Anti-tumour effect of low molecular weight heparin in localised lung cancer: a phase III clinical trial.

The anti-tumour and anti-metastatic properties of heparins have not been tested in patients with early stage cancer. Whether adjuvant low molecular weight heparin (LMWH) tinzaparin impacts the survival of patients with resected non-small cell lung cancer (NSCLC) was investigated.Patients with completely resected stage I, II or IIIA NSCLC were randomly allocated to receive subcutaneous tinzaparin 100 IU·kg-1 once a day for 12 weeks or no treatment in addition to standard of care. The trial was open-label with blinded central adjudication of study outcomes. The primary outcome was overall survival.In 549 patients randomised to tinzaparin (n=269) or control (n=280), mean±sd age was 61.6±8.9 years, 190 (34.6%) patients had stage II-III disease, and 220 (40.1%) patients received adjuvant chemotherapy. Median follow-up was 5.7 years. There was no significant difference in overall survival between groups (hazard ratio (HR) 1.24, 95% CI 0.92-1.68; p=0.17). There was no difference in the cumulative incidence of recurrence between groups (subdistribution HR 0.94, 95% CI 0.68-1.30; p=0.70).Adjuvant tinzaparin had no detectable impact on overall and recurrence-free survival of patients with completely resected stage I-IIIA NSCLC. These results do not support further clinical evaluation of LMWHs as anti-tumour agents.

The cyclooxygenase-2-prostaglandin E2 pathway maintains senescence of chronic obstructive pulmonary disease fibroblasts.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is associated with lung fibroblast senescence, a process characterized by the irreversible loss of replicative capacity associated with the secretion of inflammatory mediators. However, the mechanisms of this phenomenon remain poorly defined. OBJECTIVES: The aim of this study was to analyze the role of prostaglandin E2 (PGE2), a prostaglandin known to be increased in COPD lung fibroblasts, in inducing senescence and related inflammation in vitro in lung fibroblasts and in vivo in mice. METHODS: Fibroblasts were isolated from patients with COPD and from smoker and nonsmoker control subjects. Senescence markers and inflammatory mediators were investigated in fibroblasts and in mice. MEASUREMENTS AND MAIN RESULTS: Lung fibroblasts from patients with COPD exhibited higher expression of PGE2 receptors EP2 and EP4 as compared with nonsmoker and smoker control subjects. Compared with both nonsmoker and smoker control subjects, during long-term culture, COPD fibroblasts displayed increased senescent markers (increased senescence associated-ß galactosidase activity, p16, and p53 expression and lower proliferative capacity), and an increased PGE2, IL-6, IL-8, growth-regulated oncogene (GRO), CX3CL1, and matrix metalloproteinase-2 protein and cyclooxygenase-2 and mPGES-1 mRNA expression. Using in vitro pharmacologic approaches and in vivo experiments in wild-type and p53(-/-) mice we demonstrated that PGE2 produced by senescent COPD fibroblasts is responsible for the increased senescence and related inflammation. PGE2 acts either in a paracrine or autocrine fashion by a pathway involving EP2 and EP4 prostaglandin receptors, cyclooxygenase-2-dependent reactive oxygen species production and signaling, and consecutive p53 activation. CONCLUSIONS: PGE2 is a critical component of an amplifying and self-perpetuating circle inducing senescence and inflammation in COPD fibroblasts. Modulating the described PGE2 signaling pathway could provide a new basis to dampen senescence and senescence-associated inflammation in COPD.

