Julian L. Burton

Clinical, educational, and epidemiological value of autopsy.

The autopsy is now often regarded as of marginal use in modern clinical practice. In this Review we contend that the autopsy remains an important procedure with substantial, if largely underused, potential to advance medical knowledge and improve clinical practice. Many doctors lack familiarity with autopsy practices, and are insufficiently aware of the benefits for not only bereaved families but also present and future patients. In this Review, which has an international perspective, we consider the ascent and decline of the autopsy, the legal frameworks that govern its use, the value and potential pitfalls of alternatives to the conventional method, and the autopsys role in undergraduate medical education. We also draw attention to the continuing ability of autopsies to improve the completeness and reliability of death certification, which is important for public-health strategies and for some bereaved families.

DIFFERENTIAL EXPRESSION OF hMLH1 AND hMSH2 IS RELATED TO BLADDER CANCER GRADE, STAGE AND PROGNOSIS BUT NOT MICROSATELLITE INSTABILITY

Defects in the DNA mismatch repair proteins result in microsatellite instability and malignancy in hereditary non‐polyposis colorectal carcinoma (HNPCC). However, the role of mismatch repair (MMR) proteins and microsatellite instability (MSI) in transitional cell carcinoma of the bladder is less clear. In our study, the expression of 2 MMR proteins and the frequency of MSI in Transitional cell carcinoma of the bladder (TCC) were investigated. One hundred eleven patients with TCC of the bladder were studied, with complete clinicopathological data (median follow up of 5 years, range 5–16 years). Immunohistochemistry was used to detect the expression levels of hMLH1 and hMSH2. Microsatellite analysis for 14 loci (10 loci from the Bethesda consensus panel and the repeats in the TGFβR2, BAX, hMSH3 and hMSH6 genes) was performed on 84 tumors. Reduced expression of either MMR protein was seen in 26 of 111 tumors (23%). Reduced expression was seen more commonly in muscle invasive (p<0.03) and high grade TCC (p<0.03) than in superficial, low grade tumors. By 5 years, reduced expression of either MMR protein was associated with fewer recurrences of superficial tumors (p=0.015) and fewer relapses in all tumors (p=0.03), compared to tumors with normal expression. Nine tumors had reduced expression of both MMR proteins, analysis which suggests a synergistic reduction in expression (p=0.001). MMR expression was related to patient age, younger patients being more likely to have reduced MMR expression than older patients (p<0.01). MSI was seen at multiple loci in 1 tumor (1%) and at a single locus in 6 tumors (7%). MSI was not associated with MMR expression. Our findings indicate that reduced expression of the MMR proteins may have an important contribution in the development of a subset of TCCs and suggest a potential role for MMR expression as prognostic indicators.

Recent advances in the histopathology and molecular pathology of carcinoma of the endometrium

Endometrial carcinoma is the commonest malignancy of the female genital tract. The pathogenesis is complex and at least three pathogenetic subtypes exist with different prognostic implications. The molecular events involved remain poorly defined but several genes are involved and mutations of tp53, WAF1/CIP1, PTEN, bcl‐2 and c‐erbB‐2 have been implicated. Although care is needed in interpreting the results, the majority of these mutations can be detected immunohistochemically and therefore have the potential to aid the pathologist and surgeon in assessing the prognosis of a tumour. However, for the time being, no molecular marker is as valuable in determining prognosis as conventional parameters such as tumour type, grade and vascular space involvement.

Refining the diagnosis of hydatidiform mole: image ploidy analysis and p57KIP2 immunohistochemistry.

Aim:  To determine whether image analysis of ploidy status and immunohistochemical analysis of p57KIP2 (a paternally imprinted, maternally expressed gene) can be used to refine the diagnosis of molar pregnancy.

Over‐diagnosis of hydatidiform mole in early tubal ectopic pregnancy

Over‐diagnosis of hydatidiform mole in early tubal ectopic pregnancy

The autopsy in modern undergraduate medical education: a qualitative study of uses and curriculum considerations

Aim  Medical education has undergone dramatic changes over the past decade. In the UK, the General Medical Council (GMC), the driving force behind curriculum reform, now requires curricula to be founded on a base of educational theory and research. This qualitative study investigated the roles of the autopsy within the context of the modern medical curriculum.

What Levels of Agreement Can Be Expected Between Histopathologists Assigning Cases to Discrete Nominal Categories? A Study of the Diagnosis of Hyperplastic and Adenomatous Colorectal Polyps

Aims: To assess the levels of agreement between histopathologists for a two-class nominal categorization process—the discrimination between hyperplastic and adenomatous colorectal polyps. Fifty hyperplastic and 50 adenomatous polyps received consecutively in the laboratory were categorized by nine histopathologists, and the level of agreement between all observers and the original diagnosis was assessed using kappa statistics. Results: For the eight observers with 11 months or more experience in histopathology, there was a high level of agreement with kappa statistics ranging from 0.84 to 0.98. This process was performed rapidly with an average of 13 to 22 seconds spent on each case. One observer with only 6-weeks’ experience of histopathology had a lower overall level of agreement with kappa statistics ranging from 0.46 to 0.54, but the performance on the later cases was much higher.Conclusions: The level of agreement in the distinction between hyperplastic and adenomatous colorectal polyps is high among histopathologists with at least moderate amounts of experience in histopathology. The one virtually naïve observer showed a marked learning response during the study without feedback on case outcome. This suggests that histopathologists are very reliable in assigning cases to distinct nominal categories and that learning of these processes occurs early in a histopathologist’s career.

