Rachel Benamore

Post-mortem imaging as an alternative to autopsy in the diagnosis of adult deaths: a validation study

Summary Background Public objection to autopsy has led to a search for minimally invasive alternatives. Imaging has potential, but its accuracy is unknown. We aimed to identify the accuracy of post-mortem CT and MRI compared with full autopsy in a large series of adult deaths. Methods This study was undertaken at two UK centres in Manchester and Oxford between April, 2006, and November, 2008. We used whole-body CT and MRI followed by full autopsy to investigate a series of adult deaths that were reported to the coroner. CT and MRI scans were reported independently, each by two radiologists who were masked to the autopsy findings. All four radiologists then produced a consensus report based on both techniques, recorded their confidence in cause of death, and identified whether autopsy was needed. Findings We assessed 182 unselected cases. The major discrepancy rate between cause of death identified by radiology and autopsy was 32% (95% CI 26–40) for CT, 43% (36–50) for MRI, and 30% (24–37) for the consensus radiology report; 10% (3–17) lower for CT than for MRI. Radiologists indicated that autopsy was not needed in 62 (34%; 95% CI 28–41) of 182 cases for CT reports, 76 (42%; 35–49) of 182 cases for MRI reports, and 88 (48%; 41–56) of 182 cases for consensus reports. Of these cases, the major discrepancy rate compared with autopsy was 16% (95% CI 9–27), 21% (13–32), and 16% (10–25), respectively, which is significantly lower (p<0·0001) than for cases with no definite cause of death. The most common imaging errors in identification of cause of death were ischaemic heart disease (n=27), pulmonary embolism (11), pneumonia (13), and intra-abdominal lesions (16). Interpretation We found that, compared with traditional autopsy, CT was a more accurate imaging technique than MRI for providing a cause of death. The error rate when radiologists provided a confident cause of death was similar to that for clinical death certificates, and could therefore be acceptable for medicolegal purposes. However, common causes of sudden death are frequently missed on CT and MRI, and, unless these weaknesses are addressed, systematic errors in mortality statistics would result if imaging were to replace conventional autopsy. Funding Policy Research Programme, Department of Health, UK.

Diagnosis of coronary artery disease using minimally invasive autopsy: evaluation of a novel method of post-mortem coronary CT angiography

Diagnosis of coronary artery disease using minimally invasive autopsy: evaluation of a novel method of post-mortem coronary CT angiography I.S.D. Roberts *, R.E. Benamore , C. Peebles , C. Roobottom, Z.C. Traill b Department of Cellular Pathology, John Radcliffe Hospital, Oxford, UK Department of Radiology, Churchill Hospital, Oxford, UK Department of Radiology, Southampton General Hospital, Southampton, UK d Peninsula Medical School, University of Plymouth, Plymouth, UK

Diagnostic accuracy, safety and utilisation of respiratory physician-delivered thoracic ultrasound

Background Thoracic ultrasound-guided pleural procedures are associated with fewer adverse events than ‘blind’ procedures for patients with pleural effusion. Ultrasound is increasingly practised by respiratory physicians but there has been no prospective assessment of its safety and diagnostic accuracy when delivered by respiratory physicians. Methods The activity level, safety and diagnostic accuracy of thoracic ultrasound delivered by respiratory physicians were prospectively assessed. Diagnostic accuracy was assessed using a stepwise pragmatic approach (recording if pleural fluid was obtained or effusion was present on another radiological modality). In the absence of the above, ultrasound clips were reviewed by a blinded radiologist. The number of ultrasounds referred to radiologists and adverse events within 1u2005week were recorded. The complication rate was compared with the published literature. Results 960 ultrasound scans occurred over a 3u2005year period. The activity of the service increased over time, as a result of increased use of interventional ultrasound. The referral rate to radiology remained constant over the study period (mean proportion 4.0%). Physician-delivered ultrasound correctly identified the presence/absence of pleural fluid in 951 of 955 evaluable scans (99.6% CI 98.9% to 99.9%). The major complication rate was 3/558=0.5% (95% CI 0.1% to 1.6%), which compared favourably with the identified published literature. Conclusion Respiratory physician-delivered thoracic ultrasound appears to be safe and effective in the diagnosis/intervention of pleural effusion, and is associated with a major complication rate comparable with that of published studies. Continued liaison with the radiology service has here been demonstrated as a requirement for a physician-based service.

