Khalid Amer

Video-assisted thoracic surgery systematic mediastinal nodal dissection and stage migration: impact on clinical pathway,

OBJECTIVES The aim of this study is to investigate the role of routine systematic mediastinal nodal dissection (SND) performed during video-assisted thoracic surgery (VATS) major pulmonary resections (VMPRs) as a staging strategy for non-small-cell lung cancer (NSCLC), compared with preoperative staging by conventional positron emission tomography (PET) and computed tomography (CT) imaging. METHODS All patients suspected of having early lung cancer (T1-2, N0-1 and M0) were staged preoperatively by CT/PET. During VMPR, all lymph nodes on the right side at stations 2-4, 7, 8, 9, 10 and 11 and on the left stations 4-6, 7, 8, 9, 10, 11 and 3 when indicated were dissected en bloc. Histology was provided on the paraffin-embedded nodes, and patients staged accordingly. Preoperative and postoperative stagings were compared. Stage migration and impact on clinical pathway were noted. Stage IIa and higher were referred for adjuvant chemotherapy. RESULTS Between April 2007 and January 2011, 106 consecutive patients with suspected primary NSCLC proceeded to VMPR+SND. Histology confirmed NSCLC in 96 patients. Forty-five were men and 51 women. Median age was 68.6 (range 42.8-84.7) years. As many as 91 (94.8%) patients underwent lobectomy, three (3.1%) bilobectomy and two (2.1%) pneumonectomy. PET accurately correlated with SND histological diagnosis in 42 (43.8%) patients. The unexpected N2 disease in cN0-1 was 9/86 (10.5%). SND resulted in 25 stage migrations, upstaged 16 (16.6%) and down-staged nine (9.4%) patients. All upstagings were adenocarcinoma. Four (4.2%) PET-negative patients had multi-station N2 disease. SND resulted in changing the clinical pathway for 19 (20%) patients. Fourteen (14.6%) patients upstaged to qualify for chemotherapy, and 5/9 (5.2%) down-staged patients were saved the chemotherapy. There was no morbidity or mortality attributable to this added procedure. CONCLUSIONS SND during VMPR is safe and should be routinely performed even when nodal metastases is considered unlikely. VATS-SND is more accurate than PET in staging the mediastinum for NSCLC. PET sensitivity is significantly reduced in adenocarcinoma and might result in stage migration. Adjuvant multidisciplinary treatment should be based on SND staging.

A Novel Lung Explant Model for the Ex Vivo Study of Efficacy and Mechanisms of Anti-Influenza Drugs

Influenza A virus causes considerable morbidity and mortality largely because of a lack of effective antiviral drugs. Viral neuraminidase inhibitors, which inhibit viral release from the infected cell, are currently the only approved drugs for influenza, but have recently been shown to be less effective than previously thought. Growing resistance to therapies that target viral proteins has led to increased urgency in the search for novel anti-influenza compounds. However, discovery and development of new drugs have been restricted because of differences in susceptibility to influenza between animal models and humans and a lack of translation between cell culture and in vivo measures of efficacy. To circumvent these limitations, we developed an experimental approach based on ex vivo infection of human bronchial tissue explants and optimized a method of flow cytometric analysis to directly quantify infection rates in bronchial epithelial tissues. This allowed testing of the effectiveness of TVB024, a vATPase inhibitor that inhibits viral replication rather than virus release, and to compare efficacy with the current frontline neuraminidase inhibitor, oseltamivir. The study showed that the vATPase inhibitor completely abrogated epithelial cell infection, virus shedding, and the associated induction of proinflammatory mediators, whereas oseltamivir was only partially effective at reducing these mediators and ineffective against innate responses. We propose, therefore, that this explant model could be used to predict the efficacy of novel anti-influenza compounds targeting diverse stages of the viral replication cycle, thereby complementing animal models and facilitating progression of new drugs into clinical trials.

Is it safe to include octogenarians at the start of a video-assisted thoracic surgery lobectomy programme? §

OBJECTIVE The study aimed to investigate the safety of including patients ≥ 80 years of age at the start of a video-assisted thoracic surgery major pulmonary resection (VMPR) programme. METHODS Patients were considered for VMPR if the computed tomography/positron emission tomography (CT/PET) was suggestive of T1-3, N0-1 and M0 lesion. Age was not a criterion for exclusion at the very start of the programme. Data were collected prospectively and comparison made between two groups, (A) <80 years of age and (B) ≥ 80 years, in terms of preoperative risk factors, oncological and functional data, operative results, postoperative complications and survival. RESULTS Between April 2005 and January 2011, 200 consecutive patients were considered for VMPR. A total of 160 had non-small-cell lung cancer, of whom 136 were in group A, with a median age of 66.5 (range: 42.8-79.4 years) and 24 in group B with a median age of 82 (range: 80-85.5 years). In group B, 13 were men and 11 were women. Rate of conversion to thoracotomy was similar (3 (12.5%) in group B vs 17 (12.5%) in group A, p = 0.65), and so was the mean hospital stay (5.8 ± 3.3 days in group B vs 5.9 ± 4.6 days in group A, p = 0.899). Admission to intensive care unit and atrial fibrillation were significantly higher in octogenarians (six (25%) and six (25%) in group B vs eight (5.9%) and nine (6.6%) in group A, p = 0.008 and p = 0.012, respectively). There was significantly less mean days of air leak in octogenarians (0.06 ± 0.3 days in group B vs 2.8 ± 5.6 days in group A, p = 0.000). Otherwise, there were no age-related differences in relation to morbidity, mortality and the 3-year survival rate. CONCLUSION Octogenarians undergoing VMPR have a higher incidence of atrial fibrillation and admission to the intensive care unit for cardiopulmonary support but otherwise are no different from younger age groups when it comes to rate of conversion to thoracotomy, hospital stay, morbidity and mortality. Age should not be an excuse to deny the elderly curative VATS resection. In our experience, accepting octogenarians early in the VMPR programme did not compromise the outcome results.

Thoracoscopic Mediastinal Lymph Node Dissection for Lung Cancer

One of the main criticisms against lobectomy for lung cancer via video-assisted thoracoscopic surgery (VATS) is that mediastinal nodes are not properly assessed; however, VATS lobectomy permits complete nodal dissection that does not differ from that performed by thoracotomy.1 Because recent publications have shown a significant statistical gain in 5-year survival if patients with stage IIa non-small cell lung cancer (NSCLC) are treated with adjuvant chemotherapy,2,3 a thorough systematic mediastinal lymph node dissection (MLND) is absolutely mandatory to properly stage patients with NSCLC. Stage migration from inadequate mediastinal lymph node assessment has the potential to be detrimental to patients with NSCLC by dictating the wrong postoperative management. In addition, stage migration might lead to completely erroneous survival statistics. It should be kept in mind that randomized controlled trials rely on final histologic staging, which is possible only with an accurate systematic MLND. Surgeons might feel reluctant to extend the operating time to perform a thoracoscopic systematic MLND, but the risk of improper mediastinal staging, in our view, is by far greater than extending the duration of the operation.