Digital Pathology Transformation in a Supraregional Germ Cell Tumour Network.

BACKGROUND: In this article we share our experience of creating a digital pathology (DP) supraregional germ cell tumour service, including full digitisation of the central laboratory. METHODS: DP infrastructure (Philips) was deployed across our hospital network to allow full central digitisation with partial digitisation of two peripheral sites in the supraregional testis germ cell tumour network. We used a survey-based approach to capture the quantitative and qualitative experiences of the multidisciplinary teams involved. RESULTS: The deployment enabled case sharing for the purposes of diagnostic reporting, second opinion, and supraregional review. DP was seen as a positive step forward for the departments involved, and for the wider germ cell tumour network, and was completed without significant issues. Whilst there were challenges, the transition to DP was regarded as worthwhile, and examples of benefits to patients are already recognised. CONCLUSION: Pathology networks, including highly specialised services, such as in this study, are ideally suited to be digitised. We highlight many of the benefits but also the challenges that must be overcome for such clinical transformation. Overall, from the survey, the change was seen as universally positive for our service and highlights the importance of engagement of the whole team to achieve success.

Use of post-mortem computed tomography during the COVID-19 pandemic.

Post mortem computed tomography (PMCT) is widely used in England and Wales to supplement or replace traditional invasive Coroner's autopsy. Using PMCT and coronary angiography, the cause of death can be determined without invasive examination in approximately 70% of cases, assuming a typical Coroner's autopsy case mix. Coroner's autopsy services continued during the COVID-19 pandemic and have identified deaths resulting from COVID-19 undiagnosed in life. In some areas of England, PMCT was used to replace traditional autopsy due to concerns over infection risk to mortuary staff associated with invasive autopsy. Health and safety concerns also resulted in changes to post mortem scanning protocols. PMCT has been used to identify potential COVID-19 deaths and assist in the selection of cases for viral studies. There is typically bilateral ground-glass opacities and consolidation within the lungs on CT; although these changes are not specific for COVID-19, the diagnosis can be confirmed with post mortem nose and throat swabs.

A prospective study on the diagnostic pathway of patients with stage IIIC-IV ovarian cancer: Exploratory laparoscopy (EXL) + CT scan VS. CT scan.

OBJECTIVE: To compare the diagnostic power of CT scan to a combination of exploratory laparoscopy (EXL) and CT scan in patients with stage IIIC-IV Ovarian Cancer (OC) by anatomic areas. To investigate if adding EXL to CT can reduce unnecessary laparotomy. METHODS: In the period 2009-2017, 350 consecutive patients with FIGO Stage IIIC-IV OC underwent CT and EXL prior to Visceral-Peritoneal debulking (VPD) and were included in the study. Radiologist and surgeons filled an ad-hoc form to report CT scan and EXL of eleven key anatomic areas. The decision to proceed to EXL was based on the CT scan and the decision to proceed to laparotomy (LPT) on CT and EXL. Setting LPT findings as the gold standard, positive and negative predictive value (PPV/NPV), sensitivity, specificity, and accuracy of CT, EXL and CT + EXL were calculated. We broke down the diagnostic outcomes by anatomic areas and determined the rate of unnecessary laparotomy avoided with the findings of EXL. RESULTS: Median time for the EXL was 14 min (SD +/- 3). No complication related to EXL occurred. At EXL, 325 out of 350 patients (93%) proceeded to LPT and 25 patients (7.1%) did not because of exclusion criteria. In 307 patients out of 325 (94.4%) EXL was followed by VPD. Eighteen patients had exclusion criteria found at LPT and had no VPD. EXL reduced the rate of unnecessary/futile laparotomy from 12.2% to 5.1%. CT + EXL showed a significantly higher sensitivity for all anatomic areas except for the lymph nodes. Specificity was not significantly improved. PPV was significantly improved for small bowel, porta hepatis and stomach. NPV displayed a statistical improvement in all anatomic areas except lymph nodes, stomach, and liver. CONCLUSION: The combination CT + EXL has a higher diagnostic power than CT alone, particularly on diaphragm, small bowel serosa and mesentery. The rate of unnecessary laparotomy decreased by almost 60%.

Peripheral CD8+ T cell characteristics associated with durable responses to immune checkpoint blockade in patients with metastatic melanoma.