The idiopathic interstitial pneumonias: understanding key radiological features

Many radiologists find it challenging to distinguish between the different interstitial idiopathic pneumonias (IIPs). The British Thoracic Society guidelines on interstitial lung disease (2008) recommend the formation of multidisciplinary meetings, with diagnoses made by combined radiological, pathological, and clinical findings. This review focuses on understanding typical and atypical radiological features on high-resolution computed tomography between the different IIPs, to help the radiologist determine when a confident diagnosis can be made and how to deal with uncertainty.

High risk medicolegal autopsies: is a full postmortem examination necessary?

Aims Aiming to reduce the numbers of high risk autopsies, we use a minimally invasive approach. HIV/hepatitis C virus (HCV)-positive coronial referrals, mainly intravenous drug abusers, have full autopsy only if external examination, toxicology and/or postmortem CT scan do not provide the cause of death. In this study, we review and validate this protocol. Methods and results 62 HIV/HCV-positive subjects were investigated. All had external examination, 59 toxicology and 24 CT. In 42/62, this minimally invasive approach provided a cause of death. Invasive autopsy was required in 20/62, CT/toxicology being inconclusive, giving a potential rather than definite cause of death. Autopsy findings provided the cause of death in 6/20; in the remainder, a negative autopsy allowed more weight to be given to toxicological results previously regarded as inconclusive. In order to validate selection of cases for invasive autopsy using history, external examination and toxicology, a separate group of 57 non-infectious full autopsies were analysed. These were consecutive cases in which there was a history that suggested drug abuse. A review pathologist, provided only with clinical summary, external findings and toxicology, formulated a cause of death. This formulation was compared with the original cause of death, based on full autopsy. The review pathologist correctly identified a drug-related death or requirement for full autopsy in 56/57 cases. In one case, diagnosed as cocaine toxicity by the review pathologist, autopsy additionally revealed subarachnoid haemorrhage and Berry aneurysm. Conclusions These findings support the use of minimally invasive techniques in high risk autopsies, which result in a two-thirds reduction in full postmortems.

CTAS: a CT score to quantify disease activity in pulmonary sarcoidosis

Background A major gap in the management of sarcoidosis is the lack of accessible and objective methods to measure disease activity. Since 90% of patients have pulmonary involvement, we explored if a disease activity score based on thoracic CT scans could address this clinical issue. Methods High-resolution CT scans from 100 consecutive patients with sarcoidosis at a regional sarcoidosis service were scored for extent of CT abnormalities known to relate to granuloma or lymphocytic infiltration from published CT-pathological studies. These individual abnormality scores were then correlated against serum ACE, sIL-2R and change in FVC to identify CT abnormalities that reflect contemporaneous disease activity. The sum of these scores, or CT Activity Score (CTAS), was then validated against FVC response to treatment. Findings CT extent scores for nodularity, ground-glass opacification, interlobular septal thickening and consolidation correlated significantly with at least one of the disease activity parameters and were used to form CTAS. CTAS was found to predict FVC response to treatment at 1 year and was highly reproducible between radiologists. An abbreviated CTAS (aCTAS), constructed from presence or absence of the four CT abnormalities, also showed significant correlation with FVC response to treatment. CTAS and aCTAS also correlated with response to treatment in the fibrotic subgroup. Interpretation CTAS provides a concept for an objective and reproducible CT scoring method to quantify disease activity in sarcoidosis. The score can potentially be used to stratify patients according to disease activity, determine response to treatment and establish if fibrotic sarcoidosis is active.

A 50-Year-Old Man With a Cough and Painful Chest Wall Mass

A 50-year-old man presented with a 1-week history of a painful hard lump above his right nipple. He attended the Accident and Emergency Department when the lump suddenly grew bigger and more painful. He had been unwell for 4 weeks, with a productive cough, loss of appetite, and weight loss. He was normally well, and there was no relevant medical history. He smoked 50 cigarettes a day and drank excessive quantities of alcohol each week. He worked in a warehouse and had not traveled outside the United Kingdom. On examination, he was comfortable at rest and did not look unwell. He was apyrexial, and oxygen saturations were 98% on room air. His BP was 110/70 mm Hg, and pulse rate was 90 beats/min. There was a large, hard, tender mass above his right nipple associated with some bruis ing of the skin. On auscultation of his chest, a few crackles were audible. His dentition was poor. The remainder of his physical examination was normal.

