Loic Lang-Lazdunski

Pleurectomy/Decortication is Superior to Extrapleural Pneumonectomy in the Multimodality Management of Patients with Malignant Pleural Mesothelioma

Introduction: To compare the outcomes of two different multimodality regimens involving neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant radiotherapy versus pleurectomy/decortication (P/D), hyperthermic pleural lavage with povidone-iodine, and adjuvant chemotherapy in patients with malignant pleural mesothelioma. Methods: Nonrandomized prospective study of patients treated by multimodality therapy and operated on between January 2004 and June 2011. Second-line treatments were administered when appropriate. Survival and prognostic factors were analyzed by the Kaplan Meier method, log rank test, and Cox regression analysis. Results: Twenty-five consecutive patients received neoadjuvant chemotherapy, 22 underwent EPP, and 17 received adjuvant radiotherapy. Over the same period, 54 consecutive patients underwent P/D and hyperthermic pleural lavage and received prophylactic radiotherapy and adjuvant chemotherapy. The 30-day mortality rate was 4.5%in the EPP group and nil in the P/D group. Fifteen patients (68%) in the EPP group and 15 (27.7%) in the P/D group experienced complications. There were no differences between the EPP and P/D groups for age, sex, histology, pathologic stage, and nodal status. Trimodality therapy was completed by 68%of the patients in the EPP group and 100%in the P/D group. Survival was significantly better in the P/D group: median survival was 23 months versus 12.8 months, 2-year survival was 49%versus 18.2 %, and 5-year survival was 30.1%versus 9%, respectively (p = 0.004). At multivariate analysis, epithelioid histology, P/D, and completeness of resection were independent prognostic factors. Conclusions: In our experience, P/D, hyperthermic pleural lavage with povidone-iodine, and adjuvant chemotherapy were superior to neoadjuvant chemotherapy, EPP, and adjuvant radiotherapy.

The Mesothelioma and Radical surgery randomized controlled trial: the Mars feasibility study.

Hypothesis: The effectiveness of extrapleural pneumonectomy (EPP) to extend quality-adjusted survival in malignant pleural mesothelioma within multimodality treatment should be proven in a randomized controlled trial if this radical surgery is to be regarded as the standard of care. The question was whether randomization to surgery versus no surgery would be possible. Methods: The Mesothelioma and Radical Surgery trial was planned to randomize 50 patients to test feasibility. There was a two-stage consent process. At first consent, the patients who were possible candidates for radical surgery were registered into the trial for completion of assessment and staging. All received platinum-based chemotherapy. If still eligible, they completed a second consent to be randomized to have either EPP followed by radical hemithorax radiotherapy or to have continued best care. Results: Patients were recruited through 11 collaborating centers in the United Kingdom. One hundred twelve potentially eligible patients gave informed consent to enter the registration phase and undergo chemotherapy. One died, 27 progressed, five were inoperable, four were treated off trial, and 18 withdrew either during or after chemotherapy but before final review. Additionally six were deemed inoperable at review after completing chemotherapy and one more patient withdrew. The remaining 50 were randomized; 24 to EPP and 26 to continued best care. Conclusions: In this study, 50/112 (45%) of patients entering the evaluation and induction phase of the trial went on to be randomized. We have shown that this randomization between surgery and no surgery is feasible. This was the primary aim of the Mesothelioma and Radical Surgery trial.

The role of surgical cytoreduction in the treatment of malignant pleural mesothelioma: Meeting summary of the International Mesothelioma Interest Group Congress, September 11-14, 2012, Boston, Mass

The treatment of all solid tumors, including malignant pleural mesothelioma (MPM), is dependent on (1) macroscopic complete resection and (2) treatment of micrometastatic disease. The role of surgery in the treatment of MPM has been the subject of debate after the recent publication of the Mesothelioma and Radical Surgery (MARS) I trial. The International Mesothelioma Interest Group (IMIG) met from September 11 through 14, 2012, in Boston, Mass. During this meeting, more than 500 participants representing all the involved specialty groups met in multiple comprehensive sessions to review, critique, and extend the state of knowledge regarding the role of surgery, including both extended pleurectomy/decortication (P/D) and extrapleural pneumonectomy (EPP), in the treatment of MPM. Some of the deficiencies of the MARS I trial, which was published a year ago in Lancet Oncology, were discussed in multiple sessions of the IMIG meeting. The editorial that accompanied the publication articulated numerous shortcomings of the trial. TheMARS I trial was designed as a pilot feasibility trial, the result of which was negative in that it failed to demonstrate the feasibility of randomly allocating patients to surgery versus no surgery. Nevertheless, the