Immune checkpoint blockade (ICB) of PD-1 and CTLA-4 to treat metastatic melanoma (MM) has variable therapeutic benefit. To explore this in peripheral samples, we characterized CD8+ T cell gene expression across a cohort of patients with MM receiving anti-PD-1 alone (sICB) or in combination with anti-CTLA-4 (cICB). Whereas CD8+ transcriptional responses to sICB and cICB involve a shared gene set, the magnitude of cICB response is over fourfold greater, with preferential induction of mitosis- and interferon-related genes. Early samples from patients with durable clinical benefit demonstrated overexpression of T cell receptor-encoding genes. By mapping T cell receptor clonality, we find that responding patients have more large clones (those occupying >0.5% of repertoire) post-treatment than non-responding patients or controls, and this correlates with effector memory T cell percentage. Single-cell RNA-sequencing of eight post-treatment samples demonstrates that large clones overexpress genes implicated in cytotoxicity and characteristic of effector memory T cells, including CCL4, GNLY and NKG7. The 6-month clinical response to ICB in patients with MM is associated with the large CD8+ T cell clone count 21 d after treatment and agnostic to clonal specificity, suggesting that post-ICB peripheral CD8+ clonality can provide information regarding long-term treatment response and, potentially, facilitate treatment stratification.

Diagnostic flow-chart to identify bowel involvement in patients with stage IIIC-IV ovarian cancer: Can laparoscopy improve the accuracy of CT scan?

OBJECTIVE: This study investigates the diagnostic power of CT scan combined with exploratory laparoscopy (EXL) at identifying large bowel involvement in patients with stage IIIC-IV primary Epithelial Ovarian Cancer (EOC) by comparing with the macroscopic surgical findings at laparotomy. METHODS: All patients with FIGO Stage IIIC-IV EOC who had Visceral Peritoneal Debulking (VPD) were included in the study. Results of CT scan, EXL and laparotomy (LPT) with regards to the bowel involvement were prospectively recorded in an ad hoc study form. Setting LPT findings as the gold standard, positive and negative predictive value (PPV/NPV), sensitivity, specificity and accuracy of CT and EXL were calculated. In addition, the diagnostic power of the combination CT scan + EXL was investigated. RESULTS: Ninety-four out of 177 patients (53.2%) had a bowel resection during VPD. CT-scan alone had sensitivity, specificity, PPV, NPV and accuracy of 56.7%, 72.4%, 70.8%, 58.5% and 63.8% respectively. EXL alone 84.4%, 93.8%, 93.8%, 84.3%, 88.8%. CT combined with EXL detected bowel involvement with a sensitivity, specificity, PPV, NPV and accuracy of 87.5%, 70.4%, 77.8%, 82.6% and 79.6% and respectively. The combined tests showed a statistically significant improvement vs. CT scan alone (p < 0001) in sensitivity, NPV and accuracy, with non-significant difference in specificity and PPV. CONCLUSIONS: CT-scan alone shows a limited diagnostic power at detecting large bowel involvement in patients with stage IIIC-IV EOC. The combination of CT scan with EXL increases the diagnostic power and enables to appropriately plan the bowel resection and consent the patients.

Ultrasound, CT, MRI, or PET-CT for staging and re-staging of adults with cutaneous melanoma.

