Holmium laser enucleation of the prostate in patients with preexisting inflatable penile prostheses.

This retrospective study evaluated the safety and efficacy of holmium laser enucleation of the prostate (HoLEP) in patients with an inflatable penile prosthesis (IPP). Five men with a preexisting IPP underwent HoLEP for obstructive lower urinary tract symptoms at Baylor Scott and White Medical Center between January 2016 and September 2020. None of the patients had preexisting prostate malignancy or urethral strictures. Minimal blood loss was seen during HoLEP, with an average length of hospital stay of 1.4 days and an average time of catheterization of 1.4 days. None of the patients had any known postoperative complications, including need for transfusions, return to the operating room for postoperative bleeding, or clot evacuation. In conclusion, there was no increased risk of perioperative or postoperative complications for HoLEP in this group compared with the general population. HoLEP appears to be a safe and efficacious method for the treatment of lower urinary tract symptoms in patients with a preexisting IPP.

Pilot Trial of Midstream Urine Collection Device Versus Transurethral Catheter in Women With Lower Urinary Tract Symptoms: Practicality of Use in a Clinical Setting, Patient Preferences, and Comparison of Laboratory Findings.

OBJECTIVES: This study aimed to evaluate successful use of a midstream urine collection device in women with lower urinary tract symptoms and to assess specimen contamination. METHODS: Nonpregnant women 18 years or older without use of antibiotics in the last 4 weeks were recruited. After using the midstream urine collection device to obtain a specimen in a private restroom, a paired specimen was obtained by transurethral catheterization. Patients completed preference questionnaires. Culture organisms and microscopic urinalysis of paired specimens (device vs catheterized) were compared using the McNemar χ2 test. Bivariate analysis was performed. RESULTS: Successful use was demonstrated in 54 (77%) of 70. Reasons for failure included inadequate specimen volume and improper device use. Older median age (50 vs 72 years, P = 0.0003) and history of diabetes (7% vs 27%, P = 0.037) were associated with failed use. Organisms were discordant in 21 (41%) of 51 paired urine culture specimens. The device detected 7 (88%) of 8 uropathogens. There were no detectable differences in microscopic urinalysis. CONCLUSIONS: The midstream urine collection device could increase comfort, and many patients prefer it to transurethral catheterization. With proper patient selection and instructions for use, this device could increase satisfaction. Further studies are needed to assess contamination rates with this device.

Safety and efficacy of male urethral slings for management of persistent stress urinary incontinence after holmium laser enucleation of the prostate.

Holmium laser enucleation of the prostate gland (HoLEP) is an alternative to the traditional transurethral resection of the prostate, especially for large-volume prostates. One complication is urinary incontinence, which is usually stress urinary incontinence (SUI). Little data exist on surgical interventions for SUI after HoLEP. This retrospective case series examined the safety and possible efficacy of a midurethral sling (MUS) following HoLEP. Between January 2016 and February 2019, 610 HoLEPs were performed at our institution. Three (0.5%) had persistent, overly bothersome symptoms of SUI. All three underwent MUS placement with a transobturator AdVance® male sling after failed pelvic floor rehabilitation. The degree of SUI was evaluated by pad use pre-HoLEP, post-HoLEP, and post-MUS placement. Surgical times for HoLEP and MUS were evaluated. No patients were using pads for incontinence before HoLEP. The average pad use was 7 post-HoLEP and 0.3 post-MUS. The average morcellated prostate was 48 g, and surgical time was 68 min (52 for enucleation and 15 for morcellation). No complications were reported with MUS placement intraoperatively or postoperatively. MUS for persistent and bothersome SUI after HoLEP shows promise as a safe and effective surgical option.

Biliary damage and liver fibrosis are ameliorated in a novel mouse model lacking l-histidine decarboxylase/histamine signaling.

