Dose-dependent effect of androgen deprivation therapy for localized prostate cancer on adverse cardiac events.

OBJECTIVES: To investigate the dose-dependent effect of androgen deprivation therapy (ADT) on adverse cardiac events in elderly men with non-metastatic prostate cancer (PCa) stratified according to life expectancy. PATIENTS AND METHODS: A total of 50 384 men diagnosed with localized PCa between 1992 and 2007 were identified within the Surveillance, Epidemiology, and End Results registry areas. We compared those who received ADT within 2 years of PCa diagnosis with those who did not, calculated as monthly equivalent doses of GnRH agonists (<8, ≥8 doses), or orchiectomy. Men were further stratified according to life expectancy (<5 years, 5-10 years and >10 years). Adjusted Cox hazard models assessed the risk of new-onset coronary heart disease (CHD), acute myocardial infarction (AMI), sudden cardiac death (SCD) and cardiac-related interventions, as well as any of these events. RESULTS: Overall, patients receiving GnRH agonists were more likely to experience a cardiac event, with the most pronounced effect among those receiving ≥8 doses (hazard ratio [HR] <8 doses: 1.13, 95% confidence interval [CI] 1.09-1.16, and HR ≥8 doses: 1.18, 95% CI 1.14-1.22; both P < 0.001). The effect of prolonged (≥8 doses) GnRH agonist use on cardiac events was sustained across all strata of life expectancy; however, there was no effect among men with a life expectancy of <5 years and when use of GnRH agonists was limited to <8 doses (HR 0.99, 95% CI 0.67-1.46; P = 0.964). The use of GnRH agonists was associated with a higher risk of CHD (HR <8 doses: 1.13, 95% CI 1.09-1.17 and HR ≥8 doses: 1.17, 95% CI 1.13-1.21; both P < 0.001). Conversely, the use of GnRH was generally not associated with an increased risk of AMI or SCD, except for men who received ≥8 doses of GnRH agonists and had a life expectancy of ≥5 years, who were at a significantly higher risk of SCD (HR for life expectancy 5-10 years: 1.19, 95% CI 1.06-1.33; P = 0.003 and HR for life expectancy >10 years: 1.16, 95% CI 1.04-1.29; P = 0.006). Finally, orchiectomy was not associated with overall cardiac events, AMI or SCD, and was protective with regard to cardiac-related interventions (HR 0.78, 95% CI 0.68-0.90, P = 0.001). CONCLUSION: Exposure to ADT with GnRH agonists is associated with an increased risk of cardiac events in elderly men with localized PCa and a decent life expectancy. Clinicians should carefully weigh the risks and benefits of ADT in patients with a prolonged life expectancy. Routine screening and lifestyle interventions are warranted in at-risk subpopulations treated with ADT.

Simultaneous bilateral robotic-assisted laparoscopic procedures in children.

Our main objective is to report the feasibility of performing simultaneous robotic-assisted laparoscopic (RAL) heminephrectomy with contralateral ureteroureterostomy in children with bilateral duplicated systems. Three female children with bilateral congenital renal/ureteral anomalies underwent concurrent RAL simultaneous unilateral partial nephrectomy with ureterectomy and contralateral ureteroureterostomy with redundant ureterectomy using a four/five-port approach. Mean age at repair was 32.9 months (range 7-46 months) and mean weight was 13.7 kg (range 10.4-13.6 kg). The RAL heminephroureterectomy and contralateral ureteroureterostomy were performed via a four-port approach (five ports in one patient), and the patients were repositioned and draped when moving to the other side. Mean operative time was 446 min (range 356-503 min). Mean estimated blood loss was 23.3 cc (range 10-50 cc). Postoperative length of stay for two patients was 2 days and 1 day for one patient (mean = 1.7 days). Mean length of follow-up was 18.3 months (range 7-36 months). No significant intraoperative or postoperative complications occurred for any of the three patients. Two children had no hydronephrosis on postoperative imaging in follow-up, and one child had a small stable, residual pararenal fluid collection on the side of heminephrectomy. Two patients underwent postoperative ureteral stent removal under general anesthesia. In children with bilateral duplicated urinary tract with ureterocele, ectopic ureter, and/or vesicoureteral reflux, laparoscopic repair with robotic assistance can be accomplished safely in a single operative procedure with a short hospital stay.

Impact of smoking on perioperative outcomes after major surgery.