Telomere dysfunction causes sustained inflammation in chronic obstructive pulmonary disease.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation of unknown pathogenesis. OBJECTIVES: To investigate whether telomere dysfunction and senescence of pulmonary vascular endothelial cells (P-ECs) induce inflammation in COPD. METHODS: Prospective comparison of patients with COPD and age- and sex-matched control smokers. Investigation of mice null for telomerase reverse transcriptase (Tert) or telomerase RNA component (Terc) genes. MEASUREMENTS AND MAIN RESULTS: In situ lung specimen studies showed a higher percentage of senescent P-ECs stained for p16 and p21 in patients with COPD than in control subjects. Cultured P-ECs from patients with COPD exhibited early replicative senescence, with decreased cell-population doublings, a higher percentage of ß-galactosidase-positive cells, reduced telomerase activity, shorter telomeres, and higher p16 and p21 mRNA levels at an early cell passage compared with control subjects. Senescent P-ECs released cytokines and mediators: the levels of IL-6, IL-8, monocyte chemotactic protein (MCP)-1, Hu-GRO, and soluble intercellular adhesion molecule (sICAM)-1 were elevated in the media of P-ECs from patients compared with control subjects at an early cell passage, in proportion to the senescent P-EC increase and telomere shortening. Up-regulation of MCP-1 and sICAM-1 led to increased monocyte adherence and migration. The elevated MCP-1, IL-8, Hu-GROα, and ICAM-1 levels measured in lungs from patients compared with control subjects correlated with P-EC senescence criteria and telomere length. In Tert(-/-) and/or Terc(-/-) mouse lungs, levels of the corresponding cytokines (MCP-1, IL-8, Hu-GROα, and ICAM-1) were also altered, despite the absence of external stimuli and in proportion to telomere dysfunction. CONCLUSIONS: Telomere dysfunction and premature P-EC senescence are major processes perpetuating lung inflammation in COPD.

Electromagnetic navigation bronchoscopy localization of lung nodules for thoracoscopic resection.

BACKGROUND: Thoracoscopic localization of small peripheral pulmonary nodules is a concern. Failure can lead to larger parenchymal resection or conversion to thoracotomy. This study evaluates our experience in preoperative electromagnetic navigation bronchoscopy-guided localization of small peripheral lung lesions. METHODS: From January 2017 to March 2020 clinical, radiographic, surgical, and pathological data of patients who underwent electromagnetic navigation bronchoscopy (ENB)-guided methylene blue pleural marking of highly suspected pulmonary lesions before a full thoracoscopic resection were evaluated. Localization was performed for solid or mixed subpleural nodules measuring <10 mm, solid nodules measuring <20 mm located at more than 1 cm from the pleura and any pure ground glass opacity. Successful localization was defined as successful identification and thoracoscopic resection of target lesions. RESULTS: Forty-eight patients were included: 30 solid nodules (63%), 12 pure GGO (25%) and 6 mixed (13%). The median largest diameter at CT-scan was 11 mm (IQR, 9-14 mm) while the median distance from the pleural surface was 12 mm (IQR, 6-16 mm). The median ENB length was 25 min (19-33 min). Localization procedure was successful in 45 cases (94%). No procedural-related complications were reported. CONCLUSIONS: ENB is a safe and accurate preoperative procedure to localize small lung peripheral lesions. The high successful rate, the absence of related complications, the possibility of performing the procedure in the same operating room with a single general anesthesia, make ENB-guided dye marking an advantageous tool for thoracoscopic pulmonary resection.

Endobronchial treatment of peripheral tumors: ongoing development and perspectives.

The expanded possibilities to explore the lung deeper with new tools such as electromagnetic navigation bronchoscopy (ENB) or radial probe endobronchial ultrasonography (radial EBUS), combined with miniaturization of traditional local therapies such as radiofrequency ablation (RFA), radiotherapy, cryotherapy or photodynamic therapy, let the bronchoscopists hope for new ways of endoscopic treatments. This challenge could change the practice in the upcoming decades but raise some physical and technical issues. Safety and efficacy need to be solidly established to face the serious concurrence of stereotactic radiotherapy (SBRT) or percutaneous RFA. Here we describe ongoing development and perspectives for endobronchial treatment of peripheral lung tumors.

Early and delayed post-pneumonectomy empyemas: Microbiology, management and prognosis.

