Short-term safety of thoracoscopic talc pleurodesis for recurrent primary spontaneous pneumothorax: a prospective European multicentre study.

The safety of talc pleurodesis is under dispute following reports of talc-induced acute respiratory distress syndrome (ARDS) and death. We investigated the safety of large-particle talc for thoracoscopic pleurodesis to prevent recurrence of primary spontaneous pneumothorax (PSP). 418 patients with recurrent PSP were enrolled between 2002 and 2008 in nine centres in Europe and South Africa. The main exclusion criteria were infection, heart disease and coagulation disorders. Serious adverse events (ARDS, death or other) were recorded up to 30 days after the procedure. Oxygen saturation, supplemental oxygen use and temperature were recorded daily at baseline and after thoracoscopic pleurodesis (2 g graded talc). During the 30-day observation period following talc poudrage, no ARDS (95% CI 0.0-0.9%), intensive care unit admission or death were recorded. Seven patients presented with minor complications (1.7%, 95% CI 0.7-3.4%). After pleurodesis, mean body temperature increased by 0.41°C (95% CI 0.33-0.48°C; p<0.001) at day 1 and returned to baseline value at day 5. Pleural drains were removed after day 4 in 80% of patients. Serious adverse events, including ARDS or death, did not occur in this large, multicentre cohort. Thoracoscopic talc poudrage using larger particle talc to prevent recurrence of PSPS can be considered safe.

Rapid on-site evaluation of transbronchial aspirates: randomised comparison of two methods.

The value of different staining methods for rapid analysis of transbronchial needle aspirates during bronchoscopy has not been explored. In the present study, we compared a Papanicolaou-based rapid stain, prepared by a technologist and read by a cytopathologist, and a Wright-Giemsa-based rapid stain, prepared and read by a cytopathologist alone. Gold standard was the final laboratory report issued on each aspirate. We harvested 827 aspirates from 218 target sites in 126 consecutive patients. At least one positive aspirate was found in 99 (79%) patients. In those 99 patients, 288 of 574 (50%) aspirates were positive for neoplastic (83%) or non-neoplastic (17%) disease. False-negative aspirates and target sites were more frequent with the rapid Wright-Giemsa than with the rapid Papanicolaou stain (14.2 versus 7.3%, p = 0.008, and 13.7 versus 3.6%, p = 0.021, respectively). The sensitivity of the Wright-Giemsa-based and Papanicolaou-based rapid stains for detecting diagnostic material was 93 and 100% in patients, 83.1 and 95.5% in target sites, and 72.8 and 84.9% in aspirates, respectively. Specificity was 100% for both methods in patients and target sites, and 90.4 and 95% in aspirates. We concluded that a Papanicolaou-based stain has superior yield and accuracy to a Wright-Giemsa-based stain for rapid on-site evaluation of transbronchial needle aspirates.

Diagnostic yield and safety of ultrasound-assisted biopsies in superior vena cava syndrome.

The yield and safety of ultrasound (US)-assisted transthoracic fine needle aspirations (TTFNA) and cutting needle biopsies (CNB) in the setting of superior vena cava (SVC) syndrome are unknown. The aims of the present prospective study were to asses the diagnostic yield and safety of US-assisted TTFNA and CNB in SVC syndrome with an associated mass lesion abutting the chest wall. Over a 3-yr period, the present authors screened 59 patients with SVC syndrome, and enrolled 25 patients who had an associated mass lesion that extended to the chest wall. US-assisted TTFNA with rapid on-site evaluation (ROSE) was performed in all cases. CNBs were performed where a provisional diagnosis of bronchogenic carcinoma could not be established, and in 57.1% of patients with bronchogenic carcinoma (limited due to safety constraints). ROSE of US-assisted TTFNA confirmed diagnostically useful material in 24 patients, and cytological diagnoses were ultimately made in all of these cases (diagnostic yield 96%). US-assisted CNB had a diagnostic yield of 87.5%. Minor haemorrhage occurred in one out of 25 TTFNA and three out of 16 CNB. Neither procedure resulted in major haemorrhage nor pneumothoraces. US-assisted TTFNA and CNB have a high diagnostic yield and are safe in the setting of SVC syndrome with an associated mass lesion abutting the chest wall.

