Fergus V. Gleeson

The safety and feasibility of extracorporeal high-intensity focused ultrasound (HIFU) for the treatment of liver and kidney tumours in a Western population

High-intensity focused ultrasound (HIFU) provides a potential noninvasive alternative to conventional therapies. We report our preliminary experience from clinical trials designed to evaluate the safety and feasibility of a novel, extracorporeal HIFU device for the treatment of liver and kidney tumours in a Western population. The extracorporeal, ultrasound-guided Model-JC Tumor Therapy System (HAIFU™ Technology Company, China) has been used to treat 30 patients according to four trial protocols. Patients with hepatic or renal tumours underwent a single therapeutic HIFU session under general anaesthesia. Magnetic resonance imaging 12 days after treatment provided assessment of response. The patients were subdivided into those followed up with further imaging alone or those undergoing surgical resection of their tumours, which enabled both radiological and histological assessment. HIFU exposure resulted in discrete zones of ablation in 25 of 27 evaluable patients (93%). Ablation of liver tumours was achieved more consistently than for kidney tumours (100 vs 67%, assessed radiologically). The adverse event profile was favourable when compared to more invasive techniques. HIFU treatment of liver and kidney tumours in a Western population is both safe and feasible. These findings have significant implications for future noninvasive image-guided tumour ablation.

Non-local shape descriptor: a new similarity metric for deformable multi-modal registration

Deformable registration of images obtained from different modalities remains a challenging task in medical image analysis. This paper addresses this problem and proposes a new similarity metric for multi-modal registration, the non-local shape descriptor. It aims to extract the shape of anatomical features in a non-local region. By utilizing the dense evaluation of shape descriptors, this new measure bridges the gap between intensity-based and geometric feature-based similarity criteria. Our new metric allows for accurate and reliable registration of clinical multi-modal datasets and is robust against the most considerable differences between modalities, such as non-functional intensity relations, different amounts of noise and non-uniform bias fields. The measure has been implemented in a non-rigid diffusion-regularized registration framework. It has been applied to synthetic test images and challenging clinical MRI and CT chest scans. Experimental results demonstrate its advantages over the most commonly used similarity metric - mutual information, and show improved alignment of anatomical landmarks.

Pleural procedures and thoracic ultrasound: British Thoracic Society pleural disease guideline 2010

In hospital practice, pleural aspiration (thoracocentesis) and chest drain insertion may be required in many different clinical settings for a variety of indications. Doctors in most specialities will be exposed to patients requiring pleural drainage and need to be aware of safe techniques. There have been many reports of the dangers of large-bore chest drains and it had been anticipated that, with the previous guidelines, better training and the advent of small-bore Seldinger technique chest drains, there would have been an improvement. Unfortunately the descriptions of serious complications continue, and in 2008 the National Patient Safety Agency (NPSA) issued a report making recommendations for safer practice.1 These updated guidelines take into consideration the recommendations from this report and describe the technique of pleural aspiration and Seldinger chest drain insertion and ultrasound guidance. Much of this guideline consists of descriptions of how to do these procedures but, where possible, advice is given when evidence is available. Before undertaking an invasive pleural procedure, all operators should be appropriately trained and have been initially supervised by an experienced trainer. Many of the complications described in the NPSA report were the result of inadequate training or supervision. A recent survey of UK NHS Trusts showed that the majority did not have a formal training policy for chest drain insertion in 2008.2 Studies of clinical practice have shown that there is a wide variation in the knowledge and skills of doctors inserting chest drains. In a published study3 where doctors were asked to indicate where they would insert a chest drain, 45% indicated they would insert the drain outside of the safety triangle, …

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.).

Guidelines for radiologically guided lung biopsy

These guidelines have been developed at the request of the Standards of Care Committee of the British Thoracic Society (BTS) and with the agreement of the Royal College of Radiologists and the British Society of Interventional Radiology, and approval of the Royal College of Pathologists in respect of the pathology recommendations and the Society of Cardiothoracic Surgeons of Great Britain and Ireland. Lung biopsy is a relatively frequently performed procedure with considerable benefit for patient management but it may, on rare occasions, result in the death of the patient. It is a multidisciplinary procedure involving respiratory physicians, surgeons, and radiologists with an interest in chest diseases. The aim of the group was to produce formal evidence based guidelines for subsequent use by those referring patients for the procedure and for those performing it. The areas covered by these guidelines are as follows: The following areas are not covered by these guidelines: ### Validity and grading of recommendations The criteria for assessing the levels of evidence and grading of recommendations were based on those recommended in the Scottish Intercollegiate Guidelines Network in 19951 using the Agency of Health Care Policy and Research model used in some other BTS guidelines (tables 1 and 2). View this table: Table 1 Categories of evidence185 View this table: Table 2 Grading of recommendations It should be noted that there are very few randomised trials comparing the various aspects of lung biopsy and, for that reason, more detailed systems of categorisation such as that of the Scottish Intercollegiate Guidelines Network published in 2001 were not used.2 The papers selected by searching PubMed and Medline were assessed by the members of the working group and decisions on levels of evidence for each paper were made by …

