[Autopsy rates in Germany]. / Obduktionszahlen in Deutschland.

BACKGROUND: In 2015 the German professional Association of Pathologists conducted a survey to establish a baseline for an autopsy rate in Germany and to collect data from 2005-2014, as hospitals must meet a fixed autopsy quota to receive the supplementary payment for autopsies as stated in the law for hospital structure (KHSG 10.12.2015). MATERIAL AND METHODS: The survey comprised 12 questions and was sent to 450 institutes of pathology. The overall return rate was 38%. The data of the different institutional types was grouped and statistically analyzed. RESULTS: Of 86.416 reported autopsies on deceased adults in Germany from 2005-2014, 47% took place in university hospitals, 36% in local hospitals and 17% in privately run practices. Out of 4320 autopsies on deceased children and adolescents, the majority (83%) were performed at university hospitals, 8%, and 9%, respectively, at the other two entity types. Of the 14.047 fetal autopsies, 55% were done at university hospitals, 25% at other hospitals and 20% at private practices. From 2005 to 2014 the overall number of autopsies decreased by 30%, independently of the institute type. Within each group of institution types there was a wide range in numbers and rate of autopsies done per year: university hospitals total 0­428, quota of 3,4-19,4%; local hospitals 0­324, quota of 1,1-30,8%; private practices 0­268, quota 0,4-5,2%. CONCLUSION: To this day, there is no universal system to document and register hospital autopsy rates in Germany. Due to the high range of yearly autopsy rates even within the different groups of institute types, the threshold for the autopsy rate that must be met to obtain the supplementary payment should be low in the beginning.

[Clinical autopsies. Practical approach, legal foundations and ethical considerations]. / Klinische Obduktionen. Praktisches Vorgehen, rechtliche Grundlagen und ethische Uberlegungen.

Only an autopsy can demonstrate topographical and morphological circumstances in detail and correlate the clinical and autopsy findings based on the examination of all organs. The practical approach in a fatality is described based on the example of the Lüdenscheid Hospital. A uniform legal regulation for dealing with corpses does not exist in Germany. There are two approaches to the question under which circumstances a clinical autopsy is allowed: the extended permission solution and the objection solution. Whether a clinical autopsy can be carried out is decided by the medical specialist selected on application. Autopsies can be necessary from insurance or administrative legal grounds or in the case of an anatomical autopsy is decided by the persons themselves. In order to guarantee the quality of an autopsy it is necessary to use a standardized approach with evaluation and assessment of the results, for example using a quality assurance protocol and the production of an autopsy report. Using this approach important information can be gained not only on the accuracy of the main diagnosis and cause of death but also on additional diseases, response to therapy and the course of the disease and under circumstances can lead to modifications in the approach.

[Synovial membrane diagnostic assessment in rheumatoid arthritis]. / Synovialis-Diagnostik bei Rheumatoider Arthritis.

Rheumatoid arthritis (RA) is the most frequent inflammatory rheumatic disease. At the beginning of the disease, where, based on today's knowledge the therapeutic possibilities are largest, the diagnostic methods do not permit a differentiated estimation of the prognosis. Conventional x-rays are mostly normal and serum markers unspecific. So far--in contrast to other diseases--only little information had been drawn from the pathomorphologic substrate "synovialis" itself to assess the prognosis. Reasons therefor were found in difficulties in obtaining synovial tissue besides surgical interventions, particularly in patients with early arthritis. By minimalizing the diagnostic instruments and improvement of the technique, synovial tissue sampling in RA has become minimally invasive and it is even possible to perform on the smallest joints, such as finger joints. Hereby, synovial analysis is open for detecting pathways of inflammation and joint destruction, which might support the advancement of new therapeutic strategies, followed by a better prognosis and outcome of RA.

[Iatrogenic "metalloma" (titanoma) caused by implant failure in "metal-backed" patellar joint surface replacement]. / Iatrogenes "Metallom" (Titanom) durch Implantatversagen bei "metal-backed" Patellagelenkflächenersatz.