INTRODUCTION: Post-pneumonectomy empyema (PPE) is the most severe complication of pneumonectomy. Microbiology and its impact on management and prognosis have rarely been reported METHODS: We retrospectively reviewed the files of a series of 37 consecutive patients with PPE over a 10-year period with a special focus on microbiology, means used to treat empyema and prognosis. RESULTS: PPE occurred within 14 days of pneumonectomy in 17 cases (early PPE) and after postoperative day 16 in 20 patients (delayed PPE). PPE was monomicrobial in 57% of cases. The most frequent pathogens were Staphylococcus sp. and Streptococcus sp. Polymicrobial empyema was more frequent in patients with early PPE than delayed PPE (65% vs 25%; P = .02). Video-assisted thoracoscopic approach for cavity lavage was performed in 22 patients without broncho-pleural fistulae (BPF), associated with antimicrobial therapy and drainage, and was successful in 13 cases (59%). Seventeen patients (46%) underwent an open window thoracostomy. Overall 90-day post empyema mortality was 19%, with 6 deaths because of empyema in the early PPE group (35%), versus one (5%) in the delayed PPE group (P = .02). CONCLUSION: We distinguished 2 different PPE presentations: an early occurrence, mostly with polymicrobial cultures, including Gram-negative bacteria, and associated with a high mortality rate. By contrast, delayed PPEs were mostly monomicrobial with Gram-positive bacteria and associated with a better prognosis. VATS approach was successful in the majority of cases without BPF, even if some patients required secondary thoracostomy. PPE was associated with an excess of mortality especially when occurring in the early course after pneumonectomy.

Thoracoscopic resection of bulky intrathoracic benign lesions.

BACKGROUND: Video-assisted thoracic surgery (VATS) is used for the diagnosis and treatment of some mediastinal lesions. However, large-size tumours are usually approached by thoracotomy or sternotomy. We report our experience of a full thoracoscopic approach for bulky intrathoracic lesions. METHODS: From November 2002 to March 2007, 14 patients with a bulky intrathoracic mass were referred for resection. The study group consisted of eight females and six males with a mean age of 44 years (range: 13-74). We defined as bulky a mass with a minimal cross-sectional diameter equal to or larger than 50 mm, as measured on the specimen by the pathologist. RESULTS: Thoracoscopic resection was completed in all patients. In 4 cases, the mass originated from the pleura, and in 10 cases from the mediastinum. The larger diameter of the lesion ranged from 50 mm to 160 mm, with a median of 90.2 mm. Operative time, calculated from insertion of the first trocar to skin closure, ranged from 40 to 190 min (mean: 102). Mean chest drain duration was 2.1 days (range: 1-4 days) and the mean hospital stay was 4.3 days (range: 3-11 days). There were no major postoperative complications. The final pathological diagnoses were the following: solitary fibrous tumours of the pleura (4), benign thymic cysts (2), teratomas (2), bronchogenic cyst (1), benign thymoma (1), pleuropericardial cyst (1) and benign neurogenic tumours (3). CONCLUSIONS: With experience and use of appropriate instrumentation, resection of bulky intrathoracic lesions by thoracoscopy is feasible and safe. It should be considered as a reliable alternate for tumours that are benign and most often asymptomatic.

Sensitivity of Cytology Specimens From Bronchial Aspirate or Washing During Bronchoscopy in the Diagnosis of Lung Malignancies: An Update.