MIND: Modality independent neighbourhood descriptor for multi-modal deformable registration

Deformable registration of images obtained from different modalities remains a challenging task in medical image analysis. This paper addresses this important problem and proposes a modality independent neighbourhood descriptor (MIND) for both linear and deformable multi-modal registration. Based on the similarity of small image patches within one image, it aims to extract the distinctive structure in a local neighbourhood, which is preserved across modalities. The descriptor is based on the concept of image self-similarity, which has been introduced for non-local means filtering for image denoising. It is able to distinguish between different types of features such as corners, edges and homogeneously textured regions. MIND is robust to the most considerable differences between modalities: non-functional intensity relations, image noise and non-uniform bias fields. The multi-dimensional descriptor can be efficiently computed in a dense fashion across the whole image and provides point-wise local similarity across modalities based on the absolute or squared difference between descriptors, making it applicable for a wide range of transformation models and optimisation algorithms. We use the sum of squared differences of the MIND representations of the images as a similarity metric within a symmetric non-parametric Gauss-Newton registration framework. In principle, MIND would be applicable to the registration of arbitrary modalities. In this work, we apply and validate it for the registration of clinical 3D thoracic CT scans between inhale and exhale as well as the alignment of 3D CT and MRI scans. Experimental results show the advantages of MIND over state-of-the-art techniques such as conditional mutual information and entropy images, with respect to clinically annotated landmark locations.

Aetiology, outcome, and risk factors for mortality among adults with acute pneumonia in Kenya.

BACKGROUND Despite a substantial disease burden, there is little descriptive epidemiology of acute pneumonia in sub-Saharan Africa. We did this study to define the aetiology of acute pneumonia, to estimate mortality at convalescence, and to analyse mortality risk-factors. METHODS We studied 281 Kenyan adults who presented to two public hospitals (one urban and one rural) with acute radiologically confirmed pneumonia during 1994-96. We did blood and lung-aspirate cultures, mycobacterial cultures, serotype-specific pneumococcal antigen detection, and serology for viral and atypical agents. FINDINGS Aetiology was defined in 182 (65%) patients. Streptococcus pneumoniae was the most common causative agent, being found in 129 (46%) cases; Mycobacterium tuberculosis was found in 26 (9%). Of 255 patients followed up for at least 3 weeks, 25 (10%) died at a median age of 33 years. In multivariate analyses, risk or protective factors for mortality were age (odds ratio 1.51 per decade [95% CI 1.04-2.19]), unemployment (4.42 [1.21-16.1]), visiting a traditional healer (5.26 [1.67-16.5]), visiting a pharmacy (0.30 [0.10-0.91]), heart rate (1.64 per 10 beats [1.24-2.16]), and herpes labialis (15.4 [2.22-107]). HIV-1 seropositivity, found in 52%, was not associated with mortality. Death or failure to recover after 3 weeks was more common in patients with pneumococci of intermediate resistance to benzylpenicillin, which comprised 28% of pneumococcal isolates, than in those infected with susceptible pneumococci (5.60 [1.33-23.6]). INTERPRETATION We suggest that tuberculosis is a sufficiently common cause of acute pneumonia in Kenyan adults to justify routine sputum culture, and that treatment with benzylpenicillin remains appropriate for clinical failure due to M. tuberculosis, intermediate-resistant pneumococci, and other bacterial pathogens. However, interventions restricted to hospital management will fail to decrease mortality associated with socioeconomic, educational, and behavioural factors.

