Clinical signs associated with severe ST segment elevation in three cats with a hypertrophic cardiomyopathy phenotype.

Three cats were presented for unusual collapsing episodes. Echocardiography revealed a hypertrophic cardiomyopathy (HCM) phenotype in each cat. Continuous electrocardiographic monitoring showed that the clinical signs coincided with periods of severe ST-segment elevation in each cat. The first cat was treated with amlodipine and diltiazem but did not improve and was euthanized due to poor quality of life. Postmortem examination revealed cardiac lymphoma without obstructive coronary disease. The second cat was thought to have cardiac lymphoma, based on pericardial effusion cytology, and was euthanized before starting therapy. The third cat was diagnosed with HCM and left ventricular outflow tract obstruction and was treated with atenolol and diltiazem. This treatment reduced the frequency of episodic clinical signs, but the cat subsequently developed congestive heart failure and was euthanized. This case series describes clinical signs associated with severe ST elevation in cats with an HCM phenotype, and their outcomes. Continuous electrocardiographic monitoring was necessary to detect transient ST elevation in each case.

Thin and hypokinetic myocardial segments in cats with cardiomyopathy.

INTRODUCTION/OBJECTIVES: Thin and hypokinetic myocardial segments (THyMS) represent adverse ventricular (LV) remodeling in human hypertrophic cardiomyopathy. We describe the echocardiographic features and outcome in cats with THyMS, and in a subpopulation, the echocardiographic phenotype before LV wall thinning was detected (pre-THyMS). ANIMALS: Eighty client-owned cats. MATERIALS AND METHODS: Retrospective multicenter study. Clinical records were searched for cats with THyMS, defined as LV segment(s) with end-diastolic wall thickness (LVWT) <3 mm and hypokinesis in the presence of ≥one LV segment(s) with LVWT >4 mm and normal wall motion. When available, echocardiograms pre-THyMS were assessed. Survival time was defined as time from first presentation with THyMS to death. RESULTS: Mean thickest LV wall segment (MaxLVWT) was 6.1 mm (95% CI 5.8-6.4 mm) and thinnest (MinLVWT) was 1.7 mm (95% CI 1.6-1.9 mm). The LV free wall was affected in 74%, apex in 13% and septum in 5%. Most cats (85%) presented with heart failure and/or arterial thromboembolism. Median circulating troponin I concentration was 1.4 ng/mL ([range 0.07-180 ng/mL]). Prior echocardiography results were available for 13/80 cats, a mean of 2.5 years pre-THyMS. In segments subsequently undergoing thinning, initial MaxLVWT measured 6.7 mm (95% CI 5.8-7.7 mm) vs. 1.9 mm (95% CI 1.5-2.4 mm) at last echocardiogram (P<0.0001). Survival data were available for 56/80 cats, median survival time after diagnosing THyMS was 153 days (95% CI 83-223 days). Cardiac histopathology in one cat revealed that THyMS was associated with severe transmural scarring. CONCLUSIONS: Cats with THyMS had advanced cardiomyopathy and a poor prognosis.

Feasibility of INTACT (INcisionless TArgeted Core Tissue) biopsy procedure for perinatal autopsy.

OBJECTIVES: To determine the feasibility and tissue yield of a perinatal incisionless ultrasound-guided biopsy procedure, the INcisionless Targeted Core Tissue (INTACT) technique, in the context of minimally invasive autopsy. METHODS: Cases of perinatal death in which the parents consented for minimally invasive autopsy underwent postmortem magnetic resonance imaging and an INTACT biopsy procedure, defined as needle biopsy of organs via the umbilical cord, performed under ultrasound guidance. In each case, three cores of tissue were obtained from seven target organs (both lungs, both kidneys, heart, spleen and liver). Biopsy success was predefined as an adequate volume of the intended target organ for pathological analysis, as judged by a pathologist blinded to the case and biopsy procedure. RESULTS: Thirty fetuses underwent organ sampling. Mean gestational age was 30 weeks (range, 18-40 weeks) and mean delivery-to-biopsy interval was 12 days (range, 6-22 days). The overall biopsy success rate was 153/201 (76.1%) samples, with the success rates in individual organs being highest for the heart and lungs (93% and 91%, respectively) and lowest for the spleen (11%). Excluding splenic samples, the biopsy success rate was 150/173 (86.7%). Histological abnormalities were found in 4/201 (2%) samples, all of which occurred in the lungs and kidneys of a fetus with pulmonary hypoplasia and multicystic kidney disease. CONCLUSIONS: Incisionless ultrasound-guided organ biopsy using the INTACT procedure is feasible, with an overall biopsy success rate of over 75%. This novel technique offers the ideal combination of an imaging-led autopsy with organ sampling for parents who decline the conventional invasive approach. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Micro-CT and histological investigation of the spatial pattern of feto-placental vascular density.

