Lung neuroendocrine neoplasms: a single centre surgical series and analysis of staging.

BACKGROUND: To review the outcomes of surgically resected lung neuroendocrine neoplasms (LNEN) at a tertiary referral centre and to validate a previously published LNEN-specific staging system (NETL). METHODS: All patients who were identified on histopathology to have LNEN were included. Pre-, intra- and post-operative outcomes were collected, including long-term survival. Patients were staged by both the TNM (seventh and eighth edition) and NETL staging (seventh and eighth edition definitions). Kaplan-Meier (KM) survival analysis was performed according to histopathology and stage, along with uni- and multivariate analyses. RESULT: A total of 132 patients were included in the study, with a median age of 65 years; 55% were female. Typical carcinoid (TC) was the most common pathology (53.4%) followed by large cell neuroendocrine carcinoma (LCNEC - 23.5%), atypical carcinoid (AC - 20.5%) and small cell carcinoma (3.0%). The most common operation performed was a lobectomy (55.3%). Overall survival at 5 years was 80% (100% TC, 78.2% AC, LCNEC 40.9%) and 5-year disease free survival was 76.8% (TC 94.3%, AC 56.8%, LCNEC 56.4%). KM curves showed a trend towards NETL performing better than TNM, however, in multivariate analysis only the histological subtype was found to be significant in our study. CONCLUSION: This is the largest known Australian series of LNEN to date, showing survival comparable to international outcomes. We have demonstrated large variations in outcome, driven by histological grade. The TNM system does not correlate with survival and we have not been able to show that currently proposed NETL staging is superior.

What is the best choice for third conduit when using bilateral internal mammary arteries for coronary artery bypass grafting-radial artery or saphenous vein graft?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'What is the best choice for third conduit when using bilateral internal mammary arteries for coronary artery bypass grafting-radial artery or saphenous vein graft?'. Altogether >525 papers were found using the reported search, of which 7 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Overall, there was no survival benefit demonstrated with the use of a radial artery over the use of a saphenous vein graft as a choice of third conduit following bilateral internal mammary artery grafts for coronary artery bypass grafting. The main limitation of the current evidence available is the restricted follow-up periods and the high attrition rates with small sample sizes affecting the strength of conclusions that can be drawn beyond 10 years of follow-up. We conclude that despite previous evidence supporting improved long-term patency of radial arterial grafts, there is no strong evidence that the use of a radial artery, over a saphenous vein graft, has any survival benefit when used as the third conduit following bilateral internal mammary artery grafts.

Vein Graft Patency Rates With Aspirin Plus Clopidogrel Following Coronary Artery Bypass Grafting.

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was, "In patients who have undergone Coronary Artery Bypass Grafting, does aspirin plus clopidogrel postoperatively improve vein graft patency when compared to aspirin alone?" Altogether, 165 papers were found using the reported search, of which five represented the best evidence to answer the clinical question. Overall analysis of these papers demonstrated similar rates of vein graft patency between the two groups. There was no difference between the groups with regard to mortality, adverse bleeding-related outcomes, or composite vascular events.

Management of atrial fibrillation after cardiac surgery.

A best evidence topic in cardiac surgery was written according to a structured protocol addressing the question 'for post-cardiac surgery atrial fibrillation (AF), do clinical outcomes differ between rate or rhythm control strategies?' Altogether, 2174 papers were found using the reported searches, of which 5 represented the best evidence to answer the clinical question. Hospital length of stay ranged from 5.0 to 13.2 days for rate control and 5.2 to 10.3 days for rhythm control. Freedom from AF at follow up was achieved in 84.2-91 and 84.2-96% in rate and rhythm control groups respectively. Minimal serious adverse events were noted in all studies analysed and there was no difference between rate and rhythm control groups. We conclude that in the management of post-cardiac surgery, AF, rate control and rhythm control are equivalent in terms of hospital length of stay, freedom from arrhythmia at follow up and complication rates.

Levosimendan Following Cardiac Surgery.

