Emma J. Helm

Intrapleural Use of Tissue Plasminogen Activator and DNase in Pleural Infection

BACKGROUND More than 30% of patients with pleural infection either die or require surgery. Drainage of infected fluid is key to successful treatment, but intrapleural fibrinolytic therapy did not improve outcomes in an earlier, large, randomized trial. METHODS We conducted a blinded, 2-by-2 factorial trial in which 210 patients with pleural infection were randomly assigned to receive one of four study treatments for 3 days: double placebo, intrapleural tissue plasminogen activator (t-PA) and DNase, t-PA and placebo, or DNase and placebo. The primary outcome was the change in pleural opacity, measured as the percentage of the hemithorax occupied by effusion, on chest radiography on day 7 as compared with day 1. Secondary outcomes included referral for surgery, duration of hospital stay, and adverse events. RESULTS The mean (±SD) change in pleural opacity was greater in the t-PA-DNase group than in the placebo group (-29.5±23.3% vs. -17.2±19.6%; difference, -7.9%; 95% confidence interval [CI], -13.4 to -2.4; P=0.005); the change observed with t-PA alone and with DNase alone (-17.2±24.3 and -14.7±16.4%, respectively) was not significantly different from that observed with placebo. The frequency of surgical referral at 3 months was lower in the t-PA-DNase group than in the placebo group (2 of 48 patients [4%] vs. 8 of 51 patients [16%]; odds ratio for surgical referral, 0.17; 95% CI, 0.03 to 0.87; P=0.03) but was greater in the DNase group (18 of 46 patients [39%]) than in the placebo group (odds ratio, 3.56; 95% CI, 1.30 to 9.75; P=0.01). Combined t-PA-DNase therapy was associated with a reduction in the hospital stay, as compared with placebo (difference, -6.7 days; 95% CI, -12.0 to -1.9; P=0.006); the hospital stay with either agent alone was not significantly different from that with placebo. The frequency of adverse events did not differ significantly among the groups. CONCLUSIONS Intrapleural t-PA-DNase therapy improved fluid drainage in patients with pleural infection and reduced the frequency of surgical referral and the duration of the hospital stay. Treatment with DNase alone or t-PA alone was ineffective. (Funded by an unrestricted educational grant to the University of Oxford from Roche UK and by others; Current Controlled Trials number, ISRCTN57454527.).

Course and Variation of the Intercostal Artery by CT Scan

BACKGROUND It is conventionally taught that the intercostal artery is shielded in the intercostal groove of the superior rib. The continuous course and variability of the intercostal artery, and factors that may influence them, have not been described in a large number of arteries in vivo. METHODS Maximal intensity projection reformats in the coronal plane were produced from CT scan pulmonary angiograms to identify the posterolateral course of the intercostal artery (seventh to 11th rib spaces). A novel semiautomated computer segmentation algorithm was used to measure distances between the lower border of the superior rib, the upper border of the inferior rib, and the position of the intercostal artery when exposed in the intercostal space. The position and variability of the artery were analyzed for association with clinical factors. RESULTS Two hundred ninety-eight arteries from 47 patients were analyzed. The mean lateral distance from the spine over which the artery was exposed within the intercostal space was 39 mm, with wide variability (SD, 10 mm; 10th-90th centile, 28-51 mm). At 3 cm lateral distance from the spine, 17% of arteries were shielded by the superior rib, compared with 97% at 6 cm. Exposed artery length was not associated with age, sex, rib space, or side. The variability of arterial position was significantly associated with age (coefficient, 0.91; P < .001) and rib space number (coefficient, - 2.60; P < .001). CONCLUSIONS The intercostal artery is exposed within the intercostal space in the first 6 cm lateral to the spine. The variability of its vertical position is greater in older patients and in more cephalad rib spaces.

Imaging of the pleura.

