Adrian Pick

KRAS Mutation Is Associated with Lung Metastasis in Patients with Curatively Resected Colorectal Cancer

Purpose: Oncogene mutations contribute to colorectal cancer development. We searched for differences in oncogene mutation profiles between colorectal cancer metastases from different sites and evaluated these as markers for site of relapse. Experimental Design: One hundred colorectal cancer metastases were screened for mutations in 19 oncogenes, and further 61 metastases and 87 matched primary cancers were analyzed for genes with identified mutations. Mutation prevalence was compared between (a) metastases from liver (n = 65), lung (n = 50), and brain (n = 46), (b) metastases and matched primary cancers, and (c) metastases and an independent cohort of primary cancers (n = 604). Mutations differing between metastasis sites were evaluated as markers for site of relapse in 859 patients from the VICTOR trial. Results: In colorectal cancer metastases, mutations were detected in 4 of 19 oncogenes: BRAF (3.1%), KRAS (48.4%), NRAS (6.2%), and PIK3CA (16.1%). KRAS mutation prevalence was significantly higher in lung (62.0%) and brain (56.5%) than in liver metastases (32.3%; P = 0.003). Mutation status was highly concordant between primary cancer and metastasis from the same individual. Compared with independent primary cancers, KRAS mutations were more common in lung and brain metastases (P < 0.005), but similar in liver metastases. Correspondingly, KRAS mutation was associated with lung relapse (HR = 2.1; 95% CI, 1.2 to 3.5, P = 0.007) but not liver relapse in patients from the VICTOR trial. Conclusions: KRAS mutation seems to be associated with metastasis in specific sites, lung and brain, in colorectal cancer patients. Our data highlight the potential of somatic mutations for informing surveillance strategies. Clin Cancer Res; 17(5); 1122–30. ©2011 AACR.

Contemporary Results Show Repeat Coronary Artery Bypass Grafting Remains a Risk Factor for Operative Mortality

BACKGROUND Reoperative coronary artery bypass grafting (redo CABG) shows improving outcomes, but with varying degrees of improvement. We assessed contemporary outcomes after redo CABG to determine if redo status is still a risk factor for early postoperative complications and midterm survival. METHODS Isolated CABG procedures (June 1, 2001 to May 31, 2008) within the Australasian Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database were included. Redo status as a predictor for early outcomes was assessed with logistic regression analysis. Midterm survival was determined from the National Death Index. Effect of redo status on midterm survival was assessed using a Cox proportional hazards model. RESULTS Inclusion criteria were met by 13,436 patients, and 458 (3.4%) underwent redo CABG. Operative mortality was 4.8% for redo CABG and 1.8% for first-time CABG (p < 0.001). After adjustment, redo status remained a predictor for operative mortality (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.3 to 3.6), myocardial infarction (OR, 2.8; 95% CI, 1.6 to 6.0), and prolonged ventilation (OR, 1.5; 95% CI, 1.1 to 2.0). Unadjusted survival was lower for the redo CABG group vs the first-time CABG group at up to 6 years (p = 0.01, log-rank test. After adjusting for differences in patient variables, redo status was not a predictor of midterm survival (OR, 1.03; 95% CI, 0.78 to 1.35; p = 0.85). CONCLUSIONS Early postoperative outcomes of redo CABG are encouraging. Midterm survival is excellent; however, redo remains a significant risk factor for operative mortality in contemporary practice.

IS INFORMED CONSENT IN CARDIAC SURGERY AND PERCUTANEOUS CORONARY INTERVENTION ACHIEVABLE

Background:  Medical and legal published work regularly discusses informed consent and patient autonomy before medical interventions. Recent discussions have suggested that Cardiothoracic surgeons’ risk adjusted mortality data should be published to facilitate the informed consent process. However, as to which aspects of medicine, procedures and the associated risks patients understand is unknown. It is also unclear how well the medical profession understands the concepts of informed consent and medical negligence. The aims of this study were to evaluate patients undergoing coronary artery bypass surgery (CABG) and percutaneous coronary intervention (PCI) to assess their understanding of the risks of interventions and baseline level of understanding of medical concepts and to evaluate the medical staff’s understanding of medical negligence and informed consent.

Does Prior Percutaneous Coronary Intervention Adversely Affect Early and Mid-Term Survival After Coronary Artery Surgery?

