） was applied to assess the symptom severity of LUTS. Urodynamic tests were performed for the diagnosis of underlying detrusor overactivity（DO） in the patients with BPH. Urine samples were collected from all subjects. Urinary BDNF levels were measured using enzyme-linked immunosorbent assays and normalized by urinary creatinine（Cr） levels. Seventy-six BPH patients were divided into moderate LUTS group（n=51, 720） according to the IPSS. Of the 76 BPH patients, DO was present in 34（44.7%） according to the urodynamic test. The urinary BDNF/Cr levels were significantly higher in BPH patients with moderate LUTS（8.29±3.635, P〈0.0001） and severe LUTS（11.8±6.44, P〈0.0001） than normal controls（1.71±0.555）. Patients with severe LUTS tended to have higher urinary BDNF/Cr levels than patients with moderate LUTS（11.8±6.44 vs. 8.29±3.635, P=0.000）. The conditions of BPH with LUTS correlated with elevated urinary BDNF levels, and urinary BDNF levels were even higher in BPH-DO patients. The results of this study have provided evidence to suggest that urinary BDNF level test could evaluate the severity of LUTS in BPH patients, and BDNF level can be used as a biomarker

Are phosphodiesterase type 5 inhibitors effective for the management of lower urinary symptoms suggestive of benign prostatic hyperplasia?

AIM: To review the efficacy of phosphodiesterase type 5 inhibitors(PDE5-Is) in lower urinary tract symptoms(LUTS) suggestive of benign prostate hyperplasia(LUTS/BPH). METHODS: A comprehensive research was conducted to identify all publications relating to benign prostate hyperplasia and treatment with sildenafil, vardenafil and tadalafil. To assess the efficacy, the changes in total international prostate symptom score(IPSS), IPSS subscore including voiding, storage and quality of life(Qo L), Benign prostatic hyperplasia Impact Index(BII), maximum urinary flow rate(Qmax) and the International Index of Erectile Function(IIEF) were extracted. A meta-analytical technique was used for the analysis of integrated data from the included studies to evaluate the mean difference in the results. RESULTS: Total IPSS score, IIEF and BII showed a significant improvement in trials in which LUTS/BPH with or without erectile dysfunction(ED) were compared with the placebo. For LUTS/BPH, the mean differences of total IPSS score, IIEF and BII are-2.17, 4.88 and-0.43, P < 0.00001, respectively. For LUTS/BPH with comorbid ED, the mean difference are-1.97, 4.54 and-0.52, P < 0.00001, respectively. PDE5-Is appear to improve IPSS storage, voiding and Qo L subscore(mean difference =-0.71,-1.23 and-0.33, P < 0.00001, respectively). Although four doses of tadalafil(2.5, 5, 10 and 20 mg) failed to reach significance in Qmax(mean difference = 0.22, P = 0.10), the 5 mg dose of tadalafil significantly improved the Qmax(mean difference = 0.33, P = 0.03).CONCLUSION: PED5-Is demonstrated efficacy for improving LUTS in BPH patients with or without ED and could be considered to be the first line treatment for LUTS/BPH.

Network pharmacology research and experimental verification of Huangqi(Astragalus Radix)and Jinyingzi(Rosae Laevigatae Fructus)in treating benign prostatic hyperplasia

Objective This study aimed to analyze the mechanism of action of Huangqi(Astragalus Radix,HQ)-Jinyingzi(Rosae Laevigatae Fructus,JYZ)in the treatment of benign prostatic hyperplasia(BPH)based on network pharmacology and to verify the prediction through animal experimentation.Methods Based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine(BATMAN-TCM)databases,and literature,the active components and related target genes of HQ and JYZ were screened.The BPH target genes were screened based on the DisGeNET and GeneGards databases,and Excel was used to merge and remove duplicates.The Perl language was used to obtain drug-BPH target genes by intersecting shared target genes.A drug-component-target gene network diagram was constructed using Cytoscape software.The drug-BPH intersection target genes were inputted into the STRING database,and the key target genes were selected according to the degree algorithm.The output formed the basis for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses to determine the potential mechanism of HQ and JYZ in BPH treatment.High,medium,and low doses of HQ and JYZ extract were used to intervene in BPH rats,and then the prostate volume,wet weight,and prostate index of the BPH rats were determined.Changes in prostate histopathology and microvessel density(MVD)were evaluated using immunohistochemistry,and the optimal HQ and JYZ extract dose was confirmed.Finally,the optimal dose was used to intervene in a BPH rat model,and AKT1 and VEGF expressions were examined by immunohistochemistry.Results Based on network pharmacology,33 active components and 772 target genes were identified from HQ and JYZ,along with 817 BPH target genes and 112 drug-BPH common target genes.Among them were 10 key target genes,including AKT1,JUN,MAPK1,IL-6,TNF,ESR1,and VEGFA.KEGG enrichment analysis revealed 135 signaling pathways,including PI3K/AKT,IL-17,TNF,p53,MAPK,VEGF,JAK-STAT,and NF-κB pathways.The animal experiment showed that HQ and JYZ significantly improved prostate volume,wet weight,prostate index,and prostate histopathology of BPH rats,reducing MVD.In addition,HQ and JYZ inhibited the expression of AKT1 and VEGF in the prostate tissue of rats,promoted epithelial cell apoptosis,and inhibited angiogenesis,consistent with the prediction.Conclusion The combination of HQ and JYZ is effective for BPH therapy through multi-compound and multi-target collaboration.Its possible mechanism in treating BPH includes regulation of AKT1,VEGF protein,PI3K/Akt,and VEGF signaling pathways related to apoptosis,angiogenesis,and inflammation,with potential for clinical use and research.