Susan Charman

Assessment of survival benefit after lung transplantation by patient diagnosis

BACKGROUND Lung transplantation has become an established procedure for treating patients with endstage lung disease, resulting in broadening criteria for recipient selection. The survival benefit for some patient groups has yet to be established. METHODS We reviewed 653 patients accepted for lung transplantation at our center. Patients were categorized into 6 diagnosis groups: cystic fibrosis (174), obstructive lung disease (163), pulmonary fibrosis (100), Eisenmengers syndrome (76), pulmonary hypertension (68), bronchiectasis (51), and other (21). Using Cox regression, we estimated the time at which early operative risk of death fell below pre-operative risk levels (crossover point) and the point at which early high post-operative risk was offset by later low risk (equity point). The relative benefits of single lung vs double lung/heart-lung transplantation were assessed for patients with obstructive lung disease and pulmonary fibrosis. RESULTS Post-operative risk of death fell below pre-operative risk levels for all diagnosis groups, indicating a survival advantage. The equity point was achieved for all distinct diagnosis groups (except Eisenmengers); this survival benefit was significant for patients with obstructive lung disease, cystic fibrosis, and pulmonary hypertension. Single lung vs double lung/ heart-lung comparisons showed no significant difference in survival benefit. CONCLUSION All survival benefit patient groups achieve after lung transplantation, with the exception of patients with Eisenmengers syndrome, who may have prolonged survival while listed. Differences in survival benefit between single lung and double or heart-lung transplantation are not significant for patients with obstructive lung disease or pulmonary fibrosis.

Transperineal Magnetic Resonance Image Targeted Prostate Biopsy Versus Transperineal Template Prostate Biopsy in the Detection of Clinically Significant Prostate Cancer.

PURPOSE Multiparametric magnetic resonance imaging can be used to guide prostate biopsy by targeting biopsies to areas in the prostate at high risk for cancer. We compared the detection of clinically significant and insignificant cancer by transperineal magnetic resonance imaging targeted biopsy and transperineal template guided prostate biopsy. MATERIALS AND METHODS A total of 182 men with a lesion suspicious for cancer on multiparametric magnetic resonance imaging underwent transperineal magnetic resonance imaging targeted biopsy using a cognitive registration technique, followed by systematic transperineal template guided prostate biopsy. The primary outcome was the detection rate of clinically significant prostate cancer. Clinical significance was defined using maximum cancer core length 4 mm or greater and/or Gleason grade 3 + 4 or greater (University College London definition 2). We secondarily evaluated other commonly used thresholds of clinically significant disease, including maximum cancer core length 6 mm or greater and/or Gleason grade 4 + 3 or greater, maximum cancer core length 3 mm or greater and/or Gleason grade 3 + 4 or greater, and maximum cancer core length 2 or greater mm and/or Gleason grade 3 + 4 or greater. Strategies were statistically compared with the McNemar test. RESULTS Mean ± SD patient age was 63.3 ± 7.2 years. Median prostate specific antigen was 6.7 ng/ml (IQR 4.7-10.0). Clinically significant cancer was detected by magnetic resonance imaging targeted biopsy and template guided prostate biopsy in 103 (57%) and 113 of the 182 men (62%) (p = 0.174), and clinically insignificant cancer was detected in 17 (9.3%) and 31 (17.0%), respectively (p = 0.024). CONCLUSIONS Prostate biopsy targeted to suspicious lesions on multiparametric magnetic resonance imaging has encouraging rates of detection of clinically significant cancer while also decreasing the detection rate of clinically insignificant cancer. This is achieved with fewer biopsy cores than for systematic template guided biopsy. Further prospective, multicenter, comparative trials of the performance of targeting strategies are needed to consider magnetic resonance imaging targeted biopsy an alternative to conventional systematic biopsy.

