Adipokines: A Possible Contribution to Vascular and Bone Remodeling in Idiopathic Pulmonary Arterial Hypertension.

Osteoporosis is a major comorbidity of cardio-respiratory diseases, but the mechanistic links between pulmonary arterial hypertension and bone remain elusive. The purpose of the stud was to evaluate serum adipokines and endothelin-1 (ET-1) levels in the patients with idiopathic pulmonary arterial hypertension (IPAH) NYHA class III-IV and to determine its associations with bone mineral density (BMD). Pulmonary and hemodynamic parameters, BMD Z-scores at the lumbar spine (LS) and femoral neck (FN), serum leptin, adiponectin, visfatin and endothelin-1 (ET-1), were evaluated in 32 patients with IPAH NYHA class III-IV and 30 healthy volunteers. Leptin, adiponectin and ET-1 were higher in the patients with IPAH than in healthy subjects. Visfatin level showed a tendency to increase compared to that of healthy subjects (p = 0.076). The univariate analysis revealed a positive correlation between BMD Z-scores at both sites and 6-min walk test, and inverse relation with pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP). Adiponectin and visfatin showed positive correlations with PVR (p = 0.009 and p = 0.006). Serum adiponectin, visfatin and leptin were inversely associated with Z-scores. After adjusting for BMI and FMI, such associations persisted between visfatin and adiponectin levels and Z-scores at both sites. ET-1 related to mPAP, cardiac index and PVR. Negative correlation was observed between ET-1 and FN BMD (p = 0.01). Positive correlations have revealed between ET-1 and adiponectin (p = 0.02), visfatin (p = 0.004) in IPAH patients. These results provide further evidence that adipokine and endothelial dysregulation may cause not only a decrease in BMD, but also an increase in hemodynamic disorders of IPAH.

The Role of Tumor Necrosis Factor Alpha and TNF Superfamily Members in Bone Damage in Patients with End-Stage Chronic Obstructive Lung Disease Prior to Lung Transplantation.

A disequilibrium of tumor necrosis superfamily (TNF) members, including the serum osteoprotegerin, soluble receptor activator of nuclear factor-κB ligand, soluble TNF-related apoptosis-inducing ligand and TNF-α, was associated with the occurrence of a reduced skeletal mass and osteoporosis in male patients with end-stage chronic obstructive pulmonary disease (COPD). The purpose of this study was to explore the associations between serum biomarkers of tumor necrosis factor (TNF) superfamily and body and bone compositions in end-stage COPD males. Pulmonary function, T-score at the lumbar spine and femoral neck, lean mass, serum osteoprotegerin (OPG), soluble receptor activator of nuclear factor-κB ligand (sRANKL), TNF-α and its receptors (sTNFR-I, sTNFR-II) and soluble TNF-related apoptosis-inducing ligand (sTRAIL) levels were evaluated in 48 male patients with end-stage COPD and 36 healthy male volunteers. OPG was lower in male COPD patients than in control subjects, whereas sRANKL, TNF-α and its receptors were higher. The serum sTRAIL level showed a tendency to increase compared with that of healthy subjects (P = 0.062). Serum OPG showed a positive correlation with bone density. In contrast, serum TNF-α, sRANKL and sTRAIL were inversely associated with pretransplant bone density. We have noted the appearance of statistically significant inverse relationships between lean mass values and TNF-α, sTNFR-I and II and sRANKL levels in male COPD patients. Moreover, there was a negative correlation between sTRAIL levels with airway obstruction (P = 0.005) and hypercapnia (P = 0.042) in advanced COPD patients. Through a multiple linear regression analysis, our study revealed that a disequilibrium of TNF family members was strongly associated with the occurrence of a reduced skeletal mass and osteoporosis. These results provide further evidence that abnormal levels of TNF superfamily molecules may cause not only a decrease in BMD, but also lower muscle mass in end-stage COPD.

Risk factors for early mortality and morbidity after pneumonectomy: a reappraisal.

