Stress Incontinence Surgery Does Not Cause Pelvic Malignancy: A Population-Based Cohort Study.

PURPOSE: We sought to determine if stress urinary incontinence surgery (mesh or nonmesh) is associated with the development of pelvic malignancies later in life. MATERIALS AND METHODS: We performed a retrospective cohort study between January 1, 2002 and October 31, 2015 of all women in Ontario, Canada without a history of pelvic malignancy who underwent an index stress incontinence surgery. The primary outcome was a composite of any pelvic malignancy (including urological and gynecological cancers) following stress incontinence surgery. Secondarily, we considered each cancer individually. A survival analysis using a Cox proportional-hazards model with a 3-level categorical exposure (mesh surgery, nonmesh surgery, and control) was performed. Patients were followed until death, emigration or the study end (October 31, 2017). RESULTS: Of the women 74,968 underwent stress urinary incontinence surgery during the study period. There were 5,505,576 women in the control group. Over a median followup of 8.5 years (IQR, 5.5-11.9), 587 pelvic malignancies occurred in the surgery group. Women who underwent stress incontinence surgery had a reduced risk of pelvic malignancy independent of surgery type, compared to controls (Wald type 3 p <0.001; mesh HR, 0.68 [95% CI, 0.62-0.76]; p <0.0001; nonmesh HR, 0.37 [95% CI, 0.29-0.46]; p <0.0001). The individual pelvic cancers similarly demonstrated a reduced risk of malignancy following stress incontinence surgery. CONCLUSIONS: At a median followup of 8.5 years, women had no increased risk of pelvic malignancy following either mesh or nonmesh stress urinary incontinence surgery in a large population-based cohort.

Endoscopic Treatment of Vesicourethral Stenosis after Radical Prostatectomy: Outcomes and Predictors of Success.

PURPOSE: We describe patency outcomes and predictors of success for the endoscopic treatment of vesicourethral stenosis after radical prostatectomy. MATERIALS AND METHODS: A retrospective review identified 142 patients who underwent endoscopic treatment for vesicourethral stenosis after radical prostatectomy during a 10-year period. Clinical parameters examined were treatment modality, prior endoscopic treatment, age, concurrent radiotherapy, body mass index 35 kg/m(2) or greater, diabetes and smoking. The primary outcome measure was absence of stenosis (less than 16Fr) on followup cystoscopy. Treatment modalities were divided into 5 groups of holmium laser incision, cold knife incision, electrocautery incision, dilation or UroLume® stent. Descriptive statistics as well as univariate and multivariate logistic regression were performed. RESULTS: A total of 142 patients required 292 endoscopic treatments for a mean of 2.1 treatments per patient. The success rate of a single endoscopic treatment was 44.2%. However, 91% of the patients were ultimately treated successfully with endoscopic measures with a mean followup of 9.7 months. On multivariate analysis treatment modality (OR 0.65, 95% CI 0.52-0.80, p <0.001), prior failed treatment (OR 0.86, 95% CI 0.74-0.99, p=0.04) and smoking (OR 0.55, 95% CI 0.34-0.97, p=0.04) were associated with failure, while age (p=0.85), diabetes (p=0.25), radiotherapy (p=0.68) and body mass index 35 kg/m(2) or greater (p=0.92) were not. Compared to holmium laser incision all modalities except UroLume were associated with treatment failure. CONCLUSIONS: Most patients with vesicourethral stenosis after radical prostatectomy are treated successfully with endoscopic modalities but often require multiple procedures. Unlike anterior urethral strictures, in this specific scenario the use of repeat endoscopic treatments appears justified. Holmium laser incision may be more successful compared to other endoscopic modalities.

Postresuscitation administration of doxycycline preserves cardiac contractile function in hypoxia-reoxygenation injury of newborn piglets*.