INTRODUCTION: There are considerable variations in villous morphology within a normal placenta. However, whether there is a reproducible spatial pattern of variation in villous vascular density is not known. Micro-CT provides three-dimensional volume imaging with spatial resolution down to the micrometre scale. In this study, we applied Micro-CT and histological analysis to investigate the degree of heterogeneity of vascularisation within the placenta. METHOD: Ten term placentas were collected at elective caesarean section, perfused with contrast agent and imaged whole with Micro-CT. Eight full depth tissue blocks were then taken from each placenta and imaged. Sections were taken for histological analysis. Data was analysed to investigate vascular fill, and vascular density in relation to location from cord insertion to placental edge at each scale. RESULTS: Whole placental imaging revealed no spatially consistent difference in villous vessel density within the main placental tissue, although there was a great degree of heterogeneity. Both block imaging and histological analysis found a large degree of heterogeneity of vascular density within placentas, but no strong correlation between villous vascular density and block location (rs = 0.066, p = 0.7 block imaging, rs = 0.06, p = 0.6 histological analysis). DISCUSSION: This work presents a novel method for imaging the human placenta vascular tree using multiscale Micro-CT imaging. It demonstrates that there is a large degree of variation in vascular density throughout normal term human placentas. The three-dimensional data created by this technique could be used, with more advanced computer analysis, to further investigate the structure of the vascular tree.

Minimally invasive perinatal and pediatric autopsy with laparoscopically assisted tissue sampling: feasibility and experience of the MinImAL procedure.

OBJECTIVE: Less invasive autopsy techniques in cases of fetal or infant death have good acceptability among parents, but the published sampling adequacy in needle biopsy studies is generally poor. Minimally Invasive Autopsy with Laparoscopically assisted sampling (MinImAL) has the potential to increase the diagnostic yield of less invasive autopsy by improving the quality and quantity of tissue samples obtained, whilst permitting visualization, extraction and examination of internal organs through a small incision. The aim of this study was to present the findings of our experience with the MinImAL procedure in cases of fetal, neonatal and pediatric death. METHODS: This was a retrospective analysis of 103 prospectively recruited unselected cases of fetal, neonatal or pediatric death that underwent the MinImAL procedure at a tertiary referral center over a 5-year period. Following preprocedure 1.5-T whole-body postmortem magnetic resonance imaging, MinImAL autopsy was performed. Procedure duration, sampling adequacy and cause of death were assessed. Chi-square analysis was used to compare the 'unexplained' rate of intrauterine deaths in the cohort with that in a previously published cohort of > 1000 cases of intrauterine death examined by standard autopsy. RESULTS: MinImAL autopsy was performed successfully in 97.8% (91/93) of the cases undergoing a complete procedure. There was a satisfactory rate of adequate histological sampling in most major organs; heart (100%, 91 cases), lung (100%, 91 cases), kidney (100%, 91 cases), liver (96.7%, 88 cases), spleen (94.5%, 86 cases), adrenal glands (89.0%, 81 cases), pancreas (82.4%, 75 cases) and thymus (56.0%, 51 cases). Procedure duration was similar to that of standard autopsy in a previously published cohort of intrauterine deaths. The unexplained rate in stillbirths and intrauterine fetal deaths that underwent MinImAL autopsy was not significantly different from that following standard autopsy. CONCLUSIONS: The MinImAL procedure provides good histological yield from major organs with minimal cosmetic damage and can be learned by an autopsy practitioner. The MinImAL procedure is an appropriate minimally invasive alternative for the investigation of perinatal and pediatric deaths in which consent to full autopsy is withheld, and may have applications in both high- and low/middle-income settings. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Availability of less invasive prenatal, perinatal and paediatric autopsy will improve uptake rates: a mixed-methods study with bereaved parents.

