Michel I.M. Versteegh

Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer: a randomized trial.

CONTEXT Mediastinal nodal staging is recommended for patients with resectable non-small cell lung cancer (NSCLC). Surgical staging has limitations, which results in the performance of unnecessary thoracotomies. Current guidelines acknowledge minimally invasive endosonography followed by surgical staging (if no nodal metastases are found by endosonography) as an alternative to immediate surgical staging. OBJECTIVE To compare the 2 recommended lung cancer staging strategies. DESIGN, SETTING, AND PATIENTS Randomized controlled multicenter trial (Ghent, Leiden, Leuven, Papworth) conducted between February 2007 and April 2009 in 241 patients with resectable (suspected) NSCLC in whom mediastinal staging was indicated based on computed or positron emission tomography. INTERVENTION Either surgical staging or endosonography (combined transesophageal and endobronchial ultrasound [EUS-FNA and EBUS-TBNA]) followed by surgical staging in case no nodal metastases were found at endosonography. Thoracotomy with lymph node dissection was performed when there was no evidence of mediastinal tumor spread. MAIN OUTCOME MEASURES The primary outcome was sensitivity for mediastinal nodal (N2/N3) metastases. The reference standard was surgical pathological staging. Secondary outcomes were rates of unnecessary thoracotomy and complications. RESULTS Two hundred forty-one patients were randomized, 118 to surgical staging and 123 to endosonography, of whom 65 also underwent surgical staging. Nodal metastases were found in 41 patients (35%; 95% confidence interval [CI], 27%-44%) by surgical staging vs 56 patients (46%; 95% CI, 37%-54%) by endosonography (P = .11) and in 62 patients (50%; 95% CI, 42%-59%) by endosonography followed by surgical staging (P = .02). This corresponded to sensitivities of 79% (41/52; 95% CI, 66%-88%) vs 85% (56/66; 95% CI, 74%-92%) (P = .47) and 94% (62/66; 95% CI, 85%-98%) (P = .02). Thoracotomy was unnecessary in 21 patients (18%; 95% CI, 12%-26%) in the mediastinoscopy group vs 9 (7%; 95% CI, 4%-13%) in the endosonography group (P = .02). The complication rate was similar in both groups. CONCLUSIONS Among patients with (suspected) NSCLC, a staging strategy combining endosonography and surgical staging compared with surgical staging alone resulted in greater sensitivity for mediastinal nodal metastases and fewer unnecessary thoracotomies. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00432640.

Restrictive Annuloplasty and Coronary Revascularization in Ischemic Mitral Regurgitation Results in Reverse Left Ventricular Remodeling

Background—Data on combined coronary artery bypass grafting (CABG) and restrictive annuloplasty in patients with ischemic cardiomyopathy are scarce, and the effect on reverse left ventricular (LV) remodeling is unknown. Methods and Results—51 patients with ischemic LV dysfunction (LV ejection fraction 31±8%) and severe mitral regurgitation (grade 3 to 4+) underwent CABG and restrictive annuloplasty with stringent downsizing of the mitral annulus (by 2 sizes, Physio-ring, mean size 28±2). Serial transthoracic echocardiographic studies were performed (before surgery and within 3 months and 1.5 years after surgery) to assess mitral regurgitation, transmitral gradient, leaflet coaptation, and left atrial and LV reverse remodeling. Clinical follow-up (New York Heart Association [NYHA] class, survival, events) was assessed at 2-year follow-up. Early operative mortality was 5.6%; at 2-year follow-up, all patients were free of endocarditis and thromboembolism, and 1 needed re-operation for recurrent mitral regurgitation; 2-year survival was 84%. NYHA class improved from 3.4±0.8 to 1.3±0.4 (P<0.01), with all patients in class I/II. Intraoperative transesophageal echo showed minimal (grade 1+) mitral regurgitation in 8 patients and none in 43, without stenosis. Leaflet coaptation was 0.8±0.2 cm. These values remained unchanged; all patients had no or minimal (grade 1+) mitral regurgitation at 2-year follow-up. LV end-systolic and end-diastolic dimensions decreased from 51±10 to 43±12 mm (P<0.001) and from 64±8 to 58±11 mm (P<0.001). Left atrial dimension decreased from 53±8 to 47±7 mm (P<0.001). Conclusion—Excellent results of combined restrictive annuloplasty and CABG were obtained. Residual mitral regurgitation was absent/minimal at 2-year follow-up, associated with a significant reduction in left atrial dimension and LV reverse remodeling.