Patellofemoral problems frequently provide the cause for revisions after total knee replacements (TKR). Problems with metal-backed patellae, in particular, have been reported on in the past, with a failure rate of 33%. As a result of implant failure, there is an increase of polyethylene and metallic wear, which eventually leads to a synovialitis and metallosis. We report a case of a iatrogenic induced metallosis of the knee joint resulting from failure of a metal-backed patella component with the formation of a substantial pseudotumor within the popliteal fossa. Intraoperatively, a browny-grey, knotted and hard structure was to be seen, which histologically imposed as a hyalinated scar tissue with black particular deposits. Energy dispersive X-ray microanalysis showed a high level of titanium within the intra- and extracellular deposits. In differential diagnosis these findings were postulated as "metalloma" (titanoma). In cases of periprosthetic pseudotumors, particular those with implant failure, a iatrogenic-induced metalloma should be considered.

Magnetic resonance imaging and miniarthroscopy of metacarpophalangeal joints: sensitive detection of morphologic changes in rheumatoid arthritis.

OBJECTIVE: To evaluate and characterize magnetic resonance imaging (MRI) findings in the metacarpophalangeal (MCP) joints of rheumatoid arthritis (RA) patients macroscopically, using miniarthroscopy (MA; needle arthroscopy). METHODS: The second MCP joint of the dominant hand of 22 RA patients (13 with various RA activities/stages; 9 with early RA [< or = 1.5 years' duration]) was examined by MRI followed by MA. Findings were evaluated by standardized semiquantitative measures of synovial and bony pathologic changes of the MCP joint, and were compared with the clinical and conventional radiologic findings. RESULTS: Erosions and pre-erosions were detected in 17 of 22 patients by MRI; 2 of the other 5 patients (all early RA) displayed bony changes on MA. All 10 joints with pre-erosions on MRI (grade I bony alterations on MRI) exhibited significant cartilaginous and bony pathology on MA. Synovial membrane pathology was detected in all but 1 patient by MRI and in all patients by MA, although findings of plain radiography were normal in 6 of the 22 patients and another 9 patients had a Larsen score of 1. Semiquantitative analysis of synovial findings of MRI revealed gadolinium diethylenetriaminepentaacetic acid enhancement as a significant marker of macroscopically varied synovial vascularity and hyperemia, both of which strongly correlated with clinical activity (as measured by the Disease Activity Score). The extent of synovitis/synovial proliferation shown by MA and MRI were significantly correlated with each other, but not with any other activity or damage parameter analyzed. CONCLUSION: In RA, both MRI and MA findings support early detection and staging of synovial changes. Ongoing longitudinal studies are aimed at evaluating the value of synovial proliferation as visualized by both methods.

Clara-cell hyperplasia after quartz and coal-dust instillation in rat lung.

Bronchiolo-alveolar hyperplasia of type II cells in rat lungs after particle exposure is a well-known preneoplastic lesion. The Clara cell, stem cell of the bronchiolar epithelium and the main carrier of cytochrome P-450 isoenzyme system in the lung, has barely been evaluated with regard to this effect. The aim of this study was to examine Clara-cell hyperplasia after particle exposure and to characterize cell proliferation and its normal function. Female Wistar rats were intratracheally instilled with coal dust samples of variable quartz content, quartz (DQ12), titanium dioxide, or saline solution containing 0.5% Tween 80. After 126-129 wk, all coal mine dust- and quartz-exposed animals developed Clara-cell hyperplasia: up to 0.48% of the total lung area, which was significantly increased compared to titanium dioxide (p <.05) and control (p <.03) animals. Proliferation and hyperplasia of bronchiolar Clara cells by coal dusts was independent of their quartz content. The lack of proliferating cell nuclear antigen staining in most of the hyperplastic Clara cells suggests that following damage of alveolar epithelial cells, Clara cells migrate in and remodulate the alveolar epithelium. After the migration they keep their function in the xenobiotic metabolism, as shown by expansion of CYP2E1 active Clara cells. The minor development of Clara-cell hyperplasia in titanium dioxide-treated rats indicates that this is not a general particle effect, and is possibly due to its lower toxicity to epithelial cells.

