Correlation between metabolic syndrome and periurethral prostatic fibrosis: results of a prospective study.

BACKGROUND: Prostatic fibrosis, characterized by the accumulation of myofibroblasts and collagen deposition, is closely associated with LUTS and may lead to mechanical obstruction of the urethra. Additionally, Metabolic Syndrome (MetS), characterized by central obesity, high blood sugar, lipid metabolism disorders, and hypertension, is increasingly recognized as a proinflammatory condition linked to prostate inflammation. METHODS: Clinical data from 108 subjects who underwent transurethral resection of the prostate or bipolar plasmakinetic enucleation of the prostate were prospectively collected between June 2021 and August 2022. Patients were divided in two groups according to whether or not they had a diagnosis of MetS. Specimens were stained with Masson trichrome and the periurethral prostatic fibrosis extent was evaluated using quantitative morphometry. RESULTS: Forty-three patients (39.8%) were diagnosed with MetS. Patients with MetS showed a significantly greater extent of prostatic fibrosis than the others (68.1 ± 17.1% vs. 42.5 ± 18.2%, P < 0.001), and there was a positive correlation between the number of positive MetS parameters and the extent of prostatic fibrosis (R2 = 0.4436, P < 0.001). Multivariate regression analysis revealed that central obesity (B = 2.941, 95% confidence interval, 1.700-3.283), elevated fasting glucose (B = 1.036, 95% confidence interval, 0.293-1.780), reduced HDL cholesterol (B = 0.910, 95% confidence interval, 0.183-1.636) and elevated triglycerides (B = 1.666, 95% confidence interval, 0.824-2.508) were positively correlated to prostatic fibrosis. Elevated blood pressure, however, was unrelated to prostatic fibrosis (B = 0.009, 95% confidence interval, -0.664-0.683). CONCLUSIONS: The present findings suggest that prostatic fibrosis is positively correlated with MetS and its components including central obesity, elevated fasting glucose, reduced high density lipoprotein cholesterol and elevated triglycerides.

The P.R.OS.T.A.T.E Nomogram for the Preoperative Prediction of Clinical Efficacy of Transurethral Resection of the Prostate in Benign Prostatic Hyperplasia Patients.

Purpose: Transurethral resection of the prostate (TURP) is often indicated for benign prostatic hyperplasia (BPH). Some patients, however, fail to adequately respond to these interventions. Accordingly, a powerful prediction model for TURP efficacy is warranted. This study aimed to create a nomogram with preoperative parameters for the prediction of individual TURP efficacy. Methods: Clinical data from 356 BPH subjects who underwent TURP were retrospectively collected between November 2015 and June 2021 for nomogram development. The prediction model was developed using multivariable logistic regression analysis and presented as a nomogram. Nomogram performance was assessed through calibration curves and the concordance index (C-index). An independent validation cohort containing 177 consecutive patients in the corresponding period was used for external validation. The optimal cutoff value was determined through receiver operating characteristic curve (ROC) analysis by maximizing the Youden index, and its accuracy was assessed through sensitivity, specificity and predictive values. Results: In multivariate analysis of the primary cohort, the independent factors for TURP efficacy were age, International Prostate Symptom Score (IPSS), intravesical prostatic protrusion (IPP), bladder wall thickness (BWT), peripheral zone thickness (PT) and transitional zone thickness (TT), all of which were included in the nomogram. The calibration curve for survival probability showed good agreement between the nomogram predictions and actual observations. The C-index for predicting TURP efficacy was 0.860 (95% confidence interval [CI], 0.808-0.911). The optimal cutoff total nomogram score was 177, with a maximum Youden index of 0.643. The sensitivity, specificity, positive predictive value, and negative predictive value for predicting TURP efficacy were 70.6%, 75.6%, 90.6%, and 43.7% in the validation cohort, respectively. Logistic regression analysis in the validation cohort demonstrated that the area under the curve (AUC) was 0.806 (95% CI, 0.733-0.879). Conclusion: The P.R.OS.T.A.T.E nomogram objectively and accurately predicted TURP efficacy, thereby facilitating the clinical decision-making process.

Clinical practice guideline for transurethral plasmakinetic resection of prostate for benign prostatic hyperplasia (2021 Edition).