BACKGROUND: Routine collection of cytology specimens from bronchial aspirate or washing is thought to increase the sensitivity of bronchoscopy for diagnosing malignant lung lesions. However, the added value of this practice has not been reappraised in a context of changing epidemiology. PATIENTS AND METHODS: In a retrospective monocenter study, all cytology specimens from bronchial aspirate or washing collected between May 2011 and December 2014 and the corresponding patients' files were reviewed. The final diagnosis of malignancy was based on all available pathologic information. RESULTS: Bronchoscopy was performed in 2750 patients, and bronchial cytology specimens were collected during 667 procedures, including 474 aspirate or washing cytology specimens collected during conventional (n = 366) or ultrasound-guided (EBUS) (n = 108) bronchoscopy in 455 patients with malignant lung lesion(s). The predominant histologic types were lung adenocarcinoma (43.9%) and squamous cell carcinoma (25.2%), and 271 tumors (59.6%) were endoscopically visible. At least 1 endoscopic sample (bronchial cytology and/or biopsies and/or endobronchial ultrasound-guided samples) was positive for malignancy during 329 (69.4%) of the 474 endoscopies, including 79 samples obtained in nonvisible lesions. Only 67 bronchial cytology specimens proved positive (sensitivity, 14.7%; 95% confidence interval, 11.8%-18.3%), and only 1 specimen (0.2%) produced a diagnosis not made by other samples during the same procedure. CONCLUSION: In contrast with older studies, the added value of collecting cytology specimens from bronchial aspirate or washing during bronchoscopy in this series proved negligible, reflecting mainly the increasing prevalence of adenocarcinomas. Abandoning this technique could be considered in centers with similar expertise and patient populations.

Cytokeratin 19 fragments in patients with acute lung injury: a preliminary observation.

OBJECTIVE: Cytokeratin 19 (CK19) is a specific cytoskeletal structure for alveolar epithelium. We hypothesized that the levels of CK19 fragments in bronchoalveolar lavage (BAL) fluid could serve as an index of epithelial injury and as a prognosis marker in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). The aims of our study were, in patients with ALI/ARDS: (1) to measure CK19 fragments concentrations in BAL fluid, (2) to assess its prognostic value, and (3) to identify the cellular source of CK19 in the alveolar space. DESIGN: Prospective preliminary study. SETTING: University hospital surgical ICU. PATIENTS: Twenty-two mechanically ventilated patients with ALI/ARDS and 10 non-ventilated control patients. Plasma samples were obtained for 11 ALI/ARDS patients. MEASUREMENTS AND RESULTS: The concentration of BAL CK19 fragments was higher in patients (median 4916 pg/ml, 25th-75th percentile 2717-10533) than in controls (2208 pg/ml. 767-3923; p =0.05), and higher in 10 non-survivors (7051 pg/ml, 4372-13371) than in 12 survivors (2888 pg/ml, 1315-5639; p =0.03 among ALI/ARDS patients). BAL CK19 fragment concentration did not correlate with simplified acute physiologic score, lung injury score or PaO(2)/FIO(2) ratio, but correlated positively with BAL albumin concentration (p =0.002) and with number of BAL macrophages (p=0.0001). Plasma CK19 fragment concentrations were 10 times lower than those in BAL. Immunohistochemical staining for CK19 showed a strong labelling of injured detached epithelial cells and hyperplastic epithelium in ALI/ARDS lung samples. CONCLUSION: CK19 fragment concentrations were found to be elevated in BAL fluid in ALI/ARDS patients compared with control subjects. High BAL CK19 fragment levels were associated with a poor prognosis.

Pulmonary hemodynamics in advanced COPD candidates for lung volume reduction surgery or lung transplantation.

STUDY OBJECTIVES: To assess the pulmonary hemodynamic characteristics in COPD candidates for lung volume reduction surgery (LVRS) or lung transplantation (LT). DESIGN: Retrospective study. SETTING: One center in France. PATIENTS: Two hundred fifteen patients with severe COPD who underwent right-heart catheterization before LVRS or LT. RESULTS: Mean age was 54.6 years. Pulmonary function test results were as follows: FEV(1), 24.3% predicted; total lung capacity, 128.3% predicted; residual volume, 259.7% predicted. Mean pulmonary artery pressure (PAPm) was 26.9 mm Hg. Pulmonary hypertension (PAPm > 25 mm Hg) was present in 50.2% and was moderate (PAPm, 35 to 45 mm Hg) or severe (PAPm > 45 mm Hg) in 9.8% and in 3.7% of patients, respectively. Cardiac index was low normal. PAPm was related to Pao(2) and alveolar-arterial oxygen gradient in multivariate analysis. Cluster analysis identified a subgroup of atypical patients (n = 16, 7.4%) characterized by moderate impairment of the pulmonary mechanics (mean FEV(1), 48.5%) contrasting with high level of pulmonary artery pressure (PAPm, 39.8 mm Hg), and severe hypoxemia (mean Pao(2), 46.2 mm Hg). CONCLUSION: While pulmonary hypertension is observed in half of the COPD patients with advanced disease, moderate-to-severe pulmonary hypertension is not a rare event in these patients. We individualized a subgroup of patients presenting with a predominant vascular disease that could potentially benefit from vasodilators.