A best evidence topic was written to address if perioperative levosimendan improves mortality following cardiac surgery. Fourteen papers represented the best available evidence. An older meta-analysis summarising 11 of these trials concluded that there were fewer deaths in the levosimendan group compared to the control group (OR 0.41, p <0.001) however, this was driven by the results of three included trials by the same author. Three larger and more recent randomised controlled trials failed to demonstrate significant differences in mortality. We conclude that levosimendan lacks robust evidence to substantiate claims of mortality benefit in cardiac surgery patients and should not be used routinely in such patients.

Does minimally invasive coronary artery bypass improve outcomes compared to off-pump coronary bypass via sternotomy in patients undergoing coronary artery bypass grafting?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'In patients undergoing off-pump coronary artery bypass grafting, for single or multivessel disease, does minimally invasive direct coronary artery bypass (MIDCAB) or off-pump coronary artery bypass (OPCAB) provide the superior outcome including a reduction in morbidity and mortality?'. A total of 187 papers were found using the reported search, of which 12 represented the best evidence to answer the clinical question. The authors, date, journal and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. It was found that compared to OPCAB, MIDCAB surgery can offer decreased intensive care unit length of stay (4.5-57.4 h vs 5.2-52.7 h) and total hospital length of stay (4.5-8.5 days vs 5.2-12 days), with 1 paper showing a decrease in mortality at 1 year (3% vs 14%). However, there were several papers that showed significant risks with MIDCAB surgery in patients with either single or multivessel disease. These include increased risk of incomplete revascularization (29% vs 0%), significant early complications (22.5 vs 0%), urgent reintervention (16% vs 0%), repeat revascularization events (12.2% vs 3.7%), progression of native disease (4.8% vs 0.9%), rehospitalization by 3 months (20% vs 2%) and postoperative infarction (2.9% vs 1.45%). These risks did not translate to an increase in early mortality (0-1% vs 0-1.6%) or late mortality (0-3% vs 0-14%) in papers that included mid-term follow up. However, they do represent significant potential risks that cannot be overlooked when considering the use of MIDCAB. We conclude that MIDCAB is associated with greater morbidity and reintervention compared to OPCAB via sternotomy, but both techniques are equivalent in terms of operative and mid-term mortality.

Surgical and Hybrid Ablation of Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia in humans and is known to be associated with an increased risk of stroke, dementia, heart failure and mortality. Non-pharmacological therapy with ablation using either surgical or percutaneous techniques is recommended in drug refractory AF. Early attempts to devise procedures to ablate AF and restore sinus rhythm culminated with the Cox-Maze procedure, the first truly successful procedure. Since then, ablation surgery has been conducted predominately as a concomitant procedure. The Cox Maze procedure is complex and technically demanding and has, therefore, been extensively modified with new techniques for creating the linear ablation lines, new lesion sets, minimally invasive surgical techniques and most recently hybrid surgical-catheter ablation techniques. Surgical ablation techniques result in a marked reduction in atrial fibrillation when compared to conventional therapy with only a small increase in procedural risk. However, further research is required to more accurately quantify those benefits and to determine the optimal lesion sets, specific to the underlying arrhythmia mechanism and the optimal energy sources for ablation.

Do novel anticoagulant agents increase the risk of perioperative complications during implantable cardiac rhythm device insertion?

A best evidence topic was written according to a structured protocol. The question addressed was 'In patients requiring an implanted cardiac rhythm device, do novel oral anticoagulant agents lead to increased rates of peri-procedural complications?' Altogether 1228 papers were found using the reported search, of which 5 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The novel oral anticoagulant agents (NOACs) assessed in the included studies were dabigatran (a direct thrombin inhibitor) and rivaroxaban (a Factor Xa inhibitor). Dabigatran was included in all five studies and showed bleeding complication rates of 0-4%. Rivaroxaban was included in one study and had bleeding complication rates of 4%. Warfarin was a comparator agent in three studies and had bleeding complication rates of 4.6-8%. The incidence rate of thromboembolic complications was 0-1% with dabigatran and 0% with rivaroxaban and warfarin in all studies. Based on the available studies, there is no evidence of significantly increased risk of bleeding or thromboembolic events with NOACs compared with warfarin when used at the time of cardiac rhythm device implantation. However, not all patients in the studies were actually receiving the specified NOAC at the time of device implantation, thereby limiting the available evidence.

