Bart Pieter Van Putte

Background: Hybrid Ablation for atrial fibrillation (AF) combines epicardial and endocardial ablation through a Heart Team approach to target durable, transmural isolation of the pulmonary veins (PV) and left atrial posterior wall (LAPW). While the primary efficacy endpoint at 12 months was met with a significant benefit increase for hybrid ablation, we now report the midterm durability of those results. Purpose: To evaluate 24-months safety and effectiveness of Hybrid Ablation with left atrial appendage exclusion (LAAE) versus Catheter Ablation in patients with persistent AF/enlarged left atrium and longstanding persistent AF (LSPAF). Methods: CEASE-AF is a prospective, multi-center, 2:1 randomized controlled trial. Eligible patients were 18-75 years of age, had symptomatic, drug-refractory persistent AF and enlarged left atrium (>4 cm) or LSPAF, and were undergoing a first ablation. Hybrid Ablation consisted of two stages: thoracoscopic epicardial radiofrequency (RF) ablation for PV and LAPW isolation and epicardial LAAE followed by endocardial ablation 91-180 days later. Catheter Ablation consisted of minimum PV isolation by endocardial RF ablation, and repeat ablation was allowed between 91-180 days. In both arms, additional lesions were permitted according to institutional practices. Effectiveness was freedom from AF/atrial flutter (AFL)/atrial tachycardia (AT) off anti-arrhythmic drugs (AAD) (except AADs not exceeding doses which previously failed) and was assessed through 48-h Holter monitoring reviewed by an independent core laboratory blinded to the study. Safety was major adverse events throughout the study, adjudicated by an independent Clinical Events Committee. Results: There were 102 Hybrid Ablation and 52 Catheter Ablation patients; 26% were female, mean age was 60.7±7.9 years, mean LAD was 4.7±0.4 cm, and 19% had LSPAF with no differences between arms. The 12- and 24-month results are shown for comparison (Table). Through 24-months, effectiveness was 66.3% (63/95) in the Hybrid Arm and 33.3% (17/51) in the Catheter Arm (absolute difference 33.0% [95% CI 14.3%, 48.3%; p<0.001]). Major adverse event rates through 24-months were statistically similar at 10.8% (11/102) in the Hybrid Arm and 9.6% (5/52) in the Catheter Arm (p=1.0). Through 24-months, repeat ablations were performed in 7.4% (7/95) of the Hybrid Arm versus 37.3% (19/51) of the Catheter Arm (p<0.001), and cardioversions were performed in 14.7% (14/95) of the Hybrid Arm versus 29.4% (15/51) of the Catheter Arm (p=0.034) Conclusions: CEASE-AF demonstrated that superior effectiveness of Hybrid Ablation including LAAE versus Catheter Ablation was durable through 24-month follow-up, with 33% absolute improvement in freedom from AF/AFL/AT. Safety rates continued to be similar between arms. Three-year follow-up is ongoing.

To evaluate changes in pulmonary function tests (PFTs) at different follow-up durations after stereotactic body radiotherapy (SBRT) and surgery in stage I and II non-small-cell lung cancer (NSCLC). Differences between pre-treatment- and follow-up PFTs were analyzed in 93 patients treated with surgery and 30 patients treated with SBRT for NSCLC. Follow-up durations were categorized into: early (0-9 months), middle (10-21 months) and late (≥22 months). Wilcoxon signed-rank test was used to analyze differences between pre-treatment and follow-up PFTs. Forced expiratory volume in one second, forced vital capacity and diffusion capacity for carbon monoxide corrected for the actual hemoglobin level significantly diminished after surgery for all follow-up durations: 11-17% of predicted values. After SBRT, PFTs remained stable, but a declining trend of 6% (p=0.1) was observed after 22 months. SBRT might lead to less treatment-related toxicity measured by PFTs than surgery in both the short and long term.

An important disadvantage of the video-assisted thoracoscopic surgery (VATS) lobectomy technique remains the minithoracotomy for specimen removal resulting in some degree of traction on the ribs even without the usage of a rib retractor. We describe a new technique of VATS lobectomy in supine position consisting of complete lymph node dissection and subxyphoidal removal of the lobe(s) preventing any degree of rib traction.

Lung cancer represents a major health problem. Cytostatic and radiotherapeutic treatment is limited because of dose-limiting systemic toxicity and surgery as a result of its invasive nature. Therefore, we developed a catheterization model of selective pulmonary artery perfusion (SPAP) combining the properties of isolated lung perfusion and i.v. treatment to achieve higher local drug levels and equivalent systemic exposure. Sixteen pigs underwent SPAP using a clinically applied dose of gemcitabine (1 g/m²). They furthermore underwent thoracotomy for tissue sampling. Three groups were treated with SPAP for 2 min with normal pulmonary blood flow, 50 and 90% flow reduction. Another group had SPAP for 10 min with normal blood flow. All the SPAP groups underwent catheterization of the left pulmonary artery. An additional group (n = 4) was infused i.v. for 30 min using the same dose. Concentrations were analyzed with analysis of variance. Pulmonary peak concentrations (p = 0.01) and areas under the curve (AUC) (p = 0.001) of SPAP for 2 and 10 min were significantly higher compared with i.v., whereas SPAP for 10 min resulted in the highest AUC (p = 0.045) compared with SPAP for 2 min. Flow reduction during SPAP resulted in inhomogeneous distribution. Liver levels, AUC (serum), and wet-to-dry ratios of all the SPAP groups were not significantly different compared with i.v. SPAP resulted in higher lung concentrations, whereas systemic exposure was comparable with i.v. Therefore, we advocate SPAP as a new method to be tested clinically to achieve down-staging of the tumor and lymph node status in lung cancer.

Surgical resection is a widely accepted treatment for pulmonary metastases on the condition that a complete resection can be obtained. However, many patients will develop recurrent disease in the thorax despite the use of systemic chemotherapy, dosage of which is limited because of systemic toxicity. Similar to the basic principles of isolated limb and liver perfusion, isolated lung perfusion is an attractive and promising surgical technique for the delivery of high-dose chemotherapy with minimal systemic toxicity. The use of biological response modifiers, like tumour necrosis factor, is also feasible. Other related methods of delivering high-dose locoregional chemotherapy include embolic trapping (chemo-embolisation) and pulmonary artery infusion without control of the venous effluent. Isolated lung perfusion has proven to be highly effective in experimental models of pulmonary metastases with a clear survival advantage. Lung levels of cytostatic drugs are significantly higher after isolated lung perfusion compared to intravenous therapy without systemic exposure. Phase I human studies have shown that isolated lung perfusion is technically feasible with low morbidity and without compromising the patient’s pulmonary function. Further clinical studies are necessary to determine its definitive effect on local recurrence, long-term toxicity, pulmonary function and survival.