Deep venous thrombosis in patients with acute pulmonary embolism: prevalence, risk factors, and clinical significance.

STUDY OBJECTIVES: To determine the prevalence of lower-limb deep venous thrombosis (DVT) that can be detected by compression ultrasonography (CUS) in patients with symptomatic pulmonary embolism (PE) diagnosed with spiral CT pulmonary angiography (CTPA); and to explore the risk factors for positive CUS results and the prognostic significance of such findings. DESIGN: Post hoc analysis of data from a prospective multicenter outcome study of 1,041 patients with clinically suspected non-severe PE. All patients underwent CTPA and CUS within 24 h of enrollment and were followed up for 3 months. PATIENTS: Among the 290 patients with positive CT findings, CUS was diagnostic in 281 patients who constitute the study population. RESULTS: Mean age +/- SD was 64.3 +/- 17.7 years; 128 patients (44.8%) were men. DVT signs or symptoms were present in 90 patients (32%). CUS detected DVT in 169 patients (60.1%; 95% confidence interval [CI], 54.1 to 65.9%), including 127 patients (45.2%; 95% CI, 39.3 to 51.2%) with proximal DVT. Sensitivity and specificity of DVT symptoms for CUS-detectable DVT were 43% and 85%, respectively. Multivariate analysis showed that an age > or = 70 years (odds ratio [OR], 1.90; 95% CI, 1.14 to 3.17) and the presence of DVT signs or symptoms (OR, 4.12; 95% CI, 2.24 to 7.55) were independent risk factors for positive CUS results. DVT symptoms (OR, 4.78; 95% CI, 2.75 to 8.33) and a history of venous thromboembolism (OR, 2.59; 95% CI, 1.46 to 4.62) were independent risk factors for proximal DVT. The 3-month risk of recurrent thromboembolic event or death was not significantly different among patients with and without DVT (6.5% vs 2.7%, p = 0.15). CONCLUSION: These results do not support screening for DVT in patients with CTPA-proven symptomatic PE; however, they suggest that CUS might prove especially efficient and safe as a frontline test in elderly patients with suspected PE. Further studies are needed before these conclusions can be translated into clinical recommendations.

Lung fibroblasts share mesenchymal stem cell features which are altered in chronic obstructive pulmonary disease via the overactivation of the Hedgehog signaling pathway.

BACKGROUND: Alteration of functional regenerative properties of parenchymal lung fibroblasts is widely proposed as a pathogenic mechanism for chronic obstructive pulmonary disease (COPD). However, what these functions are and how they are impaired in COPD remain poorly understood. Apart from the role of fibroblasts in producing extracellular matrix, recent studies in organs different from the lung suggest that such cells might contribute to repair processes by acting like mesenchymal stem cells. In addition, several reports sustain that the Hedgehog pathway is altered in COPD patients thus aggravating the disease. Nevertheless, whether this pathway is dysregulated in COPD fibroblasts remains unknown. OBJECTIVES AND METHODS: We investigated the stem cell features and the expression of Hedgehog components in human lung fibroblasts isolated from histologically-normal parenchymal tissue from 25 patients--8 non-smokers/non-COPD, 8 smokers-non COPD and 9 smokers with COPD--who were undergoing surgery for lung tumor resection. RESULTS: We found that lung fibroblasts resemble mesenchymal stem cells in terms of cell surface marker expression, differentiation ability and immunosuppressive potential and that these properties were altered in lung fibroblasts from smokers and even more in COPD patients. Furthermore, we showed that some of these phenotypic changes can be explained by an over activation of the Hedgehog signaling in smoker and COPD fibroblasts. CONCLUSIONS: Our study reveals that lung fibroblasts possess mesenchymal stem cell-features which are impaired in COPD via the contribution of an abnormal Hedgehog signaling. These processes should constitute a novel pathomechanism accounting for disease occurrence and progression.