Riluzole prevents ischemic spinal cord injury caused by aortic crossclamping

BACKGROUND Recent studies support the involvement of glutamate neurotoxicity in the pathophysiology of spinal cord injury induced by aortic crossclamping. We investigated the effects of riluzole, a neuroprotective drug that blocks glutamatergic neurotransmission, in a rabbit model of spinal cord ischemia. METHODS The infrarenal aortas of New Zealand White albino rabbits (n = 40) were occluded for 40 minutes. Experimental groups were as follows: sham operation group (n = 5), control group undergoing occlusion but receiving no pharmacologic intervention (n = 10), experimental group A (n = 10) receiving 8 mg/kg riluzole intravenously 30 minutes before ischemia, experimental group B (n = 10) receiving 4 mg/kg riluzole intravenously 30 minutes before ischemia and at the onset of reperfusion, and experimental group C (n = 10) receiving 8 mg/kg riluzole intravenously at the onset of reperfusion. Neurologic status was assessed at 6, 24, and 48 hours after the operation and then daily until the fifth day. All animals were killed at 24, 48, or 120 hours after the operation. Spinal cords were harvested for histopathologic studies, immunohistochemical studies for microtubule-associated protein 2, and search for morphologic features of apoptosis by the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate-biotin nick-end labeling staining method. RESULTS All animals in the control group became paraplegic. Except for 1 rabbit in group C, all riluzole-treated animals had better neurologic function. Luxol fast blue and terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate-biotin nick-end labeling staining methods demonstrated typical morphologic changes characteristic of necrosis and apoptosis in control animals. Riluzole prevented or attenuated ischemia-induced necrosis, apoptosis, and cytoskeletal proteolysis, depending on the dose and the timing of administration. CONCLUSION Riluzole may have therapeutic utility during high-risk operations on the thoracoabdominal aorta.

Complications of video-assisted thoracic surgery: A five-year experience

BACKGROUND Although thoracoscopy was originally described in 1910, recent developments in video-assisted surgical techniques and endoscopic equipment has expanded the application of video-assisted surgical procedures in the field of thoracic surgery. METHODS In an effort to define both high-risk patients for video-assisted thoracic procedures and high-risk video-assisted thoracic surgical procedures, we reviewed the experience of four surgical institutions from June 1991 through May 1995. We looked specifically at complications resulting from the 937 video-assisted thoracic procedures performed during this period. RESULTS Perioperative incidents or complications occurred in 35 patients (3.7%), and 116 procedures (12.4%) were converted to a thoracotomy. The in-hospital mortality rate was 0.5%, and death occurred principally in patients operated on for malignant pleural effusion. The overall incidence of postoperative complications was 10.9%, and the most prevalent complications were prolonged air leak (6.7%) and pleural effusion (0.7%). CONCLUSIONS The incidence of complications was acceptable and, except for that of prolonged air leak, did not differ significantly from that resulting from analogous open procedures. Video-assisted thoracic surgery appears safe and particularly useful for some indications. However, the possibility of dramatic life-threatening perioperative complications requiring emergency conversion to thoracotomy justifies the fact that only trained thoracic surgeons should perform video-assisted thoracic surgical procedures.

Phase 2 Study of Sorafenib in Malignant Mesothelioma Previously Treated with Platinum-Containing Chemotherapy

Introduction: The incidence of mesothelioma is rising. First-line cisplatin and pemetrexed confers a survival benefit, with a median progression-free survival (PFS) of 5.7 months. Sorafenib inhibits tyrosine kinases, including receptors for vascular endothelial growth factor, which are implicated in mesothelioma pathogenesis by preclinical and clinical data. Methods: Sorafenib, at 400 mg twice daily, was assessed in a single-arm multicenter phase 2 study, using Simon’s two-stage design. Eligible patients had received platinum combination chemotherapy earlier. The primary endpoint was PFS at 6 months, with secondary endpoints, including response rate and metabolic response, assessed using fluorodeoxyglucose positron emission tomography. Published reference values for PFS in mesothelioma provide a benchmark for the null hypothesis of 28% progression-free at 6 months, and for moderate or significant clinical activity of 35% or 43% progression-free at 6 months, respectively. Results: Fifty-three patients (72%) were treated. Most had epithelioid histology. Ninety-three percent of patients had a performance status 0 or 1. Treatment was well tolerated with few grade 3 or 4 toxicities. Median PFS was 5.1 months, with 36% of patients being progression-free at 6 months. Nine percent of patients remained on study beyond 1 year. Changes in fluorodeoxyglucose positron emission tomography parameters did not predict clinical outcome. Conclusions: Sorafenib is well tolerated in patients with mesothelioma after completion of platinum-containing chemotherapy. PFS of sorafenib compares favorably with that reported for other targeted agents, and suggests moderate activity in this disease.