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline "2018 Standard Edition". However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons' surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons' skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.

A novel mouse model simulating transurethral laser vaporization prostatectomy.

Benign prostatic hyperplasia (BPH) is a common disease in elderly men, and transurethral laser prostatectomy (TULP) has been widely used in the clinic to remove bladder outlet obstruction caused by BPH. Previous animal models for wound repair after prostatectomy have many limitations, and there have been no previous reports of a mouse model of TULP. Therefore, this study aimed to establish a novel mouse model of TULP. Twelve healthy adult Kunming (KM) mice received transurethral laser vaporization prostatectomy with a 200-µm thulium laser. The mice were sacrificed, and wound specimens from the prostatic urethra and bladder neck were harvested at 1 day, 3 days, 5 days, and 7 days after surgery. Hematoxylin-eosin (HE) and immunohistochemistry were applied to confirm the establishment of the mouse TULP model. One day after the surgery, urothelium expressing uroplakin (UPK) was absent in the urethral wound site, and a large number of necrotic tissues were found in the wound site. There was no UPK-positive urothelium in the wound 3 days after surgery. At 5 days after surgery, monolayer urothelium expressing UPK was found in the wound site, indicating that the re-epithelization of the wound had been completed. On the 7th day after surgery, there were multiple layers of urothelium with UPK expression, indicating that the repair was completed. It is feasible to establish a mouse TULP model by using a microcystoscope system and a 200-µm thulium laser.

Modified bladder outlet obstruction index for powerful efficacy prediction of transurethral resection of prostate with benign prostatic hyperplasia.

BACKGROUND: The correlation between modified bladder outlet obstruction index (MBOOI) and surgical efficacy still remains unknown. The purpose of the study was to investigate the clinical value of the MBOOI and its use in predicting surgical efficacy in men receiving transurethral resection of the prostate (TURP). METHODS: A total of 403 patients with benign prostate hyperplasia (BPH) were included in this study. The International Prostate Symptom Score (IPSS), quality of life (QoL) index, transrectal ultrasonography, and pressure flow study were conducted for all patients. The bladder outlet obstruction index (BOOI) (PdetQmax-2Qmax) and MBOOI (Pves-2Qmax) were calculated. All patients underwent TURP, and surgical efficacy was accessed by the improvements in IPSS, QoL, and Qmax 6 months after surgery. The association between surgical efficacy and baseline factors was statistically analyzed. RESULTS: A comparison of effective and ineffective groups based on the overall efficacy showed that significant differences were observed in PSA, Pves, PdetQmax, Pabd, BOOI, MBOOI, TZV, TZI, IPSS-t, IPSS-v, IPSS-s, Qmax, and PVR at baseline (p < 0.05). Binary logistic regression analysis suggested that MBOOI was the only baseline parameter correlated with the improvements in IPSS, QoL, Qmax, and the overall efficacy. Additionally, the ROC analysis further verified that MBOOI was more optimal than BOOI, TZV and TZI in predicting the surgical efficacy. CONCLUSION: Although both MBOOI and BOOI can predict the clinical symptoms and surgical efficacy of BPH patients to a certain extent, however, compared to BOOI, MBOOI may be a more useful factor that can be used to predict the surgical efficacy of TURP. Trial registration retrospectively registered.

Normobaric hyperoxia plays a protective role against renal ischemia-reperfusion injury by activating the Nrf2/HO-1 signaling pathway.

