The effect of chemotherapy on health-related quality of life in mesothelioma: results from the SWAMP trial.

BACKGROUND: The effect of chemotherapy on health-related quality of life (HRQoL) in malignant pleural mesothelioma (MPM) is poorly understood. Patient-individualised prognostication and prediction of treatment response from chemotherapy is useful but little evidence exists to guide practice. METHOD: Consecutive patients with MPM who were fit for first-line chemotherapy with pemetrexed and cisplatin\carboplatin were recruited and followed up for a minimum of 12 months. This study focussed on the HRQoL outcomes of these patients using the EQ-5D, EORTC QLQ-C30 and LC13. RESULTS: Seventy-three patients were recruited of which 58 received chemotherapy and 15 opted for best supportive care (BSC). Compliance with HRQoL questionnaires was 98% at baseline. The chemotherapy group maintained HRQoL compared with the BSC group whose overall HRQoL fell (P=0.006) with worsening dyspnoea and pain. The impact of chemotherapy was irrespective of histological subtype although those with non-epithelioid disease had worse HRQoL at later time points (P=0.012). Additionally, those with a falling mesothelin or improvement on modified-RECIST CT at early follow-up had a better HRQoL at 16 weeks. CONCLUSIONS: HRQoL was maintained following chemotherapy compared with a self-selected BSC group. Once chemotherapy is initiated, a falling mesothelin or improved RECIST CT findings infer a quality-of-life advantage.

The South West Area Mesothelioma and Pemetrexed trial: a multicentre prospective observational study evaluating novel markers of chemotherapy response and prognostication.

BACKGROUND: Robust markers that predict prognosis and detect early treatment response in malignant pleural mesothelioma (MPM) would enhance patient care. METHODS: Consecutive patients with MPM who were considered fit for first-line chemotherapy were prospectively recruited. Patients of similar performance status opting for best supportive care were included as a comparator group. Baseline and interval CT, PET-CT and serum markers (mesothelin, fibulin-3 and neutrophil-lymphocyte ratio (NLR)) were obtained, and patients followed up for a minimum 12 months. FINDINGS: Seventy-three patients were recruited (58 chemotherapy/15 comparator arm). Baseline TGV (total glycolytic volume on PET-CT) was an independent predictor of worse overall survival (OS) (P=0.001). Change in interval TGV(baseline/after two cycles of chemotherapy) did not predict OS or chemotherapy response on CT. Baseline NLR<4 was an independent predictor of better OS (median survival 453 (IQR 272-576) days vs NLR⩾4, 257 (IQR 147-490), P=0.002). Although baseline serum mesothelin did not predict OS, a falling level at 8 weeks significantly predicted longer time to progression (TTP) (P<0.001). INTERPRETATION: Neutrophil-lymphocyte ratio and baseline TGV predict prognosis in malignant pleural mesothelioma (MPM), but PET-CT is unhelpful in monitoring chemotherapy response. Serum mesothelin is a useful early treatment response marker when measured serially during chemotherapy and may have a role in evaluating patients' treatment response.

The role of computerized tomography in the evaluation of gastrointestinal bleeding following negative or failed endoscopy: a review of current status.

Gastrointestinal bleeding remains an important cause for emergency hospital admission with a significant related morbidity and mortality. Bleeding may relate to the upper or lower gastrointestinal tracts and clinical history and examination may guide investigations to the more likely source of bleeding. The now widespread availability of endoscopic equipment has made a huge impact on the rapid identification of the bleeding source. However, there remains a large group of patients with negative or failed endoscopy, in whom additional techniques are required to identify the source of bleeding. In the past, catheter angiography and radionuclide red cell labeling techniques were the preferred 'next step' modalities used to aid in identifying a bleeding source within the gastrointestinal tract. However, these techniques are time-consuming and of limited sensitivity and specificity. In addition, catheter angiography is a relatively invasive procedure. In recent years, computerized tomography (CT) has undergone major technological advances in its speed, resolution, multiplanar techniques and angiographic abilities. It has allowed excellent visualization of the both the small and large bowel allowing precise anatomical visualization of many causes of gastrointestinal tract (GIT) bleeding. In addition, recent advances in multiphasic imaging now allow direct visualization of bleeding into the bowel. In many centers CT has therefore become the 'next step' technique in identifying a bleeding source within the GIT following negative or failed endoscopy in the acute setting. In this review article, we review the current literature and discuss the current status of CT as a modality in investigating the patient with GIT bleeding.

Classification of fracture and non-fracture groups by analysis of coherent X-ray scatter.

Osteoporotic fractures present a significant social and economic burden, which is set to rise commensurately with the aging population. Greater understanding of the physicochemical differences between osteoporotic and normal conditions will facilitate the development of diagnostic technologies with increased performance and treatments with increased efficacy. Using coherent X-ray scattering we have evaluated a population of 108 ex vivo human bone samples comprised of non-fracture and fracture groups. Principal component fed linear discriminant analysis was used to develop a classification model to discern each condition resulting in a sensitivity and specificity of 93% and 91%, respectively. Evaluating the coherent X-ray scatter differences from each condition supports the hypothesis that a causal physicochemical change has occurred in the fracture group. This work is a critical step along the path towards developing an in vivo diagnostic tool for fracture risk prediction.