OBJECTIVE: To investigate whether less invasive methods of autopsy would be acceptable to bereaved parents and likely to increase uptake. DESIGN: Mixed methods study. SETTING: Bereaved parents recruited prospectively across seven hospitals in England and retrospectively through four parent support organisations. SAMPLE: Eight hundred and fifty-nine surveys and 20 interviews with bereaved parents. METHODS: Cross-sectional survey and qualitative semi-structured telephone interviews. MAIN OUTCOME MEASURES: Likely uptake, preferences, factors impacting decision-making, views on different autopsy methods. RESULTS: Overall, 90.5% of participants indicated that they would consent to some form of less invasive autopsy [either minimally invasive autopsy (MIA), non-invasive autopsy (NIA) or both]; 53.8% would consent to standard autopsy, 74.3% to MIA and 77.3% to NIA. Regarding parental preferences, 45.5% preferred MIA, 30.8% preferred NIA and 14.3% preferred standard autopsy. Participants who indicated they would decline standard autopsy but would consent to a less invasive option were significantly more likely to have a lower educational level (odds ratio 0.49; 95% CI 0.35-0.70; P = 0.000062). Qualitative findings suggest that parents value NIA because of the lack of any incision and MIA is considered a good compromise as it enables tissue sampling while easing the parental burden associated with consenting to standard autopsy. CONCLUSION: Less invasive methods of autopsy are acceptable alternatives for bereaved parents, and if offered, are likely to increase uptake and improve parental experience. Further health economic, validation and implementation studies are now required to assess the viability of offering these in routine widespread clinical care. TWEETABLE ABSTRACT: Mixed methods UK study finds less invasive methods of autopsy are acceptable alternatives for bereaved parents, and if offered, are likely to increase uptake and improve parental experience.

British Neuropathological Society and International Society of Forensic Radiology and Imaging expert consensus statement for post mortem neurological imaging.

AIMS: To develop an expert consensus statement regarding appropriate clinical and forensic post mortem neurological imaging. METHODS: An expert panel of clinicians were recruited from registered members of the British Neuropathological Society (BNS) and the International Society of Forensic Radiology and Imaging (ISFRI) with post mortem expertise. Following a focus group meeting, 16 core statements were incorporated into an online modified Delphi survey and each panellist was asked to score their level of agreement. Following the first iteration, two statements that failed to reach consensus were modified and re-rated. Consensus was predefined as 75% agreement across responders. RESULTS: Seventeen experts joined the panel and 12 (70.6%) attended the focus group meeting; 14 (82%) completed both iterations of the survey. Consensus was reached for need of adequate clinical history, multidisciplinary discussion, establishment of special interest groups to discuss cases, gathering further evidence to inform imaging choices, establishment of methods for quality assessment in reporting standards and adequate funding for imaging services. The panel agreed that pathologists should be responsible for neuroimaging referrals, collating results of ancillary tests, and producing the final post mortem report. Areas requiring further discussion include the impact of double reporting, indications for neuroimaging and utilities of three-dimensional printing. CONCLUSION: The BNS/ISFRI statement represents current views of an expert panel of health professionals engaged in post-mortem neuroimaging. We hope this provides a working guideline for less experienced operators, stimulates discussion and highlights the most pressing clinical and research questions.

Post-mortem magnetic resonance (PMMR) imaging of the brain in fetuses and children with histopathological correlation.