OBJECTIVES To determine the association between previous percutaneous coronary intervention (PCI) and results after coronary artery bypass graft surgery (CABG). BACKGROUND Increasing numbers of patients undergoing CABG have previously undergone PCI. METHODS We analyzed consecutive first-time isolated CABG procedures within the Australasian Society of Cardiac and Thoracic Surgeons Database from June 2001 to May 2008. Logistic regression and propensity score analyses were used to assess the risk-adjusted impact of prior PCI on in-hospital mortality and major adverse cardiac events. Cox regression model was used to assess the effect of prior PCI on mid-term survival. RESULTS Of 13,184 patients who underwent CABG, 11,727 had no prior PCI and 1,457 had prior PCI. Mean follow-up was 3.3 +/- 2.1 years. Patients without prior PCI had a higher EuroSCORE value (4.4 +/- 3.3 vs. 3.6 +/- 3.0, p < 0.001), were older, and more likely to have left main stem stenosis and recent myocardial infarction. There was no difference in unadjusted in-hospital mortality (1.65% vs. 1.55%, p = 0.78) or major adverse cardiac events (3.0% vs. 3.0%, p = 0.99) between patients with or without prior PCI. After adjustment, prior PCI was not a predictor of in-hospital (odds ratio: 1.22, 95% confidence interval [CI]: 0.76 to 2.0, p = 0.41) or mid-term mortality at 6-year follow-up (hazard ratio: 0.94, 95% CI: 0.75 to 1.18, p = 0.62). CONCLUSIONS In this large registry study, prior PCI was not associated with increased short- or mid-term mortality after CABG. Good outcomes can be obtained in the group of patients undergoing CABG who have had previous PCI.

Epicardial High-intensity Focused Ultrasound Cardiac Ablation for Surgical Treatment of Atrial Fibrillation

BACKGROUND The available alternatives to an effective but technically complex Cox maze procedure for surgical treatment of atrial fibrillation include ablation using radiofrequency, microwave, laser, cryotherapy or ultrasound energy sources. The purpose of this study was to evaluate the safety and efficacy profile of high-intensity focused ultrasound cardiac ablation for the surgical treatment of atrial fibrillation. METHODS 14 patients underwent epicardial high-intensity focused ultrasound treatment for atrial fibrillation using the Epicor cardiac ablation system between August 2006 and August 2007. The procedure was performed on the beating heart prior to the commencement of cardiopulmonary bypass for concomitant cardiac procedures. Physical examination, electrocardiography and 24-h Holter monitoring were used to determine the postoperative heart rhythm. RESULTS There were no deaths directly related to the procedure. One patient with myelodysplastic syndrome died of septic complications. Three patients required cardioversion at 1 day, 3- and 4-month intervals postoperatively. The mean follow-up period was 9 months. Currently 10/13 (77%) patients are in sinus rhythm, one patient required insertion of a permanent pacemaker, one patient is in atrial fibrillation and another patient is in atrial flutter. CONCLUSION Epicardial high-intensity focused ultrasound ablation is a viable alternative to the Cox maze procedure for the surgical treatment of atrial fibrillation. It is a safe and efficient procedure that does not require cardiopulmonary bypass and may potentially be performed using less invasive surgical techniques.

Cadaveric Lobar Lung Transplantation: Technical Aspects

BACKGROUND The use of lobar transplantation and other size reduction techniques has allowed larger donor lungs to be utilized for smaller recipients who tend to have longer waiting times for transplantation. However, despite these advantages, the techniques have not been widely adopted. We outline the surgical and sizing issues associated with this technique. METHODS A retrospective review of 23 consecutive patients who received lung transplantation with anatomic lobar reduction was performed, focusing on surgical technique and outcomes. RESULTS All 23 patients received an anatomic lobar reduction of between 1 and 3 lobes. Survival analysis showed no difference between the lobar reduction cohort and the other historically comparable lung transplant patients from our institution (p=0.115). Percent predicted forced vital capacity and forced expiratory volume in 1 second at 3 months correlated with transplanted donor to recipient total lung capacity ratio, confirming the importance of correct sizing. CONCLUSIONS Anatomic lobar reduction in lung transplantation is a safe and effective means of transplanting pediatric and small adult recipients, and urgently listed patients.

Pilot study of operative fixation of fractured ribs in patients with flail chest

Background:  Flail chest is a serious injury in trauma with a significant mortality rate, and long‐term pain and disability. Traditionally, management has consisted of internal pneumatic splinting, leading to prolonged periods of mechanical ventilation, and its attendant complications. The aim of this study was to assess the safety of operative fixation of broken ribs in flail chest using absorbable prostheses.

