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.

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.

Complications after surgery for benign prostatic enlargement: a population-based cohort study in Ontario, Canada.

OBJECTIVES: To examine the complication rates after benign prostatic enlargement (BPE) surgery and the effects of age, comorbidity and preoperative medical therapy. DESIGN: A retrospective, population-based cohort study using linked administrative data. SETTING: Ontario, Canada. PARTICIPANTS: 52 162 men≥66 years undergoing first BPE surgery between 1 January 2003 to 31 December 2014. INTERVENTION: Medical therapy preoperatively and surgery for BPE. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was overall 30-day postoperative complication rates. Secondary outcomes included BPE-specific event rates (bleeding, infection, obstruction, trauma) and non-BPE specific event rates (cardiovascular, pulmonary, thromboembolic and renal). Multivariable analysis examined the association between preoperative medical therapy and postoperative complication rates. RESULTS: The 30-day overall complication rate after BPE surgery was 2828 events/10 000 procedures and increased annually over the study period. Receipt of preoperative α-blocker monotherapy (relative rate (RR) 1.05; 95% CI 1.00 to 1.09; p=0.033) and antithrombotic medications (RR 1.27; 95% CI 1.22 to 1.31; p<0.0001) was associated with increased complication rates. Among the ≥80-year-old group, the rate of complications increased by 39% from 2003 to 2014 (RR 1.39; 95% CI 1.21 to 1.61; p<0.0001). The mean duration of medical and conservative management increased by a mean of 2.1 years between 2007 and 2014 (p<0.0001 for trend). CONCLUSIONS: Thirty-day complication rates after BPE surgery have increased annually between 2003 and 2014. Preoperative medical therapy with alpha blockers or antithrombotics was independently associated with higher rates of complications. Over this time, the duration of conservative therapy also increased.

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.

Exhaled CO2 Parameters as a Tool to Assess Ventilation-Perfusion Mismatching during Neonatal Resuscitation in a Swine Model of Neonatal Asphyxia.

BACKGROUND: End-tidal CO2 (ETCO2), partial pressure of exhaled CO2 (PECO2), and volume of expired CO2 (VCO2) can be continuously monitored non-invasively to reflect pulmonary ventilation and perfusion status. Although ETCO2 ≥14 mmHg has been shown to be associated with return of an adequate heart rate in neonatal resuscitation and quantifying the PECO2 has the potential to serve as an indicator of resuscitation quality, there is little information regarding capnometric measurement of PECO2 and ETCO2 in detecting return of spontaneous circulation (ROSC) and survivability in asphyxiated neonates receiving cardiopulmonary resuscitation (CPR). METHODS: Seventeen newborn piglets were anesthetized, intubated, instrumented, and exposed to 45-minute normocapnic hypoxia followed by apnea to induce asphyxia. Protocolized resuscitation was initiated when heart rate decreased to 25% of baseline. Respiratory and hemodynamic parameters including ETCO2, PECO2, VCO2, heart rate, cardiac output, and carotid artery flow were continuously measured and analyzed. RESULTS: There were no differences in respiratory and hemodynamic parameters between surviving and non-surviving piglets prior to CPR. Surviving piglets had significantly higher ETCO2, PECO2, VCO2, cardiac index, and carotid artery flow values during CPR compared to non-surviving piglets. CONCLUSION: Surviving piglets had significantly better respiratory and hemodynamic parameters during resuscitation compared to non-surviving piglets. In addition to optimizing resuscitation efforts, capnometry can assist by predicting outcomes of newborns requiring chest compressions.

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.

3:1 compression to ventilation ratio versus continuous chest compression with asynchronous ventilation in a porcine model of neonatal resuscitation.

OBJECTIVE: In contrast to the resuscitation guidelines of children and adults, guidelines on neonatal resuscitation recommend synchronized 90 chest compressions with 30 manual inflations (3:1) per minute in newborn infants. The study aimed to determine if chest compression with asynchronous ventilation improves the recovery of bradycardic asphyxiated newborn piglets compared to 3:1 Compression:Ventilation cardiopulmonary resuscitation (CPR). INTERVENTION AND MEASUREMENTS: Term newborn piglets (n=8/group) were anesthetized, intubated, instrumented and exposed to 45-min normocapnic hypoxia followed by asphyxia. Protocolized resuscitation was initiated when heart rate decreased to 25% of baseline. Piglets were randomized to receive resuscitation with either 3:1 compressions to ventilations (3:1C:V CPR group) or chest compressions with asynchronous ventilations (CCaV) or sham. Continuous respiratory parameters (Respironics NM3(®)), cardiac output, mean systemic and pulmonary artery pressures, and regional blood flows were measured. MAIN RESULTS: Piglets in 3:1C:V CPR and CCaV CPR groups had similar time to return of spontaneous circulation, survival rates, hemodynamic and respiratory parameters during CPR. The systemic and regional hemodynamic recovery in the subsequent 4h was similar in both groups and significantly lower compared to sham-operated piglets. CONCLUSION: Newborn piglets resuscitated by CCaV had similar return of spontaneous circulation, survival, and hemodynamic recovery compared to those piglets resuscitated by 3:1 Compression:Ventilation ratio.

