Evaluation of medical decision support systems (DDX generators) using real medical cases of varying complexity and origin.

BACKGROUND: Medical decision support systems (CDSSs) are increasingly used in medicine, but their utility in daily medical practice is difficult to evaluate. One variant of CDSS is a generator of differential diagnoses (DDx generator). We performed a feasibility study on three different, publicly available data sets of medical cases in order to identify the frequency in which two different DDx generators provide helpful information (either by providing a list of differential diagnosis or recognizing the expert diagnosis if available) for a given case report. METHODS: Used data sets were n = 105 cases from a web-based forum of telemedicine with real life cases from Afghanistan (Afghan data set; AD), n = 124 cases discussed in a web-based medical forum (Coliquio data set; CD). Both websites are restricted for medical professionals only. The third data set consisted 50 special case reports published in the New England Journal of Medicine (NEJM). After keyword extraction, data were entered into two different DDx generators (IsabelHealth (IH), Memem7 (M7)) to examine differences in target diagnosis recognition and physician-rated usefulness between DDx generators. RESULTS: Both DDx generators detected the target diagnosis equally successfully (all cases: M7, 83/170 (49%); IH 90/170 (53%), NEJM: M7, 28/50 (56%); IH, 34/50 (68%); differences n.s.). Differences occurred in AD, where detection of an expert diagnosis was less successful with IH than with M7 (29.7% vs. 54.1%, p = 0.003). In contrast, in CD IH performed significantly better than M7 (73.9% vs. 32.6%, p = 0.021). Congruent identification of target diagnosis occurred in only 46/170 (27.1%) of cases. However, a qualitative analysis of the DDx results revealed useful complements from using the two systems in parallel. CONCLUSION: Both DDx systems IsabelHealth and Memem7 provided substantial help in finding a helpful list of differential diagnoses or identifying the target diagnosis either in standard cases or complicated and rare cases. Our pilot study highlights the need for different levels of complexity and types of real-world medical test cases, as there are significant differences between DDx generators away from traditional case reports. Combining different results from DDx generators seems to be a possible approach for future review and use of the systems.

[Ten years of telepathology for a mission hospital in Tanzania]. / 10 Jahre Telepathologie für ein Missionskrankenhaus in Tansania.

BACKGROUND: A collaboration between a hospital in Tanzania and a German institute for pathology was initiated in 2007 with the aim of establishing a working telepathological connection using the internet-based platform iPath to transmit static histological images. OBJECTIVES: This study aimed to describe the diagnostic spectrum evaluated in the course of an aid project in a developing country in Africa. MATERIAL AND METHODS: A total of 5230 diagnoses were analyzed, including cases that could only be definitively concluded after a second analysis of the paraffin-embedded material in Germany. The most frequent diagnoses in the five largest diagnostic groups from 17 different anatomical locations were surveyed. In addition, cases sampled from children/young adults and rare diagnoses were assessed separately. RESULTS: Altogether we diagnosed 2934 (56.1%) benign and 2134 (40.8%) malignant diseases. The number of cases sent to Germany for a second opinion was 734 (14%). The five most common anatomical locations were the uterine cervix (n = 1211), the prostate (n = 728), skin (n = 626), breast (n = 524), and lymph nodes (n = 340). Children comprised 504 cases (9.6%). Typical tropical diseases were only rarely seen in the whole collective of cases. CONCLUSIONS: By means of telepathology histopathological diagnoses can be supplied in a short period of time. Difficulties occurred mainly due to the unstable staff situation on site and because the quality of sampled biopsy material was not always sufficient for further investigations. Furthermore, it became clear in the course of this aid project that a predominance of standard diagnostic findings routinely seen in the pathology of tumors and infections can be anticipated rather than exotic diseases.

[Testicular metastasis of a metachronous small cell neuroendocrinic prostate cancer after anti-hormonal therapy of a prostatic adenocarcinoma. Case report and literature review]. / Hodenmetastase eines metachronen kleinzelligen neuroendokrinen Prostatakarzinoms nach Hormontherapie eines Adenokarzinoms der Prostata. Fallbericht und Literaturübersicht.

Secondary malignant testicular tumors are rare, with the exception of infiltrations by lymphomas and leukemias. Metastases are sometimes found in cancers of the lung, gastrointestinal tract, kidney, skin and prostate. Less than about 200 cases of testicular metastasis of prostate cancer have been described in the literature. This is this a very small number in comparison to the high incidence of prostate cancer and the vast number of orchiectomies for operative hormone deprivation in advanced cases. The testicle metastases described are mostly unilateral and are often found as ductal carcinoma of the prostate. In our case, the testicular metastasis from a small cell prostate carcinoma appeared 2.5 years after androgen deprivation of an adenocarcinoma of the prostate.