ERS/ESTS clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemo-radiotherapy).

A collaboration of multidisciplinary experts on the functional evaluation of lung cancer patients has been facilitated by the European Respiratory Society (ERS) and the European Society of Thoracic Surgery (ESTS), in order to draw up recommendations and provide clinicians with clear, up-to-date guidelines on fitness for surgery and chemo-radiotherapy. The subject was divided into different topics, which were then assigned to at least two experts. The authors searched the literature according to their own strategies, with no central literature review being performed. The draft reports written by the experts on each topic were reviewed, discussed and voted on by the entire expert panel. The evidence supporting each recommendation was summarised, and graded as described by the Scottish Intercollegiate Guidelines Network Grading Review Group. Clinical practice guidelines were generated and finalized in a functional algorithm for risk stratification of the lung resection candidates, emphasising cardiological evaluation, forced expiratory volume in 1 s, systematic carbon monoxide lung diffusion capacity and exercise testing. Contrary to lung resection, for which the scientific evidences are more robust, we were unable to recommend any specific test, cut-off value, or algorithm before chemo-radiotherapy due to the lack of data. We recommend that lung cancer patients should be managed in specialised settings by multidisciplinary teams.

Management of life-threatening haemoptysis in an area of high tuberculosis incidence.

BACKGROUND: Emergency admissions with life-threatening haemoptysis in an area of high tuberculosis (TB) incidence at the University of Stellenbosch and Tygerberg Academic Hospital, South Africa. It is unclear if lung resection is regularly indicated to prevent recurrence following bronchial artery embolisation (BAE). OBJECTIVE: To prospectively evaluate risk factors for recurrence as selection criteria for surgery following embolisation: lack of complete cessation of haemoptysis, need for blood transfusion, presence of aspergilloma and absence of active TB. DESIGN: Prospective interventional study with 1-year follow-up. RESULTS: Within a 7-month period, 101 consecutive patients were admitted. Seven were excluded and 12 died shortly after admission. Haemoptysis ceased on medical treatment alone within 24 h in 21 of the remaining 82 patients. Their 1-year mortality was 10%. Eleven of 61 patients referred for emergency embolisation died before discharge. Of the 50 patients remaining at risk of recurrence, 38 (76%) were at low risk and 12 (24%) at high risk. Five of these patients (10% of those at risk) underwent surgery. Patients at low risk and operated patients had an uneventful course over 1 year, but two deaths occurred among the seven inoperable patients at high risk. CONCLUSION: Lung resection surgery following successful BAE for life-threatening haemoptysis can safely be avoided in patients at low risk of recurrence.

Smoking cessation should have more emphasis within Tobacco Control? The case for.

Smoking cessation is usually mentioned last in the chain of established measures to improve Tobacco Control. This seems logical, as smoking cessation is a secondary or tertiary preventative measure only. In the recently proposed Tobacco Control Scale (TCS) using 6 Tobacco Control measures pricing is considered most important, and smoking cessation least important. For current smokers secondary or tertiary preventative measures are necessary with smoking cessation being the most effective one as its impact on health is immediate. Pricing, on the other hand, is less effective in inciting current smokers to quit. Further, the vast majority of smokers would like to quit if they were able; so help in achieving this goal is welcome. Other Tobacco Control measures, on the other hand, are mostly negatively perceived by smokers because they perceive them as curtailment of their freedom. This is a psychological advantage the health professional active in this area has over other people involved in Tobacco Control and must be exploited. There is also strong evidence that smoking cessation is cost-effective, especially when comparing costs involved in addressing other important health risk factors, such as hyperlipidemia and arterial hypertension. Finally, the role of smoking cessation in helping to decrease social acceptability of smoking should not be underrated as every smoker who quits sets an example for other smokers to follow or for children not to start. In summary, smoking cessation continues to be of paramount importance among Tobacco Control measures, and should get more emphasis especially in health care settings.

Clinical and radiological grading of superior vena cava obstruction.