Comparison of shuttle walk with measured peak oxygen consumption in patients with operable lung cancer

Background: The relationship between the shuttle walk test and peak oxygen consumption in patients with lung cancer has not previously been reported. A study was undertaken to examine this relationship in patients referred for lung cancer surgery to test the hypothesis that the shuttle walk test would be useful in this clinical setting. Methods: 125 consecutive patients with potentially operable lung cancer were prospectively recruited. Each performed same day shuttle walking and treadmill walking tests. Results: Shuttle walk distances ranged from 104 m to 1020 m and peak oxygen consumption ranged from 9 to 35 ml/kg/min. The shuttle walk distance significantly correlated with peak oxygen consumption (r = 0.67, p<0.001). All 55 patients who achieved more than 400 m on the shuttle test had a peak oxygen consumption of at least 15 ml/kg/min. Seventy of 125 patients failed to achieve 400 m on the shuttle walk test; in 22 of these the peak oxygen consumption was less than 15 ml/kg/min. Nine of 17 patients who achieved less than 250 m had a peak oxygen consumption of more than 15 ml/kg/min. Conclusion: The shuttle walk is a useful exercise test to assess potentially operable lung cancer patients with borderline lung function. However, it tends to underestimate exercise capacity at the lower range compared with peak oxygen consumption. Our data suggest that patients achieving 400 m on the shuttle walk test do not require formal measurement of oxygen consumption. In patients failing to achieve this distance we recommend assessment of peak oxygen consumption, particularly in those unable to walk 250 m, because a considerable proportion would still qualify for surgery as they had an acceptable peak oxygen consumption.

The accuracy of multiparametric MRI in men with negative biopsy and elevated PSA level--can it rule out clinically significant prostate cancer?

Purpose To assess the performance of multiparametric magnetic resonance imaging (mp-MRI) in patients with previous negative transrectal ultrasound (TRUS) guided prostate biopsy. Materials and methods Fifty-four patients with at least 1 previous negative TRUS prostate biopsy underwent mp-MRI in the form of T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging. This was followed by transperineal template systematic prostate biopsies. Analysis was done based on 2 sectors per prostate, right and left (108 sectors out of 54 prostates). mp-MRI was scored using an ordinal scale 1 to 5 based on the suspicion of the presence of clinically significant disease. We used 6 different definitions for clinically significant disease and tested the performance of mp-MRI at each single definition. Results Median age was 64 (range, 39–75), median PSA level was 10 (range, 2–23), and median number of biopsies was 45 (range, 21–137). Cancer of any volume and any grade was detected in 34 of 54 (63%) patients. mp-MRI accuracy at detection of clinically significant cancer using University College London (UCL) definition 2 (any Gleason score of 4 or maximum cancer core length of ≥4 mm or both) showed sensitivity of 76%, specificity of 42%, positive predictive value of 38%, and negative predictive value of 79%. For a different definition of significant tumor (UCL definition 1; dominant Gleason score 4 or maximum cancer core length ≥6 mm or both), the sensitivity was 90%, specificity 42%, positive predictive value 26%, and negative predictive value 95%. Conclusions mp-MRI showed good performance at both detection and ruling out clinically significant disease, according to the definition used. mp-MRI can then be used as a triage test in the population with persistently elevated or rising PSA levels to select patients that can avoid unnecessary prostate biopsy.

Performance of multiparametric MRI in men at risk of prostate cancer before the first biopsy: a paired validating cohort study using template prostate mapping biopsies as the reference standard.

Background:Multiparametric magnetic resonance imaging (mpMRI) has the potential to serve as a non-invasive triage test for men at risk of prostate cancer. Our objective was to determine the performance characteristics of mpMRI in men at risk before the first biopsy using 5 mm template prostate mapping (TPM) as the reference standard.Methods:One hundred and twenty-nine consecutive men with clinical suspicion of prostate cancer, who had no prior biopsy, underwent mpMRI (T1/T2-weighted, diffusion-weighting, dynamic contrast enhancement) followed by TPM. The primary analysis used were as follows: (a) radiological scores of suspicion of ⩾3 attributed from a five-point ordinal scale, (b) a target condition on TPM of any Gleason pattern ⩾4 and/or a maximum cancer core length of ⩾4 mm and (c) two sectors of analysis per prostate (right and left prostate halves). Secondary analyses evaluated the impact of changing the mpMRI score threshold to ⩾4 and varying the target definition for clinical significance.Results:One hundred and forty-one out of 258 (55%) sectors of analysis showed ‘any cancer’ and 77/258 (30%) had the target histological condition for the purpose of deriving the primary outcome. Median (with range) for age, PSA, gland volume and number of biopsies taken were 62 years (41–82), 5.8 ng ml−1 (1.2–20), 40 ml (16–137) and 41 cores (20–93), respectively. For the primary outcome sensitivity, specificity, positive and negative predictive values and area under the receiver-operating curve (with 95% confidence intervals) were 94% (88–99%), 23% (17–29%), 34% (28–40%), 89% (79–98%) and 0.72 (0.65–0.79), respectively.Conclusions:MpMRI demonstrated encouraging diagnostic performance characteristics in detecting and ruling out clinically significant prostate cancer in men at risk, who were biopsy naive.