Air contamination for predicting wound contamination in clean surgery: A large multicenter study.

BACKGROUND: The best method to quantify air contamination in the operating room (OR) is debated, and studies in the field are controversial. We assessed the correlation between 2 types of air sampling and wound contaminations before closing and the factors affecting air contamination. METHODS: This multicenter observational study included 13 ORs of cardiac and orthopedic surgery in 10 health care facilities. For each surgical procedure, 3 microbiologic air counts, 3 particles counts of 0.3, 0.5, and 5 µm particles, and 1 bacteriologic sample of the wound before skin closure were performed. We collected data on surgical procedures and environmental characteristics. RESULTS: Of 180 particle counts during 60 procedures, the median log10 of 0.3, 0.5, and 5 µm particles was 7 (interquartile range [IQR], 6.2-7.9), 6.1 (IQR, 5.4-7), and 4.6 (IQR, 0-5.2), respectively. Of 180 air samples, 50 (28%) were sterile, 90 (50%) had 1-10 colony forming units (CFU)/m(3) and 40 (22%) >10 CFU/m(3). In orthopedic and cardiac surgery, wound cultures at closure were sterile for 24 and 9 patients, 10 and 11 had 1-10 CFU/100 cm(2), and 0 and 6 had >10 CFU/100 cm(2), respectively (P < .01). Particle sizes and a turbulent ventilation system were associated with an increased number of air microbial counts (P < .001), but they were not associated with wound contamination (P = .22). CONCLUSIONS: This study suggests that particle counting is a good surrogate of airborne microbiologic contamination in the OR.

Medical literature and vena cava filters: so far so weak.

STUDY OBJECTIVE: With the development of percutaneous inferior vena cava (IVC) filters, IVC interruption has become a widely used procedure in patients with or at risk for venous thromboembolism. In an attempt at clarifying the indications for filter placement, a systematic literature review was undertaken. DESIGN: Bibliographic search and analysis. MEASUREMENTS AND RESULTS: A systematic MEDLINE search about vena cava filters produced a total of 568 references with abstracts between 1975 and 2000 inclusively. Each reference was analyzed according to predetermined criteria. Nearly two thirds (65.0%) of these publications were retrospective studies or case reports (33.3 and 31.7%, respectively), 12.9% were animal or in vitro studies, 7.4% were prospective studies, 6.7% were reviews, and 8.1% reported on miscellaneous related topics. Among the prospective studies, only 16 studies included > or = 100 patients, only 1 study was a randomized controlled trial (0.02% of 568 references), and heterogeneity among series precluded any relevant comparison. In a similar search about heparin and venous thromboembolism, 47.4% of 531 references were randomized controlled trials. CONCLUSIONS: Until more relevant data become available, literature reviews about vena cava filters will remain narrative, and many if not most indications for filter placement will remain a matter of opinion.

Parathyroid hormone-related protein in epithelial lining fluid in humans negatively correlates with the severity of lung injury.