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.

Cardiopulmonary resuscitation with chest compressions during sustained inflations: a new technique of neonatal resuscitation that improves recovery and survival in a neonatal porcine model.

BACKGROUND: Guidelines on neonatal resuscitation recommend 90 chest compressions (CCs) and 30 manual inflations (3:1) per minute in newborns. The study aimed to determine whether CC s during sustained inflations (SIs) improves the recovery of asphyxiated newborn piglets in comparison with coordinated 3:1 resuscitation. METHODS AND RESULTS: Term newborn piglets (n=8/group) were anesthetized, intubated, instrumented, and exposed to 45-minute normocapnic hypoxia followed by asphyxia. Piglets were randomly assigned to receive either 3:1 resuscitation (3:1 group) or CCs during SIs (SI group) when the heart rate decreased to 25% of baseline. Piglets randomly assigned to the SI group received SIs with a pressure of 30 cm H2O for 30 s. During the SI, CCs at a rate of 120/min were provided. SI was interrupted after 30 s for 1 s before a further 30-s SI was provided. CCs were continued throughout SIs. CCs and SI were continued until the return of spontaneous circulation. Continuous respiratory parameters, cardiac output, mean systemic and pulmonary artery pressures, and regional blood flows were measured. Mean (standard deviation) time for return of spontaneous circulation was significantly reduced in SI group versus 3:1 group (32 [11] s versus 205 [113] s, respectively). In the SI group, administration of oxygen and epinephrine was significantly lower, whereas minute ventilation and exhaled CO2 were significantly increased. The SI group had significantly higher mean systemic and pulmonary arterial pressures during resuscitation in comparison with the 3:1 group (51 [10] versus 31 [5] mm Hg; 41[7] versus 31 [7] mm Hg, respectively; all P<0.05), with improved cardiac output and carotid blood flow. CONCLUSIONS: Combining CCs and SIs significantly improved the return of spontaneous circulation with better hemodynamic recovery in asphyxiated newborn piglets in comparison with standard coordinated 3:1 resuscitation.

Low-dose vasopressin improves cardiac function in newborn piglets with acute hypoxia-reoxygenation.

Cardiovascular dysfunction in asphyxiated neonates contributes significantly to their morbidity and mortality. We have recently shown that a low-dose vasopressin infusion (0.005 - 0.01 units/kg per hour) may improve myocardial oxygen transport balance in a swine model of neonatal hypoxia-reoxygenation. We aimed to compare the systemic and regional hemodynamic effects of low-dose vasopressin to dobutamine, a synthetic beta-adrenoreceptor agonist. Piglets (1 - 5 days old, 1.6 - 2.2 kg) were anesthetized and instrumented to continuously monitor systemic hemodynamic parameters, including cardiac output and mesenteric flow indices. After 2 h of hypoxia (10% - 15% O2), piglets had normoxic reoxygenation for 4 h. In a blinded randomized fashion, piglets received infusion of either vasopressin (0.01 units/kg per hour started at 30 min of reoxygenation) or dobutamine (20 µg/kg per minute started at 2 h of reoxygenation) (n = 8 per group). Hypoxia-reoxygenation controls (placebo, n = 8) and sham-operated (n = 5) piglets were also studied. Tissue lactate, glutathione, glutathione disulfide, and lipid hydroperoxides levels and histology of the left ventricle and the small bowel were analyzed. Plasma was also analyzed for troponin-I and intestinal fatty acid-binding protein levels. Piglets subjected to hypoxia-reoxygenation had cardiogenic shock and metabolic acidosis, which improved on reoxygenation. During recovery, cardiac output and mesenteric flows gradually deteriorated and were increased similarly in vasopressin- and dobutamine-treated piglets (P < 0.05 vs. controls). Plasma troponin-I and left ventricular lactate levels were lower in the vasopressin and dobutamine groups (P < 0.05 vs. controls), with no difference in the histological analysis among groups. The intestinal GSSG/GSH ratio and lipid hydroperoxides level were lower in the vasopressin and dobutamine groups (P < 0.05 vs. controls). This study is the first to demonstrate that a low-dose vasopressin infusion used in the setting of neonatal swine model of hypoxia-reoxygenation is associated with an improvement in cardiac output and mesenteric perfusion.