Neointimal smooth muscle cells in human cardiac allograft coronary artery vasculopathy are of donor origin.

BACKGROUND Transplant coronary artery vasculopathy (CAV) is a fibro-proliferative process that leads to lumen occlusion and cardiac failure. Current theories suggest that the process evolves over time in response to inflammation and proliferation of donor derived medial smooth muscle cells (SMC). Animal models of cardiac transplantation have suggested that the neointima is formed by recipient derived circulating progenitor cells. The aim of this investigation is to determine the origin of the neointimal SMC within epicardial coronary arteries from human cardiac allografts by using sex mis-matched recipients and donors, and a Y specific chromosome probe. METHODS Coronary arteries from 14 patients previously assessed histologically to have CAV were analyzed-eight male recipients of female donor organs, 2 female-to-female, and 4 male-to-male transplants. A double immunocytochemistry and in-situ hybridization technique using a Y chromosome DNA probe and either antibodies to smooth muscle actin or Ham-56 a macrophage marker were employed. RESULTS No Y chromosome bodies could be identified in the female-to-female allografts. In the 4 male donor and male recipient cases, cells positive for the Y chromosome probe were identified. In sex mis-matched transplants, female to male, inflammatory cells marked with Ham-56 were also positive for Y chromosome probe. Flattened cells positive for Y chromosome were observed just beneath the endothelial surface. When double stained, these were identified as infiltrating macrophages. No double staining smooth muscle cells and Y chromosome positive cells could be identified within the neointima. CONCLUSIONS This study confirms the source of SMC of the neointima of CAV lesions from epicardial coronary arteries to be of donor origin. In contrast to animal models, circulating progenitor cells do not appear to play a role within the neointima of human transplant CAV.

Swan-Ganz catheter assessment of donor hearts: outcome of organs with borderline hemodynamics

BACKGROUND High-dosage inotrope use or periods of hypotension may cause rejection of donor hearts for transplantation. At our institution, we do not refuse potential donor organs based on these criteria alone before Swan-Ganz catheter (SGC) assessment. In this study, we evaluate the role of the SGC in donor heart resuscitation and selection and assess the outcome of using borderline organs. METHODS We retrospectively analyzed 129 donors assessed between 1996 and 1999, all with complete hemodynamic data. Two sets of SGC measurements were analyzed: one set from the initial assessments, and one set from assessments made just before organ harvesting. The physiologic targets were mean blood pressure >60 mm Hg, central venous pressure <12 mm Hg, pulmonary capillary wedge pressure <12 mm Hg, left ventricular stroke work index >15 x g.m/m(2), and use of only one inotrope. A poorly functioning heart was defined as an organ failing on 2 or more of these criteria. Hemodynamic categories were defined as A, good function throughout assessment; B, sub-optimal function and then improvement; and C, decreasing or poor function throughout. We have a policy to avoid allocating sub-optimal organs to high-risk recipients. RESULTS One hundred fourteen donor hearts went on to be transplanted: 75 as orthotopic hearts and 39 as heart-lungs (5 of these were heart, lung, and liver transplantations, not reported further here). Of the 75 donor hearts used for heart transplantations, 53 were from Category A, 9 were from Category B, and 13 were from Category C. Of the donor hearts used for the 34 heart-lung transplantations 16 were from Category A, 10 were from Category B, and 8 were from Category C. Three patients died of donor organ failure: 1 of the corresponding hearts was from Category B, and 2 were from Category C. When comparing separately the outcome of the 2 procedures, we found no significant difference in duration of stay in the intensive care unit, requirement for mechanical support, 30-day mortality, or 1-year survival among patients with hearts from Categories A, B, and C. Ischemic time was the only significant risk factor for death (p = 0.006). CONCLUSIONS Use of organs from Categories B and C permitted expansion of the donor pool without compromising short-term outcome. However, these organs should be used with caution in combination with other risk factors, in particular long ischemic time.