Following renal ischemia-reperfusion injury (RIRI), because of the decrease in oxygen supply to the kidney, a large amount of oxygen-free radicals is generated, and in severe cases, tissue cells will undergo apoptosis or even die. Normobaric hyperoxia (NBHO) is a very common clinical adjuvant treatment. It restores the oxygen supply after renal ischemia and combats oxidative stress in tissues, thus playing a protective role. In this study, our aim is to elucidate the protective mechanism of NBHO inhalation in a rat RIRI model. We performed a surgical excision of the left kidney of the rat and established a right kidney solitary kidney model. Later, the right renal pedicle of the rat was clamped using a non-invasive vascular clamp for 45 min. After the vascular clamp was released and reperfused for 24 h, the rat was placed in a closed oxygen chamber. It was subjected to inhalation of high-concentration oxygen (50%-55%), 2 h daily, for 7 days.RIRI induces postoperative weight loss, impaired renal function, increased oxygen free radicals, reduced antioxidant substances, increased histopathological damage, and increased levels of apoptosis. These effects were significantly improved after treatment with NBHO. At the same time, NBHO significantly increased the expression levels of Nrf2 and HO-1 in the tissues after RIRI. To verify whether HO-1 induced by Nrf2 is involved in the resistance to oxidative stress, after the rat RIRI and before inhaling NBHO, we intraperitoneally injected HO-1 specific inhibitor zinc protoporphyrin (ZnPP) (45 µmol/Kg). However, we found that ZnPP reversed the protective effect of NBHO on RIRI in rats. Combining all the results, we have demonstrated the protective effect of NBHO on RIRI, which can be at least partially attributed to the activation of the Nrf2/HO-1 antioxidative stress pathway.

miR-155-5p Promotes Oxalate- and Calcium-Induced Kidney Oxidative Stress Injury by Suppressing MGP Expression.

Oxalate and calcium are the major risk factors for calcium oxalate (CaOx) stone formation. However, the exact mechanism remains unclear. This study was designed to confirm the potential function of miR-155-5p in the formation of CaOx induced by oxalate and calcium oxalate monohydrate (COM). The HK-2 cells were treated by the different concentrations of oxalate and COM for 48 h. We found that oxalate and COM treatment significantly increased ROS generation, LDH release, cellular MDA levels, and H2O2 concentration in HK-2 cells. The results of qRT-PCR and western blot showed that expression of NOX2 was upregulated, while that of SOD-2 was downregulated following the treatment with oxalate and COM in HK-2 cells. Moreover, the results of miRNA microarray analysis showed that miR-155-5p was significantly upregulated after oxalate and COM treated in HK-2 cells, but miR-155-5p inhibitor treatment significantly decreased ROS generation, LDH release, cellular MDA levels, and H2O2 concentration in HK-2 cells incubated with oxalate and COM. miR-155-5p negatively regulated the expression level of MGP via directly targeting its 3'-UTR, verified by the Dual-Luciferase Reporter System. In vivo, polarized light optical microphotography showed that CaOx crystal significantly increased in the high-dose oxalate and Ca2+ groups compared to the control group. Furthermore, IHC analyses showed strong positive staining intensity for the NOX-2 protein in the high-dose oxalate and Ca2+-treated mouse kidneys, and miR-155-5p overexpression can further enhance its expression. However, the expression of SOD-2 protein was weakly stained. In conclusion, our study indicates that miR-155-5p promotes oxalate- and COM-induced kidney oxidative stress injury by suppressing MGP expression.

Urine can speed up the re-epithelialization process of prostatic urethra wounds by promoting the proliferation and migration of prostate epithelial cells.

OBJECTIVES: The present study aimed to investigate the influence of urine on re-epithelialization in canine prostatic urethra after prostatectomy and explore possible causes. METHOD: We established two groups of prostatic canine models. The first group contained urine that canines underwent the surgery by two-micron laser resection of the prostate-tangerine technique (TmLRP-TT), and no transurethral catheter was required. The second group was without urine that canines accepted the surgery by TmLRP-TT add ureter skin ostomy urine bypass. Histopathology of re-epithelialization of repair in trauma in canine prostatic urethra was observed by hematoxylin and eosin (HE) staining, and immunochemistry was used to determine the expression of transforming growth factor-ß1 (TGF-ß1). Human prostate epithelial line (BPH-1) cells were cultured with or without urine and the abilities of proliferation and migration were tested by CCK-8 and transwell assays, respectively. RESULTS: The histology displayed that there was distinct proliferation of prostatic cell under the wound after 3 days, re-epithelialization began after 9 days, and finished after 28 days at urine group. The TGF-ß1 like-IR in prostatic epithelium cells and fibroblast cells under the wound at urine group were strikingly increased as compared with the cells at no urine group after 3, 9, and 11 days, respectively (p < 0.05). In CCK-8 and Transwell assays, an increase of cells' proliferation and migration was detected in urine culture group compared with no urine culture group (p < 0.05). CONCLUSION: Urine may speed up the re-epithelialization process for prostatic urethra wounds by promoting proliferation and migration of prostate epithelial cells.