Post-mortem magnetic resonance (PMMR) imaging is rapidly emerging as an alternative, "less invasive", and more widely accepted investigative approach for perinatal deaths in the UK. PMMR has a high diagnostic accuracy for congenital and acquired fetal neuropathological anomalies compared to conventional autopsy, and is particularly useful when autopsy is non-diagnostic. The main objectives of this review are to describe and illustrate the range of common normal and abnormal central nervous system (CNS) findings encountered during PMMR investigation. This article covers the standard PMMR sequences used at our institution, normal physiological post-mortem findings, and a range of abnormal developmental and acquired conditions. The abnormal findings include diseases ranging from neural tube defects, posterior fossa malformations, those of forebrain and commissural development as well as neoplastic, haemorrhagic, and infectious aetiologies. Neuropathological findings at conventional autopsy accompany many of the conditions we describe, allowing readers to better understand the underlying disease processes and imaging appearances.

Stillbirth and intrauterine fetal death: role of routine histological organ sampling to determine cause of death.

OBJECTIVES: Guidelines for the investigation of intrauterine death and sudden unexpected death in infancy (SUDI) recommend, based on expert opinion, autopsy procedures and tissue sampling strategies for histological analysis. Although stillbirth is much more common than SUDI, there have been no large-scale studies published which evaluate the usefulness of histological evaluation of specific organs in stillbirth for determining cause of death. Our aim was to evaluate the use of macroscopic and microscopic assessment of internal organs to determine cause of intrauterine death. METHODS: As part of a larger study evaluating several aspects of autopsy findings in intrauterine death, a dedicated database was used to collate antenatal and postmortem examination details for cases of intrauterine death examined between 2005 and 2013 at two tertiary specialist centers in London, UK. Histological findings for all organs were examined in relation to the final cause of death, as determined by objective criteria. RESULTS: Among 1064 intrauterine deaths, the majority (> 80%) of cases had internal organs that were normal on both macroscopic and microscopic examination. There was no case in which histological cardiac examination provided the cause of death when the macroscopic appearance of the heart was normal. Microscopic examination of lung tissue revealed 13 (1%) cases with histological abnormalities that provided the cause of death when the macroscopic appearance was normal, but there was only one (0.1%) case in which the diagnosis would not have been apparent on placental examination: a case of congenital cytomegalovirus infection. There was no case in which microscopic examination of macroscopically normal liver, kidneys, adrenals, spleen, thymus, intestines, pancreas, brain or thyroid provided the cause of death. CONCLUSION: In this large series of autopsies in cases of intrauterine death, only around 1% of cases demonstrated histological abnormalities which provided the cause of death when the internal organs appeared normal macroscopically. There was no case in which routine histological examination of most tissues provided diagnostically useful information that was not apparent from other examinations, such as placental pathology. There is little benefit, purely in terms of determining cause of death, in obtaining tissue from most macroscopically normal organs for routine histological examination. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Stillbirth and intrauterine fetal death: factors affecting determination of cause of death at autopsy.

OBJECTIVES: There have been several attempts to classify cause of death (CoD) in stillbirth; however, all such systems are subjective, allowing for observer bias and making comparisons between systems challenging. This study aimed to examine factors relating to determination of CoD using a large dataset from two specialist centers in which observer bias had been reduced by classifying findings objectively and assigning CoD based on predetermined criteria. METHODS: Detailed autopsy reports from intrauterine deaths in the second and third trimesters during 2005-2013 were reviewed and findings entered into a specially designed database, in which CoD was assigned using predefined objective criteria. Data regarding CoD categories and factors affecting determination of CoD were examined. RESULTS: There were 1064 intrauterine deaths, including 246 early intrauterine fetal deaths (IUFD) (< 20 weeks), 179 late IUFDs (20-23 weeks) and 639 stillbirths (≥ 24 weeks' gestation). Overall, around 40% (n = 412) had a clear CoD identified, whilst around 60% (n = 652) were classified as 'unexplained', including around half with identified risk factors or lesions of uncertain significance, with the remaining half (n = 292 (45%)) being entirely unexplained. A stepwise increase in the proportion of unexplained deaths was observed with increasing maceration. Black and Asian women had significantly greater proportions of deaths due to ascending infection, whilst women aged over 40 years had significantly increased placenta-related CoDs. There was no significant difference in CoD distribution according to maternal body mass index or with increasing postmortem interval. Around half of those with an identifiable CoD could be identified from clinical review and external fetal examination or imaging, with most of the remainder being determined following placental examination. CONCLUSIONS: Based on objective criteria, many intrauterine deaths throughout gestation remain unexplained despite autopsy examination. The rate of unexplained death varies from around 30% to 60% depending on interpretation of the significance of features. CoD determination is dependent on both the classification system used and subjective interpretation, such that variation in the proportion of 'unexplained' cases is based largely on speculation regarding mechanisms of death. Novel methods to determine objectively the mechanism of death at postmortem examination are required. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Stillbirth and intrauterine fetal death: role of routine histopathological placental findings to determine cause of death.