Diffusional behaviour of metals in a passive sampling system for monitoring aquatic pollution.

Passive sampling systems are an emerging technology for detecting pollutants in the aquatic environment. A passive sampling system has been developed based on diffusion through a porous surface to a receiving phase, where the analyte is removed by chelation at a solid phase. The diffusion process can be described by Fickian diffusion through the sampler. The sampler has a well-defined surface area, which permits calibration in terms of concentration. Passive sampling systems can be used to determine pollutant concentrations if the diffusion process can be described and understood within environmental limits. In natural water systems, diffusion coefficients for metal transport across the porous membrane will be affected by external conditions, including biofouling and variation in turbulence and temperature. Uptake rates for the analytes Cu, Cd and Pb have been determined for the complete passive sampling system. Two different cases have been investigated, a batch case, where the bulk concentration decreases with time, and a flow-through case, where the bulk concentration remains constant. Diffusion coefficients were determined for the two conditions and compared with the calculated value obtained for the Stokes-Einstein equation in pure water. Diffusion coefficients for metals were found to be lower than for diffusion in pure water, a difference attributed to the effect of the porous membrane. The effect of the hydraulic conditions on the metal diffusion was studied for both a conventional magnetic stirrer creating turbulence in the system and for a rotated sampler, the latter providing a well-defined boundary layer system. The boundary layer was found to be negligible compared with the diffusion limiting membrane in the presence of sufficient turbulence or if the rotation of the sampler was high.

[Benign tenosynovial giant cell tumor in the region of the upper ankle joint. A rare differential diagnosis of a soft tissue tumor of the foot]. / Der benigne tenosynoviale Riesenzelltumor im Bereich des oberen Sprunggelenks. Seltene Differentialdiagnose eines Weichteiltumors am Fuss.

The giant cell synovioma is a benign neoplasia classically located in the fingers. It mostly rises from tendon sheaths, sometimes from the synovia. Other locations than the fingers are rare. Making a differential diagnosis to lipomas, gangliomas or even malignant soft tissue tumors can be very difficult especially in rare locations. We report the case of a 21 years old man suffering from a giant cell synovioma in the area of the right ankle joint. The clinical, radiological and patho-morphological findings are documented. The tumor was excised totally, other foci were not found. The problems of making the right diagnosis are described.

Miniarthroscopy of metacarpophalangeal joints in rheumatoid arthritis. Rating of diagnostic value in synovitis staging and efficiency of synovial biopsy.

OBJECTIVE: To evaluate miniarthroscopy (MA) (needle arthroscopy) of involved joints in rheumatoid arthritis (RA) in the early detection and staging of synovitis and its application in visual guided synovial biopsies. METHODS: 1.0 and 1.9 mm (0 degree/30 degrees) arthroscopes were used in a 2 portal technique. MA performance was developed and evaluated first on hand cadavers (n = 20) and then transferred to metacarpophalangeal (MCP) joints under local anesthesia conditions. Joints of 20 patients with RA with different disease activity and duration were scoped and rated according to scores adapted from arthroscopy of other joints. RESULTS: In 20/20 cases MA provided visualizing and magnification of intraarticular features of MCP joints in RA and allowed grading of synovial alterations, chondromalacia, and bony alterations. Synovial surface changes, thickness, and fibrosis were related to disease duration, as was damage to cartilage and bone. The degree of acute inflammatory reactions like vascularity and hyperemia varied independently of chronic changes; synovial proliferation was reflected to some extent by C-reactive protein. In 2 patients with early RA, synovitis criteria were found macroscopically and histologically. In 18/20 joints, biopsies were taken under visual control; in the other 2, progression of disease (Larsen score >3) limited arthroscopy to 1.0 scope imaging only. Sampling sizes were sufficient for histologic and molecular analysis. CONCLUSION: The developed standardized procedure of MCP arthroscopy is minimally invasive, practicable, and well tolerated by patients, and may allow synovitis monitoring, staging, and biopsy in patients with early as well as chronic arthritis.