Outcomes of transplantation of livers from donation after circulatory death donors in the UK: a cohort study

Objectives Outcomes of liver transplantations from donation after circulatory death (DCD) donors may be inferior to those achieved with donation after brain death (DBD) donors. The impact of using DCD donors is likely to depend on specific national practices. We compared risk-adjusted graft loss and recipient mortality after transplantation of DCD and DBD livers in the UK. Design Prospective cohort study. Multivariable Cox regression and propensity score matching were used to estimate risk-adjusted HR. Setting 7 liver transplant centres in the National Health Service (NHS) hospitals in England and Scotland. Participants Adults who received a first elective liver transplant between January 2005 and December 2010 who were identified in the UK Liver Transplant Audit. Interventions Transplantation of DCD and DBD livers. Outcomes Graft loss and recipient mortality. Results In total, 2572 liver transplants were identified with 352 (14%) from DCD donors. 3-year graft loss (95% CI) was higher with DCD livers (27.3%, 21.8% to 33.9%) than with DBD livers (18.2%, 16.4% to 20.2%). After adjustment with regression, HR for graft loss was 2.3 (1.7 to 3.0). Similarly, 3-year mortality was higher with DCD livers (19.4%, 14.5% to 25.6%) than with DBD livers (14.1%, 12.5% to 16.0%) with an adjusted HR of 2.0 (1.4 to 2.8). Propensity score matching gave similar results. Centre-specific adjusted HRs for graft loss and recipient mortality seemed to differ among transplant centres, although statistical evidence is weak (p value for interaction 0.08 and 0.24, respectively). Conclusions Graft loss and recipient mortality were about twice as high with DCD livers as with DBD livers in the UK. Outcomes after DCD liver transplantation may vary between centres. These results should inform policies for the use of DCD livers.

The effect of aspirin and low-molecular-weight heparin on venous thromboembolism after hip replacement: A non-randomised comparison from information in the National Joint Registry

We compared thromboembolic events, major haemorrhage and death after total hip replacement in patients receiving either aspirin or low-molecular-weight heparin (LMWH). We analysed data from the National Joint Registry for England and Wales linked to an administrative database of hospital admissions in the English National Health Service. A total of 108,584 patients operated on between April 2003 and September 2008 were included and followed up for 90 days. Multivariable risk modelling and propensity score matching were used to estimate odds ratios (OR) adjusted for baseline risk factors. An OR < 1 indicates that rates are lower with LMWH than with aspirin. In all, 21.1% of patients were prescribed aspirin and 78.9% LMWH. Without adjustment, we found no statistically significant differences. The rate of pulmonary embolism was 0.68% in both groups and 90-day mortality was 0.65% with aspirin and 0.61% with LMWH (OR 0.93; 95% CI 0.77 to 1.11). With risk adjustment, the difference in mortality increased (OR 0.84; 95% CI 0.69 to 1.01). With propensity score matching the mortality difference increased even further to 0.65% with aspirin and 0.51% with LMWH (OR 0.77; 95% CI 0.61 to 0.98). These results should be considered when the conflicting recommendations of existing guidelines for thromboprophylaxis after hip replacement are being addressed.

The PICTURE study — Prostate Imaging (multi-parametric MRI and Prostate HistoScanning™) Compared to Transperineal Ultrasound guided biopsy for significant prostate cancer Risk Evaluation

OBJECTIVE The primary objective of the PICTURE study is to assess the negative predictive value of multi-parametric MRI (mp-MRI) and Prostate HistoScanning™ (PHS) in ruling-out clinically significant prostate cancer. PATIENTS AND METHODS PICTURE is a prospective diagnostic validating cohort study conforming to level 1 evidence. PICTURE will assess the diagnostic performance of multi-parametric Magnetic Resonance Imaging (mp-MRI) and Prostate HistoScanning™ (PHS) ultrasound. PICTURE will involve validating both index tests against a reference test, transperineal Template Prostate Mapping (TPM) biopsies, which can be applied in all men under evaluation. Men will be blinded to the index test results and both index tests will be reported prospectively prior to the biopsies being taken to ensure reporter blinding. Paired analysis of each of the index tests to the reference test will be done at patient level. Those men with an imaging lesion will undergo targeted biopsies to assess the clinical utility of sampling only suspicious areas. The study is powered to assess the negative predictive value of these imaging modalities in ruling-out clinically significant prostate cancer. DISCUSSION The PICTURE study aims to assess the performance characteristics of two imaging modalities (mp-MRI and Prostate HistoScanning) for their utility in the prostate cancer pathway. PICTURE aims to identify if either imaging test may be useful for ruling out clinically significant disease in men under investigation, and also to examine if either imaging modality is useful for the detection of disease. Recruitment is underway and expected to complete in 2014.