OBJECTIVES: Placental abnormalities are a common cause of death in stillbirth, ranking second only to unexplained deaths, though there is wide variation in the proportion attributed to placental disease. In clinical practice, interpretation of the significance of placental findings is difficult, since many placental features in stillbirths overlap with those in live births. Our aim was to examine objectively classified placental findings from a series of > 1000 autopsies following intrauterine death in order to evaluate the role of placental histological examination in determining the cause of death. METHODS: As part of a larger study evaluating several aspects of autopsy findings in intrauterine death, a dedicated database was used to collate antenatal and postmortem examination details for all cases examined between 2005 and 2013 at two tertiary specialist centers in London, UK. Histological findings for placentas were evaluated in relation to the final cause of death. RESULTS: Among 1064 intrauterine deaths, 946 (89%) cases had the placenta submitted for examination as part of the autopsy. Of these, 307 (32%) cases had the cause of death assigned to abnormalities of the placenta, cord or membranes. Around one third of stillbirths (≥ 24 weeks) had some isolated placental histological abnormality identified, many of uncertain significance, a significantly greater proportion than in cases of second-trimester intrauterine fetal demise (P < 0.0001). The cause of death was ascending infection in 176/946 (19%) cases, peaking at 22 weeks' gestation, with significantly more black mothers having ascending infection compared with other ethnicities (P < 0.0001). Maternal vascular malperfusion was the largest category of placental abnormalities in stillbirth, with peak prevalence in the early third trimester. There were 18 (2%) cases with specific histological abnormalities, including chronic histiocytic intervillositis and massive perivillous fibrin deposition. CONCLUSIONS: Placental pathologies represent the largest category of cause of intrauterine death. Placental histological examination is the single most useful component of the autopsy process in this clinical setting. A minority of cases are associated with specific placental pathologies, often with high recurrence rates, that can be diagnosed only on microscopic examination of the placenta. Many deaths remain unexplained, although placental histological lesions may be present which are of uncertain significance. A rigorous, systematic approach to placental pathology research and classification may yield better understanding of the significance of placental findings and reduce the rate of unexplained intrauterine deaths. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Effects of intrauterine retention and postmortem interval on body weight following intrauterine death: implications for assessment of fetal growth restriction at autopsy.