Finasteride accelerates prostate wound healing after thulium laser resection through DHT and AR signalling.

OBJECTIVES: Urinary tract infection, urinary frequency, urgency, urodynia and haemorrhage are common post-operative complications of thulium laser resection of the prostate (TmLRP). Our study mainly focuses on the role of finasteride in prostate wound healing through AR signalling. MATERIALS AND METHODS: TmLRP beagles were randomly distributed into different treatment groups. Serum and intra-prostatic testosterone and DHT level were determined. Histological analysis was conducted to study the re-epithelialization and inflammatory response of the prostatic urethra in each group. We investigated the role of androgen in proliferation and inflammatory response in prostate. In addition, the effects of TNF-α on prostate epithelium and stromal cells were also investigated. RESULTS: Testosterone and DHT level increased in testosterone group and DHT decreased in finasteride group. Accelerated wound healing of prostatic urethra was observed in the finasteride group. DHT suppressed proliferation of prostate epithelium and enhanced inflammatory response in prostate. We confirmed that DHT enhanced macrophages TNF-α secretion through AR signalling. TNF-α suppressed proliferation of prostate epithelial cells and retarded cell migration. TNF-α also played a pivotal role in suppressing fibroblasts activation and contraction. CONCLUSION: Testosterone treatment repressed re-epithelialization and wound healing of prostatic urethra. Finasteride treatment may be an effective way to promote prostate re-epithelialization.

Androgen Deprivation Accelerates the Prostatic Urethra Wound Healing After Thulium Laser Resection of the Prostate by Promoting Re-Epithelialization and Regulating the Macrophage Polarization.

BACKGROUND: Complications after a thulium laser resection of the prostate (TmLRP) are related to re-epithelialization of the prostatic urethra. Since prostate growth and development are induced by androgen, the aim of this study was to determine the role and explore the mechanism of androgen in wound healing of the prostatic urethra. METHODS: Beagles that received TmLRPs were randomly distributed into a castration group, a testosterone undecanoate (TU) group, and a control group. The prostate wound was assessed once a week using a cystoscope. Histological analysis was then carried out to study the re-epithelialization of the prostatic urethra in each group. The inflammatory response in the wound tissue and urine was also investigated. RESULTS: The healing of the prostatic urethra after a TmLRP was more rapid in the castration group and slower in the TU group than that in the control group. Castration accelerated re-epithelialization by promoting basal cell proliferation in the wound surface and beneath the wound and by accelerating the differentiation of basal cells into urothelial cells. Castration reduced the duration of the inflammatory phase and induced the conversion of M1 macrophages to M2 macrophages, thus accelerating the maturation of the wound. By contrast, androgen supplementation enhanced the inflammatory response and prolonged the inflammatory phase. Moreover, the anti-inflammatory phase was delayed and weakened. CONCLUSION: Androgen deprivation promotes re-epithelialization of the wound, regulates the inflammatory response, and accelerates wound healing of the prostatic urethra after a TmLRP. Prostate 77:708-717, 2017. © 2017 Wiley Periodicals, Inc.

[New understanding of dog's prostatic urethral re-epithelial underwent two-micron laser prostatic vaporesection].

OBJECTIVE: To study the re-epithelialization of dog's prostate urethra after two-micron laser resection of the prostate (TmLRP) and the role of CK34 (CK34ßE12)-positive cells in this process. METHODS: TmLRP were performed in 15 elder male dogs and wound specimens harvested at Days 3, 7 and 14 respectively. Immunohistochemical staining was performed to determine the expression levels of CK34 and prostate specific antigen (PSA) in prostatic urethra urothelial cells. RESULTS: There was no CK34-positive cells in surgical wounds after 3 days while a cluster of CK34-positive cells were found to cover surgical wounds after 7 days, and these cells attached to residual prostate tissues. At Day 14 post-operation, positive expression of CK34 was found in basal cells of newborn urothelium. CONCLUSION: Prostate tissues are the important organizations for re-epithelialization of prostatic urethra after benign prostate hyperplasia surgery, and CK34-positive basal cells play an important role in this process.