Primary sclerosing cholangitis (PSC) is characterized by biliary damage and fibrosis. Multidrug resistance-2 gene knockout (Mdr2-/-) mice and PSC patients have increased histamine (HA) levels (synthesized by l-histidine decarboxylase, HDC) and HA receptor (HR) expression. Cholestatic HDC-/- mice display ameliorated biliary damage and hepatic fibrosis. The current study evaluated the effects of knockout of HDC-/- in Mdr2-/- mice (DKO) on biliary damage and hepatic fibrosis. WT, Mdr2-/- mice, and homozygous DKO mice were used. Selected DKO mice were treated with HA. We evaluated liver damage along with HDC expression and HA serum levels. Changes in ductular reaction were evaluated along with liver fibrosis, inflammation and bile acid signaling pathways. The expression of H1HR/PKC-α/TGF-ß1 and H2HR/pERK/VEGF-C was determined. In vitro, cholangiocyte lines were treated with HA with/without H1/H2 inhibitors before measuring: H1/H2HR, TGF-ß1, and VEGF-C expression. Knockout of HDC ameliorates hepatic damage, ductular reaction, fibrosis, inflammation, bile acid signaling and H1HR/PKC-α/TGF-ß1 and H2HR/pERK/VEGF-C signaling. Reactivation of the HDC/HA axis increased these parameters. In vitro, stimulation with HA increased HR expression and PKC-α, TGF-ß1, and VEGF-C expression, which was reduced with HR inhibitors. Our data demonstrate the key role for the HDC/HA axis in the management of PSC progression.

Downregulation of hepatic stem cell factor by Vivo-Morpholino treatment inhibits mast cell migration and decreases biliary damage/senescence and liver fibrosis in Mdr2-/- mice.

Primary sclerosing cholangitis (PSC) is characterized by increased mast cell (MC) infiltration, biliary damage and hepatic fibrosis. Cholangiocytes secrete stem cell factor (SCF), which is a chemoattractant for c-kit expressed on MCs. We aimed to determine if blocking SCF inhibits MC migration, biliary damage and hepatic fibrosis. METHODS: FVB/NJ and Mdr2-/- mice were treated with Mismatch or SCF Vivo-Morpholinos. We measured (i) SCF expression and secretion; (ii) hepatic damage; (iii) MC migration/activation and histamine signaling; (iv) ductular reaction and biliary senescence; and (v) hepatic fibrosis. In human PSC patients, SCF expression and secretion were measured. In vitro, cholangiocytes were evaluated for SCF expression and secretion. Biliary proliferation/senescence was measured in cholangiocytes pretreated with 0.1% BSA or the SCF inhibitor, ISK03. Cultured HSCs were stimulated with cholangiocyte supernatant and activation measured. MC migration was determined with cholangiocytes pretreated with BSA or ISK03 loaded into the bottom of Boyden chambers and MCs into top chamber. RESULTS: Biliary SCF expression and SCF serum levels increase in human PSC. Cholangiocytes, but not hepatocytes, from SCF Mismatch Mdr2-/- mice have increased SCF expression and secretion. Inhibition of SCF in Mdr2-/- mice reduced (i) hepatic damage; (ii) MC migration; (iii) histamine and SCF serum levels; and (iv) ductular reaction/biliary senescence/hepatic fibrosis. In vitro, cholangiocytes express and secrete SCF. Blocking biliary SCF decreased MC migration, biliary proliferation/senescence, and HSC activation. CONCLUSION: Cholangiocytes secrete increased levels of SCF inducing MC migration, contributing to biliary damage/hepatic fibrosis. Targeting MC infiltration may be an option to ameliorate PSC progression.

Comprehensive Review of Molecular Mechanisms during Cholestatic Liver Injury and Cholangiocarcinoma.

Cholestatic liver injury is characterized by damage induced on the biliary tree and cholangiocytes, the cells lining the biliary tree, thus they are termed "cholangiopathies". Cholangiopathies include diseases such as Primary Biliary Cholangitis, Primary Sclerosing Cholangitis, Biliary Atresia and Cholangiocarcinoma. These pathologies lack viable therapies and most patients are diagnosed during late stage disease progression (with the exception of Biliary Atresia, which is found shortly after birth). The lack of therapies for these diseases has put a significant burden on the need for liver transplantation as this is the only indicative "cure" for cholangiopathies. The molecular mechanisms for cholangiopathies have been extensively studied; however, and unfortunately, the lack of effective biomarkers and therapeutics remains. In this review article we highlight the latest studies to investigate the molecular mechanisms regulating cholangiopathies and the potential therapeutics that might be discovered.