OBJECTIVE: According to the classification system used, 15-60% of stillbirths remain unexplained, despite undergoing recommended autopsy examination, with variable attribution of fetal growth restriction (FGR) as a cause of death. Distinguishing small-for-gestational age (SGA) from pathological FGR is a challenge at postmortem examination. This study uses data from a large, well-characterized series of intrauterine death autopsies to investigate the effects of secondary changes such as fetal maceration, intrauterine retention and postmortem interval on body weight. METHODS: Autopsy findings from intrauterine death investigations (2005-2013 inclusive, from Great Ormond Street Hospital and St George's Hospital, London) were collated into a research database. Growth charts published by the World Health Organization were used to determine normal expected weight centiles for fetuses born ≥ 24 weeks' gestation, and the effects of intrauterine retention (maceration) and postmortem interval were calculated. RESULTS: There were 1064 intrauterine deaths, including 533 stillbirths ≥ 24 weeks' gestation with a recorded birth weight. Of these, 192 (36%) had an unadjusted birth weight below the 10th centile and were defined as SGA. The majority (86%) of stillborn SGA fetuses demonstrated some degree of maceration, indicating a significant period of intrauterine retention after death. A significantly greater proportion of macerated fetuses were present in the SGA population compared with the non-SGA population (P = 0.01). There was a significant relationship between increasing intrauterine retention interval and both more severe maceration and reduction in birth weight (P < 0.0001 for both), with an average artifactual reduction in birth weight of around -0.8 SD of expected weight. There was an average 12% reduction in fetal weight between delivery and autopsy and, as postmortem interval increased, fetal weight loss increased (P = 0.0001). CONCLUSION: Based on birth weight alone, 36% of stillbirths are classified as SGA. However, fetuses lose weight in utero with increasing intrauterine retention and continue to lose weight between delivery and autopsy, resulting in erroneous overestimation of FGR. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Stillbirth and intrauterine fetal death: contemporary demographic features of >1000 cases from an urban population.

OBJECTIVES: Of 780 000 births annually in the UK, around 3300 are stillborn, a rate of approximately 4 per 1000 births. Traditional epidemiological associations are based on historic data. The aim of this study was to document contemporary demographic findings in a large series of > 1000 deaths in utero in London and compare these with national datasets. METHODS: From a dedicated database, including > 400 data fields per case, of fetal, infant and pediatric autopsies performed at Great Ormond Street Hospital and St George's Hospital, London, we extracted information on all intrauterine deaths, excluding terminations of pregnancy, from 2005 to 2013, inclusive. Demographic data were analyzed according to the gestational age at which fetal death occurred (second-trimester intrauterine fetal death (IUFD), subdivided into early (< 20 weeks) and late (20-23 weeks) IUFD, and third-trimester stillbirth (≥ 24 weeks)) and compared with national datasets when available, using Mann-Whitney U-test and comparison of proportions testing as appropriate. RESULTS: Data were available from 1064 individual postmortem reports examining intrauterine deaths delivered between 12 and 43 weeks' gestation, including 425 IUFDs (246 early and 179 late) and 639 stillbirths. Compared with the overall UK pregnant population, women in whom an intrauterine death occurred were significantly older and more obese. White mothers had a higher proportion of stillbirths (as opposed to IUFDs) than did non-white mothers, whereas black mothers had a higher proportion of IUFDs relative to stillbirths. Increased body mass index was associated with increased risk across all groups. Women who had uterine fibroids, those who had a history of vaginal bleeding in early pregnancy and those who had undergone assisted conception had a relatively higher proportion of IUFDs than stillbirths. CONCLUSIONS: Based on a large series of >1000 autopsies in cases of intrauterine death, these data highlight the increased risk for fetal loss associated with maternal demographic factors in contemporary clinical practice, particularly associations with increased maternal age and body mass index. Among women in whom an intrauterine death occurs, maternal ethnicity, mode of conception and gynecological history are associated with differing timing of fetal loss. Further research is required to understand the mechanisms involved in such maternal factors in order to develop preventative strategies. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Organ weights and ratios for postmortem identification of fetal growth restriction: utility and confounding factors.

