Lung volume reduction surgery in nonheterogeneous emphysema

Patients with a homogeneous type of emphysema have been excluded a priori from LVRS in many centers because of the fear of removing parenchyma, which potentially contributes to gas exchange, and because the observation that heterogeneity of emphysema is a predictor of functional improvement. It is obvious that resection of functionless tissue, such as in heterogeneous emphysema with bullae, can be advised to the patient with a relative low risk. However, as the main positive effect of LVRS is its improvement on respiratory mechanics, it is not surprising that well-selected patients with homogeneous emphysema also benefit from surgery. Their selection has to be done cautiously. It is crucial to exclude patients with a very low functional reserve, such as with diffusing capacity below 20% predicted or with pulmonary hypertension, and with extreme parenchymal loss (vanished lungs) on CT from LVRS. Additionally, cofactors which may potentially interfere with a smooth postoperative course, such as previous recurrent infections, extensive scarring of the lungs, or previous surgery, have to be taken into consideration. When respecting these caveats, LVRS in patients with complete homogeneous emphysema provides a comparable symptomatic and almost the same functional improvement as in patients with heterogeneous emphysema. Although the perioperative mortality is low, patients with homogeneous emphysema have a slightly reduced long-term survival without lung transplantation compared with patients with heterogeneous emphysema. Based on our own experience, we conclude that LVRS can be recommended to selected symptomatic patients with advanced homogenous emphysema associated with severe hyperinflation, if diffusing capacity is not below 20% of predicted values and if the CT scan does not show aspects of vanished lungs

Repeated lung volume reduction surgery is successful in selected patients

OBJECTIVES Lung volume reduction surgery (LVRS) improves dyspnoea, quality of life and may even prolong survival in carefully selected patients with end-stage emphysema. The benefit may be sustained for several years and vanishes with the natural progression of the disease. Data on repeated surgical treatment of emphysema are scarce. The aim of this study was to evaluate the safety, effects and outcomes of repeated LVRS (Re-LVRS) in patients no longer benefiting from their initial LVRS. METHODS Between June 2002 and December 2013, 22 patients (9 females) with advanced emphysema underwent Re-LVRS at a median of 60 months (25–196) after their initial LVRS. While initial LVRS was performed thoracoscopically as a bilateral procedure, Re-LVRS was performed unilaterally by a video-assisted thoracoscopic technique in 19 patients and, due to adhesions, by thoracotomy in 3 patients. Pulmonary function test (PFT) was performed at 3 and 12 months postoperatively. RESULTS Lung function at Re-LVRS was similar to that prior to the first LVRS. The 90-day mortality rate was 0%. The first patient died 15 months postoperatively. The median hospitalization time after Re-LVRS was significantly longer compared with the initial LVRS [14 days, interquartile range (IQR): 11–19, vs 9 days, IQR: 8–14; P = 0.017]. The most frequent complication was prolonged air leak with a median drainage time of 11 days (IQR: 6–13); reoperations due to persistent air leak were necessary in 7 patients (32%). Five patients (23%) had no complications. Lung function and Medical Research Council (MRC) score improved significantly for up to 12 months after Re-LVRS, with results similar to those after initial bilateral LVRS. The average increase in the forced expiratory volume in 1 s (FEV1) was 25% (a 7% increase over the predicted value or 0.18 l) at 3 months, and the mean reduction in hyperinflation, assessed by relative decrease in RV/TLC (residual volume/total lung capacity), was 12% at 3 months (a decrease of 8% in absolute ratios). The mean MRC breathlessness score decreased significantly after 3 months (from 3.7 to 2.2). CONCLUSIONS Re-LVRS can be performed successfully in carefully selected patients as a palliative treatment. It may be performed as a bridge to transplantation or in patients with newly diagnosed intrapulmonary nodules or during elective cardiac surgery. Morbidity is acceptable and outcomes may be satisfactory with significantly improved lung function and reduced dyspnoea for at least 12 months postoperatively

Volumetry - an alternative to assess therapy response for malignant pleural mesothelioma?