BACKGROUND: Superior vena cava obstruction (SVCO) is commonly caused by neoplastic venous compression and presents with typical symptoms and signs. Its clinical severity presumably depends on the degree of obstruction and the adequacy of venous collateral formation. OBJECTIVES: The development of novel clinical and radiological scoring systems based on the postulate that a reproducible relationship exists between the degree of SVCO, the presence of collateral circulation and the extent of clinical symptoms. METHODS: We prospectively evaluated consecutive cases of acute and subacute SVCO with a newly developed clinical scoring system, which is based on easily detectable clinical symptoms and signs of SVCO. In parallel, we recorded and scored the degree of SVCO and the extent of collaterals visible on contrast-enhanced computed tomography (CT). RESULTS: Thirty-four cases of SVCO were evaluated: 8 (23.5%) were clinically mild, 16 (47%) moderate and 10 (29.5%) severe. Lung cancer was the underlying histological diagnosis in 94% of cases. Radiologically, 53% had complete SVCO. A well-developed collateral system was found in 14 (41%). A scoring system subtracting a 'collateral score' from an 'obstruction score' showed a significant correlation with the clinical score (r = 0.75, p < 0.01). CONCLUSIONS: Clinical severity of SVCO depends upon the degree of SVCO and is ameliorated by collateral formation. The novel clinical scoring system can predict the underlying CT features in SVCO and may be valuable in the bedside assessment of SVCO severity.

Risk factors for recurrence of haemoptysis following bronchial artery embolisation for life-threatening haemoptysis.

SETTING: Life-threatening haemoptysis is a frequent and often fatal complication in areas with a high prevalence of tuberculosis (TB). Bronchial artery embolisation remains the standard initial treatment. Subsequent curative measures, such as surgical resection of the focus of haemorrhage, are generally recommended to prevent recurrence, but risk-based selection criteria have not been established. OBJECTIVES: To identify risk factors for the recurrence of haemoptysis following embolisation. DESIGN: Baseline characteristics were obtained from consecutive patients with life-threatening haemoptysis who were successfully embolised and followed up for at least 12 months. RESULTS: Recurrence of haemoptysis was observed in 47% and was associated with increased mortality compared to patients without recurrence (31% vs. 10%, P = 0.021). Patients with recurrence experienced residual mild haemoptysis beyond the first week after embolisation (odds ratio [OR] 7.2), received blood transfusions (OR 5.3) or presented with an aspergilloma (OR 5.1). Conversely, the presence of active TB amenable to treatment (OR 0.3) protected patients from these events. Radiographic or angiographic appearance did not predict recurrence. CONCLUSIONS: Recurrence of haemoptysis following embolisation for life-threatening haemoptysis is common and is associated with high mortality. The results of this study can contribute to the risk assessment of these patients and guide decisions regarding the urgency of definitive therapy.

Evaluation of newer prognostic markers for adult soft tissue sarcomas.

PURPOSE: In addition to tumor size, grade, location, and the presence of metastases, other factors may be useful in prognostication for adults with soft tissue sarcoma (STS). This study examines the relationship of MDR-1 mRNA, p-glycoprotein (P-gp), Ki-67 expression, and DNA content expression to clinical outcome in adults with STS. PATIENTS AND METHODS: Snap-frozen STS specimens from 65 patients were analyzed and compared with clinical outcomes. Immunohistochemistry was performed for the Ki-67 antigen and P-gp. DNA content was determined using the Feulgen reaction and quantitated using image analysis. MDR-1 mRNA expression was determined using a reverse-transcriptase polymerase chain reaction (RT-PCR)-based assay. RESULTS: P-glycoprotein expression was found by immunohistochemistry in 48% of cases with 5-year overall (54% v 14%, P = .07) and disease-free survival rates (32% v 18%, P = .039) higher in high-grade tumors that did not express P-gp. MDR-1 mRNA was detected in 51% of cases and no patient with high levels of MDR-1 mRNA expression was a long-term survivor. Patients with diploid tumors had significantly better survival than those with nondiploid tumors (51% v 31%, P = .03). High levels of Ki-67 were associated with poorer overall survival (46% v 31%, P = .04). On multivariate analysis, American Joint Committee on Cancer (AJCC) staging, DNA content, Ki-67, and P-gp staining were significant prognostic factors for 5-year overall and disease-free survival. CONCLUSION: P-gp expression, high-level Ki-67 expression, and nondiploid DNA content are independent prognostic indicators that correlate with poor outcomes in STS patients. However, MDR-1 mRNA was not found to be predictive of survival. These newer markers are useful additions to AJCC staging for prognostication for patients with STS. Such markers may be useful in selecting high-risk STS patients who could benefit from systemic adjuvant therapy.

