Thomas Mairinger

Pathologists' attitudes to implementing telepathology

If pathologists will benefit so much from using telepathology, why is it taking so long to be introduced? This question has been discussed between experts, but the potential users are rarely asked for their opinions. A questionnaire was sent to the 256 members of the Austrian Society of Pathology; this addressed general aspects of telemedicine, telepathology in frozen-section services and expert consultation, videoconferencing technologies, teleteaching and teletraining. The response rate was 46 . In general, the pathologists thought that telemedicine could become valuable in their daily routine. However, pathologists were most afraid of sampling errors in remote diagnosis and would not readily accept an alternative to the conventional method of looking at a sample. This is only possible using realtime, remotely controlled microscopes. Telepathology systems providing only still images would not be acceptable to most respondents. There was interest in the use of videoconferencing for clinicopathological conferences. Teleteaching and teletraining were seen as welcome additional techniques, but were nevertheless judged unable to replace classical methods of teaching and training.

Capillary deposition of the complement fragment C4d in cardiac allograft biopsies is associated with allograft vasculopathy

Cardiac allograft vasculopathy (CAV) is a long‐term threat in heart transplant recipients and its exact pathogenesis remains to be established. As complement activation contributes to early and late allograft dysfunction, we hypothesized that deposition of the complement fragment, C4d, in capillaries of cardiac allograft biopsies may be associated with CAV. A polyclonal anti‐C4d antibody was used for immunohistochemistry on endomyocardial biopsies obtained from heart transplant recipients during the first year post‐transplantation. CAV was assessed by intracoronary ultrasound performed at 1‐year post‐transplantation. We were able to show that CAV is highly associated with C4d deposition in capillaries of cardiac allografts and that serial C4d studies may predict development of CAV at 1‐year post‐transplantation.

Optimized preembedding method improves the histologic yield of prostatic core needle biopsies

The aim of this study was to optimize the core shape of prostatic core needle biopsies using a novel preembedding method, and to investigate the influence of the number of cores per tissue block on the histologic yield per section level.

What do students think about telemedicine

A questionnaire was distributed to 300 medical students attending a conference in 1996. The return rate was 32 . The majority of students believed that telemedicine will become very important in future. About a quarter of students had had practical experience of telemedicine in a hospital. More than 75 of the respondents said that they would attend telemedicine lectures if they were offered by their university. There were no major concerns among medical students about telematics and its applications in medicine. There was a clear need for more information, which suggests that universities should offer special lectures and practical courses in telemedicine. The interest of students in tele-learning was very high. This interest would justify more attempts to introduce tele-learning by the universities.

RADICAL PROSTATECTOMY: THE VALUE OF PREOPERATIVE, INDIVIDUALLY LABELED APICAL BIOPSIES

PURPOSE Involvement of the prostatic apex with adenocarcinoma is a relatively common finding, as is a positive surgical margin at this location. We evaluated whether a positive apical core biopsy provides preoperative information that may be used as a basis for the subsequent surgical approach in individuals. MATERIALS AND METHODS We evaluated apical prostate cancer in 240 individually labeled, preoperative apical core biopsies and the corresponding prostatectomy specimen in 120 patients who underwent radical prostatectomy for clinically localized prostate cancer. Sensitivity, specificity, and positive and negative predictive values were calculated for the ability of an individual apical core to predict the side of tumor in the surgical specimen using 2 x 2 contingency tables. Moreover, univariate subset analysis was done for positive biopsies to assess the ability of histopathological characteristics, including Gleason score, cancer length, percent of cancer in the core and distance of cancer from the inked rectal core end, to predict a positive surgical margin at the apex. RESULTS The positive predictive value of a single positive apical core for identifying tumor location correctly in the prostatectomy specimen was 71.1%, while absent cancer in the apical biopsy had a negative predictive value of 75.5%. Sensitivity was 44.5% for a positive biopsy core. In this context the predictive value of an individual positive apical core biopsy was only 28.8% for predicting surgical margin positivity at the apex. CONCLUSIONS Cancer and its histopathological characteristics in an individual core biopsy failed to predict apical tumor involvement as well as a positive apical margin at subsequent radical prostatectomy.

Acceptance of Telepathology in Daily Practice

The availability of pathology services differs greatly in our environment. Although pathology would be especially suitable for being practised at a distance by transporting digital image information, the spread of telepathology into everyday work still is relatively slow. The article describes the situation of diffusion of this innovative technology by reviewing the literature and discussing this in context to data based on questionnaires dealing with the acceptance of telepathology. The current situation of telepathology can be discussed by five items for innovation spead: (1) communication and influence; (2) economic costs and benefits; (3) knowledge barriers and learning; (4) feasibility of techniques offered for the demands of the users; (5) clarification of the legal status and other factors concerning international collaboration. All these head lines do not represent realistic obstacles for the more widespread use of telepathology. The real drawbacks may therefore be found behind certain professional habits of pathologists. The most important causes may be that (a) telediagnosis is not as easy as it may seem at the first glance; (b) telepathology is seen as a potential highway to a world‐wide competition of pathology service providers. As soon as these mostly unjustified prejudices are corrected and telepathology is percepted as additional technique in pathology, it will become a diagnostic tool as common and as useful as the telephone.