Guideline on antiplatelet and anticoagulation management in cardiac surgery

This document presents a professional view of evidence-based recommendations around the issues of antiplatelet and anticoagulation management in cardiac surgery. It was prepared by the Audit and Guidelines Committee of the European Association for Cardio-Thoracic Surgery (EACTS). We review the following topics: evidence for aspirin, clopidogrel and warfarin cessation prior to cardiac surgery; perioperative interventions to reduce bleeding including the use of aprotinin and tranexamic acid; the use of thromboelastography to guide blood product usage; protamine reversal of heparin; the use of factor VIIa to control severe bleeding; anticoagulation after mechanical, tissue valve replacement and mitral valve repair; the use of antiplatelets and clopidogrel after cardiac surgery to improve graft patency and reduce thromboembolic complications and thromboprophylaxis in the postoperative period. This guideline is subject to continuous informal review, and when new evidence becomes available. The formal review date will be at 5 years from publication (September 2013).

Strain analysis in patients with severe aortic stenosis and preserved left ventricular ejection fraction undergoing surgical valve replacement

AIMS To evaluate myocardial multidirectional strain and strain rate (S-and-SR) in severe aortic stenosis (AS) patients with preserved left ventricular (LV) ejection fraction (EF), using two-dimensional speckle-tracking strain imaging (2D-STI). The long-term effect of aortic valve replacement (AVR) on S-and-SR was also evaluated. METHODS AND RESULTS Changes in LV radial, circumferential, and longitudinal S-and-SR were evaluated in 73 severe AS patients (65 +/- 13 years; aortic valve area 0.8 +/- 0.2 cm2) with preserved LVEF (61 +/- 11%), before and 17 months after AVR. Strain and strain rate data were compared with data from 40 controls (20 healthy individuals and 20 patients with LV hypertrophy) matched by age, gender, body surface area, and LVEF. Compared with controls, severe AS patients had significantly decreased values of LV S-and-SR in the radial (33.1 +/- 14.8%, P = 0.2; 1.7 +/- 0.5 s(-1), P = 0.003), circumferential (-15.2 +/- 5.0%, P = 0.001; -0.9 +/- 0.3 s(-1), P < 0.0001), and longitudinal (-14.6 +/- 4.1%, P < 0.0001; -0.8 +/- 0.2 s(-1), P < 0.0001) directions. At 17 months after AVR, LV S-and-SR significantly improved in all the three directions, whereas LVEF remained unchanged (60 +/- 12%, P = 0.7). CONCLUSION In severe AS patients, impaired LV S-and-SR existed although LVEF was preserved. After AVR, a significant S-and-SR improvement in all the three directions was observed. These subtle changes in LV contractility can be detected by 2D-STI.

Endoscopic Ultrasound–Guided Fine-Needle Aspiration in the Diagnosis and Staging of Lung Cancer and Its Impact on Surgical Staging

PURPOSE The diagnosis and staging of lung cancer critically depends on surgical procedures. Endoscopic ultrasound (EUS) -guided fine-needle aspiration (FNA) is an accurate, safe, and minimally invasive technique for the analysis of mediastinal lymph nodes (LNs) and can additionally detect tumor invasion (T4) in patients with centrally located tumors. The goal of this study was to assess to what extent EUS-FNA could prevent surgical interventions. PATIENTS AND METHODS Two hundred forty two consecutive patients with suspected (n = 142) or proven (n = 100) lung cancer and enlarged (> 1 cm) mediastinal LNs at chest computed tomography were scheduled for mediastinoscopy/tomy (94%) or exploratory thoracotomy (6%). Before surgery, all patients underwent EUS-FNA. If EUS-FNA established LN metastases, tumor invasion, or small-cell lung cancer (SCLC), scheduled surgical interventions were cancelled. Surgical-pathologic verification occurred when EUS-FNA did not demonstrate advanced disease. Cancelled surgical interventions because of EUS findings was the primary end point. RESULTS EUS-FNA prevented 70% of scheduled surgical procedures because of the demonstration of LN metastases in non-small-cell lung cancer (52%), tumor invasion (T4) (4%), tumor invasion and LN metastases (5%), SCLC (8%), or benign diagnoses (1%). Sensitivity, specificity, and accuracy for EUS in mediastinal analysis were 91%, 100% and 93%, respectively. No complications were recorded. CONCLUSION EUS-FNA qualifies as the initial staging procedure of choice for patients with (suspected) lung cancer and enlarged mediastinal LNs. Implementation of EUS-FNA in staging algorithms for lung cancer might reduce the number of surgical staging procedures considerably.