A proposed new imaging pathway for patients with suspected lung cancer

AIMSnPET-CT scans are routinely performed in patients with lung cancer after investigation by chest x-ray (CXR) and CT scan, when these have demonstrated potentially curable disease. If the majority of patients with lung cancer potentially suitable for curative treatment could be identified earlier in the diagnostic pathway on the basis of CXR findings they could be referred for PET-CT imaging without a prior CT scan. We investigated the clinical and financial implications of adopting such a strategy.nnnMATERIALS AND METHODSnThe details of 1187 patients referred with suspected lung cancer between July 2006 and August 2009 were analysed. The initial CXR and subsequent imaging of patients fit for curative treatment (Performance Status 0/1, FEV1 > 1.0) were reviewed (n = 251). The clinical and financial implications of referring patients for first line PET-CT if deemed potentially curable based on CXR findings were assessed.nnnRESULTSn107 of 1187 patients had potentially curable lung cancer on PS, lung function, CT and PET-CT. 96 of these 107 patients (90%) were correctly identified on CXR. 149 patients overall were diagnosed as potentially curable on CXR. Referring suitable patients for an immediate PET-CT scan resulted in a reduction in the time to complete staging investigations.nnnCONCLUSIONSnEarly PET-CT scanning for patients with suspected lung cancer, potentially suitable for curative therapy could result in more efficient staging with little additional cost.

Leptomeningeal carcinomatosis in non-small-cell lung cancer: initial response to erlotinib followed by relapse despite continuing radiological resolution of disease

A 60-year-old male was diagnosed with T3, N3, M1b epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma. Five months later he developed significant headaches, weakness and numbness of the left leg, and unsteadiness of gait. Magnetic resonance imaging (MRI) brain demonstrated subtle gyral enhancement indicative of early leptomeningeal infiltration. He was commenced on second-line erlotinib which improved his lower limb symptoms. Three months later he developed increased urinary frequency and redeveloped leg symptoms. MRI brain showed improvement in the gyral enhancement. Four weeks later, the patient developed new onset confusion and decrease in mobility. Examination of the cerebrospinal fluid (CSF) demonstrated leptomeningeal carcinomatosis. This case demonstrates radiological and clinical response of leptomeningeal disease to erlotinib in EGFR mutant lung cancer with subsequent clinical relapse despite continued radiological resolution of leptomeningeal disease. This suggests that CSF examination should be considered when monitoring leptomeningeal disease response following treatment as the disease can be undetectable on repeat radiological imaging.

S96 A combination score of raised sACE, lymphopenia and hypergammaglobulinaemia correlates with active disease on thoracic CT scan of patients with pulmonary sarcoidosis

Introduction Clinical decisions about treatment in pulmonary sarcoidosis, and phenotyping research studies are hampered by inability to objectively measure disease activity. We reviewed 120 consecutive patients from our Sarcoidosis Clinic and observed that raised sACE, immunoglobulin and/or presence of lymphopenia were associated with clinical decisions to change treatment. We question if these markers could be combined to form an objective measure of disease activity in pulmonary sarcoidosis. Methods As there is no ‘gold standard’ for disease activity in sarcoidosis, we used thoracic CT scan to reflect disease activity on the basis that ground glass opacity, nodularity, consolidation, interlobular septal thickening and conglomeration reflect T cell alveolit is, cellular infiltrate and granulomatous deposits1–2. Using Fleischner Society definition of terms3, we designed a scoring system (“CT activity score; CTAS”) to quantify this, and examined if a composite clinical score (“clinical activity score; CAS”; IgG>13 g/l= 1, Lymphocytes <1x10^9/l = 1, sACE <55 U/l = 0, 56–100 U/l = 1, >100 U/l = 2) correlated with changes in CTAS. An enhanced CAS incorporating extent of defined CXR abnormalities was also examined. We collected data from 100 consecutive patients diagnosed according to WASOG/ATS criteria (with histological confirmation), who had thoracic CT scan, CXR and blood parameters within three months of each other. Two radiologists scored the CT scans blindly. We present results for the first 20 cases. Results CTAS score (maximum possible 81) in our patients ranged from 0 to 40; CAS from 0–4 (maximum 5); when including CXR score - from 1–12 (maximum 12). We found a strong correlation between CAS and CTAS (Figure 1). No correlation was observed between the CTAS and FVC, TLCO or KCO, supporting the premise that severe irreversible functional loss can be inactive. Conclusions A combination score incorporating lymphopenia, sACE levels, and hypergammaglobulinemia is strongly correlated with CT quantification of disease activity in pulmonary sarcoidosis. Addition of CXR scoring improved the correlation. This score could be used as an indicator of disease activity to aid clinical decisions on treatment, and paves the way for collation of larger numbers and longitudinal studies to further validate the tool. References Nishimura K et al. Radiology 1993. Oberstein A et al. Sarc Vasc Diffuse Lung Dis 1997. Hansell DM et al. Radiology 2008. Abstract S96 Graph 1