OBJECTIVES: The postmortem fetal brain:liver weight ratio is commonly used as a marker of nutrition for diagnosis of fetal growth restriction (FGR). However, there are limited data regarding the effects of intrauterine retention, fetal maceration and postmortem interval on organ weights and their ratios at autopsy. Our aims were to examine the relationships between gestational-age-adjusted and sex-adjusted fetal organ weights at autopsy, cause of intrauterine death and effects of intrauterine retention, and to determine whether the brain:liver weight ratio is a reliable marker of FGR in intrauterine death. METHODS: As part of a larger study examining autopsy findings in intrauterine death, data from two specialist centers in London were collated in a specially designed database. Autopsy and clinical information for > 1000 intrauterine deaths between 2005 and 2013 were extracted. Adjusted (delta) organ weights were calculated by plotting against gestational age female and male brain, liver, thymus, heart, combined kidney, combined lung, spleen and combined adrenal gland weights. Polynomial regression was used to determine best fit and to calculate expected (50th centile) organ weights and deviations from expected. We compared adjusted organ weights and body:organ weight ratios in fetuses which were small-for-gestational age (SGA) at autopsy (birth weight < 10th centile for normal live births) vs those in fetuses which were not, and in macerated vs non-macerated fetuses. RESULTS: The majority of fetal organs (brain, liver, heart, thymus, lungs, kidneys and thyroid) in SGA fetuses were significantly lighter than those in non-SGA fetuses. Body:organ weight ratios for thymus, liver and spleen were significantly greater in SGA fetuses, indicating these organs to be disproportionately small. The majority of organs were significantly lighter in macerated compared with non-macerated fetuses and body:organ weight ratios for most organs (liver, thymus, lung, pancreas, adrenal gland, kidney, heart) were significantly greater in macerated compared with non-macerated fetuses. When SGA cases with demonstrable placental histological abnormalities were compared with other SGA cases, there was a significant difference in the brain:liver weight ratio (median, 6 vs 3.5). CONCLUSION: Changes after intrauterine death lead to loss of fetal weight, with preferential weight loss of visceral organs such as the liver. Maceration therefore affects the brain:liver weight ratio and adjustment should be made for such changes during interpretation of ratios. Fetal organ weights may be affected significantly by mechanism of death and postmortem changes. The fetal brain:liver weight ratio may provide useful information regarding intrauterine growth status at time of death, provided that adjustment is made for effects of intrauterine retention and that appropriate cut-off values are used. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Pleural fluid accumulation detectable on paediatric post-mortem imaging: a possible marker of interval since death?

OBJECTIVES: The aim of this preliminary study is to evaluate whether pleural fluid accumulates following death in a predictable manner, in particular whether such collections are related to post-mortem interval. METHODS: Images acquired by post-mortem magnetic resonance imaging (PMMR) were both subjectively and objectively assessed for extent of pleural fluid accumulation. Total thoracic volume and pleural fluid volume were calculated using segmentation functions on OSIRIX software. The percentage of pleural fluid as a percentage of thoracic volume was calculated, to account for variation in subject size. The cause of death as per the final autopsy report and the interval from death to imaging were also recorded. RESULTS: Twelve perinatal deaths/stillbirths (mean gestation 38 weeks, range 24-48 weeks, male/female 5:7) and 11 childhood deaths (mean age 1 year, range 1 day-4 years, male/female 3:8) were assessed. The mean interval from death to imaging for all cases was 7.5 days (range 1-23 days). Pleural fluid was present in almost all cases, and the mean percentage pleural effusion as a proportion of thoracic volume was 3.3 % (range 0.2-9.5 %). There was a significant correlation between the post-mortem interval and the amount of pleural fluid in childhood deaths (p < 0.05) but no significant relationship for perinatal deaths. CONCLUSION: The accumulation of pleural fluid detectable on PMMR in children is related to post-mortem interval. If this holds for a larger population, it may therefore be a useful marker for estimating time of death. A similar relationship was not found for perinatal deaths and stillbirths, the reasons for which remain uncertain.

Clinical utility of postmortem microcomputed tomography of the fetal heart: diagnostic imaging vs macroscopic dissection.