Diagnostic errors in interactive telepathology.

Telepathology (TP) as a service in pathology at a distance is now widely used. It is integrated in the daily workflow of numerous pathologists. Meanwhile, in Germany 15 departments of pathology are using the telepathology technique for frozen section service; however, a common recognised quality standard in diagnostic accuracy is still missing. In a first step, the working group Aurich uses a TP system for frozen section service in order to analyse the frequency and sources of errors in TP frozen section diagnoses for evaluating the quality of frozen section slides, the important components of image quality and their influences an diagnostic accuracy. The authors point to the necessity of an optimal training program for all participants in this service in order to reduce the risk of diagnostic errors. In addition, there is need for optimal cooperation of all partners involved in TP service.

Image quality and acceptance of Telepathology.

Aim: To evaluate the quality of components of electronic image, colortruth brightness and sharpness, via two capturing systems on acceptance of images, diagnostic accuracy and training effect. Methods: Ten histological and 4 cytological cases of routined breast specimens were capturing by a pathologist in Germany via two different capturing systems. The images were digitalized and saved on a recordable compact disc with brief clinical informations, and sent to a pathologist in Thailand. The test pathologist viewed the images at his own station, imitating the environment as daily work and noted the results for the analysis. Slides were sent to perform glass-slide diagnosis (GD) and recorded. The results were analyzed concerning: overall image quality in each system; viewing time; diagnostic accuracy; training effect. Main results: Results of 102 images are recorded as: number of images; score of the components of image quality; viewing Time; telepathology diagnosis (TD); glass-slide diagnosis (GD). Conclusions: 1. The capturing part plays an important role performing image quality and viewing time, resulting in the acceptance. 2. Electronic images of cytological cases are better in quality. 3. Training effect to view electronic images helped the acceptance of images used in telepathology, but did not help to increase the diagnostic accuracy in this study. 4. The reliability of electronic images is as high as viewing microscopic images in this investigation, especially in cytological cases via a good capturing machine.

Electric properties of an embedded piezoelectric layer.

The one-dimensional vibration mode of a piezoelectric layer under different load conditions has been reconsidered. Derived analytical expressions for admittance and impedance at special frequencies are listed. Based on the expressions derived, two applications are proposed involving electrical measurements on a piezoelectric plate. Concerned are first the determination of such plate material parameters which are relevant for its thickness mode of vibration. Difficulties due to spurious vibration modes are avoided in this approach. The second application deals with an alternative determination of acoustic material-impedances otherwise not easily obtainable: a piezoelectric plate is coupled to the material surface by a liquid. The influence of the coupling layer thickness is discussed and a measurement procedure is given by which the detrimental layer thickness effect is minimized.

Effects of Nd-YAG laser and cryosurgery on the oral mucosa in rabbits.

In 32 rabbits, lesions of comparable depths were created in the oral mucosa using a Nd-YAG laser (Medilas II, 1.06 microns, MBB Co., Munich) and a cryosurgery unit (Kryo-S, Erbe Co., Hannover). Histologic specimens were examined between 1 h and up to 8 weeks following operation. The laser lesion was restricted horizontally to the laser-exposed area; the full extent of the lesion could already be seen after 1 day. Cryosurgical lesions showed their maximum extent 3 days following treatment. Wound healing processes following laser application, were accelerated compared to cryosurgical procedure.

[The prognostic value of lymphangiosis carcinomatosa and malignancy grading in T1/T2-N0 cancers of the breast using 10 or fewer examined axillary lymph nodes]. / Prognostischer Wert der Lymphangiosis carcinomatosa und der Malignitätsgraduierung bei T1/T2-N0-Karzinomen der Brustdrüse mit 10 und weniger untersuchten axillären Lymphknoten.

