Twenty-Year Survival of Patients Operated on for Non-Small-Cell Lung Cancer: The Impact of Tumor Stage and Patient-Related Parameters.

Surgery is the mainstay treatment of non-small-cell lung cancer (NSCLC), but its impact on very-long-term survival (beyond 15 years) has never been evaluated. METHODS: All patients operated on for major lung resection (Jun. 2001-Dec. 2002) for NSCL in the Thoracic Surgery Department at Paris-Hôtel-Dieu-University-Hospital were included. Patients' characteristics were prospectively collected. Vital status was obtained by checking INSEE database and verifying if reported as "non-death" by the hospital administrative database and direct phone interviews with patients of families. RESULTS: 345 patients were included. The 15- and 20-year survival rates were 12.2% and 5.7%, respectively. At univariate analysis, predictors of worse survivals were: increasing age at surgery (p = 0.0042), lower BMI (p = 0.009), weight loss (p = 0.0034), higher CRP (p = 0.049), pathological stage (p = 0.00000042), and, among patients with adenocarcinoma, higher grade (p = 0.028). Increasing age (p = 0.004), cumulative smoking (p = 0.045), lower BMI (0.046) and pathological stage (p = 0.0026), were independent predictors of long-term survival at Cox multivariate analysis. In another model, increasing age (p = 0.013), lower BMI (p = 0.02), chronic bronchitis (p = 0.03), lower FEV1% (p = 0.00019), higher GOLD class of COPD (p = 0.0079), and pathological stage (p = 0.000024), were identified as independent risk factors. CONCLUSIONS: Very-long-term survivals could be achieved after surgery of NSCLC, and factors classically predicting 5- and 10-years survival also determined longer outcomes suggesting that both initial tumor aggressiveness and host's characteristics act beyond the period usually taken into account in oncology.

Total Psoas Area and Total Muscular Parietal Area Affect Long-Term Survival of Patients Undergoing Pneumonectomy for Non-Small Cell Lung Cancer.

There is no standardization in methods to assess sarcopenia; in particular the prognostic significance of muscular fatty infiltration in lung cancer patients undergoing surgery has not been evaluated so far. We thus performed several computed tomography (CT)-based morphometric measurements of sarcopenia in 238 consecutive non-small cell lung-cancer patients undergoing pneumonectomy from 1 January 2007 to 31 December 2015. Sarcopenia was assessed by the following CT-based parameters: cross-sectional total psoas area (TPA), cross-sectional total muscle area (TMA), and total parietal muscle area (TPMA), defined as TMA without TPA. Measures were performed at the level of the third lumbar vertebra and were obtained for the entire muscle surface, as well as by excluding fatty infiltration based on CT attenuation. Findings were stratified for gender, and a threshold of the 33rd percentile was set to define sarcopenia. Furthermore, we assessed the possibility of being sarcopenic at both the TPA and TPMA level, or not, by taking into account of not fatty infiltration. Five-year survival was 39.1% for the whole population. Lower TPA, TMA, and TPA were associated with lower survival at univariate analysis; taking into account muscular fatty infiltration did not result in more powerful discrimination. Being sarcopenic at both psoas and parietal muscle level had the optimum discriminating power. At the multivariable analysis, being sarcopenic at both psoas and parietal muscles (considering the whole muscle areas, including muscular fat), male sex, increasing age, and tumor stage, as well as Charlson Comorbidity Index (CCI), were independently associated with worse long-term outcomes. We conclude that sarcopenia is a powerful negative prognostic factor in patients with lung cancer treated by pneumonectomy.

Patients experiencing early acute respiratory failure have high postoperative mortality after pneumonectomy.