Time-course analysis of type II cell hyperplasia and alveolar bronchiolization in rats treated with different particulates.

In this study, we compared the morphological reaction patterns in rat lungs following a single intratracheal instillation of 20 mg quartz, 20 mg coal mine dust (15.3% quartz), or 25 mg talc. Control animals received a single dose of 0.5 ml saline solution intratracheally. Investigations by light microscopy, morphometry, and DNA image cytometry were carried out 3, 6, 12, and 18 mo after dust administration. During the investigation period, we observed a temporary increase in the number, area, and proliferative activity of the type II cells, which differed in intensity among the three dusts. After 18 mo, however, type II cells in treated animals did not differ from control animals. On the other hand, the expansion of a multifocal alveolar bronchiolization as putative preneoplastic lesion had progressed enormously by the end of the test (1-3% of the investigated lung area). Consistent with this, the proliferative activity of the epithelial cells in terminal bronchi of the coal mine dust- and quartz-treated animals was enhanced by the end of the 18-mo investigation period, while the reaction to talc was minimal (0.2% of totally investigated lung area). Our data suggest that in bronchiolo-alveolar regions, especially in the epithelium of terminal bronchi, there is an overshoot regeneration after cell damage that leads to an alveolar bronchiolization.

Fiber-specific molecular features of tumors induced in rat peritoneum.

Molecular markers such as mutational spectra or mRNA expression patterns may give some indication of the mechanisms of carcinogenesis induced by fibers and other carcinogens. In our study, tumors were induced by application of crocidolite asbestos or benzo[a]pyrene (B[a]P) to rat peritoneum. DNA and RNA of these tumors were subjected to analysis of point mutations and to investigation of mRNA expression patterns. With both assays we found typical features depending on the type of carcinogen applied. The analysis of point mutations in the tumor suppressor gene p53 revealed mutations in the B[a]P-induced tumors. However, in the tumors induced by crocidolite asbestos that were of the same tumor type as those induced by B[a]P, mutations in p53 were not detectable. Every mutation detected on the DNA level causes an amino acid substitution within one of the functional domains of the tumor suppressor protein. Therefore, these mutations seem to be of biological relevance for tumor progression and indicate a difference in the carcinogenesis regarding the type of the carcinogenic substance. An additional specificity of crocidolite-induced tumors was detectable by analyzing the mRNA expression of the tumor suppressor gene WT1, which is known to be expressed in human mesothelial and mesothelioma cells. A relatively high amount of WT1 mRNA was measured by quantitative competitive reverse transcription-polymerase using RNA extracted from crocidolite-induced tumors. However, WT1 seems to be expressed on a rather low level in tumors induced by B[a]P.

P53 mutations in tumours induced by intraperitoneal injection of crocidolite asbestos and benzo[a]pyrene in rats.

Mutation analysis of the tumour suppressor gene p53 in tumours induced in the peritoneal cavity of rats revealed differences in the mutational pattern with regard to the carcinogenic substances applied. In tumours induced by benzo[a]pyrene a considerable amount of p53 mutations resulting in an altered protein structure could be detected. For the development of these tumours an escape from the p53 mediated cell cycle control can be assumed. However, in tumours of the same tumour type induced by crocidolite asbestos no mutations could be observed. Since there were even no spontaneous p53 mutations detectable in this tumour group, it is obvious that in these tumours the escape from cell cycle control does not take place via inactivation of p53. Therefore, it is concluded that the molecular mechanisms of carcinogenesis and tumour development in this tumour type depend on the type of carcinogen applied.

[Physiologic and pathologic patterns of reaction to silicone breast implants]. / Physiologische und pathologische Reaktionsmuster auf Silikonprothesen der Mamma.