BACKGROUND: To investigate the impact of smoking on perioperative outcomes in patients undergoing one of the 16 major cardiovascular, orthopedic, or oncologic surgical procedures. METHODS: We relied on the American College of Surgeons National Surgical Quality Improvement Program database (2005 to 2011). Procedure-specific multivariable logistic regression models assessed the association between smoking status (non, former, or current smokers) and risk of 30-day morbidity and mortality. RESULTS: Overall, 141,802 patients were identified. A total of 12.5%, 14.6%, and 14.9% of non, former, and current smokers, respectively, experienced at least one complication (P < .001). In multivariable models, current smokers had higher odds of overall, pulmonary, wound, and septic/shock complications following most cardiovascular and oncologic surgeries compared with nonsmokers. The odds of experiencing such adverse outcomes were significantly lower in former smokers compared with current smokers, but still higher compared with nonsmokers. CONCLUSIONS: The effect of smoking on perioperative outcomes is procedure dependent. Current and, even though mitigated, former smoking negatively influence outcomes following cardiovascular or oncologic procedures. Patients undergoing major procedures should be encouraged to discontinue tobacco smoking to achieve optimal procedural outcomes.

An evaluation of the timing of surgical complications following nephrectomy: data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP).

PURPOSE: The rates of complications following radical/partial nephrectomy (RN/PN) are well known; however, the data regarding timing are opaque. Accordingly, we sought to assess the median time-to-event for 19 principal postoperative complications within 30 days following surgery. METHODS: Patients undergoing RN/PN were identified within the American College of Surgeons National Surgical Quality Improvement Program database (2005-2011). Primary endpoint was time-to-complication. Secondary endpoints included length-of-stay (LOS), re-intervention, re-admission and 30-day mortality. Multivariable regression models assessed the predictors for pre-/post-discharge complications and the effect of time-to-complication on secondary outcomes. RESULTS: Overall, 3820 patients underwent nephrectomy (RN = 63.6 %). The overall complication rate was 16.8 %, and the median LOS was 4 days. The majority of major complications (88.1 %), including bleeding/transfusion, renal, septic, deep venous thrombosis or pulmonary embolism, pulmonary, cardiac and neurologic, occurred prior to discharge. Conversely, the relatively minor complications, including wound and urinary tract infections, occurred predominantly post-discharge (70.7 %). The median time to major complications was 3 versus 13 days for minor complications. In multivariable analyses, age [odds ratio (OR) 1.02, p < 0.001], American Society of Anesthesiologists score ≥ 2 (p < 0.01) and PN (p < 0.001) were predictors of pre-discharge complications, while female gender (OR 1.67, p < 0.001), hypertension (OR 1.28, p = 0.007) and diabetes (OR 1.48, p < 0.001) were predictors of post-discharge complications. Creatinine ≥ 1.2 mg/dl and hematocrit < 30 increased (p < 0.01), whereas a minimally invasive approach decreased the odds (p < 0.05) for both pre-/post-discharge complications. For a given complication, time-to-complication did not affect the odds for mortality (p = 0.343) or re-intervention (p = 0.872). CONCLUSIONS: Approximately one in six patients suffers a complication following RN/PN; major complications tend to occur early with the majority occurring pre-discharge. Knowledge regarding the timing and risk factors for complications may facilitate improved patient-physician communication, both at admission and at discharge.

An evaluation of the 'weekend effect' in patients admitted with metastatic prostate cancer.

OBJECTIVES: To investigate whether mortality is increased for patients with metastatic prostate cancer (mCaP) admitted over the weekend. PATIENTS AND METHODS: Using the Nationwide Inpatient Sample (NIS) between 1998 and 2009, admitted patients with a diagnosis of prostate cancer and concomitant metastases were identified. Rates of in-hospital mortality, complications, use of imaging and procedures were assessed. Adjusted logistic regression models examined associations of mortality and complications. RESULTS: A weighted sample of 534,011 patients with mCaP was identified, including 81.7% weekday and 18.3% weekend admissions. Of these, 8.6% died after a weekday vs 10.9% after a weekend admission (P < 0.001). Patients admitted over the weekend were more likely to be treated at rural (17.8% vs 15.7%), non-teaching (57.6% vs 53.7%) and low-volume hospitals (53.4% vs 49.4%) (all P < 0.001) compared with weekday admissions. They presented higher rates of organ failure (25.2% vs 21.3%), and were less likely to undergo an interventional procedure (10.6% vs 11.4%) (all P < 0.001). More patients admitted over the weekend had pneumonia (12.2% vs 8.8%), pyelonephritis (18.3% vs 14.1%) and sepsis (4.5% vs. 3.5%) (all P < 0.001). In multivariate analysis, weekend admission was associated with an increased likelihood of complications (odds ratio [OR] 1.15, 95% confidence Interval [CI] 1.11-1.19) and mortality (OR 1.20, 95% CI 1.14-1.27). CONCLUSION: In patients with mCaP weekend admissions are associated with a significant increase in mortality and morbidity. Our findings suggest that weekend patients may present with more acute medical issues; alternatively, the quality of care over the weekend may be inferior.