The micro-architecture of human cancellous bone from fracture neck of femur patients in relation to the structural integrity and fracture toughness of the tissue.

Osteoporosis is clinically assessed from bone mineral density measurements using dual energy X-ray absorption (DXA). However, these measurements do not always provide an accurate fracture prediction, arguably because DXA does not grapple with 'bone quality', which is a combined result of microarchitecture, texture, bone tissue properties, past loading history, material chemistry and bone physiology in reaction to disease. Studies addressing bone quality are comparatively few if one considers the potential importance of this factor. They suffer due to low number of human osteoporotic specimens, use of animal proxies and/or the lack of differentiation between confounding parameters such as gender and state of diseased bone. The present study considers bone samples donated from patients (n = 37) who suffered a femoral neck fracture and in this very well defined cohort we have produced in previous work fracture toughness measurements (FT) which quantify its ability to resist crack growth which reflects directly the structural integrity of the cancellous bone tissue. We investigated correlations between BV/TV and other microarchitectural parameters; we examined effects that may suggest differences in bone remodelling between males and females and compared the relationships with the FT properties. The data crucially has shown that TbTh, TbSp, SMI and TbN may provide a proxy or surrogate for BV/TV. Correlations between FT critical stress intensity values and microarchitecture parameters (BV/TV, BS/TV, TbN, BS/BV and SMI) for osteoporotic cancellous tissue were observed and are for the first time reported in this study. Overall, this study has not only highlighted that the fracture model based upon BMD could potentially be improved with inclusion of other microarchitecture parameters, but has also given us clear clues as to which of them are more influential in this role.

X-ray diffraction from bone employing annular and semi-annular beams.

There is a compelling need for accurate, low cost diagnostics to identify osteo-tissues that are associated with a high risk of fracture within an individual. To satisfy this requirement the quantification of bone characteristics such as 'bone quality' need to exceed that provided currently by densitometry. Bone mineral chemistry and microstructure can be determined from coherent x-ray scatter signatures of bone specimens. Therefore, if these signatures can be measured, in vivo, to an appropriate accuracy it should be possible by extending terms within a fracture risk model to improve fracture risk prediction.In this preliminary study we present an examination of a new x-ray diffraction technique that employs hollow annular and semi-annular beams to measure aspects of 'bone quality'. We present diffractograms obtained with our approach from ex vivo bone specimens at Mo Kα and W Kα energies. Primary data is parameterized to provide estimates of bone characteristics and to indicate the precision with which these can be determined.

An unusual case of Ecstasy poisoning.

We describe a case of poisoning with 3,4-methylenedioxymet-amphetamine Ecstasy that presented with all the features suggestive of a fatal outcome, including a creatinine phosphokinase level markedly higher than any previously reported. The patient, a paraplegic, was treated with dantrolene and made a full recovery.

Multimodality imaging features of hereditary multiple exostoses.

Hereditary multiple exostoses (HME) or diaphyseal aclasis is an inherited disorder characterised by the formation of multiple osteochondromas, which are cartilage-capped osseous outgrowths, and the development of associated osseous deformities. Individuals with HME may be asymptomatic or develop clinical symptoms, which prompt imaging studies. Different modalities ranging from plain radiographs to cross-sectional and nuclear medicine imaging studies can be helpful in the diagnosis and detection of complications in HME, including chondrosarcomatous transformation. We review the role and imaging features of these different modalities in HME.

Generalized skull vault thickening in association with a large arteriovenous malformation.

Generalized thickening of the skull is unusual but has a number of recognized associations such as chronic severe anaemia, Paget disease and phenytoin therapy. We report a case of generalized skull vault thickening seen in association with a large arteriovenous malformation of the brain.

The imaging of intussusception.

Intussusception is defined as the telescoping of one segment of the gastrointestinal tract into an adjacent one. It is relatively common in children and is the second most common cause of an acute abdomen in this age group. It is much less common in adults and accounts for less than 5% of cases of mechanical small bowel obstruction. Whereas the diagnosis is usually already suspected in children before imaging, it is often made unexpectedly in adults. In addition, although in children there is usually no specific underlying cause, an underlying lead point is often present in adults. Plain film radiography, barium studies and ultrasound imaging play major roles in both the diagnosis and management of this condition, and it is increasingly common for the diagnosis to be made by CT and MRI, particularly in adults. This pictorial essay reviews the imaging features that may be found in patients with bowel intussusception. As well as describing the imaging features of the more commonly used tests, we also stress the role of emerging technologies such as MRI using ultrafast half-fourier sequences with single shot turbo spin echo.