In 270 cases of T1 and T2 carcinomas of the breast with ten or less axillary lymph nodes having been examined, the prognostic relevance of the histopathological statement of nodal negativity was assessed in a retrospective study. In this collective study, the mean number of lymph nodes examined was 4.1 +/- 1.9 for the 153 N0 carcinomas and 4.4 +/- 2.2 for the 117 cases with axillary lymph node metastases, respectively. The patients with N0 carcinomas were grouped according to the number of lymph nodes examined, thus resulting three subgroups, those with 1-2, 3-6, and 7-9 lymph nodes having been sampled and subjected to histopathologic evaluation. There was an approximately equal distribution in these three groups with respect to tumor size and tumor types; a correlation between the patients' age and the number of lymph nodes examined could not be found. A comparison of the three groups revealed conspicuous differences among the N0 carcinomas regarding both the disease-free survival time (DFS) and the overall survival time (OS), whereas a higher representativity of the determination of the nodal state, correlating with the number of lymph nodes examined, could not be confirmed. The disease-free survival time, the rate of disease recurrence as well as the median survival time and the 5-year survival rate, however, could be shown to be significantly dependent on tumor-related conditions, especially the grade of malignancy in connection with the presence or absence of peritumoral lymphatic or blood vessel invasion.(ABSTRACT TRUNCATED AT 250 WORDS)

[Comparison of raster mammography and real time sonography with histology in carcinoma of the breast]. / Vergleich der Rastermammographie und der Real-time-Sonographie mit Histologie bei Karzinomen der Brustdrüse.

In a retrospective study, the results of real-time sonography and grid mammography in 161 patients with histologically confirmed breast cancer were analyzed and compared with the histopathologic characteristics of the tumours to assess the diagnostic accuracy of these preoperative image-producing methods. The results showed the determination of the tumour size as obtained by the image-producing methods to correlate closely with the histopathologic findings. Furthermore, both real-time sonography and mammography yielded certain indications allowing prognostically valuable conclusions in respect of malignancy and invasiveness of the carcinomas. Taking into account the different but complementing diagnostic results of both methods, the combination of grid mammography and real-time sonography must be considered as the presently most reliable preoperative diagnostic procedure.

[Determination of the growth fraction using monoclonal antibody Ki-67 in breast cancers]. / Détermination de la fraction de croissance à l'aide de l'anticorps monoclonal Ki-67 dans les cancers du sein.

In 329 breast tissues (120 benign lesions and 209 invasive breast carcinomas) the growth fraction was determined using the monoclonal antibody Ki-67. The percentage of Ki-67 positive cells or the Ki-67 growth fraction was determined on histologic and cytologic specimens after immunoperoxidase staining. In benign breast lesions, the Ki-67 growth fraction never exceeded 11%, whereas in breast cancer 14.4 +/- 9.9% of cells were Ki-67 positive ranging from 1 to 48%. Breast carcinomas were classified according to the histologic grading system of Bloom and Richardson (G1-G3). Poorly differentiated carcinomas. (G3) had significantly higher Ki-67 growth fractions than well differentiated tumors (G1). Ki-67 was also correlated with axillary lymph node status. Growth fractions of N+ carcinomas were significantly higher than those of N0 tumors (16.4 +/- 10.4% versus 12.4 +/- 9.4%; p = 0.006). Thus, this new method yields similar results to those obtained by other researchers through the use of flow cytometry and thymidine labelling. As determination of Ki-67 growth fractions is an easy and rapid technique, it is ideal for routine clinical use. Ki-67 may be useful in prognosis and in the selection of patients for various treatment modalities such as adjuvant therapy. A wide-spread use of Ki-67 would be helpful to gain further experience.

Determination of growth fractions in benign breast disease (BBD) with monoclonal antibody Ki-67.

Certain types of benign breast disease (BBD) carry an increased risk of malignancy. Several morphological criteria such as an atypia score are used to define this group, and the use of a kinetic parameter may provide additional information. Therefore, the growth fractions of 120 benign breast lesions were determined using the monoclonal antibody Ki-67. The values obtained range from 0.3% to 10.8% (average 3.1% +/- 2.2%) compared to breast carcinomas with an average of 15.3% +/- 10.1%, range 0.8% to 47.8%. All specimens were classified using the terminology of Azzopardi. The prevailing histological entities were cystic disease, fibroadenoma, and blunt duct adenosis. Between these groups no differences in growth fractions were observed. Postmenopausal patients had slightly lower values than premenopausal women. Further prospective studies are needed to evaluate whether those cases of BBD with a high number of Ki-67 positive cells have an increased risk of breast cancer, independently from conventional histological classifications.

The correlation of growth fractions with histologic grading and lymph node status in human mammary carcinoma.