OBJECTIVE: Post-pneumonectomy acute respiratory failure leading to invasive mechanical ventilation carries a severe prognosis especially when acute respiratory distress syndrome occurs. The aim of this study was to describe risk factors and outcome of acute respiratory failure. METHODS: We retrospectively reviewed clinical files of all patients who underwent pneumonectomy in a single center between 2005 and 2015. Risk factors and outcome of acute respiratory failure were assessed in univariate and multivariate analysis. RESULTS: Among the 543 patients who underwent pneumonectomy in the period of study, 89 (16.4%) needed reintubation within the 30th postoperative day and 60 of these (11% of all pneumonectomies) developed acute respiratory distress syndrome. In multivariate analysis, right-side of pneumonectomy (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.24-4.22), chronic cardiac disease (OR, 2.15; 95% CI, 1.08-4.25), Charlson Comorbidity Index (OR, 1.35; 95% CI, 1.14-1.61), carinal resection (OR, 3.23; 95% CI, 1.26-8.29), and extrapleural pneumonectomy (OR, 8.36; 95% CI, 3.31-21.11) were identified as independent risk factors of reintubation. Thirty-day mortality was 7.7% for all pneumonectomies, 41.6% (37/89) in the invasive ventilation group, and 53.3% (32/60) in patients with acute respiratory distress syndrome. In non-reintubated patients, 30-day mortality was 1.1% (5/454). In reintubated patients, 5-year survival was 27.1% (95% CI, 17.8-41.4). CONCLUSIONS: Early acute respiratory failure requiring reintubation remains a severe complication of pneumonectomy with a poor outcome.

Systemic inflammation, nutritional status and tumor immune microenvironment determine outcome of resected non-small cell lung cancer.

BACKGROUND: Hypothesizing that nutritional status, systemic inflammation and tumoral immune microenvironment play a role as determinants of lung cancer evolution, the purpose of this study was to assess their respective impact on long-term survival in resected non-small cell lung cancers (NSCLC). METHODS AND FINDINGS: Clinical, pathological and laboratory data of 303 patients surgically treated for NSCLC were retrospectively analyzed. C-reactive protein (CRP) and prealbumin levels were recorded, and tumoral infiltration by CD8+ lymphocytes and mature dendritic cells was assessed. We observed that factors related to nutritional status, systemic inflammation and tumoral immune microenvironment were correlated; significant correlations were also found between these factors and other relevant clinical-pathological parameters. With respect to outcome, at univariate analysis we found statistically significant associations between survival and the following variables: Karnofsky index, American Society of Anesthesiologists (ASA) class, CRP levels, prealbumin concentrations, extent of resection, pathologic stage, pT and pN parameters, presence of vascular emboli, and tumoral infiltration by either CD8+ lymphocytes or mature dendritic cells and, among adenocarcinoma type, tumor grade (all p<0.05). In multivariate analysis, prealbumin levels (Relative Risk (RR): 0.34 [0.16-0.73], p = 0.0056), CD8+ cell count in tumor tissue (RR = 0.37 [0.16-0.83], p = 0.0162), and disease stage (RR 1.73 [1.03-2.89]; 2.99[1.07-8.37], p = 0.0374- stage I vs II vs III-IV) were independent prognostic markers. When taken together, parameters related to systemic inflammation, nutrition and tumoral immune microenvironment allowed robust prognostic discrimination; indeed patients with undetectable CRP, high (>285 mg/L) prealbumin levels and high (>96/mm2) CD8+ cell count had a 5-year survival rate of 80% [60.9-91.1] as compared to 18% [7.9-35.6] in patients with an opposite pattern of values. When stages I-II were considered alone, the prognostic significance of these factors was even more pronounced. CONCLUSIONS: Our data show that nutrition, systemic inflammation and tumoral immune contexture are prognostic determinants that, taken together, may predict outcome.

Noninvasive ventilation for acute respiratory failure after lung resection: an observational study.

BACKGROUND: A single prospective randomized study found that, in selected patients with acute respiratory failure (ARF) following lung resection, noninvasive ventilation (NIV) decreases the need for endotracheal mechanical ventilation and improves clinical outcome. METHOD: We prospectively evaluated early NIV use for ARF after lung resection during a 4-year period in the setting of a medical and a surgical ICU of a university hospital. We documented demographics, initial clinical characteristics and clinical outcomes. NIV failure was defined as the need for tracheal intubation. RESULTS: Among 690 patients at risk of severe complications following lung resection, 113 (16.3%) experienced ARF, which was initially supported by NIV in 89 (78.7%), including 59 with hypoxemic ARF (66.3%) and 30 with hypercapnic ARF (33.7%). The overall success rate of NIV was 85.3% (76/89). In-ICU mortality was 6.7% (6/89). The mortality rate following NIV failure was 46.1%. Predictive factors of NIV failure in univariate analysis were age (P = 0.046), previous cardiac comorbidities (P = 0.0075), postoperative pneumonia (P = 0.0016), admission in the surgical ICU (P = 0.034), no initial response to NIV (P < 0.0001) and occurrence of noninfectious complications (P = 0.037). Only two independent factors were significantly associated with NIV failure in multivariate analysis: cardiac comorbidities (odds ratio, 11.5; 95% confidence interval, 1.9-68.3; P = 0.007) and no initial response to NIV (odds ratio, 117.6; 95% confidence interval, 10.6-1305.8; P = 0.0001). CONCLUSION: This prospective survey confirms the feasibility and efficacy of NIV in ARF following lung resection.