BACKGROUND: Melanoma is one of the most aggressive forms of skin cancer, with the potential to metastasise to other parts of the body via the lymphatic system and the bloodstream. Melanoma accounts for a small percentage of skin cancer cases but is responsible for the majority of skin cancer deaths. Various imaging tests can be used with the aim of detecting metastatic spread of disease following a primary diagnosis of melanoma (primary staging) or on clinical suspicion of disease recurrence (re-staging). Accurate staging is crucial to ensuring that patients are directed to the most appropriate and effective treatment at different points on the clinical pathway. Establishing the comparative accuracy of ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)-CT imaging for detection of nodal or distant metastases, or both, is critical to understanding if, how, and where on the pathway these tests might be used. OBJECTIVES: Primary objectivesWe estimated accuracy separately according to the point in the clinical pathway at which imaging tests were used. Our objectives were:• to determine the diagnostic accuracy of ultrasound or PET-CT for detection of nodal metastases before sentinel lymph node biopsy in adults with confirmed cutaneous invasive melanoma; and• to determine the diagnostic accuracy of ultrasound, CT, MRI, or PET-CT for whole body imaging in adults with cutaneous invasive melanoma:○ for detection of any metastasis in adults with a primary diagnosis of melanoma (i.e. primary staging at presentation); and○ for detection of any metastasis in adults undergoing staging of recurrence of melanoma (i.e. re-staging prompted by findings on routine follow-up).We undertook separate analyses according to whether accuracy data were reported per patient or per lesion.Secondary objectivesWe sought to determine the diagnostic accuracy of ultrasound, CT, MRI, or PET-CT for whole body imaging (detection of any metastasis) in mixed or not clearly described populations of adults with cutaneous invasive melanoma.For study participants undergoing primary staging or re-staging (for possible recurrence), and for mixed or unclear populations, our objectives were:• to determine the diagnostic accuracy of ultrasound, CT, MRI, or PET-CT for detection of nodal metastases;• to determine the diagnostic accuracy of ultrasound, CT, MRI, or PET-CT for detection of distant metastases; and• to determine the diagnostic accuracy of ultrasound, CT, MRI, or PET-CT for detection of distant metastases according to metastatic site. SEARCH METHODS: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists as well as published systematic review articles. SELECTION CRITERIA: We included studies of any design that evaluated ultrasound (with or without the use of fine needle aspiration cytology (FNAC)), CT, MRI, or PET-CT for staging of cutaneous melanoma in adults, compared with a reference standard of histological confirmation or imaging with clinical follow-up of at least three months' duration. We excluded studies reporting multiple applications of the same test in more than 10% of study participants. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2)). We estimated accuracy using the bivariate hierarchical method to produce summary sensitivities and specificities with 95% confidence and prediction regions. We undertook analysis of studies allowing direct and indirect comparison between tests. We examined heterogeneity between studies by visually inspecting the forest plots of sensitivity and specificity and summary receiver operating characteristic (ROC) plots. Numbers of identified studies were insufficient to allow formal investigation of potential sources of heterogeneity. MAIN RESULTS: We included a total of 39 publications reporting on 5204 study participants; 34 studies reporting data per patient included 4980 study participants with 1265 cases of metastatic disease, and seven studies reporting data per lesion included 417 study participants with 1846 potentially metastatic lesions, 1061 of which were confirmed metastases. The risk of bias was low or unclear for all domains apart from participant flow. Concerns regarding applicability of the evidence were high or unclear for almost all domains. Participant selection from mixed or not clearly defined populations and poorly described application and interpretation of index tests were particularly problematic.The accuracy of imaging for detection of regional nodal metastases before sentinel lymph node biopsy (SLNB) was evaluated in 18 studies. In 11 studies (2614 participants; 542 cases), the summary sensitivity of ultrasound alone was 35.4% (95% confidence interval (CI) 17.0% to 59.4%) and specificity was 93.9% (95% CI 86.1% to 97.5%). Combining pre-SLNB ultrasound with FNAC revealed summary sensitivity of 18.0% (95% CI 3.58% to 56.5%) and specificity of 99.8% (95% CI 99.1% to 99.9%) (1164 participants; 259 cases). Four studies demonstrated lower sensitivity (10.2%, 95% CI 4.31% to 22.3%) and specificity (96.5%,95% CI 87.1% to 99.1%) for PET-CT before SLNB (170 participants, 49 cases). When these data are translated to a hypothetical cohort of 1000 people eligible for SLNB, 237 of whom have nodal metastases (median prevalence), the combination of ultrasound with FNAC potentially allows 43 people with nodal metastases to be triaged directly to adjuvant therapy rather than having SLNB first, at a cost of two people with false positive results (who are incorrectly managed). Those with a false negative ultrasound will be identified on subsequent SLNB.Limited test accuracy data were available for whole body imaging via PET-CT for primary staging or re-staging for disease recurrence, and none evaluated MRI. Twenty-four studies evaluated whole body imaging. Six of these studies explored primary staging following a confirmed diagnosis of melanoma (492 participants), three evaluated re-staging of disease following some clinical indication of recurrence (589 participants), and 15 included mixed or not clearly described population groups comprising participants at a number of different points on the clinical pathway and at varying stages of disease (1265 participants). Results for whole body imaging could not be translated to a hypothetical cohort of people due to paucity of data.Most of the studies (6/9) of primary disease or re-staging of disease considered PET-CT, two in comparison to CT alone, and three studies examined the use of ultrasound. No eligible evaluations of MRI in these groups were identified. All studies used histological reference standards combined with follow-up, and two included FNAC for some participants. Observed accuracy for detection of any metastases for PET-CT was higher for re-staging of disease (summary sensitivity from two studies: 92.6%, 95% CI 85.3% to 96.4%; specificity: 89.7%, 95% CI 78.8% to 95.3%; 153 participants; 95 cases) compared to primary staging (sensitivities from individual studies ranged from 30% to 47% and specificities from 73% to 88%), and was more sensitive than CT alone in both population groups, but participant numbers were very small.No conclusions can be drawn regarding routine imaging of the brain via MRI or CT. AUTHORS' CONCLUSIONS: Review authors found a disappointing lack of evidence on the accuracy of imaging in people with a diagnosis of melanoma at different points on the clinical pathway. Studies were small and often reported data according to the number of lesions rather than the number of study participants. Imaging with ultrasound combined with FNAC before SLNB may identify around one-fifth of those with nodal disease, but confidence intervals are wide and further work is needed to establish cost-effectiveness. Much of the evidence for whole body imaging for primary staging or re-staging of disease is focused on PET-CT, and comparative data with CT or MRI are lacking. Future studies should go beyond diagnostic accuracy and consider the effects of different imaging tests on disease management. The increasing availability of adjuvant therapies for people with melanoma at high risk of disease spread at presentation will have a considerable impact on imaging services, yet evidence for the relative diagnostic accuracy of available tests is limited.

