(1/578) An assessment of the operation of an external quality assessment (EQA) scheme in histopathology in the South Thames (West) region: 1995-1998.
AIMS: To describe the design and organisation of a voluntary regional external quality assessment (EQA) scheme in histopathology, and to record the results obtained over a three year period. METHODS: A protocol is presented in which circulation of EQA slides alternated with teaching sessions. Procedures for the choice of suitable cases, evaluation of submitted diagnoses, and feedback of results to participants are described. The use of teaching sessions, complementary to the slide circulations, and dealing with current diagnostic problems is also outlined. RESULTS: Participation rates in the nine slide circulations varied between 66% and 89%, mean 85%. Overall scores were predictably high but 4% of returns, from 10 pathologists, were unsatisfactory. These low scores were typically isolated or intermittent and none of the participants fulfilled agreed criteria for chronic poor performers. CONCLUSIONS: This scheme has been well supported and overall performances have been satisfactory. The design was sufficiently discriminatory to reveal a few low scores which are analysed in detail. Prompt feedback of results to participants with identification of all "incomplete" and "wrong" diagnoses is essential. Involvement of local histopathologists in designing, running, and monitoring such schemes is important. (+info)
(2/578) The efficacy and limitations of repeated slide conferences for improving interobserver agreement when judging nuclear atypia of breast cancer. The Japan National Surgical Adjuvant Study of Breast Cancer (NSAS-BC) Pathology Section.
BACKGROUND: The pathology section of the Japan National Surgical Adjuvant Study of Breast Cancer protocol study was set up to establish histological criteria for assessing high-risk node-negative breast cancers and standardize the subjective criteria used by collaborating pathologists for nuclear grading of cancers. METHODS: In order to standardize the nuclear atypia criteria, five slide conferences were held. A total of 57 observers assigned nuclear atypia scores to 119 breast carcinomas that were presented using a slide projector or a TV monitor and discussed their histological findings. The percentage interobserver agreements per tumor and per conference and kappa value per conference were estimated and compared among the conferences. The percentage intraobserver reproducibility per tumor between the last two conferences was compared with the percentage interobserver agreement for 20 tumors. The kappa value was also calculated for each of 27 observers to evaluate scoring reproducibility. RESULTS: The percentage interobserver agreement per conference was constant (75-78%) throughout the five meetings and the rate of tumors with > 80% agreement per tumor became higher in later conferences. The kappa value was 0.42, 0.25, 0.42, 0.51 and 0.50 for the first, second, third, fourth and fifth conferences, respectively. The tumors with a lower percentage interobserver agreement also had a lower percentage intraobserver reproducibility and such scoring variations were attributed to the intermediate nature of the degree of tumor atypia. In 26 of 27 observers, intraobserver agreement for 20 tumors was estimated from the kappa value to range from moderate to almost perfect. CONCLUSION: We concluded that the repeated slide conferences conducted by the pathology section were an effective means of standardizing the subjective histopathological criteria used to assess tumors. However, the achievement of a good scoring agreement would be difficult for tumors with an intermediate degree of atypia. (+info)
(3/578) Attracting and training more chemical pathologists in the United Kingdom.
I have attempted to define the function of the medical graduate in the clinical biochemistry laboratory and have examined data on recrutiment in the United Kingdom into clinical biochemistry. If trainee pathologists were encouraged to become proficient in both a branch of clinical medicine and in research techniques, the resulting chemical pathologists should be able to improve the consultative and investigative functions of the laboratory. To this end I have suggested some changes in the training regulations and in the role of the chemical pathologists. (+info)
(4/578) The pathologist and toxicologist in pharmaceutical product discovery.
Significant change is occurring in the drug discovery paradigm; many companies are utilizing dedicated groups from the toxicology/ pathology disciplines to support early stage activities. The goal is to improve the efficiency of the discovery process for selecting a successful clinical candidate. Toxicity can be predicted by leveraging molecular techniques via rapid high-throughput, low-resource in vitro and in vivo test systems. Several important activities help create a platform to support rapid development of a new molecular entity. The proceedings of this symposium provide excellent examples of these applied concepts in pharmaceutical research and development. Leading biopharmaceutical companies recognize that a competitive advantage can be maintained via rapid characterization of animal models, the cellular identification of therapeutic targets, and improved sensitivity of efficacy assessment. The participation of the molecular pathologist in this quest is evolving rapidly, as evidenced by the growing number of pathologists that interact with drug discovery organizations. (+info)
(5/578) Mechanisms of disease and injury: utilization of mutants, monoclonals, and molecular methods.