OBJECTIVE: Cardiac injury is common in asphyxiated neonates and is associated with matrix metalloproteinase-2 activation. Although studies have demonstrated the cardioprotective effects of matrix metalloproteinase inhibition, this has not been tested in clinically translatable models of hypoxia-reoxygenation injury. We aimed to elucidate the effect of doxycycline, a matrix metalloproteinase inhibitor, on cardiac injury and functional recovery in a swine model of neonatal hypoxia-reoxygenation. DESIGN: Thirty-three newborn piglets were acutely instrumented for continuous monitoring of cardiac output and systemic arterial pressure. After stabilization, normocapnic alveolar hypoxia (10-15% oxygen) was instituted for 2 hours followed by 4 hours of normoxic reoxygenation. Piglets were blindly, block randomized to receive IV boluses of normal saline (control) and doxycycline at 5 minutes of reoxygenation (n = 7/group). Sham-operated piglets (n = 5) received no hypoxia-reoxygenation. Markers of myocardial injury (plasma and myocardial tissue troponin I; myocardial lactate) and oxidative stress (lipid hydroperoxides) were measured by enzyme-linked immunosorbent assay and Western blot. Myocardial matrix metalloproteinase-2 activity was quantified by gelatin zymography and immunoprecipitation. SETTING: University animal laboratory. SUBJECTS: Piglets (1-4 d old, weighing 1.4-2.5 kg). INTERVENTIONS: IV doxycycline (3, 10, or 30 mg/kg) given during resuscitation. MEASUREMENTS AND MAIN RESULTS: Hypoxic piglets had cardiogenic shock (cardiac output 58% ± 1% of baseline), hypotension (systemic arterial pressure 31 ± 1 mm Hg), and acidosis (pH 7.02 ± 0.02). Doxycycline improved cardiac and stroke volume index with no chronotropic effect in doxycycline-treated piglets compared with controls. Systemic arterial pressure was higher and the pulmonary artery pressure/systemic arterial pressure ratio was lower in doxycycline groups, with reduced levels of markers of myocardial injury and oxidative stress in doxycycline-treated piglets compared with controls. Negative correlations were found between markers of myocardial injury (plasma troponin I, myocardial lactate) and functional recovery and between myocardial tissue and plasma troponin I. Doxycycline-treated piglets had lower myocardial matrix metalloproteinase-2 activity compared with controls. CONCLUSIONS: Postresuscitation administration of doxycycline attenuates cardiac injury and improves functional recovery in newborn piglets with hypoxia-reoxygenation.

Surgical management of benign prostatic obstruction: 20-year population-level trends.

INTRODUCTION: Benign prostatic obstruction (BPO) due to histological benign prostatic hyperplasia is highly prevalent among older men. Despite widespread use of medical therapy, surgical treatment remains a mainstay in the management of BPO. We sought to characterize trends in the surgical management of BPO in Ontario, Canada. METHODS: We performed an interrupted time-series analysis using segmented regression among men aged 18 years and older undergoing surgical treatment for BPO between January 1, 1994 and December 31, 2014 in Ontario, Canada. The passage of time was considered the primary exposure. The primary outcome was the proportion of all BPO surgeries performed using each of the following modalities: transurethral resection of the prostate (TURP), endoscopic laser prostatectomy, open/laparoscopic prostatectomy, and others. RESULTS: We identified 136 459 men who underwent BPO surgery between 1994 and 2014. The annual age-adjusted rate of BPO surgery declined significantly over time (24 to 10 per 10 000 population in 1994 and 2014, respectively). From 1994-2001, there were no significant changes in the distribution of BPO surgical modalities, with TURP the most common throughout (97.2% and 97% in 1994 and 2001, respectively). From 2002-2014, there was a significant decline in the use of TURP (92.1% to 76.9%; p=0.027) with a corresponding increase in the use of endoscopic laser prostatectomy (3.5% to 21.9%; p=0.0008). CONCLUSIONS: This study demonstrates a shift in the management of BPO, with increasing use of endoscopic laser prostatectomy, beginning in 2002. However, TURP remains the most common treatment modality.

Doxycycline attenuates renal injury in a swine model of neonatal hypoxia-reoxygenation.

Acute kidney injury in asphyxiated neonates is common. The renal protective effects of doxycycline, a known matrix metalloproteinase (MMP) inhibitor, have been demonstrated in rat ischemic-reperfusion models of injury. These effects have not been tested in large-animal models designed to reflect true clinical scenarios of neonatal hypoxia-reoxygenation (H-R). Newborn piglets were surgically instrumented for hemodynamic monitoring and subjected to 2 h of hypoxia followed by 4 h of normoxic reoxygenation. Piglets were blindly randomized to receive i.v. saline or doxycycline (3, 10, or 30 mg/kg) 5 min into reoxygenation (n = 7 per group). Sham-operated piglets (n = 5) received no H-R. Renal injury was investigated by histologic examination and measuring serum creatinine, urinary N-acetyl-D-glucosaminidase activity and renal tissue lactate with enzyme-linked immunosorbent assay. Renal tissue oxidative stress (lipid hydroperoxides) and total MMP-2 activity were measured with enzyme-linked immunosorbent assay and gelatin zymography, respectively. Piglets treated with doxycycline had significantly improved cardiac index, systemic arterial pressure, renal artery blood flow, and oxygen delivery, with no difference observed in heart rate compared with controls. The H-R piglets had significantly higher urinary N-acetyl-D-glucosaminidase activity, renal tissue lipid hydroperoxides, lactate, and MMP-2 activity, which were attenuated to varied degrees in a dose-related manner in piglets treated with doxycycline (P = 0.08 to P < 0.05). Serum creatinine and histologic features of H-R were not different among groups. Postresuscitation administration of doxycycline improved renal perfusion, attenuated renal injury, and reduced tissue oxidative stress and MMP-2 activity in a clinically translatable newborn swine model of H-R.