Predictors of Mitral Regurgitation Recurrence in Patients With Heart Failure Undergoing Mitral Valve Annuloplasty

Restrictive mitral annuloplasty is a surgical treatment option for patients with heart failure (HF) and functional mitral regurgitation (MR). However, recurrent MR has been reported at mid-term follow-up. The aim of the present study was to identify the echocardiographic predictors of recurrent MR in patients with HF undergoing mitral annuloplasty. During a mean follow-up of 2.6 +/- 1.6 years, 109 patients with HF (49% ischemic and 51% idiopathic dilated cardiomyopathy) who had undergone mitral valve repair were followed up (of 122 total patients). The severity of MR was quantified, and the following parameters were measured before intervention and at the mid-term follow-up examination: left ventricular (LV) and left atrial volumes and dimensions, LV sphericity index, mitral annular area, and mitral valve geometry parameters. At mid-term follow-up, 21 patients presented with significant MR (grade 2 to 4), and 88 patients had only MR grade 0 to 1. Both groups of patients had had a similar preoperative MR grade, mitral annular area, and LV volume and dimension. In contrast, patients with recurrent MR had had increased preoperative posterior and anterior leaflet angles, tenting height, tenting area, and LV sphericity index compared to the patients without recurrent MR. Of the different parameters of mitral and LV geometry, the distal mitral anterior leaflet angle (hazard ratio 1.48, 95% confidence interval 1.32 to 1.66, p <0.001) and posterior leaflet angle (hazard ratio 1.13, 95% confidence interval 1.07 to 1.19, p <0.001) were independent determinants of MR at mid-term follow-up. In conclusion, in patients with HF of ischemic or idiopathic etiology and functional MR, distal mitral leaflet tethering and posterior mitral leaflet tethering were associated with recurrent MR after restrictive mitral annuloplasty.

Mediastinal restaging: EUS-FNA offers a new perspective

STUDY OBJECTIVE We hypothesized that transoesophageal endoscopic ultrasound guided fine needle aspiration (EUS-FNA) has the potential to be a valuable and accurate new diagnostic technique for mediastinal restaging in non-small cell lung cancer (NSCLC) after induction chemotherapy. The current restaging modalities either have a low diagnostic accuracy (computed tomography (CT) scan of the thorax) or they are invasive, can be technically difficult and are therefore not commonly performed (remediastinoscopy). METHODS AND PATIENTS Nineteen consecutive patients with NSCLC and proven ipsilateral or subcarinal lymph node metastases (N2 disease) who had been treated with induction chemotherapy underwent mediastinal restaging by EUS-FNA. Patients had either a partial response (n=14) or stable disease (n=5) based on sequential CT scans of the thorax. INTERVENTIONS EUS-FNA was performed in an ambulatory setting with biopsy of mediastinal lymph nodes (LN). No complications occurred. When EUS-FNA restaged the mediastinum as no regional lymph node metastasis (N0), surgical resection of the tumour with lymph node sampling or dissection was performed. RESULTS The positive predictive value, negative predictive value, sensitivity, specificity and diagnostic accuracy of EUS-FNA in restaging mediastinal LN were 100, 67, 75, 100 and 83%, respectively. CONCLUSIONS AND SIGNIFICANCE EUS-FNA qualifies as an accurate, safe and minimally invasive diagnostic technique for the restaging of mediastinal lymph nodes after induction therapy in NSCLC. In the future EUS-FNA might play an important role in the mediastinal restaging in NSCLC, particularly to identify the subgroup of down staged patients who benefit most from further surgical treatment.