The Canadian general surgery resident: defining current challenges for surgical leadership.

BACKGROUND: Surgery training programs in Canada and the United States have recognized the need to modify current models of training and education. The shifting demographic of surgery trainees, lifestyle issues and an increased trend toward subspecialization are the major influences. To guide these important educational initiatives, a contemporary profile of Canadian general surgery residents and their impressions of training in Canada is required. METHODS: We developed and distributed a questionnaire to residents in each Canadian general surgery training program, and residents responded during dedicated teaching time. RESULTS: In all, 186 surveys were returned for analysis (62% response rate). The average age of Canadian general surgery residents is 30 years, 38% are women, 41% are married, 18% have dependants younger than 18 years and 41% plan to add to or start a family during residency. Most (87%) residents plan to pursue postgraduate education. On completion of training, 74% of residents plan to stay in Canada and 49% want to practice in an academic setting. Almost half (42%) of residents identify a poor balance between work and personal life during residency. Forty-seven percent of respondents have appropriate access to mentorship, whereas 37% describe suitable access to career guidance and 40% identify the availability of appropriate social supports. Just over half (54%) believe the stress level during residency is manageable. CONCLUSION: This survey provides a profile of contemporary Canadian general surgery residents. Important challenges within the residency system are identified. Program directors and chairs of surgery are encouraged to recognize these challenges and intervene where appropriate.

Therapeutic strategies to protect the immature newborn myocardium during resuscitation following asphyxia.

Perinatal asphyxia contributes to over one million newborn deaths worldwide annually, and may progress to multiorgan failure. Cardiac dysfunction, of varying severity, is seen in 50%-70% of asphyxiated newborns. Resuscitation is necessary to restore oxygenation to deprived tissues, including the heart. However, reoxygenation of asphyxiated newborns may lead to generation of reactive oxygen species (ROS) and further myocardial damage, termed reperfusion injury. The newborn heart is especially vulnerable to oxidative stress and reperfusion injury due to immature antioxidant defense mechanisms and increased vulnerability to apoptosis. Currently, newborn myocardial protective strategies are aimed at reducing the generation of ROS through controlled reoxygenation, boosting antioxidant defenses, and attenuating cellular injury via mitochondrial stabilization.

Peptic ulcer bleeding outcomes adversely affected by end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease (ESRD) and peptic ulcer disease (PUD) bleeding may be at high risk of bleeding complications. OBJECTIVE: To investigate the outcomes of patients with ESRD and PUD bleeding. DESIGN: ESRD patients with PUD bleeding were evaluated retrospectively. SETTING: Two tertiary, university-affiliated hospitals. PATIENTS: A total of 150 PUD bleeding patients were evaluated in 3 groups; end-stage renal disease (ESRD) patients on dialysis (ESRD group) (n = 50) were age matched with patients with chronic kidney disease (CKD) not requiring dialysis (CKD group) (n = 50) and those with normal kidney function (normal group) (n = 50). MAIN OUTCOME MEASUREMENTS: Rebleeding, transfusions, length of hospitalization, mortality. RESULTS: Multivariate analysis showed significant predictors of rebleeding to be ESRD and high-risk stigmata. The ESRD group had an odds ratio (OR) of 3.8 (95% CI, 1.4-10.5; P = .008) for rebleeding compared with the normal group, and an OR of 3.8 (95% CI, 1.4-10.3; P = .01) compared with the CKD group. The mean number of (+/- SD) transfusions was higher in the ESRD group (6.3 +/- 5.7 units) than in the normal group (3.6 +/- 3.9 units; P = .01). The mean length of hospitalization was higher in the ESRD group than in the normal group (34.0 vs 16.6 days; P = .01). A greater level of comorbidity was the only significant predictor of mortality (OR 6.0; 95% CI, 2.9-12.3; P = .001). LIMITATION: Retrospective study. CONCLUSION: ESRD dialysis patients with PUD bleeding have greater rebleeding than patients not on dialysis. ESRD patients should be managed as a high-risk group.