Prostate Artery Embolization in Patients with Prostate Volumes of 80 mL or More: A Single-Institution Retrospective Experience of 93 Patients.

PURPOSE: To evaluate the safety and efficacy of prostate artery embolization (PAE) for the treatment of benign prostatic hyperplasia for prostates ≥ 80 mL. PATIENTS AND METHODS: A retrospective review was conducted of 93 patients with prostate volumes (PVs) ≥ 80 mL treated with PAE from April 2014 through October 2017. Mean patient age was 68.5 years (range 52-88) and mean age-adjusted Charlson comorbidity index was 3.2 (range 1-8). Exclusion criteria included history of biopsy-proven prostate cancer or catheter dependency. Clinical and urodynamic outcomes were reviewed at 1, 3, 6, and 12 months. Adverse events were graded according to the Clavien-Dindo classification. RESULTS: Mean PV decreased significantly from 141.7 mL to 98.1 mL at 3 months (P < .01) and 82.2 mL at 12 months (P < .01). Significant improvements were seen in 3- and 12-month mean International Prostate Symptom Scores (IPSS) (22.3 vs 7.1 and 7.3, respectively; P < .01 for both), quality of life (QOL) (4.4 vs 1.2 and 1.3; P < .01 for both), and postvoid residual volume (196.7mL vs 92.1 and 61.2 mL; P < .01 and P < .01, respectively). Significant improvement was also seen in 3-month mean maximum urinary flow: 7.7 mL/s vs 12.8 mL/s (P < .01). One grade II complication of stroke occurred; all other complications were self-limited and grade I. CONCLUSIONS: PAE achieved a clinically and statistically significant improvement in symptom burden and secondary outcome measures in patients with PVs ≥ 80 mL. PAE may be an alternate treatment for patients for whom conventional surgical options are limited or associated with significant morbidity.

Efficacy of Prostatic Artery Embolization for Catheter-Dependent Patients with Large Prostate Sizes and High Comorbidity Scores.

PURPOSE: To evaluate efficacy and safety of prostate artery embolization (PAE) in urinary catheter-dependent patients with large prostate volumes and high comorbidity scores. MATERIALS AND METHODS: A retrospective single-center review was conducted of 30 patients with urinary retention at time of PAE from November 2014 through February 2017. Mean (range) age was 73.1 years (48-94 y), age-adjusted Charlson comorbidity index was 4.5 (0-10), duration of urinary retention was 63.4 days (2-224 d), International Prostate Symptom Score quality-of-life (IPSS-QOL) was 5.3 (3-6), and prostate volume was 167.3 cm3 (55-557 cm3). These parameters were collected at 3, 6, and 12 months after PAE. Trials of voiding were performed approximately 2 weeks after PAE and, if failed, every 2 weeks thereafter. Adverse events were graded using the Clavien-Dindo classification. RESULTS: At a mean (range) of 18.2 days (1-72 d), 26 (86.7%) patients were no longer reliant on catheters. Follow-up was obtained in all patients eligible at 3 and 6 months and 17 of 20 (85.0%) patients eligible at 1 year. Mean (range) IPSS-QOL improved significantly to 1.2 (0-5), 0.7 (0-4), and 0.6 (0-4) at 3, 6, and 12 months (all P < .001). Mean (range) prostate volume decreased significantly to 115.9 cm3 (27-248 cm3) at 3 months (P < .001). Two patients experienced grade II urosepsis complications, which were successfully treated with intravenous antibiotics. All other complications were self-limited grade I complications. CONCLUSIONS: PAE represents a safe and effective option for management of patients with urinary retention, especially patients with large prostates who are not ideal surgical candidates.

Prostate Artery Embolization via Transradial or Transulnar versus Transfemoral Arterial Access: Technical Results.