MRI to Evaluate Left Atrial and Ventricular Reverse Remodeling After Restrictive Mitral Annuloplasty in Dilated Cardiomyopathy

BACKGROUND Data on reverse remodeling of the left atrium (LA) and left ventricle (LV) after restrictive annuloplasty in patients with dilated cardiomyopathy are scarce, and follow-up studies are performed with echocardiography. METHODS AND RESULTS Twenty patients with dilated cardiomyopathy and severe mitral regurgitation selected for restrictive mitral annuloplasty underwent serial MRI studies (within 1 week before surgery, and 2 months [n =18] and 1 year [n =13] after surgery). Early mortality was 10%; all patients were free from endocarditis and thromboembolism. New York Heart Association class improved from 3.2+/-0.4 to 1.2+/-0.9. Only 1 patient developed recurrent severe mitral regurgitation during follow-up and it was re-repaired. LA end-systolic volumes decreased significantly over time (from 165+/-48 mL to 109+/-23 mL to 111+/-28 mL; P < 0.01), as did LA end-diastolic volumes (from 92+/-32 mL to 71+/-22 mL to 75+/-17 mL; P = 0.01). LV end-diastolic volumes decreased significantly (from 244+/-56 mL to 184+/-54 mL to 195+/-67 mL; P < 0.01), whereas end-systolic volumes did not change significantly. LV ejection fraction increased significantly (from 35+/-8% to 46+/-13% to 46+/-15%; P < 0.01) and LV mass decreased significantly (from 150+/-43 grams to 132+/-39 grams to 136+/-33 grams; P = 0.02). CONCLUSIONS Restrictive annuloplasty in patients with dilated cardiomyopathy yielded excellent clinical results associated with significant LA and LV reverse remodeling over time as demonstrated by MRI.

Prognostic factors in pulmonary metastasized high-grade osteosarcoma.

Resection of pulmonary metastases has previously been reported to improve outcome in high‐grade osteosarcoma (OS) patients. Factors influencing survival in OS patients with pulmonary metastases are important for clinical decision making.

Tranexamic acid and aprotinin in low- and intermediate-risk cardiac surgery: a non-sponsored, double-blind, randomised, placebo-controlled trial §

OBJECTIVE Tranexamic acid has been suggested to be as effective as aprotinin in reducing blood loss and transfusion requirements after cardiac surgery. Previous studies directly comparing both antifibrinolytics focus on high-risk cardiac surgery patients only or suffer from methodological problems. We wanted to compare the effectiveness of tranexamic acid versus aprotinin in reducing postoperative blood loss and transfusion requirements in the patient group representing the majority of cardiac surgery patients: low- and intermediate-risk patients. METHODS We conducted a non-sponsored, double-blind, randomised, placebo-controlled trial in which 298 patients scheduled for low- or intermediate-risk (mean logistic EuroSCORE 4.1) first-time heart surgery with use of cardiopulmonary bypass were randomised to receive either tranexamic acid, high-dose aprotinin, or placebo. All patients had preoperative normal renal function. End points of the study were monitored from the time of surgery until patient discharge. This trial was executed between June 2004 and October 2006. RESULTS Both antifibrinolytics significantly reduced blood loss and transfusion requirements when compared with placebo. Aprotinin was about twice as effective as tranexamic acid in reducing total postoperative blood loss (estimated median difference 155 ml, 95% confidence interval (CI) 60-260; p < 0.001). Accordingly, aprotinin reduced packed red blood cell transfusions more than tranexamic acid, although the difference did not reach statistical significance. Only aprotinin significantly reduced the proportion of transfused patients when compared with placebo (mean difference -20.9%, 95% CI 7.3-33.5; p = 0.013), and only aprotinin completely abolished bleeding-related re-explorations (mean difference 6.8%, 95% CI 1.6-13.4%; p = 0.004). Neither antifibrinolytic agent increased the incidence of mortality (mean difference tranexamic acid -0.4%, 95% CI -4.6 to 4.4; p = 0.79, mean difference aprotinin -1.3%, 95% CI -6.2 to 3.5; p = 0.62) or other serious adverse events when compared with placebo. CONCLUSION Aprotinin has clinically significant advantages over tranexamic acid in patients with normal renal function scheduled for low- or intermediate-risk cardiac surgery.