OBJECTIVE: To determine the concentration of parathyroid hormone-related protein (PTHrP; an autocrine/paracrine regulator of type-2 alveolar epithelial cells proliferation and apoptosis) in the epithelial lining fluid (ELF) from patients without pulmonary disease and from patients with acute lung injury (ALI), and to evaluate whether PTHrP concentrations correlated with the intensity of lung injury. DESIGN: Prospective study. SETTING: An adult trauma/surgical ICU in an urban teaching hospital. PATIENTS: A total of 20 patients with ALI receiving mechanical ventilation (patients), and 10 patients without pulmonary disease not receiving mechanical ventilation (control subjects). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: PTHrP was detected in all BAL fluids, and ELF PTHrP concentrations (median; 25% to 75% percentiles) tended to be higher in patients (52.2 nmol/mL; 20.8 to 65.6 nmol/mL) than in control subjects (25.4 nmol/mL; 20.5 to 35.4 nmol/mL; p = 0.18). In patients, ELF PTHrP concentration correlated positively with the PaO(2)/fraction of inspired oxygen ratio (r = 0.53; p = 0.005), and negatively with lung injury score (r = - 0.44; p = 0.02), radiologic score (r = - 0.40; p = 0.04), and BAL albumin concentration (r = - 0.42; p = 0.02). CONCLUSION: PTHrP is present in biologically significant concentrations in the alveolar milieu in humans. In patients with ALI, the PTHrP concentration correlates negatively with the degree of lung injury.

Detection of pelvic vein thrombosis by magnetic resonance angiography in patients with acute pulmonary embolism and normal lower limb compression ultrasonography.

STUDY OBJECTIVE: In patients with proven acute pulmonary embolism (PE), a systematic search for "residual" deep vein thrombosis (DVT) using venography or compression duplex ultrasonography (CDUS) of the lower limbs is negative in 20 to 50% of patients. We hypothesized that undetectable pelvic vein thrombosis (from the external iliac vein to the inferior vena cava) could account for a substantial proportion of patients with negative CDUS findings. Using a noninvasive test, magnetic resonance angiography (MRA), the objective of the study was to assess the prevalence of pelvic DVT in patients with acute PEs and normal findings on lower limb CDUS. DESIGN: Prospective study. SETTING: A 35-bed respiratory unit in a 680-bed Parisian teaching hospital. PATIENTS: From June 1995 to October 1996, 24 patients (mean age, 49 years; age range, 18 to 83 years) with acute PEs and normal findings on lower limb CDUS underwent pelvic MRA. MEASUREMENTS AND RESULTS: MRA disclosed pelvic DVT in seven patients (29%). The common iliac vein was involved in five patients. Internal iliac vein (hypogastric) thrombosis was imaged in two patients, but no patients had DVT limited to this vein. Three patients underwent subsequent venography studies that confirmed the MRA findings. In three other patients, a new MRA at the end of anticoagulant therapy showed the resolution of the DVT. CONCLUSIONS: Our data support the view that, among patients with negative findings on CDUS, a substantial proportion of the DVTs that are responsible for PE originates in the pelvic veins. This study provides additional arguments to suggest that MRA might become the reference test for the exploration of pelvic DVT.

Primary graft failure following lung transplantation: predictive factors of mortality.

STUDY OBJECTIVES: To assess incidence, outcome, and early predictors of mortality for patients with primary graft failure (PGF) following lung transplantation (LTx), and to develop an injury severity score able to accurately predict ICU mortality for these patients. DESIGN: Retrospective cohort analysis. SETTING: Two LTx centers in Paris. PATIENTS: Two hundred fifty-nine patients who underwent LTx over a 12-year period. MEASUREMENTS AND RESULTS: One hundred thirty-one patients (50.6%) met PGF criteria: radiographic graft infiltrate within the first 3 days following LTx associated with gas exchange impairment (PaO(2)/fraction of inspired oxygen ratio < 300 mm Hg). This syndrome was associated with an increased duration of mechanical ventilation (9.1 +/- 1 days vs 3.1 +/- 0.6 days, mean +/- SD; p < 0.001) and ICU mortality (29% vs 10.9%; p < 0.01). The patients with PGF were randomly assigned to developmental (n = 85) and validation (n = 46) samples. Using logistic regression analysis, four variables were found associated with ICU mortality in these patients: age, degree of gas exchange impairment, graft ischemic time, and severe early hemodynamic failure. An ischemia/reperfusion injury severity score was derived using these four variables. Model calibration was good in the developmental and validation samples, as was model discrimination (area under receiver operating characteristic curves, 0.93 and 0.85, respectively). CONCLUSION: PGF following LTx is a frequent event, with significant ICU morbidity and mortality. We demonstrate that four simple factors allow prediction of ICU mortality with good accuracy.