Do rapid deployment aortic valves improve outcomes compared with surgical aortic valve replacement?

A best evidence topic was written according to a structured protocol. The question addressed was 'In patients requiring an aortic valve replacement, are rapid deployment aortic valve systems better than conventional aortic valve prostheses in terms of mortality, morbidity and/or valve function?' A total of 508 papers were found using the reported search, of which 11 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The rapid deployment valves (RDVs) implanted in these studies include balloon expandable [Intuity (Edwards Lifesciences, CA, USA) and 3F Enable (Medtronic, MN, USA)] and self-expanding [Perceval (Sorin, Saluggia, Italy)] stented bioprostheses. Available data from these studies demonstrate that rapid deployment valves are invariably associated with shorter aortic cross-clamp times (30-56 vs 49-88 min). Despite this, postoperative mortality (0-5.8 vs 0-6%), ICU (1-3 vs 0.9-2.8 days) and hospital length of stay (6-14.1 vs 6-15.9 days) are similar compared with conventional aortic valve replacement (AVR). However, reduced postoperative bleeding (328 vs 564 ml), blood transfusion requirements (1.4 vs 2.4 units), ventilation time (4.9-9.5 vs 7-16.6 h) and renal injury (5.3 vs 14.7%) have been demonstrated with RDVs indicating possible clinical benefit to shorter procedural time. Importantly, patient risk profiles were similar to or higher across studies in patients undergoing RDVs compared with conventional AVR. From a functional perspective, transvalvular gradients were frequently lower with rapid deployment valves compared with conventional AVR, indicating an improved haemodynamic profile. However, in some studies using the Perceval RDV, the transvalvular gradients were higher than with conventional AVR. Also, mean valve sizes were often larger in those receiving RDVs. Rates of paravalvular regurgitation were similar between RDVs and conventional AVR in most studies, although pacemaker implantation occurred more often with RDV in some studies (2-28.5 vs 0-8.5%). Accepting these limitations, and without long-term data, RDVs would appear to be a reasonable alternative to conventional aortic valve prostheses in selected cases.

Outcomes of aortic arch replacement surgery after previous cardiac surgery.

BACKGROUND: Aortic arch replacement is a potentially high-risk operation and in the re-operative setting has been found to be a risk factor for poor outcome, yet there is a dearth of published data specifically on this topic. The aim of the study was to review our unit's outcomes in this re-operative setting. METHOD: Data were collated for all patients who underwent aortic arch replacement surgery after previous cardiac surgery from January 1988 to November 2011. The patients were divided based primarily on elective versus non-elective and also early (≤2005) and late (≥2006) series. RESULTS: Twenty-seven eligible patients (22 male; median age: 53.0 years; elective: 14, non-elective: 13) were identified. There was a mean period of 14.5 years between the first operation and the subsequent aortic arch replacement. The overall 30-day mortality rate was 22.2% - 0% elective and 46.2% non-elective (P = 0.004). Overall permanent neurological dysfunction was 21.7% - 28.6% elective and 11.1% non-elective (P = 0.463). There were 11 early-series patients and 16 late-series patients. For early-series patients, 90.9% were non-elective versus 18.8% in the late-series patients. The 30-day mortality rate was 54.5% early series versus 0% late series. CONCLUSION: Aortic arch replacement is high risk in the re-operative setting. These risks are even greater for non-elective procedures. This highlights the need for aggressive first-time surgery to reduce re-operative procedures and good long-term follow-up programmes to allow elective procedures if required.

Evolution in the techniques and outcomes of aortic arch surgery: a 22 year single centre experience.