Development of a best-practice clinical guideline for the use of bleomycin in the treatment of germ cell tumours in the UK.

Bleomycin, a cytotoxic chemotherapy agent, forms a key component of curative regimens for lymphoma and germ cell tumours. It can be associated with severe toxicity, long-term complications and even death in extreme cases. There is a lack of evidence or consensus on how to prevent and monitor bleomycin toxicity. We surveyed 63 germ cell cancer physicians from 32 cancer centres across the UK to understand their approach to using bleomycin. Subsequent guideline development was based upon current practice, best available published evidence and expert consensus. We observed heterogeneity in practice in the following areas: monitoring; route of administration; contraindications to use; baseline and follow-up investigations performed, and advice given to patients. A best-practice clinical guideline for the use of bleomycin in the treatment of germ cell tumours has been developed and includes recommendations regarding baseline investigations, the use of pulmonary function tests, route of administration, monitoring and patient advice. It is likely that existing heterogeneity in clinical practice of bleomycin prescribing has significant economic, safety and patient experience implications. The development of an evidence-based consensus guideline was supported by 93% of survey participants and aims to address these issues and homogenise practice across the UK.

Changing Practice Evaluation-Stage 1 Seminoma: Outcomes With Adjuvant Treatment Versus Surveillance: Risk Factors for Recurrence and Optimizing Follow-up Protocols-Experience From a Supraregional Center.

BACKGROUND: Stage 1 seminoma is frequently cured by radical orchiectomy; however, the management strategies after this diagnosis vary in terms of the use of adjuvant treatment and the nature of the follow-up protocols. We analyzed stage 1 seminomas treated in the Thames Valley Cancer Network for outcomes to determine whether any factors are predictive of recurrence. We also studied relapses to determine the optimal follow-up schedule and protocol. MATERIALS AND METHODS: Data were obtained from centers within the Thames Valley Cancer Network for a 12-year period from 2004 to 2016. We identified 501 patients with stage 1 seminoma. RESULTS: Relapses occurred in 6.2% of the patients receiving adjuvant treatment and 6.1% of those who did not. The only statistically significant predictive factor identified for relapse was rete testis invasion, and the risk was greater when only stromal rete invasion was included, rather than pagetoid as well. A trend was seen toward an increased risk with increased tumor size, but the difference was not statistically significant. Recurrences developed within the first 2 years after surgery in nearly 75% of cases and were identified through surveillance computed tomography scans in 54.8% of the patients. All relapses were treated curatively. CONCLUSION: Active surveillance leads to excellent outcomes for stage 1 seminoma; however, adjuvant treatment should be reserved for those with high-risk disease. Follow-up schedules should include computed tomography imaging during the first 3 years, long-term measurement of tumor markers, and mechanisms for patients to be seen promptly should symptoms of tumor recurrence occur.

Whole-genome sequencing identifies homozygous BRCA2 deletion guiding treatment in dedifferentiated prostate cancer.