Thoracic Ultrasound in the diagnosis of Malignant Pleural Effusion

Background: Malignant pleural effusion (MPE) is a common clinical problem with described investigation pathways. While thoracic ultrasound (TUS) has been shown to be accurate in pleural fluid detection, its use in the diagnosis of malignant pleural disease has not been assessed. A study was undertaken to assess the diagnostic accuracy of TUS in differentiating malignant and benign pleural disease. Methods: 52 consecutive patients with suspected MPE underwent TUS and contrast-enhanced CT (CECT). TUS was used to assess pleural surfaces using previously published CT imaging criteria for malignancy, diaphragmatic thickness/nodularity, effusion size/nature and presence of hepatic metastasis (in right-sided effusions). A TUS diagnosis of malignant or benign disease was made blind to clinical data/other investigations by a second blinded operator using anonymised TUS video clips. The TUS diagnosis was compared with the definitive clinical diagnosis and in addition to the diagnosis found at CECT. Results: A definitive malignant diagnosis was based on histocytology (30/33; 91%) and clinical/CT follow-up (3/33; 9%). Benign diagnoses were based on negative histocytology and follow-up over 12 months in 19/19 patients. TUS correctly diagnosed malignancy in 26/33 patients (sensitivity 73%, specificity 100%, positive predictive value 100%, negative predictive value 79%) and benign disease in 19/19. Pleural thickening >1 cm, pleural nodularity and diaphragmatic thickening >7 mm were highly suggestive of malignant disease. Conclusion: TUS is useful in differentiating malignant from benign pleural disease in patients presenting with suspected MPE and may become an important adjunct in the diagnostic pathway.

British Thoracic Society guidelines for the investigation and management of pulmonary nodules: accredited by NICE

This guideline is based on a comprehensive review of the literature on pulmonary nodules and expert opinion. Although the management pathway for the majority of nodules detected is straightforward it is sometimes more complex and this is helped by the inclusion of detailed and specific recommendations and the 4 management algorithms below. The Guideline Development Group (GDG) wanted to highlight the new research evidence which has led to significant changes in management recommendations from previously published guidelines. These include the use of two malignancy prediction calculators (section ‘Initial assessment of the probability of malignancy in pulmonary nodules’, algorithm 1) to better characterise risk of malignancy. There are recommendations for a higher nodule size threshold for follow-up (≥5 mm or ≥80 mm3) and a reduction of the follow-up period to 1 year for solid pulmonary nodules; both of these will reduce the number of follow-up CT scans (sections ‘Initial assessment of the probability of malignancy in pulmonary nodules’ and ‘Imaging follow-up’, algorithms 1 and 2). Volumetry is recommended as the preferred measurement method and there are recommendations for the management of nodules with extended volume doubling times (section ‘Imaging follow-up’, algorithm 2). Acknowledging the good prognosis of sub-solid nodules (SSNs), there are recommendations for less aggressive options for their management (section ‘Management of SSNs’, algorithm 3). The guidelines provide more clarity in the use of further imaging, with ordinal scale reporting for PET-CT recommended to facilitate incorporation into risk models (section ‘Further imaging in management of pulmonary nodules’) and more clarity about the place of biopsy (section ‘Non-imaging tests and non-surgical biopsy’, algorithm 4). There are recommendations for the threshold for treatment without histological confirmation (sections ‘Surgical excision biopsy’ and ‘Non-surgical treatment without pathological confirmation of malignancy’, algorithm 4). Finally, and possibly most importantly, there are evidence-based recommendations about the information that people …

Local anaesthetic thoracoscopy: British Thoracic Society pleural disease guideline 2010

Thoracoscopy under local anaesthetic and intravenous sedation, also known as local anaesthetic thoracoscopy, medical thoracoscopy or pleuroscopy, is increasingly being performed by chest physicians in the UK. In 1999, 11 centres across the UK offered a local anaesthetic thoracoscopy service, increasing to 17 centres in May 20041 and 37 centres in 2009 (Dr N Downer, personal communication). This document, which will use the term ‘local anaesthetic thoracoscopy’, aims to consider the following issues and to make appropriate recommendations on the basis of evidence where available: Creation of this guideline followed the Appraisal of Guidelines Research and Evaluation/Scottish Intercollegiate Guidelines Network (AGREE/SIGN) methodology of evidence assessment and integration (see introduction to pleural disease guidelines). Is there a need for a physician-based local anaesthetic thoracoscopy service in the UK? The majority of local anaesthetic thoracoscopy is carried out in the context of an undiagnosed exudative pleural effusion, the commonest cause of which is malignancy.2 This section of the document will therefore focus mainly on local anaesthetic thoracoscopy in the context of malignant disease. ### The increasing burden of pleural disease Malignant pleural effusion is a common clinical problem. Although the incidence of lung cancer in the UK is falling, the incidence of other cancers is rising. With increasing life expectancy in an ageing population and at current cancer incidence rates, an additional 100 000 cases of cancer per year are expected by 2025.3 Up to 15% of patients who die with malignancy have a pleural effusion at autopsy.4 Studies suggest that exudative effusions are caused by malignancy …