A bite into the history of the autopsy : From ancient roots to modern decay.

The autopsy has had a checkered history, much of which has been surrounded by controversy. The roots of human dissection are found in the ancient world where rumors flourished that the prosectors of the day were engaged in vivisection as well as dissection. Bound up with the prevailing religious and political systems of the day, the autopsy has alternately been prohibited and encouraged, used to explore the nature of disease, and conceal questionable political policy. This review explores the history of the autopsy from its ancient roots in Egypt, Mesopotamia, Alexandria, and the Far East through the dark ages to medieval times and beyond into the renaissance. The development of the autopsy in Europe during the 17th to 19th centuries is discussed before briefly considering the decline of this diagnostic tool in the 20th century.

Videos have a role in postgraduate necropsy education

Aims: This is the first study to investigate the usefulness of structured, scripted videos as an adjunct to the mortuary based training of histopathology trainees in necropsy techniques. Methods: Four structured and scripted videos describing aspects of necropsy health and safety, evisceration, general dissection techniques, specialist dissection techniques, and reconstruction were shown to histopathology trainees attending the 2001 University of Sheffield short course on the autopsy. Delegates who agreed to participate in the study were asked to complete a short questionnaire seeking Likert-type and free text responses concerning the usefulness of the videos in postgraduate necropsy training. Free text responses were analysed using a themed content analysis. Results: All 38 delegates who viewed the videos agreed to participate in the study. Of these, 35 found the videos enjoyable and 34 found them interesting. Thirty one felt the videos enhanced their learning experience. Advantages of the videos included the ability to learn about specialist techniques rarely encountered in the mortuary, the ability to teach large numbers of students at once, allowing students to learn at their own pace, and as a tool for revision. Repetition between the videos, a lack of interactivity, and a lack of sufficient detail on general necropsy techniques were felt by participants to be the principal disadvantages of this teaching tool. Conclusions: Videos are an acceptable teaching tool for students. They have a valuable role to play as an adjunct to dissection in teaching junior histopathology trainees about specialist necropsy dissection techniques.

Evidence-based learning: a lack of evidence - Letter to the Editor

In their recent article, Eitel & Steiner (1999) highlight medical educators’ resistance to change in pedagogy despite empirical evidence that the adoption of problem-based learning (PBL) induces lifelong learning. Such resistance has often led to the failure of reforms in medical education. It is, however, generally recogn ized that educational outcomes (e.g. examination results) do not fully correlate with competence in medical practice. Factual overload and the graduation of students with professional de® ciencies has prompted a review of the traditional medical curriculum and the teaching format in the UK (GMC, 1993) and elsewhere. The authors suggest the synthesis of PBL with a critical appraisal of the literature to produce `evidencebased learning’ (EBL) as a model to conceptualize a change in pedagogy which fosters an intrinsic motivation to learn. In the model proposed, students are faced with a problem and encouraged to `brainstorm’ a solution. A moderator encourages the students to reach a consensus view which is then documented in the form of a concept map or algorithm. The students are next directed to information sources (e.g. the library, Medline, the Internet) and encouraged to gather and critically appraise evidence for comparison with the group’s solution.The evidence is compared with the original opinion, modifying the original concept map if necessary to produce an evidence-based concept map.The map is evaluated for its ease of implementation. The authors note the similarity between the seven steps of this process and those of evidence-based medicine and thus derive the term `evidence-based learning’ . We suggest that this term is misleading.While we do not deny that the theoretical design and goal of this teaching method (a to compare the best evidence of the literature with one’s own and the group’s conduct directed towards quality educationo ) is laudable, we question the nature of this paper which is presented as a `case study’ . The authors offer `data’ in their results in the form of numerical correlations between concepts of instructional design criteria (quality of teaching, student autonomy, feedback and social integration) with learners’ perceptions (self-efficacy and competence, feeling of autonomy and intrinsic motivation). How these values were derived is not stated; this type of de ® ciency would render a paper non-contributory to evidence-based medicine. Furthermore, in an attempt to promote the adoption of EBL the authors suggest that resistance to pedagogical change can be reduced by a series of actions including: a search for the value inherent in the endeavour; interpreting the problem on an empirical basis; de® ning clear objectives; and audit goal attainment and feedback. As medical practitioners and medical educators, we are exposed to the values of evidence-based practice, requiring evidence that change will produce a measurable improvement in outcomes. The lack of evidence in this paper typi ® es the pseudoscience masquerading as research in medical education. We are not resistant to pedagogical change, but (as in our medical practice) require quantitative or qualitative evidence before accepting `change’ as `improvement’ . The lack of such evidence, we suggest, is the principal reason why medical practitioners have been so reluctant to change their educational practice. Why should the evaluation of changes in medical education be exempt from the academic rigour with which we conduct our other professional activities?