Carbon dioxide insufflation in open-chamber cardiac surgery: A double-blind, randomized clinical trial of neurocognitive effects

OBJECTIVE The aims of this study were first to analyze neurocognitive outcomes of patients after open-chamber cardiac surgery to determine whether carbon dioxide pericardial insufflation reduces incidence of neurocognitive decline (primary end point) as measured 6 weeks postoperatively and second to assess the utility of carbon dioxide insufflation in cardiac chamber deairing as assessed by transesophageal echocardiography. METHODS A multicenter, prospective, double-blind, randomized, controlled trial compared neurocognitive outcomes in patients undergoing open-chamber (left-sided) cardiac surgery who were assigned carbon dioxide insufflation or placebo (control group) in addition to standardized mechanical deairing maneuvers. RESULTS One hundred twenty-five patients underwent surgery and were randomly allocated. Neurocognitive testing showed no clinically significant differences in z scores between preoperative and postoperative testing. Linear regression was used to identify factors associated with neurocognitive decline. Factors most strongly associated with neurocognitive decline were hypercholesterolemia, aortic atheroma grade, and coronary artery disease. There was significantly more intracardiac gas noted on intraoperative transesophageal echocardiography in all cardiac chambers (left atrium, left ventricle, and aorta) at all measured times (after crossclamp removal, during weaning from cardiopulmonary bypass, and at declaration of adequate deairing by the anesthetist) in the control group than in the carbon dioxide group (P < .04). Deairing time was also significantly longer in the control group (12 minutes [interquartile range, 9-18] versus 9 minutes [interquartile range, 7-14 minutes]; P = .002). CONCLUSIONS Carbon dioxide pericardial insufflation in open-chamber cardiac surgery does not affect postoperative neurocognitive decline. The most important factor is atheromatous vascular disease.

Fast-track cardiac surgery: application in an Australian setting.

In response to the current state of healthcare in Australia, our unit has employed a fast-track policy for low-risk cardiac surgery patients since January 2000. This study was designed to examine the safety and efficacy of this policy. From July 2001 to June 2004, 342 (23%) of 1,488 patients undergoing cardiac surgery were identified preoperatively as suitable for fast-track recovery. There was a significantly shorter median time to extubation (4 hr vs 9 hr), reduced intensive care unit stay (8 hr vs 26 hr), and a lower rate of readmission to the intensive care unit (0.6% vs 4.2%) for those fast tracked compared to the other patients. The fast-track group had a lower incidence of complications and significantly decreased median length of hospital stay (5 vs 7 days). We concluded that this policy accurately identifies the low-risk cardiac surgery patients suitable for less intensive postoperative recovery.

Prophylaxis Against Atrial Fibrillation after Cardiac Surgery: Beneficial Effect of Perioperative Metoprolol

INTRODUCTION Multiple agents have been investigated to prevent atrial fibrillation (AF) after cardiac surgery. Several studies have investigated the use of β-blockers such as metoprolol or amiodarone with promising results. We aimed to investigate perioperative pharmacologic prophylaxis against AF using metoprolol, and amiodarone in combination with metoprolol. METHODS We conducted a prospective, randomised, single-blind, controlled pilot study in patients undergoing elective cardiac surgery. Subjects were randomised pre-operatively to one of three treatment groups: standard therapy (control) or metoprolol (5 mg IV over 5 min on commencement of bypass then 5 mg IV qid for 24h then 25-50 mg tds orally until discharge) or amiodarone (300 mg over 1h starting shortly after the commencement of bypass, then 900 mg over 24h then 400 mg orally tds until discharge) plus metoprolol as above. Patients had ECG monitoring for the occurrence of AF for six days or until discharge. RESULTS Two hundred and fifteen patients were enrolled. Between-group differences in AF in an intention-to-treat analysis were not significant: control 34% (23-45%), metoprolol 35% (24-46%), combined 22% (12-33%) (p = 0.21). However 87 patients (40%) did not receive the assigned treatment mainly due to side effects, especially bradycardia. The remaining 128 patients were analysed on a per-protocol basis with the overall difference between the three groups bordering on significance: control 34% (23-45%), metoprolol 26% (9-43%), combined 11% (0-23%) (p = 0.06). Logistic regression analysis, correcting for age and gender, was used to separate the individual effects of metoprolol and amiodarone in the presence of metoprolol which showed that compared to control there was a significant effect of metroprolol on AF incidence (O.R. 0.31 (0.10-0.99), p = 0.048) but not of amiodarone (O.R. 0.97 (0.19-5.02), p = 0.97). CONCLUSIONS (1) Perioperative metoprolol but not amiodarone itself in combination with metoprolol is associated with a significant reduction in postoperative AF. (2) Perioperative administration of metoprolol and combination of metoprolol with amiodarone is associated with a high incidence of side effects, especially bradycardia. (3) Further studies are indicated to confirm these preliminary findings but in the meantime it would not be unreasonable to implement the use of perioperative metoprolol for routine prophylaxis of AF.