Purpose: Although often investigated in locally advanced esophageal cancer (EC), the impact of neoadjuvant chemoradiotherapy (NCRT) in early stages is unknown. The aim of this multicenter randomized phase III trial was to assess whether NCRT improves outcomes for patients with stage I or II EC. Methods: The primary end point was overall survival. Secondary end points were disease-free survival, postoperative morbidity, in-hospital mortality, R0 resection rate, and prognostic factor identification. From June 2000 to June 2009, 195 patients in 30 centers were randomly assigned to surgery alone (group S; n = 97) or NCRT followed by surgery (group CRT; n = 98). CRT protocol was 45 Gy in 25 fractions over 5 weeks with two courses of concomitant chemotherapy composed of fluorouracil 800 mg/m² and cisplatin 75 mg/m². We report the long-term results of the final analysis, after a median follow-up of 93.6 months. Results: Pretreatment disease was stage I in 19.0%, IIA in 53.3%, and IIB in 27.7% of patients. For group CRT compared with group S, R0 resection rate was 93.8% versus 92.1% (P = .749), with 3-year overall survival rate of 47.5% versus 53.0% (hazard ratio [HR], 0.99; 95% CI, 0.69 to 1.40; P = .94) and postoperative mortality rate of 11.1% versus 3.4% (P = .049), respectively. Because interim analysis of the primary end point revealed an improbability of demonstrating the superiority of either treatment arm (HR, 1.09; 95% CI, 0.75 to 1.59; P = .66), the trial was stopped for anticipated futility. Conclusion: Compared with surgery alone, NCRT with cisplatin plus fluorouracil does not improve R0 resection rate or survival but enhances postoperative mortality in patients with stage I or II EC.

Purpose: We conducted a phase III study to compare the survival impact of concurrent versus sequential treatment with radiotherapy (RT) and chemotherapy (CT) in unresectable stage III non–small-cell lung cancer (NSCLC). Patients and Methods: Patients were randomly assigned to one of the two treatment arms. In the sequential arm, patients received induction CT with cisplatin (120 mg/m²) on days 1, 29, and 57, and vinorelbine (30 mg/m²/wk) from day 1 to day 78, followed by thoracic RT at a dose of 66 Gy in 33 fractions (2 Gy per fraction and 5 fractions per week). In the concurrent arm, the same RT was started on day 1 with two concurrent cycles of cisplatin 20 mg/m²/d and etoposide 50 mg/m²/d (days 1 to 5 and days 29 to 33); patients then received consolidation therapy with cisplatin 80 mg/m² on days 78 and 106 and vinorelbine 30 mg/m²/wk from days 78 to 127. Results: Two hundred five patients were randomly assigned. Pretreatment characteristics were well balanced between the two arms. There were six toxic deaths in the sequential arm and 10 in the concurrent arm. Median survival was 14.5 months in the sequential arm and 16.3 months in the concurrent arm (log-rank test P = .24). Two-, 3-, and 4-year survival rates were better in the concurrent arm (39%, 25%, and 21%, respectively) than in the sequential arm (26%, 19%, and 14%, respectively). Esophageal toxicity was significantly more frequent in the concurrent arm than in the sequential arm (32% v 3%). Conclusion: Although not statistically significant, clinically important differences in the median, 2-, 3-, and 4-year survival rates were observed, with a trend in favor of concurrent chemoradiation therapy, suggesting that is the optimal strategy for patients with locally advanced NSCLC.

Video-assisted thoracoscopic anatomical resections are increasingly used in Europe to manage primary lung cancer. The purpose of this study was to compare the outcome following thoracoscopic versus open lobectomy in case-matched groups of patients from the European Society of Thoracic Surgeon (ESTS) database. All patients having lobectomy as the primary procedure via thoracoscopy [video-assisted thoracoscopic surgery (VATS)-L)] or thoracotomy (TH-L) were identified in the ESTS database (January 2007 to December 2013). A propensity score was constructed using several patients' baseline characteristics. The matching using the propensity score was responsible for the minimization of selection bias. A propensity score-matched analysis was performed to compare the incidence of postoperative major complications (according to the ESTS database definitions) and mortality at hospital discharge between the matched groups. After exclusions, 28 771 patients were identified: 26 050 having thoracotomy and 2721 having thoracoscopy. Propensity score yielded two well-matched groups of 2721 patients. Numeric variables were compared by Student's t -tests and categorical variables were compared by McNemar's tests. Compared with TH-L, VATS-L was associated with a lower incidence of total complications [ n = 792 (29.1%) vs 863 (31.7%), P = 0.0357], major cardiopulmonary complications [ n = 316 (15.9%) vs 435 (19.6%), P = 0.0094], atelectasis requiring bronchoscopy [ n = 65 (2.4%) vs 150 (5.5%), P < 0.0001], initial ventilation >48 h [ n = 18 (0.7%) vs 38 (1.4%), P = 0.0075] and wound infection [ n = 6 (0.2%) vs 17 (0.6%), P = 0.0218]. There was no difference in the incidence of postoperative atrial fibrillation between the two groups ( P = 0.14). Postoperative hospital stay was 2 days shorter in the VATS-L patients (mean: 7.8 vs 9.8 days; P = 0.0003). In terms of outcome at hospital discharge, there were 27 deaths in the VATS-L group (1%) versus 50 in the TH-L group (1.9%, P = 0.0201). Data from the ESTS database confirmed that lobectomy performed through VATS is associated with a lower incidence of complications compared with thoracotomy.