Pulmonary artery compliance: its role in right ventricular-arterial coupling.

OBJECTIVE: The aim was to investigate the ventricular/vascular coupling of the intact right heart under conditions of normal operation and acute pulmonary hypertension. METHODS: Right ventricular contractility was obtained by calculating the end systolic pressure-volume relationship (Ees) and the effective pulmonary arterial elastance (Ea), applying the Windkessel parameters of the pulmonary arterial input impedance. Coupling between the ventricle and its load could be determined in terms of Ees and Ea. Acute pulmonary hypertension was induced by injecting glass microspheres into the pulmonary vascular bed until a mean pulmonary arterial pressure of more than 35 mm Hg had been reached. Experimental subjects were Landras/Large white pigs (n = 11), studied under general anaesthesia. Ees was obtained by normalising the right ventricle pressure-diameter equivalent of Ees to stroke volume. The lumped element parameters of the Windkessel analogue were calculated from the pulmonary artery pressure and blood flow. Stroke work was calculated from the pressure-volume loop and oxygen consumption derived from the pressure-volume area. Efficiency was taken to be the ratio between stroke work and oxygen consumption. RESULTS: Ea increased significantly as mean pulmonary artery pressure rose, while Ees remained linear and constant. Stroke work, as well as efficiency, increased, with the maximum of the stroke work curve lying to the right of the efficiency maximum. At the control step (before pulmonary artery hypertension), Ees = 1.71 Ea (n = 11). CONCLUSIONS: Under control conditions, the right ventricle operates at maximum efficiency and submaximal work output. Compliance of the pulmonary artery is a significant factor in decoupling the right ventricle from its vascular load. As the compliance decreases with acute pulmonary hypertension, the maximum stroke work against load point shifted in such a manner that the right ventricle changed its operational status from a flow to a pressure pump, resulting in a decreased stroke volume.

A phase I study of adenovirus-mediated wild-type p53 gene transfer in patients with advanced non-small cell lung cancer.

Mutations of the tumor suppressor gene p53 are the most common genetic alterations observed in human cancer. Loss of wild-type p53 function impairs cell cycle arrest as well as repair mechanisms involved in response to DNA damage. Further, apoptotic pathways as induced by radio- or chemotherapy are also abrogated. Gene transfer of wild-type p53 was shown to reverse these deficiencies and to induce apoptosis in vitro and in preclinical in vivo tumor models. A phase I dose escalation study of a single intratumoral injection of a replication-defective adenoviral expression vector encoding wild-type p53 was carried out in patients with incurable non-small cell lung cancer. All patients enrolled had p53 protein overexpression as a marker of mutant p53 status in pretreatment tumor biopsies. Treatment was performed either by bronchoscopic intratumoral injection or by CT-guided percutaneous intratumoral injection of the vector solution. Fifteen patients were enrolled in two centers, and were treated at four different dose levels ranging from 10(7) to 10(10) PFU (7.5 x 10(9) to 7.5 x 10(12) particles). No clinically significant toxicity was observed. Successful transfer of wild-type p53 was achieved only with higher vector doses. Vector-specific wild-type p53 RNA sequences could be demonstrated in posttreatment biopsies of six patients. Transient local disease control by a single intratumoral injection of the vector solution was observed in four of those six successfully transduced patients. There was no evidence of clinical responses at untreated tumor sites. Wild-type p53 gene therapy by intratumoral injection of a replication-defective adenoviral expression vector is safe, feasible, and biologically effective in patients with advanced non-small cell lung cancer.

P21 gene expression as an indicator for the activity of adenovirus-p53 gene therapy in non-small cell lung cancer patients.