Oncologic outcomes at 10 years following robotic radical prostatectomy.

BACKGROUND: Reports on long-term oncologic outcomes for patients who undergo robot-assisted radical prostatectomy (RARP) are scant, as for radical prostatectomy covering only the contemporary prostate-specific antigen (PSA) era. OBJECTIVE: To evaluate cancer control in men who underwent RARP at least 10 yr ago. DESIGN, SETTING, AND PARTICIPANTS: From 2001 to 2003, we followed 483 consecutive men with localized prostate cancer who underwent RARP at a high-volume tertiary center. INTERVENTION: RARP as first-line therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We calculated biochemical recurrence -free survival (BCRFS), metastasis-free survival (MFS), and cancer-specific survival (CSS). Actuarial rates were estimated via Kaplan-Meier. Cox proportional hazards models were used to identify variables predictive of biochemical recurrence (BCR), receipt of salvage therapy, and metastases. RESULTS AND LIMITATIONS: There were 108 patients with BCR at a median follow-up of 121 mo (interquartile range: 97-132). Actuarial BCRFS, MFS, and CSS rates at 10 yr were 73.1%, 97.5%, and 98.8%, respectively. On multivariable analysis, D'Amico risk groups or pathologic Gleason grade, stage, and margins were the strongest predictors of BCR depending on whether preoperative or postoperative variables were considered. The value of the detectable PSAs together with disease severity were independent predictors of receipt of salvage therapy, together with a persistent PSA for metastases. CONCLUSIONS: In contemporary patients with localized prostate cancer, RARP confers effective 10-yr cancer control. Disease severity and PSA measurements can be used to guide more personalized and cost-effective postoperative surveillance regimens. PATIENT SUMMARY: Robot-assisted radical prostatectomy confers effective 10-yr cancer control for men with localized disease, similar to the open approach. Recurrence is best predicted by postoperative disease severity. Persistent disease signals the risk of progression likely requiring early salvage treatment; lower postoperative risk warrants protracted surveillance beyond 5 yr from surgery, and those with higher risk may require follow-up beyond 10 yr.

Cardiac-targeted transgenic mutant mitochondrial enzymes: mtDNA defects, antiretroviral toxicity and cardiomyopathy.

Mitochondrial (mt) DNA biogenesis is critical to cardiac contractility. DNA polymerase gamma (Pol gamma) replicates mtDNA, whereas thymidine kinase 2 (TK2) monophosphorylates pyrimidines intramitochondrially. Point mutations in POLG and TK2 result in clinical diseases associated with mtDNA depletion and organ dysfunction. Pyrimidine analogs (NRTIs) inhibit Pol gamma and mtDNA replication. Cardiac "dominant negative" murine transgenes (TGs; Pol gamma Y955C, and TK2 H121N or I212N) defined the role of each in the heart. mtDNA abundance, histopathological features, histochemistry, mitochondrial protein abundance, morphometry, and echocardiography were determined for TGs in "2 x 2" studies with or without pyrimidine analogs. Cardiac mtDNA abundance decreased in Y955C TGs ( approximately 50%) but increased in H121N and I212N TGs (20-70%). Succinate dehydrogenase (SDH) increased in hearts of all mutants. Ultrastructural changes occurred in Y955C and H121N TGs. Histopathology demonstrated hypertrophy in H121N, LV dilation in I212N, and both hypertrophy and dilation in Y955C TGs. Antiretrovirals increased LV mass ( approximately 50%) for all three TGs which combined with dilation indicates cardiomyopathy. Taken together, these studies demonstrate three manifestations of cardiac dysfunction that depend on the nature of the specific mutation and antiretroviral treatment. Mutations in genes for mtDNA biogenesis increase risk for defective mtDNA replication, leading to LV hypertrophy.