Whole-genome sequencing (WGS) has transformed the understanding of the genetic drivers of cancer and is increasingly being used in cancer medicine to identify personalized therapies. Here we describe a case in which the application of WGS identified a tumoral BRCA2 deletion in a patient with aggressive dedifferentiated prostate cancer that was repeat-biopsied after disease progression. This would not have been detected by standard BRCA testing, and it led to additional treatment with a maintenance poly ADP ribose polymerase (PARP) inhibitor following platinum-based chemotherapy. This case demonstrates that repeat biopsy upon disease progression and application of WGS to tumor samples has meaningful clinical utility and the potential to transform outcomes in patients with cancer.

Value of Supraregional Multidisciplinary Review for the Contemporary Management of Testicular Tumors.

PURPOSE: Testicular cancers are an uncommon and highly curable group of tumors that are typically managed by specialist multidisciplinary teams (MDTs). Although recent guidelines have emphasized the importance of tumor prognostic factors in predicting recurrence and personalizing therapy in early-stage disease, the role of central pathology review in determining these factors is unclear. PATIENTS AND METHODS: We compared the referral histopathology reports with those obtained after expert central review for all cases reviewed by the UK Thames Valley Cancer Network testicular tumor MDT from August 2004 to September 2012. For cases in which the findings differed, we recorded the effect of the alteration on the estimates of patient prognosis and predicted clinical management using international (European Society of Medical Oncology [ESMO]) and local guidelines. RESULTS: The histopathology reports were altered after central review in 129 of 465 cases (27.7%) referred to the testicular tumor MDT during the study period. These resulted in changes in the estimation of prognosis for 42 patients (9.0% total), with a predicted affect on management according to the ESMO guidelines in 30 cases (6.5%). These proportions were broadly similar for both seminoma and nonseminoma, although the reasons for the discrepancies differed between the 2 (principally errors in categorization of rete testis invasion in seminoma and of lymphovascular invasion in nonseminoma). Changes to the tumor type were uncommon (2 cases). CONCLUSION: Central MDT review results in frequent, clinically relevant alterations to testicular tumor histopathology reports for testicular tumors. The results of our study demonstrate the importance of specialist MDTs to inform patient-centered care and ensure best practice in the management of these uncommon cancers.

Porta hepatis peritonectomy and hepato-celiac lymphadenectomy in patients with stage IIIC-IV ovarian cancer: Diagnostic pathway, surgical technique and outcomes.

OBJECTIVE: To report the surgical technique of ovarian cancer resection at the porta hepatis (PH) and hepato-celiac lymph nodes (HCL). To assess surgical and survival outcomes. Define the accuracy of an integrated diagnostic pathway. METHODS: Patients with FIGO stage IIIC-IV ovarian cancer that underwent Visceral-Peritoneal Debulking (VPD). Data of patients with disease at the PH/HCL during VPD were extracted from our database. The CT scan findings were compared with the exploratory laparoscopy. Accuracy of CT scan, intra- and post-operative morbidity, rate of complete resection (CR), disease free and overall survival are reported. RESULTS: Thirty one patients out of 216 (14.3%) had tumor at the PH and/or HCL. In 8 patients out of 31 (25.8%) it was only found with the aid of the exploratory laparoscopy. CR was achieved in 28 patients out of 31 (90.3%). Pathology confirmed disease in the PH/HCL specimens of all but one patient. Overall morbidity relating to the VPD was 29.2%. No complication was specifically related to the PH/HCL. Median disease free survival was 19months and median overall survival was 42months. CONCLUSION: PH/HCL surgery was required in 15% of patients with FIGO stage IIIC-IV. The surgery was feasible, safe and significantly contributed to CR. CT scan failed to identify the disease in 31% of the patients. CT and laparoscopy correctly identified all patients.

A Novel Optical Bioimaging Method for Direct Assessment of Ovarian Cancer Chemotherapy Response at Laparoscopy.

In patients with advanced ovarian cancer (AOC), additional imaging of disseminated disease at laparoscopy could complement conventional imaging for estimation of chemotherapy response. We developed an image segmentation method and evaluated its use in making accurate and objective measurements of peritoneal metastases in comparison to Response Evaluation Criteria In Solid Tumors (RECIST) criteria. A software tool using a custom ImageJ macro-based approach was employed to estimate lesion size by converting image pixels into unit length. The software tool was tested as a proof-of-principle in an AOC patient with two isolated peritoneal deposits. Image analysis of representative laparoscopic snapshots before and after three cycles of neoadjuvant chemotherapy (NACT) revealed an average tumor nodule response ratio (TNRR) of 40% (partial response), which was in concordance with RECIST evaluation by computed tomography (CT). We demonstrated the feasibility of using this novel anatomical analysis for direct assessment of chemotherapy response in an AOC patient as an adjunct to RECIST criteria.