Computer-assisted image analysis–derived intermediate endpoints

The development of prostatic lesions undergoes a slow progression. To establish efficacy of chemopreventive intervention it is therefore necessary to define surrogate endpoint biomarkers. Such biomarkers should be sensitive in their ability to indicate response. They should be objective, ie, the result of measurement, and numerically defined so that a statistical validation of response is possible. They should be able to indicate not only a halt of progression of a lesion, but also a reversal of progression. The spatial and statistical distribution of nuclear chromatin in the secretory and luminal cells in prostatic intraepithelial neoplastic lesions has been shown to be well defined. It can be represented by a set of features. These have been used to define a progression curve along which progression or regression of a lesion can be assessed. One could define a fixed endpoint, or one might choose to accept a statistically significant regression along the progression curve as criterion for chemopreventive efficacy. Expected difficulties could arise from lesion heterogeneity, as it would affect the sampling, and from multifocal lesions of differing progressions. Lesion heterogeneity thus limits the precision with which regression could be detected. These problems might be partially overcome by observations taken in histologically normal appearing regions of the prostate. The nuclear chromatin pattern of secretory cell nuclei measured in such tissue regions from prostates harboring intraepithelial or malignant lesions has been shown to exhibit distinctive changes from the chromatin pattern seen in secretory cell nuclei from prostates free from any such lesions. These changes appear to be expressed in the tissue up to a substantial distance from a lesion. The expression of changes in the nuclear chromatin suggests the existence of an intraepithelial preneoplastic lesion that can be detected by biomarkers, but which is not apparent from visual microscopic inspection. Since chemoprevention might be expected to be most effective at the earliest stages of lesion development, the assessment of such early alterations is seen as highly relevant to efforts to validate the efficacy of chemopreventive intervention.

DNA-ploidy analysis correlates with the histogenetic classification of thymic epithelial tumours

The ploidy values of the epithelial component were determined in a series of thymomas and organotypic thymic carcinomas using image cytometry and the results were compared with the histological tumour subtypes according to the histogenetic classification introduced by Marino, Müller Hermelink, and Kirchner (MMHK). Forty‐six cases of thymic epithelial tumours were included in the study. After reclassification according to the MMHK classification, the distribution among the subtypes was as follows: three medullary, nine mixed type, five predominantly cortical (organoid), 16 cortical thymomas, and 13 well‐differentiated thymic carcinomas. Single cell preparations were made from paraffin‐embedded tumour tissue and stained according to Feulgen. Ploidy analysis was performed using an automated image analysis system. In five cases, DNA cytometry could not be performed, for technical reasons. The remaining 41 cases consisted of 11 diploid and 30 non‐diploid tumours. The percentage of aneuploid tumours in the different subtypes increased from medullary (0 per cent) through mixed type (44·4 per cent), predominantly cortical (75 per cent), cortical (83·3 per cent) to well‐differentiated thymic carcinomas (100 per cent). DNA‐ploidy determination using image cytometry correlates with the concept of the MMHK classification of thymomas. Copyright

Atypical Carney’s triad with coincidental clear cell renal carcinoma in an 84-year old patient—a finding at autopsy

Carneys triad is a syndrome of unknown etiology, representing a combination of gastrointestinal stromal tumors, bronchial chondromas and vagal, adrenal or paraadrenal paragangliomas. Two of the Carneys triad components-the paragangliomas and the gastrointestinal stromal tumors-are potentially lethal. Since its first description in 1977, 79 cases have been reported so far. We report an 84-year-old male patient, who died of a hypertensive cerebral hemorrhage. Well-differentiated clear cell carcinoma of the right kidney, chondroma of the right bronchus and multiple jejunal stromal tumors were detected at autopsy. To our knowledge, this is the first report of a coincidental clear cell renal carcinoma in a patient with an atypical Carneys triad.

Are nuclear texture features a suitable tool for predicting non-organ-confined prostate cancer?

PURPOSE We investigated the possibility of determining organ confinement of prostate cancer using multiple nuclear texture features determined by fully automated high resolution image analysis combined with preoperative serum PSA levels. MATERIALS AND METHODS The study population consisted of 145 patients (61 organ confined and 84 non-organ-confined cases). Nuclear texture features were determined using single cell preparations of radical prostatectomy specimens. Nuclear texture features were extracted and analyzed by multivariate logistic regression analysis in order to build a classifier for distinguishing between organ confined and non-organ-confined tumors. The classifier was designed in a cell by cell model and tested on a case by case analysis. RESULTS The predictive probability of the trained classifier in the cell by cell analysis had a sensitivity of 63%, a specificity of 53%, a positive predictive value of 75% and a negative predictive value of 38% and an area under the ROC curve of 0.58. In the case by case analysis the sensitivity was 70%, the specificity was 54%, positive predictive value 78%, negative predictive value 74%, area under the ROC curve 0.62. When preoperative PSA was included in the algorithm, sensitivity raised to 80%, specificity to 60%, the positive predictive value raised to 79%, the negative predictive value to 52% and the area under the ROC curve to 0.70. CONCLUSIONS In contrast to former studies using tissue sections, our results suggest that nuclear texture features extracted from single cell preparations cannot be used as a reliable parameter for the determination of organ confinement in prostatic adenocarcinomas.