BACKGROUND: Pneumonectomy remains a high-risk procedure. Comprehensive patient selection should be based on analysis of proven risk factors. METHODS: The records of 323 pneumonectomy patients were retrospectively reviewed. Multiple demographic data were collected. End points were operative mortality at 30 and at 90 days, major procedurally related complications, and cardiovascular events. Univariate and multivariate statistical analyses were performed. RESULTS: Smoking habits, chronic obstructive pulmonary disease (COPD) status, induction chemotherapy status, diabetes, and obesity had no statistical influence on short-term outcomes. After right pneumonectomy, 30-day mortality (p = 0.045) and the incidence of bronchopleural fistulas (p = 0.009) were increased. Multivariate analysis for postoperative bronchopleural fistulas discovered that right pneumonectomies are the sole risk factor (p = 0.015). Univariate analysis for postoperative atrial fibrillation showed that male gender, age 70 and older, hypertension, and dyslipidemia are risk factors. Multivariate analysis found no definite risk factor. Patients with coronary artery disease had more postoperative cardiovascular events (p = 0.003). Among patients free of coronary artery disease, COPD led to an increased 90-day mortality rate (p = 0.028). CONCLUSIONS: Patients with right pneumonectomies are at increased risk. Postoperative cardiovascular events are more frequent in coronary artery disease patients. COPD is a risk factor in patients free of coronary disease.

Persistent N2 disease after induction therapy does not jeopardize early and medium term outcomes of pneumonectomy.

BACKGROUND: Operative management of patients with persistent N2 disease after induction therapy is still debated. METHODS: One hundred fifty-three consecutive patients underwent pneumonectomy from January 1999 until July 2005; 28 patients (18.3%) had persistent N2 disease after induction therapy (group 1), 32 patients (20.9%) had pathologic stage N0 or N1 after induction therapy (group 2), and 93 patients (60.8%) with pathologic N2 disease underwent immediate surgery (group 3). Short-term end points were operative mortality at 30 and 90 days and major complications. Long-term end points were 5-year survival and disease-free survival rates. RESULTS: Demographics of the three groups were similar (age, sex, side of operation, type of chemotherapy, smoking status, and comorbidity such as coronary artery disease, diabetes, and chronic obstructive pulmonary disease). Thirty-day postoperative mortality was 10.7% in group 1, 3.1% in group 2 (p = 0.257), and 4.3% in group 3 (p = 0.201); 90-day postoperative mortality was 10.7% in group 1, 12.5% in group 2 (p = 0.577), and 9.7% in group 3 (p = 0.558). Incidence of major postoperative complications was similar. Five-year survival rate was 32.2% (median, 28 months; 95% confidence interval, 7 to 43) in group 1, 34.8% (median, 27 months; 95% confidence interval, 7 to 47) in group 2 (p = 0.685), and 12.4% (median, 15 months; 95% confidence interval, 11 to 19) in group 3 (p = 0.127). No statistical difference was found in terms of 5-year event-free survival, or regarding the side of pneumonectomy. CONCLUSIONS: Our results suggest that pneumonectomy is justified in patients with persistent N2 disease after induction chemotherapy.

Induction chemotherapy does not increase the operative risk of pneumonectomy!

BACKGROUND: There is an ongoing debate whether induction therapy increases post-operative mortality and morbidity, especially when performing pneumonectomy. We therefore reviewed a consecutive series of patients having undergone pneumonectomy in a single center. METHODS: The charts of 298 patients operated on between January 1999 and July 2005 were reviewed. Patients were divided into two groups: group 1 included those who received induction chemotherapy (60 patients, 20.1%), and group 2 included those who underwent surgery alone (238 patients, 79.9%). Endpoints were operative mortality at 30 and at 90 days, and major complications such as empyema, bronchial fistula and acute respiratory distress syndrome. Statistical analyses were performed using SPSS 11.0 software. RESULTS: Demographic data were similar for both groups when considering side of operation, comorbidity and weaning from tobacco; patients were older in group 2 (61.83+/-9.58 years vs 57.75+/-8.94 years; p=0.003) and there were more female patients in group 2 (17.2% vs 5.0%; p=0.010). Post-operative mortality at 30 days was 6.7% in group 1 and 5.5% in group 2 (p=0.458), and 11.7% for group 1 and 10.9% in group 2 at 90 days (p=0.512). Incidence of empyema was 1.7% in group 1 and 2.1% in group 2 (p=0.652); incidence of bronchopleural fistulas was 1.7% in group 1 and 5.5% in group 2 (p=0.188); incidence of acute respiratory distress syndrome was 3.3% in group 1 and 3.4% in group 2 (p=0.675). CONCLUSION: In opposition to previous reports, induction chemotherapy did not significantly jeopardize post-operative outcome following pneumonectomy in our experience.