Should we change antibiotic prophylaxis for lung surgery? Postoperative pneumonia is the critical issue.

BACKGROUND: The recommended antibiotic prophylaxis by second-generation cephalosporins reduces the incidence of wound infection and empyema, but its effectiveness on postoperative pneumonias (POPs) after major lung resection lacks demonstration. We investigated risk factors and characteristics of POPs occurring when antibiotic prophylaxis by second-generation cephalosporin or an alternative prophylaxis targeting organisms responsible for bronchial colonization was used. METHODS: An 18-month prospective study on all patients undergoing lung resections for noninfectious disease was performed. Prophylaxis by cefamandole (3 g/24 h, over 48 hours) was used during the first 6 months, whereas amoxicillin-clavulanate (6 g/24 h, over 24 hours) was used during the subsequent 12 months. Intraoperative bronchial aspirates were systematically cultured. Patients with suspicion of pneumonia underwent bronchoscopic sampling for culture. RESULTS: Included were 168 patients in the first period and 277 patients in the second period. The incidence of POP decreased by 45% during the second period (P = 0.0027). A significant reduction in antibiotic therapy requirement for postoperative infections (P = 0.0044) was also observed. Thirty-day mortality decreased from 6.5% to 2.9% (P = 0.06). Multivariate analysis showed that type of resection, intraoperative colonization, chronic obstructive pulmonary disease, gender, body mass index, and type of prophylaxis were independent risk factors of POP. A case control-study that matched patients of the two periods according to these risk factors (except for antibiotic prophylaxis) confirmed that the incidence of POP was lowered during the second period. CONCLUSIONS: Targeted antibiotic prophylaxis may decrease the rate of POPs after lung resection and improve outcome.

Postoperative pneumonia after major lung resection.

BACKGROUND: Postoperative pneumonia (POP) is a life-threatening complication of lung resection. The incidence, causative bacteria, predisposing factors, and outcome are poorly understood. DESIGN: Prospective observational study. METHODS: A prospective study of all patients undergoing major lung resections for noninfectious disease was performed over a 6-mo period. Culture of intraoperative bronchial aspirates was systematically performed. All patients with suspicion of pneumonia underwent bronchoscopic sampling and culture before antibiotherapy. RESULTS: One hundred and sixty-eight patients were included in the study. Bronchial colonization was identified in 31 of 136 patients (22.8%) on analysis of intraoperative samples. The incidence of POP was 25% (42 of 168). Microbiologically documented and nondocumented pneumonias were recorded in 24 and 18 cases, respectively. Haemophilus species, Streptococcus species, and, to a much lesser extent, Pseudomonas and Serratia species were the most frequently identified pathogens. Among colonized and noncolonized patients, POP occurred in 15 of 31 and 20 of 105 cases, respectively (p = 0.0010; relative risk, 2.54). Death occurred in 8 of 42 patients who developed POP and in 3 of 126 of patients who did not (p = 0.0012). Patients with POP required noninvasive ventilation or reintubation more frequently than patients who did not develop POP (p < 0.0000001 and p = 0.00075, respectively). POP was associated with longer intensive care unit and hospital stay (p < 0.0000001 and p = 0.0000005, respectively). Multivariate analysis showed that chronic obstructive pulmonary disease, extent of resection, presence of intraoperative bronchial colonization, and male sex were independent risk factors for POP. CONCLUSIONS: Pneumonia acquired in-hospital represents a relatively frequent complication of lung resections, associated with an important percentage of postoperative morbidity and mortality.