Background: Esophagectomy induces a systemic inflammatory response whose extent has been recognized as a predictive factor of postoperative respiratory morbidity. The aim of this study was to determine the effectiveness of a protective ventilatory strategy to reduce systemic inflammation in patients undergoing esophagectomy. Methods: The authors prospectively investigated 52 patients undergoing planned esophagectomy for cancer. Patients were randomly assigned to a conventional ventilation strategy (n = 26; tidal volume of 9 ml/kg during two-lung and one-lung ventilation; no positive end-expiratory pressure) or a protective ventilation strategy (n = 26; tidal volume of 9 ml/kg during two-lung ventilation, reduced to 5 ml/kg during one-lung ventilation; positive end-expiratory pressure 5 cm H2O throughout the operative time). Results: Plasmatic levels of interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor alpha were measured perioperatively and postoperatively. Pulmonary function and postoperative evolution were also evaluated. Patients who received protective strategy had lower blood levels of IL-1beta, IL-6, and IL-8 at the end of one-lung ventilation (0.24 [0.15-0.40] vs. 0.56 [0.38-0.89] pg/ml, P < 0.001; 91 [61-117] vs. 189 [127-294] pg/ml, P < 0.001; and 30 [22-45] vs. 49 [29-69] pg/ml, P < 0.05, respectively) and 18 h postoperatively (0.18 [0.13-0.30] vs. 0.43 [0.34-0.54] pg/ml, P < 0.001; 54 [36-89] vs. 116 [78-208] pg/ml, P < 0.001; 16 [11-24] vs. 35 [28-53] pg/ml, P < 0.001, respectively). Protective strategy resulted in higher oxygen partial pressure to inspired oxygen fraction ratio during one-lung ventilation and 1 h postoperatively and in a reduction of postoperative mechanical ventilation duration (115 +/- 38 vs. 171 +/- 57 min, P < 0.001). Conclusion: A protective ventilatory strategy decreases the proinflammatory systemic response after esophagectomy, improves lung function, and results in earlier extubation.

The purpose of this prospective postmortem study was to assess the diagnostic accuracy of bronchoscopic techniques (bronchoalveolar lavage [BAL] and protected specimen brush [PSB]) and nonbronchoscopic techniques (blind bronchial sampling [BBS] and mini-BAL) in the diagnosis of ventilator-associated pneumonia (VAP). The results of each technique were compared with histology and culture of lung tissue specimens obtained by surgical pneumonectomies in 38 patients who died after at least 72 h of mechanical ventilation. Histology was positive for VAP in 18 patients and negative in 20 patients. There were 12 definite VAP (positive histology and positive lung cultures) and 6 histologic VAP (positive histology and negative cultures). Clinical pulmonary infection score (CPIS) at a threshold of 6 achieved a sensitivity of 72% and a specificity of 85%. When the CPIS was combined with the logarithmic concentration of the predominant microorganism obtained from the BBS sample culture, specificity was increased to 95%, for a threshold of 10. Using 10(3) cfu/ml as the threshold of positivity for cultures obtained with PSB and mini-BAL samples and 10(4) cfu/ml for cultures obtained with BBS and BAL, the respective sensitivities of these techniques for definite VAP were 42, 67, 83, and 58%. The sensitivity of BBS was significantly higher than that of PSB (p < 0.05). The area under the receiver operator characteristic curve was significantly greater for BBS than PSB (p < 0.05). Given that it is more sensitive and noninvasive, BBS is preferable to PSB for the diagnosis of VAP.