The purpose of this study was to assess robustness of volumetric measurement of malignant pleural mesothelioma (MPM) before and after chemotherapy to modified RECIST. Thirty patients with digitally available chest CT scan before and after 3 cycles of chemotherapy were included. Three readers assessed independently tumour response using two different methods: Modified RECIST criteria and tumour volumetric approach using dedicated software (Myrian, Intrasense, France). Inter-rater reliability of uni-dimensional and volumetric measurements was assessed using intraclass correlation. tumour response classification for modified RECIST was compared to volumetric approach applying uni-dimensional RECIST volumetric equivalent criteria. The determination of uni-dimensional tumour measurement (RECIST) revealed a low inter-rater reliability (0.55) and a low interobserver agreement for tumour response classification (general kappa 0.33). Only 14 patients were classified equally. A high inter-rater reliability (0.99) and interobserver agreement (general kappa 0.9)) was found for absolute tumour volumes (volumetric measurements). 27 cases were classified equally. The number of cases classified as "stable disease" was higher for volumetric approach using tumour equivalent criteria compared to modified RECIST. Volumetric measurement of MPM on CT-scan using Myrian software is a reliable, reproducible and sensitive method to measure tumour volume and hence therapy response after induction chemotherapy

Persistent benefit from lung volume reduction surgery in patients with homogeneous emphysema

BACKGROUND: The purpose of this study was to evaluate whether favorable short-term results achieved by lung volume reduction surgery in selected patients with homogeneous emphysema would persist for longer periods. Their symptoms, lung function, and survival for several years were analyzed in comparison to patients with heterogeneous emphysema. METHODS: Two hundred fifty consecutive patients (105 women), mean (+/- standard deviation) age 64 +/- 8.4 years, with advanced emphysema underwent bilateral thoracoscopic lung volume reduction surgery. Forced expiratory volume in 1 second was 28% +/- 8% of predicted, 6-minute walking distance was 245 +/- 118 m, and Medical Research Council dyspnea score was 3.5 +/- 0.7. In 138 patients (55%) computed tomography revealed homogeneous emphysema (including 82 intermediate type) distribution and in 112 patients (45%) heterogeneous emphysema. Baseline characteristics were otherwise similar in the two groups that were prospectively observed for several years. RESULTS: Thirty-day mortality was 2.4%. Both groups revealed significant improvements 3 months after lung volume reduction surgery: in homogeneous emphysema, predicted forced expiratory volume in 1 second was 38% +/- 14% (35% improvement), 6-minute walk distance was 324 +/- 87 m, and dyspnea score was 1.8 +/- 0.9 (p < 0.05 all outcomes). Corresponding results in heterogeneous emphysema were 44% +/- 15% (61% improvement), 382 +/- 95 m, and 1.3 +/- 0.9 points (p < 0.05 versus baseline; not significant versus homogeneous). Median time until predicted forced expiratory volume in 1 second and 6-minute walk distance had returned to baseline was 36 months in both groups. One-year survival was similar in both groups. At 5 years, median survival without lung transplantation was 64% in the homogeneous and 73% in the heterogeneous group (Cox proportional hazard, 0.81; 95% confidence interval, 0.66 to 0.98; p = 0.03). CONCLUSIONS: In selected patients with homogeneous pulmonary emphysema, lung volume reduction surgery can be successfully performed with low perioperative mortality. Significant improvements in dyspnea, lung function, and exercise capacity are maintained for several years

Induction of senescence markers after neo-adjuvant chemotherapy of malignant pleural mesothelioma and association with clinical outcome: an exploratory analysis

The aim of this study was to assess the induction of senescence markers versus apoptosis pathways in malignant pleural mesothelioma (MPM) tumour samples before and after neo-adjuvant platinum-based chemotherapy and to investigate their relationship with clinical outcome. Specific senescence pathways were assessed by quantifying the expression of p21 and plasminogen activator inhibitor-1 (PAI-1) for the p21-p53 pathway, IGFBP7 for the IGF pathway and ALDH1A3 for the IFN pathway. p21 and PAI-1 expression were also assessed by immunohistochemistry. In addition, beta-galactosidase activity staining at pH 6.0 was performed. Apoptosis was determined by TUNEL assay. Clinical outcome was assessed by modified RECIST criteria, progression-free and overall survival. In a training set (n=9 patients) paired comparison demonstrated a significant increase in p21 (p<0.05), PAI-1 (p<0.01) and apoptosis (p<0.01) after neo-adjuvant chemotherapy. The patients with the highest increase in PAI-1 had stable disease, whilst patients with little change in senescence markers accompanied by a high increase in apoptosis had an objective response after chemotherapy. The hypothesis that stable disease might be associated with an increase in senescence markers was confirmed in a tissue microarray (n=26 patients) using p21 and PAI-1 immunohistochemistry as readouts. For patients where survival and time to progression data were available, increased PAI-1 levels were significantly associated with a worst outcome. Our results demonstrate induction of senescence markers by neo-adjuvant chemotherapy in a proportion of patients with MPM and its potential association with a poor outcome