Pleural disease is a problem of global significance which causes significant morbidity and mortality. Pleural disease is usually first suspected on chest x‐ray but further imaging, often ultrasound, is usually required as part of the diagnostic work‐up. Complex imaging with computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)‐CT are less often performed but are routinely required in patients with mesothelioma and occasionally required in patients with pleural infection and other pleural diseases. Cross‐sectional imaging may be used to suggest the diagnosis of pleural disease, quantify disease severity, guide biopsy, and even predict prognosis. This review will focus on the contributions of CT, MRI, and PET to the management of pleural disease with discussion of their relative strengths and weaknesses. J. Magn. Reson. Imaging 2010;32:1275–1286.

Pleural procedures and pleuroscopy

Pleural procedures are commonly performed by physicians from a range of specialities. These procedures vary in complexity, from relatively straightforward pleural aspiration to more challenging procedures such as pleuroscopy. After appropriate training, even complex pleural procedures have a low risk of complications. Nevertheless, an appreciation of procedural risks is essential for physician training and forms the crux of a valid patient consent process. This review presents a systematic evaluation of the potential complications of common pleural procedures.

Impact of lung transplantation on serum lipids in adults with cystic fibrosis

BACKGROUND Cystic fibrosis (CF) is an inherited condition that causes progressive respiratory failure and is the third most common indication for adult bilateral lung transplantation. Post-transplant hyperlipidemia commonly affects lung transplant recipients, but the impact of lung transplantation on serum lipids in the adult CF population is not well studied. The aim of this study was to examine the impact of lung transplantation on the prevalence of hyperlipidemia in CF adults. METHODS We retrospectively analyzed prospectively collected data in 108 CF adults undergoing bilateral sequential lung transplantation from 1996 to 2007 at our institution. RESULTS The prevalence of hypercholesterolemia (>5.2 mmol/liter) and hypertriglyceridemia (>2.2 mmol/liter) increased significantly after lung transplant (14.8% vs 32.4%, p = 0.002; 8.3% vs 41.7%, p < 0.0001, respectively). Cyclosporine A (CsA) use was associated with significantly higher post-transplant total and LDL cholesterol compared with tacrolimus use. Post-transplant calculated Framingham risk score was <10% in all but 1 subject. CONCLUSION Hyperlipidemia was common in our cohort of post-lung transplant CF adults, with a higher prevalence in those receiving CsA. Despite these findings, calculated cardiovascular risk remained low and none of these subjects developed clinically evident cardiovascular disease.

Random walk-based automated segmentation for the prognosis of malignant pleural mesothelioma

In this paper we apply the random walk-based segmentation method to mesothelioma CT image datasets, aiming to establish an automatic segmentation routine that can provide volumetric assessments for monitoring progression of the disease and its treatments. We have validated the applicability of this method to our image data through a series of experimental trials, and demonstrated the superior performance and benefits of random walk compared to other segmentation algorithms such as level sets.

Intussusception in Adults with Cystic Fibrosis: A Case Series with Review of the Literature

Intussusception occurs when a proximal segment of bowel (intussusceptum) telescopes into the lumen of the adjacent distal segment (intussuscepiens). It is a relatively common cause of an acute abdomen in the first two years of life, but is uncommon in older children [1]. The diagnosis is rare in adult life, with presentations in adulthood comprising 5% of all intussusceptions and 1% of bowel obstructions [2]. In children it is most commonly idiopathic, in contrast with adults, for most of whom an underlying etiology is found. Cystic fibrosis (CF) is the most common fatal inherited condition in Caucasians [3]. It is caused by abnormal function of the cystic fibrosis transmembrane conductance regulator (CFTR), an epithelial chloride channel. This primary defect causes epithelial secretions to be abnormally dehydrated and viscous, affecting several organs including the lungs, pancreas, intestines, and liver. CF is a well-recognized risk factor for childhood intussusception, with an incidence of 1% reported in the largest case series [4]. The peak age of presentation in this case series was between 9 and 12 years of age, much older than in the nonCF population. Although the clinical presentation and management of intussusception in children with CF is well described, that of adults is less well characterized. We therefore present a case series of CF adults diagnosed with symptomatic intussusception at our centers and perform a systematic review of the literature in order to identify previously described cases. Our aim is to examine the clinical and imaging findings of intussusception in CF adults in order to identify features of the presentation that should suggest this diagnosis.

