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.

[Renal transplantation in HIV-infected patients in Spain]. / Trasplante renal en pacientes con infección VIH en España.

HIV infection has experienced dramatic improvement in morbidity and mortality with the highly active antiretroviral therapy (HAART). This prompted a reevaluation of organ-solid transplantation as a treatment option for HIV-infected patients. Some trials in the United States have shown that one- and 2-year graft and patient survival is comparable to HIV-negative transplant population. In Europe the experience is still scarce. The aim of this study is to analyse the outcome and the clinical characteristics of HIV-infected patients who received kidney transplantation in Spain in the HAART era. Ten patients were transplanted in our country since 2001. Only one patient was black. The main cause of end-stage renal disease reported was glomerulonephritis. Six of the recipients were coinfected by hepatitis C virus. Inclusion criteria included undetectable HIV viral load and CD4 counts greater than 200/pL. Immunosuppression consisted of steroids, tacrolimus and mycophenolate mofetil, with antibody induction in 4 cases. The median and mean follow-up was 11 and 16.3+/-15.6 (3-46) months, respectively. One recipient lost his graft because of early renal venous thrombosis. The remaining patients are functioning graft with mean serum creatinina level of 1.5 +/- 0.5 mg/dl. Biopsy-proven acute rejection was diagnosed in 4 recipients and was reversed in all cases with antirejection treatment. The plasma HIV RNA levels have remained controlled and CD4 counts have been stable in excess of 200 cell/microL. None of patients have developed AIDS complications. Recipients receiving protease inhibitor-based HAART regimens required significant dosing modification to maintain appropriate tacrolimus levels. Our results show that renal transplantation can be a safe and effective treatment in select HIV-infected patients. Like other series, the acute rejection rate was higher than in non-HIV recipients. The reasons of this rejection incidence remain unknown.

VEGF and sVEGFR-1 in malignant pleural effusions: association with survival and pleurodesis outcomes.

VEGF is a key mediator of tumour growth and metastasis and is considered central to the formation of exudative pleural effusions. This study examined the relationship between levels of VEGF and its soluble receptor, sVEGFR-1 in the pleural fluid and plasma of patients with malignant pleural effusions and their association with pleurodesis outcomes and survival. 103 patients with malignant pleural effusions were recruited at their first presentation. Follow-up was to 6 months or death. Survival and pleurodesis outcomes were robustly ascertained. VEGF and sVEGFR-1 were measured in pleural fluid and plasma by ELISA. VEGF and sVEGFR-1 were present in significantly higher concentrations in pleural fluid than plasma. There was no significant correlation between mediators within or between sample types. There was no association between baseline pleural fluid VEGF or sVEGFR-1 levels and pleurodesis failure. In both sample types, survival was inversely associated with sVEGFR-1 and within the non-small cell lung cancer sub-group (n=26), a highly significant association between increased pleural fluid VEGF and sVEGFR-1 and reduced survival was demonstrated (p=0.02 and 0.004 respectively). In conclusion, we have shown for the first time that sVEGFR-1 can be reproducibly measured in pleural fluid from malignant effusions. High levels at presentation in those with non-small cell carcinoma are strongly associated with poor outcomes.

Low-light imaging technology in the life sciences.

Photon imaging is an increasingly important technique for the measurement and analysis of chemiluminescence and bioluminescence. New high-performance low-light level imaging systems have recently become available for the life sciences. These systems use advances in camcera design and digital image processing and are now being used for a wide range of luminescence applications. They offer good sensitivity for photon detection and large dynamic range, and are suitable for quantitative analysis. This is achieved using a range of software techniques including image arithmetic, histogramming or summing regions of interest, feature extraction and multiple image processing for kinetics or assay screening. Improvements in image-processing hardware and software have increased the usefulness of these systems in the biosciences. Low-light imaging is a rapid and non-invasive method for the sensitive detection and analysis of luminescent assays. As such it offers a powerful and sensitive tool for investigating processes, both at the cellular level (luc and lux reporter genes, intracellular signalling) and for measurement of macro samples (immunoassays, gels and blots, tissue sections).

CCD imaging of luciferase gene expression in single mammalian cells.

Quantitative and sensitive imaging of chemiluminescence, bioluminescence and fluorescence emissions is emerging as an increasingly important technique for a range of biomedical applications (Hooper et al., 1990). A brief review of low-light-level imaging is presented, with particular reference to charge-coupled devices (CCD). Detectors for sensitive imaging are described and compared, including various CCDs and photon-counting devices. Image analysis techniques based on digital image processing, may be applied to quantify luminescent processes with these detectors. Images of luciferase gene expression in single mammalian cells have been obtained using a particular high-sensitivity intensified CCD camera. The method is illustrated using cell monolayers infected with recombinant vaccinia virus encoding the firefly luciferase, luc gene (Rodriguez et al., 1988). The CCD camera has been used to detect luciferase expression in single, recombinant infected cells amongst over one million non-infected cells. The rapid detection of luciferase-expressing viruses may be used for the selection of virus deletion mutants into which the luciferase gene has been cloned at specific sites. This is particularly useful in the case of viruses such as cytomegalovirus which have slow replication cycles. This direct imaging technique is simple and versatile. It offers a rapid, non-invasive method for the sensitive detection of luciferase activity in single, luciferase-expressing cells. One can envisage the use of luciferase as a sensitive and convenient co-selection marker gene in the analysis of both gene expression and protein function. These methods offer tremendous potential in the fields of molecular and cellular biology.