Minimally invasive autopsy employing post-mortem CT and targeted coronary angiography: evaluation of its application to a routine Coronial service.

AIMS: Post-mortem imaging is a potential alternative to traditional medicolegal autopsy. We investigate the reduction in number of invasive autopsies required by use of post-mortem CT ± coronary angiography. METHODS AND RESULTS: A total of 120 adult deaths referred to the Coroner were investigated by CT, with coronary angiography employed only for the second series of 60 cases, in order to determine the added value of angiography. The confidence of imaging cause of death was classified as definite (no autopsy), probable, possible or unascertained. Invasive autopsy was not required in 38% of cases without coronary angiography and 70% of cases with angiography. Full autopsy, including brain dissection, was required in only 9% of cases. There was complete agreement between autopsy and radiological causes of death in the cases with a 'probable' imaging cause of death, indicating that cases for which imaging provides an accurate cause of death without autopsy were identified correctly. In two patients, CT demonstrated unsuspected fractures, not detected at subsequent autopsy. CONCLUSIONS: A two-thirds reduction in the number of invasive coronial autopsies can be achieved by use of post-mortem CT plus coronary angiography. At the same time, use of post-mortem CT may improve accuracy of diagnosis, particularly for traumatic deaths.

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.

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

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.

Seizures after aneurysmal subarachnoid hemorrhage treated with coil embolization.

OBJECTIVE: We sought to determine the incidence of seizures among patients treated with endovascular coil embolization for ruptured intracranial aneurysms because data on which to base antiepileptic drug (AED) prescriptions and advice to patients regarding driving motor vehicles and other high-risk activities are currently lacking. METHODS: We conducted a single-institute, single-operator observational study of 243 patients referred for endovascular treatment after aneurysmal subarachnoid hemorrhage. Prospective data collection was performed, and all successfully treated patients were followed. The incidence of seizures was compared with published surgical data, and logistic regression analysis of potential clinical associations was performed. Patients were followed for up to 7.7 years (mean follow-up period, 21.9 mo). RESULTS: Ictal seizures occurred at the time of subarachnoid hemorrhage in 26 (11%) of 243 patients and correlated with middle cerebral artery aneurysm location, loss of consciousness at ictus, and AED prescription. No patients experienced periprocedural seizures during their hospitalization. Seven of 233 successfully treated patients (3%) experienced seizures more than 30 days after treatment: late seizures occurred de novo in four patients (1.7%) and in three patients (1.4%) were caused by preexisting epilepsy. Two patients (0.85%) who had de novo seizures developed epilepsy. Late seizures correlated with a history of previous seizures, the presence of a cerebrospinal fluid shunt, and the use of AEDs. CONCLUSION: The low incidence of seizures does not justify the use of prophylactic AED therapy after aneurysmal subarachnoid hemorrhage in patients treated solely with coil embolization, nor does it justify subsequent restrictions on the driving of motor vehicles if the patient is otherwise fit to drive.

The double contrast barium enema: a retrospective single centre audit of the detection of colorectal carcinomas.

AIM: To determine retrospectively the sensitivity and specificity of the double contrast barium enema (DCBE) as performed in one institution for the detection of colorectal carcinoma. SUBJECTS AND METHODS: Eight hundred and eighty barium enema reports were reviewed of consecutive adult patients who underwent DCBE and also had hospital case notes with a minimum follow up of two years, a later diagnostic colonoscopy, or operative and histological findings. RESULTS: Seventy-four true positive cases of colorectal carcinoma diagnosed at DCBE were confirmed at surgery and histological examination. There were four false positive diagnoses of carcinoma at DCBE. Eight false negative cases at DCBE were demonstrated within a two-year follow-up period. The sensitivity of the DCBE for detecting colorectal carcinoma was therefore 90.2% and the specificity was 99.5%. CONCLUSION: DCBE is a sensitive and highly specific investigation for the detection of colorectal carcinoma.