Rapid advances in our ability to localize and quantify macromolecular changes in health and disease are being brought about by the availability of genetically altered animals (mutants), purified reagents such as monoclonal antibodies, and new molecular methods. Targeted gene deletion (knockouts) and gene insertions (transgenics) in animals can allow identification of the importance and function of macromolecules. Monoclonal antibodies and fluorescent labels coupled with advances in microscopy provide exacting and multi-dimensional information about localization and cellular changes in proteins, carbohydrates, and lipids using immunohistochemistry, fluorescent activated cell sorting, and immunoprecipitation. Similarly, new applications of molecular methods can be used to identify and localize nucleic acids in tissues via in situ hybridization, polymerase chain reaction (PCR), reverse transcription (RT) PCR, differential display RT-PCR, RNase protection assays, and microchip arrays. The ligand for CD40 (CD40L), an important immunoregulatory molecule, is an example of the successful application of mutants, monoclonal antibodies, and molecular methods to cloning and biological characterization of new molecules. CD40L knockout mice, monoclonal antibodies, and several molecular methods were used to identify mutations in CD40L as the genetic basis for hyper-IgM syndrome in humans, to provide new insights into the pathobiology of Pneumocystis carinii infection, and to evaluate CD40L for immunotherapy of tumors and opportunistic infections. (+info)
(6/578) Computer-based teaching of pathology at the Zagreb University School of Medicine.
AIM: To review the experience gained in transferring USA computer-based teaching system of medical school pathology to Croatia. METHODS: Computer-based teaching program of pathology developed at the University of Kansas School of Medicine, Kansas City, Kansas, USA, was transferred to the University of Zagreb School of Medicine, Zagreb, Croatia. The experimental group of 49 students was enrolled into this computer-based program. Their performance was compared with that of 195 classmates enrolled in the standard course. Objective (performance on the examinations) and subjective data (students' interviews and written evaluations of the course) were analyzed. RESULTS: The computer program was operational 5 months from the inception of the transfer. It was well received by the students, even though many initially complained that it required more effort and a continuous commitment. The major problems concerned scheduling, reflecting various requirements i mposed on students by other departments teaching in parallel with the Pathology course. Objective data gathered so far indicate that the students enrolled in the computer-based program took the first midterm examination at a significantly higher rate than the rest of the class (p<0.001), and passed the examination with significantly better grades (p<0.001). CONCLUSION: Computer-based teaching programs can be readily transferred to other countries. Full implementation of the program, however, may require significant changes in the existing curriculum in the medical school to which such a program has been transferred or considerable modifications in the program adopted for transfer. It appears that the students enrolled in the computer-based program perform better than students in the standard pathology course. (+info)
(7/578) A century of pathology at Yale: personal reflections.
This history is largely about the players on the stage of the Yale Pathology Department acting out their roles as observed by the author in over a half century as a member of the department and as associate dean of the medical school. (+info)
(8/578) An evaluation of the Banff classification of early renal allograft biopsies and correlation with outcome.
BACKGROUND: The Banff classification for assessment of renal allograft biopsies was introduced as a standardized international classification of renal allograft pathology and acute rejection. Subsequent debate and evaluation studies have attempted to develop and refine the classification. A recent alternative classification, known as the National Institutes of Health Collaborative Clinical Trials in Transplantation (NIH-CCTT) classification, proposed three distinct types of acute rejection. The 1997 Fourth Banff meeting appeared to move towards a consensus for describing transplant biopsies, which incorporated both approaches. Patients who received a renal allograft at the Oxford Transplant Centre were managed by a combination of protocol and clinically indicated biopsies. We have undertaken a retrospective analysis of the biopsies correlated with the clinical outcome to test the prognostic value of the original Banff (Banff 93-95) and NIH-CCTT classifications. METHODS: Three hundred and eighty-two patients received renal allografts between May 1985 and December 1989, and were immunosuppressed using a standard protocol of cyclosporine, azathioprine and steroid. Adequate 5-year follow-up data were available on 351 patients, and of these, 293 had at least one satisfactory biopsy taken between days 2 and 35 after transplantation, the latter patients forming the study group. The D2-35 biopsies taken from these patients, which were not originally reported according to the Banff classification, were re-examined and classified according to the Banff 93-95 protocols. For each patient the biopsy found to be the most severely abnormal was selected, and the Banff and NIH-CCTT grading compared with the clinical outcome. RESULTS: Seven hundred and forty-three biopsies taken from 293 patients between days 2 and 35 after transplantation were examined and the patients categorized on the basis of the 'worst' Banff grading as follows. Normal or non-rejection, 20%; borderline, 34%; acute rejection grade I (AR I), 18%; AR IIA, 6%; AR IIB, 14%; AR III, 1%; AR IIIC, 3%; widespread necrosis 3%. The clinical outcome for the last two groups combined was very poor with 18% of grafts functioning at 3 months and 6% at 5 years. The other groups with vascular rejection (AR IIB and AR III) had an intermediate outcome, graft survival being 78% at 3 months and 61% at 5 years. The remaining four groups (normal, borderline, cellular AR I and AR IIA) had the best outcome: graft survival 95% at 3 months and 78% at 5 years with virtually no difference between the four groups. Three forms of acute rejection, namely tubulo-interstitial, vascular and transmural vascular, were identified, but only the latter two categories were associated with a poor outcome. CONCLUSIONS: The eight sub-categories of the Banff classification of renal allograft biopsies are associated with three different prognoses with respect to graft survival in the medium term. These three prognostic groups correspond to the three NIH-CCTT types. The data provide support for the consensus developed at Banff 97 separating tubulo-interstitial, vascular and transmural vascular rejection (types I, II and III acute rejection). (+info)