Long-term results of endoscopic thoracic sympathectomy for upper limb hyperhidrosis.

BACKGROUND: Immediate results of endoscopic thoracic sympathectomy (ETS) for hyperhidrosis are good. Adverse effects are well known but are supposed to decrease with time. We report the long-term results of ETS with regard to efficacy, side effects and patient satisfaction. METHODS: From 1993 to 1998, 382 patients suffering from hyperhidrosis of the upper limbs were operated on by means of bilateral ETS. One hundred twenty-five could be reached. There were 91 females and 34 males with a mean age of 28 years. The mean follow-up was 3.8 years (range: 24 to 84 months). Patients answered a detailed questionnaire from an independent observer addressing the following issues: stability of the initial result, outcome of side effects, degree of satisfaction. RESULTS: The global recurrence rate was 8.8%: 6.6% for palmar hyperhidrosis and 65% for axillary hyperhidrosis. Compensatory sweating was observed in 86.4% of the patients. It was considered as minor by 61% of them, as embarrassing by 31.5%, and as disabling by 7.5%. Other reported side effects were: Horner's syndrome in 3 patients (2.4%), healing in 2 of them; chronic rhinitis in 3 (2.4%); gustatory sweating in 9 (7.2%); and hand dryness in 42%. Sixty-five percent of the patients were fully satisfied, 28.7% were globally satisfied, and 6.3% regretted the operation. Ninety-two percent of the patients claimed they would ask for the operation if it were to be redone. CONCLUSIONS: This study confirms that results of ETS are good and stable for palmar hyperhidrosis but deteriorate for axillary hyperhidrosis. Compensatory sweating does not improve with time and is the main cause of dissatisfaction. Recommendations drawn from these results are the following: (1) patients suffering from isolated axillary hyperhidrosis should rather be treated by local therapy; (2) patients should be better informed of adverse effects.

Totally thoracoscopic major pulmonary resections: an analysis of perioperative complications.

BACKGROUND: Reports of recent large series support the safety of video-assisted thoracoscopic major pulmonary resections (MPR). However, although their rate of postoperative complications is low, the real incidence of intraoperative complications is unknown. METHODS: Clinical data from patients who underwent MPR through a full thoracoscopic approach between 2007 and 2012 were reviewed. Data were collected prospectively and analyzed retrospectively. RESULTS: A thoracoscopic MPR was attempted in 338 patients; 68.6% of the patients underwent a lobectomy and 31.4%, an anatomic segmentectomy. The mean operation time was 182 minutes (range, 80 to 300), and the mean intraoperative blood loss was 80 mL (range, 10 to 400 mL). Inhospital mortality rate was 0.3%. The overall complication rate was 32.8%. Intraoperative adverse events and conversion to open thoracotomy occurred in 2.7% and 5.6% of patients, respectively. Risk factors for conversion were preoperative forced expiratory volume of air in 1 second (p<0.001) and a fused fissure (p=0.001). A fused fissure (p=0.007) and surgical experience (p=0.022) were independent factors associated with a longer duration of operation. Major adverse events and reoperation occurred, respectively, in 8.9% and 3% of cases. Surgical complications were mostly vascular injury (n=9), laryngeal nerve palsy (n=5), chylothorax (n=3), and bronchus injury (n=1). On multivariate analysis, the only independent risk factors for major postoperative complications were smoking status and surgical experience. CONCLUSIONS: Although its overall rate of complications is low, a complete thoracoscopic approach might cause unusual adverse events. Surgeons must be aware of these complications to prevent them and anticipate their handling.