PURPOSE: To compare safety and feasibility of prostate artery embolization (PAE) via transradial/transulnar access (TR/UA) and transfemoral access (TFA). MATERIALS AND METHODS: A retrospective analysis was conducted for 3 cohorts: the first 32 consecutive PAE procedures performed via TFA (initial TFA, January 2014 to August 2015), the following 32 procedures performed via TFA (advanced TFA, August 2015 to February 2016), and the first 32 procedures performed via TR/UA (February 2016 to July 2016). Indications included lower urinary tract symptoms (n = 68), urinary retention (n = 24), and preoperative embolization before prostatectomy (n = 4). A single operator performed all procedures at a single institution. RESULTS: Technical success was achieved in 29/32 (90.6%) initial TFA procedures, 31/32 (96.9%) advanced TFA procedures, and 30/32 (93.8%) TR/UA procedures. Mean procedure time was 110.0 minutes in TR/UA group, 155.1 min in initial TFA group, and 131.3 minutes in advanced TFA group (P < .01 and P = .03 relative to TR/UA); mean fluoroscopy time was 38.8 minutes in TR/UA group, 56.5 minutes in initial TFA group, and 48.0 minutes in advanced TFA group (P < .01 and P = .02 relative to TR/UA). Access site-related and overall adverse events did not vary significantly among study cohorts (P > .15 and P > .05, respectively). CONCLUSIONS: TR/UA represents a safe and feasible approach to PAE with a comparable safety profile to TFA. Reduced procedure and fluoroscopy times might be attributable to the learning curve or method of arterial access.

Evidence to support mitochondrial neuroprotection, in severe traumatic brain injury.

Traumatic brain injury (TBI) is still the leading cause of disability in young adults worldwide. The major mechanisms - diffuse axonal injury, cerebral contusion, ischemic neurological damage, and intracranial hematomas have all been shown to be associated with mitochondrial dysfunction in some form. Mitochondrial dysfunction in TBI patients is an active area of research, and attempts to manipulate neuronal/astrocytic metabolism to improve outcomes have been met with limited translational success. Previously, several preclinical and clinical studies on TBI induced mitochondrial dysfunction have focused on opening of the mitochondrial permeability transition pore (PTP), consequent neurodegeneration and attempts to mitigate this degeneration with cyclosporine A (CsA) or analogous drugs, and have been unsuccessful. Recent insights into normal mitochondrial dynamics and into diseases such as inherited mitochondrial neuropathies, sepsis and organ failure could provide novel opportunities to develop mitochondria-based neuroprotective treatments that could improve severe TBI outcomes. This review summarizes those aspects of mitochondrial dysfunction underlying TBI pathology with special attention to models of penetrating traumatic brain injury, an epidemic in modern American society.

Interaction of HIF-1α and Notch3 Is Required for the Expression of Carbonic Anhydrase 9 in Breast Carcinoma Cells.

Expression of carbonic anhydrase 9 (CA9) is associated with poor prognosis and increased tumor aggressiveness and does not always correlate with HIF-1α expression. Presently, we analyzed the regulation of CA9 expression during hypoxia by HIF-1α, Notch3, and the von Hippel-Lindau (VHL) in breast carcinoma cells. Both HIF-1α and Notch3 were absolutely required for the expression of CA9 mRNA, protein, and reporter. Reciprocal co-immunoprecipitation of HIF-1α, Notch3 intracellular domain (NICD3), and pVHL demonstrated their association. The presence of common consensus prolyl hydroxylation and pVHL binding motifs (L(XY)LAP);LLPLAP(2191) suggested an oxygen-dependent regulation for NICD3. However, unlike the HIF-1α protein, NICD3 protein levels were not modulated with hypoxia or hypoxia-mimetic agents. Surprisingly, mutations of the common prolyl hydroxylation and pVHL binding domain lead to the loss of CA9 mRNA, protein, and reporter activity. Chromatin immunoprecipitation assay demonstrated the association of NICD3, HIF-1α, and pVHL at the CA9 promoter. Further, the NICD3 mutant defective in prolyl hydroxylation and subsequent pVHL binding caused a reduction in cell proliferation of breast carcinoma cells. We show here for the first time that the interaction of HIF-1α with NICD3 is important for the regulation of CA9 expression. These findings suggest that although CA9 is a hypoxia-responsive gene, its expression is modulated by the interaction of HIF-1α, Notch3, and VHL proteins. Targeting the expression of CA9 by targeting upstream regulators could be useful in cancer/stem cell therapy.