Use of dynamic CT in acute respiratory distress syndrome (ARDS) with comparison of positive and negative pressure ventilation

Negative pressure ventilation via an external device (‘iron lung’) has the potential to provide better oxygenation with reduced barotrauma in patients with ARDS. This study was designed to see if oxygenation differences between positive and negative ventilation could be explained by CT. Six anaesthetized rabbits had ARDS induced by repeated saline lavage. Rabbits were ventilated with positive pressure ventilation (PPV) and negative pressure ventilation (NPV) in turn. Dynamic CT images were acquired over the respiratory cycle. A computer-aided method was used to segment the lung and calculate the range of CT densities within each slice. Volumes of ventilated lung and atelectatic lung were measured over the respiratory cycle. NPV was associated with an increased percentage of ventilated lung and decreased percentage of atelectatic lung. The most significant differences in ventilation and atelectasis were seen at mid-inspiration and mid-expiration (ventilated lung NPV = 61%, ventilated lung PPV = 47%, p < 0.001; atelectatic lung NPV = 10%, atelectatic lung PPV 19%, p < 0.001). Aeration differences were not significant at end-inspiration. Dynamic CT can show differences in lung aeration between positive and negative ventilation in ARDS. These differences would not be appreciated if only static breath-hold CT was used.

Iatrogenic injury to the intercostal artery: aetiology, diagnosis and therapeutic intervention

Pleural interventions are commonly performed in both elective and emergency settings. They include simple thoracocentesis, closed pleural biopsy (with or without image guidance), intercostal drain (ICD) insertion, in-dwelling pleural catheter insertion and medical thoracoscopy. Complications of pleural procedures are common but their incidence is often under-recognised. Higher operator experience and the use of image guidance are key factors demonstrated to significantly reduce the frequency of complications.1 Injury to the intercostal artery (ICA) is an infrequent but potentially life-threatening complication of all pleural interventions. Pleural haemorrhage is reported to occur in up to 2% of thoracocenteses, up to 13% of ICD insertions and up to 4% of thoracoscopies.2 The true incidence of ICA laceration and consequent pleural haemorrhage is likely to be higher due to under-reporting of complications seen in retrospective case series. The British Thoracic Society has published guidelines for the insertion of ICDs,1 aiming to reduce the potential harm of ICD insertion. Although these recommendations are likely to reduce certain complications such as drain insertion into abdominal or thoracic viscera, they do not specifically address the possibility of ICA injury. Proper site selection for pleural interventions is important as this minimises the likelihood of ICA laceration. In a recent large study, Helm et al 3 identified that ICA is exposed within the intercostal space in the first 6 cm lateral to the spine using CT pulmonary angiograph and mapping of the ICA course. The variability of ICA is greater in older people and in more cephalad rib spaces and decreases with lateral distance from the spinous process. Additionally, another important parameter is the management protocol for intrapleural haemorrhage. This should be in place prior to any pleural interventions to avoid life-threatening delays. We present three cases of iatrogenic ICA injury in different clinical circumstances, from three different …

An Automatic Wavelet-Based Approach for Lung Segmentation and Density Analysis in Dynamic CT

Acute respiratory distress syndrome (ARDS) can occur in people with or without previous lung disease. Analysis of aeration in artificial ventilation for ARDS is one of the major applications of computed tomography (CT) lung density examination. A movie of an affected rabbit lung over the respiratory cycle was produced by dynamic CT with a cine loop technique. This technique can produce thousands of CT images for analysis with a single experiment. A fully automated algorithm based on the capability of wavelet transformation to detect edges in the image is proposed. This method accurately and consistently segments the lung in pulmonary CT images. The speed and accuracy of this technique allows it to outperform other methods when dealing with the large number of images created by dynamic computed tomography