The monoclonal antibody Ki-67 reacts with a human nuclear associated with cell proliferation that is expressed only in the G1, S, G2, and M phases of continuously cycling cells. This offers a simple opportunity to determine the growth fraction of tumors by immunostaining of fresh tissue. One hundred fifty-four invasive carcinomas of the breast were used in this study. The average number of Ki-67 positive cells was 15.3 +/- 10.1% (range, 1%-48%), whereas in 41 benign lesions of the breast only 4.4 +/- 2.6% (range, 1%-10%) of cells were positive. A correlation was found between growth fractions and histologic grading. On average, N+ tumors with less than four positive lymph nodes had a significantly higher growth fraction (20.4 +/- 14.2%) than N0 tumors (13.0 +/- 9.2%), whereas N+ tumors with more than three lymph node metastases had only 17.3 +/- 3.6% Ki-67 positive cells. This method yielded similar results to those obtained by other researchers through the use of flow cytometry and thymidine labeling. Determination of growth fractions by Ki-67 is suitable for routine use and may be useful in prognosis and in the selection of patients for various treatment modalities.

Growth fractions in breast cancers determined in situ with monoclonal antibody Ki-67.

The growth fractions of 160 mammary carcinomas and 30 benign mammary lesions were determined in situ by immunostaining with the monoclonal antibody Ki-67. Benign lesions had a mean value of 3% Ki-67 positive cells, whereas the mean value of mammary carcinomas was 16.6%. A comparison of the mean values of Ki-67 positive cells with the histological grade of the tumours showed a correlation between these two variables--that is, histological grade 1 showed 9%, grade 2 16%, and grade 3 26% proliferating cells. Considering the individual Ki-67 values in the different histological grades, it was evident that there was considerable scatter in the number of proliferating cells, so that the proliferation rates of grades 1, 2, and 3 overlapped each other. This indicates a dissociation between histological grade of malignancy and size of the growth fraction in most breast cancers. Follow up studies are needed to establish which of the two variables--that is, morphological degree of malignancy, or the proportion of Ki-67 positive cells--correlates better with response to treatment and survival in individual cases.

[Mastopathy and breast cancer: is there a typical hormone profile?]. / Mastopathie und Mammakarzinom: Besteht ein typisches Hormonprofil?

Carcinoma of the breast and mastopathy are statistically correlated with the functioning of the gonads. The authors studied whether in 58 women with carcinoma of the breast and in 36 patients with mastopathy any change was seen in the secretory pattern of gonadal steroids and whether there were any latent changes in the secretion of prolactin and TSH. A group of 43 women with benign gynaecological diseases served as controls. Before making the diagnosis via immediate section for microscopic examination we determined the basal values of prolactin, LH, FSH, TSH and the oestrogen fractions E1, E2, E3, total oestrogens and progesterone. In addition, we measured the increase in prolactin and TSH after stimulation with metoclopramide. Postoperatively this was followed by measuring the basal values of prolactin and TSH and their secretory performance in respect of TRH. All histological diagnoses were made by an experienced pathologist. Examinations were performed under strictly standardised conditions, taking into account stress, circadian variation and the nutritional status. The following group-specific significant results were obtained (p less than 0.05-0.01): Mastopathy: high serum values of all oestrogen fractions and of total oestrogens, high PRL release through MTC stimulation, prolactin secretory effect after MTC in accordance with the degree of severity of epithelial proliferation, early onset of menopause. Carcinoma of the breast: Low PRL and TSH release on MTC stimulation, low progesterone concentrations during the second cycle phase, relatively high serum concentrations of oestradiol during the first cycle phase, PRL basal values increased postoperatively, compared with preoperative values. The results led to the following conclusions: In mastopathy patients there is a connection between high oestrogen concentrations and consecutively high prolactin release. The morphological substrate is represented by an enhanced proliferation of epithelium. In patients with cancer of the breast reduced progesterone concentrations during the second half of the cycle lead us to suspect an increased incidence of luteal insufficiency; in addition, it appears that the daily prolactin secretion rate in this group is on a reduced level.

[Endometrioses in a surgical patient sample]. / Endometriosen im chirurgischen Krankengut.

In general surgery patients, endometrioses can occur in the gastro-intestinal tract; they can also appear as cicatricial endometrioses or can be manifested as other, rare localisations of endometriosis tissue. In many cases it is not possible to arrive at a pre-operative diagnosis which is histologically established. Hence, treatment in endometriosis of the colon is surgical resection in order to delineate it against carcinoma and for the purpose of treating cicatricial stenosis which is usually associated with endometriosis. In cicatricial endometrioses and cysts in the inguinal region, diagnosis became possible only after surgery and postoperative histological examination.