Bronchoplastic lobectomy: do early results depend on the underlying pathology? A comparison between typical carcinoids and primary lung cancer.

BACKGROUND: This study evaluates the impact of the underlying disease upon the surgical outcome of bronchoplastic lobectomy, comparing typical carcinoid tumours with primary lung carcinoma. PATIENTS AND METHODS: This retrospective study includes 98 consecutive patients (78 males, 20 females). Eighteen patients had a typical carcinoid tumour (group 1), and 80 had a primary bronchial carcinoma (group2). Fifty-six patients underwent bronchoplasty with full sleeve resection (10 patients from group 1, 46 from group 2) and 42 patients had a bronchoplasty with bronchial wedge resection (8 from group 1 and 34 from group 2). Right upper lobectomy was the most common procedure. We compared demographic data, surgical indications, the type of bronchoplasty and postoperative complications. RESULTS: The average age in group 1 (38.5+/-16.3 years; range 15-77) was significantly lower than in group 2 (61.4+/-9.5 years; range 14-75) (p<0.001). There were no postoperative deaths. Procedure-specific complications (anastomotic dehiscence and atelectasis) were found in 7 patients (8.75%) in group 2 (of which, three had a combination of two of the above-mentioned complications) but none (0%) in group 1 (p=0.23). Seven patients from group 2 (8.75%) required treatment for a residual pneumothorax for none (0%) in group 1 (p=0.23). The mean duration for air leak was comparable in both groups (p=0.366). Three patients (16.67%) from group 1 had non-surgical complications compared to 17 (21.25%) in group 2 (of which, one had a combination of two non-surgical complications) (p=0.35). CONCLUSION: Bronchoplastic resection is a safe operation in patients with carcinoid tumours and should be the reference for treatment.

Sampling or node dissection for intraoperative staging of lung cancer: a multicentric cross-sectional study.

OBJECTIVE: This study compares accuracy of sampling versus formal node dissection in patients with primary lung cancer. PATIENTS AND METHODS: During a 4-month period, 208 consecutive patients (172 men, 36 women) without bulky disease underwent resection for primary lung cancer in three centers. The surgeon first sampled the main lymph node stations, and subsequently performed a radical mediastinal dissection. Endpoints were accuracy of prediction for stage N2 and radicality of node sampling compared to dissection. RESULTS: Resection consisted of 1 segmentectomy, 142 standard lobectomies, 6 bilobectomies, 14 sleeve-lobectomies, and 45 pneumonectomies. There were 108 squamous cell carcinomas, 621 adenocarcinomas, 18 bronchoalveolar carcinomas, 8 large cell carcinomas, 4 adenosquamous carcinomas and 8 neuroendocrine carcinomas. Primary tumor was stage T1 in 49 patients, T2 in 110, T3 in 43, and T4 in 6. Lymph node status (dissection) was N0 in 113, N1 in 35, and N2 in 60 patients. N2 disease concerned a single node in 16, a single node station in 19, and multiple levels in 25. Both N1 and N2 nodes were diseased in 36 patients. Sampling adequately recognized N2 disease in 31 patients (52%). Multiple level N2 was accurately identified in 10 patients (40%). Resection based on sampling would have been incomplete in 53 patients (88%). CONCLUSION: Radical mediastinal dissection is a mandatory adjunct to resection for lung cancer with curative attempt.