Section 1 -

The Autopsy Sebastian Lucas

Utility of the autopsy The diagnostic autopsy dominated pathology for more than a century, but is now under significant threat as pathology practice changes (at least in industrialised countries). Nonetheless it still has a vital role in Diagnosis of cause of death Feedback to clinicians and for audit of medical practice Education for health care workers and the public Developing a knowledge base of disease and research into clinical pathology and diagnostics Monitoring changes in disease clinical pathology as medical practice changes Surveillance and identification of unusual and new patterns of clinical pathology Over the last 30 years, the autopsy has proved its role in diagnosis and description of new and re-emerging diseases including: HIV pandemic (1981 - ) Haemorrhagic fever outbreaks (1995 - ) SARS (2003 - ) In particular, when a disease is emerging and common, a cross-sectional autopsy study of deaths can provide reasonably accurate data on the prevalences of specific aspects of that disease. These prevalences may vary considerably between different countries. In HIV disease this was very evident: tuberculosis was (and is) very common in African countries, whilst pneumocystis was very uncommon; the reverse pertained in UK among the gay HIV+ population. Many regions have HIV-related opportunistic infections that are specifically local: eg Chagas' disease in South America and penicilliosis in the far East. Autopsy quality Feedback to clinicians on individual cases through mortality meetings necessitates high quality autopsy examinations, otherwise the clinical staff do not obtain answers to their questions on pathophysiology and therapeutics, and may regard the autopsy as an unilluminating waste of time. This is a particular issue when forensic pathologists, whose primary interest is homicide, are employed in the investigation of complex medical, infectious and post-intervention deaths [see NCEPOD reports]. Impact on medical practice The impact of autopsy on changing and improving medical practice (and thus patient outcome) should be self-evident, but actually is poorly documented. The AHRQ report noted that there were no peer-reviewed publications that specifically showed how autopsy feedback had improved medical care. This is because it is not an area that pathologists or clinicians have focussed upon in research or audit reviews hitherto, and it does not appear in keywords for published articles. One positive example, however, is the cause of focal brain lesions in patient with HIV infection in West Africa: autopsy showed that the great majority were toxoplasmosis, and that cerebral lymphoma was rare. This enabled clinicians to manage such clinical presentations empirically and effectively [Lucas et al, 1993]. In the same publication, the problem of differentiating pre-mortem pulmonary tuberculosis from nocardiosis is also addressed, through autopsy data. Changing patterns of disease Whilst it cannot be proved that the autopsy has directly changed medical practice, the results of autopsy are part of the evidence base that notes how clinical pathology of a disease alters over time. HIV is a good and recent example. In the first decade of the HIV pandemic, before anti-retroviral (ARV) therapy significant extended life expectancy, the common causes of death – in industrialised countries - in HIV+ persons were predominantly classical opportunistic infections and tumours such as pneumocystosis and Kaposi's sarcoma. Since 1997 and the widespread uptake of ARV, these have declined as cause of death, whilst other diseases such as chronic liver disease (HCV related), ischaemic heart disease, renal disease, non-HIV related cancer, and sepsis have increased. Lymphoproliferative disease has a more complex evolving pattern as survival on ARVs improves. Treatment complications New effective treatments often have significant toxic side effects. HIV disease has demonstrated this many times. Two particular side effects are noted: Direct toxicity - non-nucleoside reverse transcriptase inhibitors can induce steatosis in the liver and lactic acidosis, which may be fatal. These happen because of mitochondrial toxicity. Immune restoration inflammatory syndrome (IRIS) - many infections present or recrudesce with expansive inflammatory lesions when immune competence improves on ARV therapy. If in the lung or brain, this may be fatal The autopsy has demonstrated many examples of these effects. In resource-poor countries, when treated HIV+ patients come to autopsy, careful note of potential toxicity-induced pathologies should be made and the information relayed back to the central HIV programme agencies. Technical requirements for satisfactory autopsy practice In the mortuary: The obvious requirements are a well equipped mortuary and competent staff. The mortuary building should have: Facility for storing bodies in refrigerators Adequate space for cadaver examination Appropriate protective clothing for pathologists and anatomical pathology technologists (APTs) Proper dissection tables and related surfaces Good lighting Good ventilation (cross or down-draft) Water for the tables and for cleaning Dissection tools including saw (mechanical or electrical) for opening the head Safe cleaning and disposal facilities for soiled instruments and clothing Formalin fixative for organ and tissue preservation Access to high quality histopathology laboratory For autopsy histopathology: Good quality tissue processing Good H&E slide preparation Special stains: minimum - Ziehl-Neelsen, PAS, Grocott, Gram Immunocytochemistry: CMV, herpes simplex, toxoplasma, HHV8, lymphoma markers (or access to a lab with these methods) Archiving facilities for tissue blocks and slides Health & safety Since HIV and other emerging infections are potentially transmissible to health care workers (pathologists and APTs), and may cause acute, chronic and fatal disease, it is critical to be aware of the hazards and how to reduce them to a minimum acceptable by all relevant staff. The UK guidelines [HSAC] are a model that can be adapted to local needs. A critical factor is education of all relevant health care workers; APTs are often poorly educated and therefore more prone to infectious risk. It is the responsibility of the better educated and informed pathologists to ensure that his co-workers are placed in unacceptable hazardous conditions. References Agency for Healthcare Research & Quality (AHRQ). Publication 03-E002. 'The autopsy as an outcome and performance measure'. October 2002. www.ahrq.gov. Lucas S et al. The mortality and pathology of HIV disease in a West African city. AIDS 1993, 7: 1569-1579. Lipman & Breen. Immune reconstitution inflammatory syndrome in HIV. Current Opinion in Infectious Disease, 2006, 19:20-25. Bower M et al. AIDS-related malignancies: changing epidemiology and the impact of highly active antiretroviral therapy. Curr Opin Infect Dis. 2006 Feb;19(1):14-9. Review. Palella F et al. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV Outpatient Study. J.Acq.Immune.Defic.Syndr. 2006 July 25 epub ahead of print. Krentz HB et al. Changing mortality rates and causes of death for HIV-infected individuals living in Southern Alberta, Canada. HIV Medicine 2005, 6:99-106. Hwang DM et al. Pulmonary pathology of severe acute respiratory syndrome in Toronto. Mod Pathol. 2005;18:1-10. Zaki SR et al. A novel immunohistochemical assay for the detection of Ebola virus in skin: implications for diagnosis, spread, and surveillance of Ebola hemorrhagic fever. J Infect Dis. 1999 Feb;179 Suppl 1:S36-47. Health Services Advisory Committee (HSAC). Safe working and prevention of infection in the mortuary and post-mortem room. London 2003. www.hse.gov.uk National Confidential Enquiry into Patient Outcome & Death (NCEPOD). Reports since 1990. www.ncepod.org.uk