OBJECTIVES: Congenital cardiac malformations are commonly identified at perinatal autopsy, which can be challenging in fetuses of early gestation and in macerated fetuses. Our objective was to examine fetal complex congenital heart disease by microcomputed tomography (micro-CT), using standard autopsy as the gold standard. METHODS: In this ethically approved study, ex-vivo isolated fetal heart and fetal heart-lung blocks underwent iodine preparation prior to micro-CT, and were fixed in formalin after the micro-CT examination. Images were acquired using a microfocus-CT scanner with individual specimen image optimization. Twenty-one indices assessed normally at autopsy were evaluated for each dataset. Cardiac dissection was performed using a dissecting microscope within 24 h of the micro-CT examination. RESULTS: We examined six fetal hearts, comprising five with complex congenital cardiac malformations at a gestational age of 17-23 weeks and an anatomically normal heart of 23 weeks' gestation for reference. All specimens demonstrated excellent internal contrast at micro-CT examination, and the correct overall diagnosis was made in all cases. There was agreement for 114/126 indices assessed on micro-CT and at autopsy dissection (overall concordance of 95.8% (95% CI, 90.5-98.2%)). Micro-CT was particularly useful in the assessment of ventricular morphology in macerated fetuses. CONCLUSIONS: Micro-CT of small ex-vivo fetal specimens can provide highly accurate three-dimensional rendering of complex congenital fetal heart disease. This approach represents a significant advance in postmortem imaging and confirms the potential of this technology for non-invasive examination of small fetuses and organs.

Prognostic significance of p27 expression in carcinoma of the oral cavity and oropharynx.

OBJECTIVE: To study the role of p27, a cyclin-dependent kinase inhibitor, as a prognostic indicator in squamous cell carcinoma of the oral cavity and oropharynx. STUDY DESIGN: Retrospective review of 35 patients with squamous cell carcinoma of the oral cavity and oropharynx who presented to Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois, between 1986 and 1995. METHODS: Inclusion criteria were the availability of clinical information, archival pretreatment biopsy material, and a minimum follow-up of 24 months. p27 staining was scored for frequency and intensity of tumor cell expression following immunoperoxidase staining using standard techniques. Samples of squamous epithelium from the uvula of 15 nonsmoking patients without past or present squamous cell carcinoma were used as normal controls. RESULTS: The association of p27 staining and other factors with response to treatment was evaluated by Fisher's Exact Test and with overall and disease-free survival by the Kaplan-Meier method with multivariate Cox regression. Low levels of p27 expression correlated significantly with unfavorable treatment response (P<.0001), shorter overall survival (P = .0001), and shorter disease-free survival (P = .003). Tumor site (alveolus) was also associated with shorter disease-free (though not overall) survival, but the association with p27 was independent of stage and site in multivariate analysis.

Regulators of proliferation and apoptosis in carcinoma of the larynx.

Expression of interrelated gene products regulating cell proliferation and apoptosis may be disordered in squamous cell carcinoma (SCC) of the larynx compared with normal squamous mucosa. Certain of these abnormalities, alone or in combination, may be of prognostic significance in low-stage carcinomas of the larynx. A retrospective study of archival material was made. Expression of the Bcl-2 family of apoptosis-related genes (bcl-2, bcl-X, mcl-1, and bax) and the proliferation- and apoptosis-related genes p53 and cyclin D-1 were determined in 40 low-T-stage laryngeal carcinomas and in uvular epithelium from patients without SCC. Among the antiapoptotic members of the Bcl-2 family, Bcl-X and Mcl-1 showed more intense and widespread staining than Bcl-2 itself in both normal squamous mucosa and SCC. The well-ordered expression patterns of Bcl-2-related proteins found in normal epithelium were lost in SCC, and patterns of expression varied widely among individual tumors. Also, mean expression levels for Bax and cyclin D-1 were significantly lower than in normal epithelium (P = .036 and P = .009, respectively), whereas expression of p53 was higher in tumors (P = .034). Expression of Bcl-X and Mcl-1 was greater in poorly differentiated than in well-differentiated tumors (P = .014 and P = .031, respectively). No associations were seen between marker expression patterns and clinical outcome in this group of patients. Bcl-x and Mcl-1 appear to be the most abundantly expressed antiapoptotic proteins of the Bcl-2 family in both normal squamous mucosa and SCC of the larynx. Multiple genes regulating proliferation and apoptosis are expressed abnormally in laryngeal SCC compared with normal epithelium. In particular, loss or measurable decrease in expression of the proapoptotic protein Bax in tumors may contribute to the deranged growth control of SCC. Further study is needed to evaluate the prognostic significance of particular patterns of disordered expression of proteins regulating proliferation and apoptosis in SCC of different head and neck sites.