Alterations in the tumor suppressor gene p53 lead to impaired cell cycle control, allowing for the development and growth of tumors. To restore a loss of p53 function, we performed a phase I study of intratumoral gene therapy with adenovirus expressing wild-type p53 in patients with non-small cell lung cancer carrying mutations in the p53 gene. Furthermore, in a phase II study, gene therapy was complemented with simultaneous cisplatin/vinorelbine treatment. Biopsies were obtained from all treated patients before and 24-48 hours after gene therapy to study changes in the expression of p53 target genes. We report here that in most of the cases, the target gene p21 was up-regulated, especially when injection of higher doses of p53-expressing adenovirus was combined with simultaneous chemotherapy, whereas Pig3, previously reported to be highly up-regulated by p53, generally did not show a clear increase. Interestingly, a clear p21 gene response was observed only in tumors showing stabilization or regression. We conclude that p21 appears to be up-regulated after adenovirus-mediated p53 gene transfer and is the most sensitive marker tested for biological response to gene therapy in the small cohort of non-small cell lung cancers that were studied.

The effect of prostaglandin E1 on acute pulmonary artery hypertension during oleic acid-induced respiratory dysfunction.

This study examined the general effect of intravenous PGE1 on RV Ees and effective PA elastance (EA) during acute pulmonary hypertension associated with oleic acid infusion. In eight pigs, RV end-systolic elastance was quantified with the Ees and Ea was defined with reference to the Windkessel model. Oleic acid infusion increased mean PAP and Ea. Prostaglandin E1 reduced PAP and decreased Ea. Ees did not change throughout the study. Mean arterial pressure was reduced and the pulmonary shunt was increased after PGE1 infusion. The PaO2 was reduced. Data from this study suggest that although PGE1 is effective in reducing PAP, it is not as effective in reducing RV afterload. Furthermore, PGE1 does have significant side effects such as reduction of systemic arterial pressure and an increase in pulmonary shunt.

Treatment of multiple rib fractures. Randomized controlled trial comparing ventilatory with nonventilatory management.

We studied the treatment of multiple rib fractures in NIC, comparing ventilatory with nonventilatory methods in 69 patients who were randomly allocated to one of the following two treatments: (1) a CPAP mask combined with regional analgesia (n = 36); or (2) endotracheal intubation and mechanical ventilation with PEEP (n = 33). Clinical outcome was as follows: mean duration of treatment, 4.5 +/- 2.3 days for the group with CPAP and 7.3 +/- 3.7 days for the intubated group (p = 0.0003); mean number of days spent in intensive care, 5.3 +/- 2.9 days and 9.5 +/- 4.4 days, respectively (p = less than 0.0001); mean period of hospitalization, 8.4 +/- 7.1 days and 14.6 +/- 8.6 days, respectively (p = 0.0019); and patients developing complications: 28 percent (10/36) and 73 percent (24/33), respectively. Infections caused the difference in complications, primarily pneumonias, which occurred in 14 percent (5/36) of the group with CPAP but in 48 percent (16/33) of the intubated group. We conclude that treatment with a CPAP mask combined with regional analgesia can shorten and simplify treatment in these patients, mainly through a decreased infection rate, when compared with intubation and mechanical ventilation, and we recommend this treatment in patients similar to our sample.

The flow-volume loop in bilateral vocal cord paralysis.

A 38-year-old man with posttraumatic bilateral vocal cord paralysis and a surgically repaired avulsion of the extrathoracic trachea presented with a slight increase of exertional dyspnea (grade 2). Spirometry showed high normal FEV1 for FVC variables, but the F-V loop was characteristic for highly variable UAO with an increased FEV1/PEF ratio of 11 ml/L/min as well as a MEF50/MIF50 of 4.55. Endoscopy during forced respiration showed near total inspiratory obstruction of the larynx due to paradoxical behavior of the vocal cords. In extrathoracic airway obstruction a FEV1/PEF ratio > 10 ml/L/min combined with a MEF50/MIF50 ratio > 4 is suggestive of variable UAO caused by bilateral vocal cord paralysis rather than by a tracheal lesion.