Successful resection of giant intrapericardial lipoma

We report a case of giant extracavitary cardiac lipoma weighing 4,800 g. The mode of presentation, the preoperative evaluation, and the radiographic features are presented. The surgical management of this very rare cardiac pathology is discussed. This is one of the largest cardiac tumors ever reported.

Catamenial Pneumothorax: Surgical Repair of the Diaphragm and Hormone Treatment

Catamenial pneumothorax is defined as spontaneous pneumothoraces occurring within 72 h before or after onset of menstruation. It is rare but clinical index of suspicion should be high in ovulating women with spontaneous pneumothoraces. The mechanism is unclear but is thought to involve pre-existing or acquired diaphragmatic defects and endometrial implants. Traditional therapy involving hormonal treatment or surgical pleurodesis alone is associated with high rates of recurrence. A series of four patients with catamenial pneumothorax managed at our institution is presented to highlight the condition to various surgical specialties to whom it may present, and to emphasise the importance of both surgical and hormonal interventions in preventing recurrence. Each patient underwent video-assisted thoracoscopic inspection of the diaphragm, mechanical pleurodesis and, most importantly, repair of diaphragmatic defects with an artificial mesh. Surgical treatment was strictly followed by a course of gonadotrophin-releasing hormone analogue therapy in three patients, with no recurrence to date (longest follow-up 45 months). The fourth patient suffered a postoperative recurrence when hormonal treatment was delayed for 6 weeks, stressing the importance of hormonal treatment in conjunction with surgery.

Management of giant coronary artery aneurysm with fistulization into the right atrium

A giant right coronary artery aneurysm communicating with the right atrium is reported. Its diagnosis using echocardiography, computed tomography of the chest, and angiography is illustrated. The operative management of this rare cardiac pathology is described. The role of operation in such a large aneurysm is emphasized.

Pleurectomy/Decortication, Hyperthermic Pleural Lavage with Povidone-Iodine Followed by Adjuvant Chemotherapy in Patients with Malignant Pleural Mesothelioma

Introduction: Malignant pleural mesothelioma is a fatal neoplasm related to asbestos exposure. We investigated the effects of pleurectomy/decortication (P/D), hyperthermic pleural lavage with povidone-iodine and adjuvant chemotherapy in patients with malignant pleural mesothelioma. Patients and Methods: Observational prospective study of patients referred for multimodality therapy and operated on at our institution between October 2004 and May 2010. Thirty-six selected patients underwent P/D and hyperthermic pleural lavage, prophylactic radiotherapy, and adjuvant chemotherapy. All patients were reviewed at 4 weeks and then 6 monthly in the outpatient clinic, with positron-emission tomography-computed tomography. Second-line treatments were administered when appropriate. Results: Thirty-day mortality was nil. Nine patients experienced postoperative complications: persistent air leak (n = 5, 13.9%), chylothorax requiring surgical intervention (n = 4, 11%), and adult respiratory distress syndrome (n = 1, 3.9%). Fourteen of 36 patients were alive at last follow-up (median follow-up: 33 months, range: 12–63 months). Ten patients were alive with no evidence of disease recurrence, four patients were alive with disease recurrence, and 22 patients had died of disease progression. Overall median survival (Kaplan-Meier) was 24 months (95% confidence interval: 18.5–29.4 months). One-year survival was 91.7%, and 2-year survival was 61%. Patients undergoing complete macroscopical resection (R0–R1) had a significantly better survival than those undergoing an incomplete macroscopical resection (R2) (median overall survival: 32 months versus 18.9 months, p = 0.012). Conclusion: In our experience, P/D combined with hyperthermic pleural lavage with povidone-iodine and adjuvant chemotherapy is a well-tolerated multimodality treatment associated with low morbidity and mortality. This multimodality treatment compares favorably with classical trimodality regimens involving chemotherapy, extrapleural pneumonectomy, and adjuvant radiotherapy, in our experience. Study limitations include small sample size, nonrandomization, and patient selection bias.