BACKGROUND: Aortic arch replacement is a complicated and high risk procedure. There have been many advances over recent years. We review the changes in our unit's techniques and outcomes over the past 22 years. METHODS: Data were collated from databases and medical records for all patients who underwent aortic arch replacement surgery from January 1989 to December 2010. The patients were divided into two groups - Group A (1989-2005) and Group B (2006-2010). Data were analysed to compare early and late series patients' outcomes. Logistic regression was used to identify variables that predicted mortality. RESULTS: Seventy-five eligible patients (56 males; mean age: 57.5 years; Group A: 40, Group B 35) were identified. There were great changes in the technique and the methods of cerebral protection. The overall mortality rate was 30.7% - Group A: 50% and Group B: 8.6% (p<0.001). Overall permanent neurological dysfunction was 23.7% - Group A: 40% and Group B: 11.8% (p=0.012). Cardiovascular disease and circulatory arrest time were significant predictors of mortality. CONCLUSIONS: Increased experience and volume and advances in techniques over 22 years have resulted in major improvements in outcomes for patients having aortic arch replacement, allowing the procedure to be performed with greatly improved outcomes.

Can predictors of response to NSAIDs be identified in patients with acute low back pain?

OBJECTIVES: The aim of this study was to determine whether certain patient characteristics could identify people with acute low back pain who were more likely to respond to nonsteroidal anti-inflammatory drugs (NSAIDs), when administered in combination with paracetamol. METHODS: This study involved a secondary analysis of a randomized controlled trial investigating the efficacy of diclofenac in 239 patients presenting to general practitioners for acute low back pain. All patients received advice to "stay active" and take regular paracetamol and then were randomized to receive either diclofenac (50 mg twice daily) or placebo. The primary outcome was days to recovery from pain. The ability of 14 patient characteristics to identify those who respond best to diclofenac was assessed using interaction terms in Cox regression models. RESULTS: Most of the 14 baseline characteristics investigated were uninformative in identifying those who respond best to diclofenac when added to paracetamol. Patients' sex and levels of fear regarding movement and pain were both independent statistically significant predictors of response to NSAIDs for one definition of recovery but not for the other. The interaction between fear avoidance (physical activity) and NSAIDs treatment was statistically significant (P=0.042, hazard ratio=1.059, 95% confidence interval 1.002 to 1.118) for recovery defined as a pain score of 0 or 1. The interaction between sex and NSAID treatment was statistically significant (P=0.044, hazard ratio=1.755, 95% confidence interval 1.014 to 3.038) for recovery defined as a pain score of 0 or 1 maintained for 7 consecutive days. DISCUSSION: This study did not find any baseline patient characteristics, which consistently identified patients with acute low back pain who respond best to NSAIDs when provided in addition to paracetamol and advice. A patient's sex and level of fear avoidance may be weak predictors and warrant further prospective investigation.

A systematic review of paracetamol for non-specific low back pain.

The objective of this study was to assess the efficacy of paracetamol (acetaminophen) in the treatment of pain and disability in patients with non-specific low back pain. We conducted a systematic review of randomized controlled trials to assess the efficacy of paracetamol in the treatment of pain and disability in patients with non-specific low back pain. A search for randomized controlled trials was conducted using the Medline, Embase and CINAHL databases. Trials were eligible if they were randomized controlled trials comparing paracetamol to no treatment, placebo or another treatment in patients with non-specific low back pain. Two of the authors independently assessed trials for methodological quality on the PEDro Scale and extracted data. Continuous pain and disability data were converted to a common 0-10 scale; ordinal data were dichotomized (e.g., no pain, pain). The data was analyzed using the MIX version 1.61 meta-analysis software. Out of 205 unique articles found in the searches, 7 eligible trials were identified. The trials enrolled a total of 676 participants with 5 investigating acute low back pain, 1 investigating chronic low back pain and 1 investigating both. No trial provided data comparing paracetamol to placebo and only one trial compared paracetamol to no treatment. In general the trials were small (only 1 trial had >25 subjects per group) and of low methodological quality (only 2 had a score above 6 on the quality scale). All but one of the trials provided imprecise estimates of the effects of treatment with confidence intervals spanning clinically important beneficial and also harmful effects of paracetamol. No trial reported a statistically significant difference in favor of paracetamol. There is insufficient evidence to assess the efficacy of paracetamol in patients with low back pain. There is a clear need for large, high quality randomized controlled trials evaluating paracetamol, to provide reliable evidence of paracetamol's effectiveness in patients with low back pain and to establish the validity of the recommendations in clinical guidelines.