Local morphological reaction patterns on breast implants can be of high significance as possible starting point for controversely discussed systemic immune response triggered by silicon or silicone. Therefore, the collagenous capsules of 149 explanted mammoplasty prostheses were examined macroscopically, under a scanning electron microscope and light-microscopically using antibodies to the macrophage antigen CD68, vimentin, muscle actin, and the proliferation antigen MIB1, and were then correlated with anamnestic data (implanted type of prosthesis, indication for im- or explantation). According to our examinations, the in-vivo durability of the prostheses' shells is considerably decreasing with the expansion of their surfaces. Regardless of the type of the prostheses' surface regularly a chronic-proliferating inflammation pattern could be identified in the periprosthetic capsulectomy specimens starting with a synovial metaplasia of proliferating CD-68-negative and vimentin-positive mesenchymal cells in the area surrounding the implants and ending by its transformation into a stage of dense hyaline collagenous fibrous tissue after an advanced implantation period (> 2 years). By this, the texturing of the prosthesis surface modifies only the course, but not the quality of the chronically fibrosing inflammation. Bleeding of prosthesis as well as the incorporation of the polyurethane-foam coating of different prosthesis types into the periprosthetic breast capsule lead to a significant lymphoplasmacytic infiltration, partly with participation of local vessels as defined in a "silicone vasculitis". Morphological signs of an at least local immune response are detectable in 8.3% of the examined fibrotic capsules even without a morphologically identifiable foreign-body embedding. They can be possibly referred to- as well as the complete absence of hyaline collagenous fibrous tissue in 30% of the cases-a yet not causally clarified, inter-individually different susceptibility of the implant bearers. Only the systematic registration of the above-mentioned morphological reaction patterns in a "prosthesis-passport" together with the additional clinical observation of the patients can ensure in future the realistic estimation of potential health risks caused by silicone breast implants.

[Local effects and changes in wound drainage in the free peritoneal cavity]. / Lokale Auswirkungen und Veränderungen von Wunddrainagen in der freien Bauchhöhle.

In a prospective randomised study 30 mongrel rabbits received two standard colon-resections. Three types of drains were tested: (latex-rubber-) Penrose-drains, rubbertube- and silicontube-drains, which were placed in the lower abdomen. As a closed drainage-system the extraperitoneal tip of the drain was placed in a closed subcutis-pocket. One of the two colon-anastomoses also was drained. The findings were recorded on the 7th postoperative day. A single mechanic alteration was found, an ulcer caused by a silicon-drain, that pushed against the abdominal wall. The other signs of mechanic irritation were microscopically unspecified inflammatory reactions to the foreign body drain. There was no ascending infection caused by the drain. All infections came from complications of the colon resections. In contrast to common opinions the drains in the lower abdomen showed no adhesions to the abdominal wall or organs. Only the entrance of the drain into the peritoneum and the cotton-gaze of Penrose-drains showed in nearly all cases adhesions. The large amount of adhesions to the anastomosis-drains came from complications of the colon-anastomoses. As a cause of material, rubber- and latex-rubber-drains showed large fibrin-clots on their surfaces. 7 days after the operation only about 20% of the drains had sufficient function. The rest was occluded by fibrin-clots in the lumen of the drain or the cotton-gaze. Over all there is no difference in changes and effects of the three different types of drains, but silicon as material showed advantages.

[Calcifying granulomatous peritendinitis after local dexamethasone treatment]. / Kalzifizierende granulomatöse Peritendinitis nach lokaler Dexamethasonbehandlung.

In this article we report on a 43-year-old man, who had been treated with two cortisone injections containing soja bean oil for epicondylitis humeri radialis. Four weeks after the second injection necrotized fat which had been extracted surgically was sent to us for histological examination. We could show a calcifying collagen fibre necrosis being cleared by a granulomatous reaction and resorbed by granulation tissue. The calcifying necrosis of collagen fibres might have been induced by soja bean oil which were used as carrier of the drug.

Silicotic lymph node reactions in mice: genetic differences, correlation with macrophage markers, and independence from T lymphocytes.

Quartz was injected into a hind food of BALB/c and DBA/2 mice and on days 40, 90, and 180 the progressive response ensuing in the draining popliteal lymph node (PLN) was investigated by histopathology and immunohistopathology. The area of silicotic nodules (ASN) was measured by morphometry, and, by this parameter, strain BALB/c proved to be a high responder to quartz, and strain DBA/2 a low responder, albeit both strains showed a similar degree of reactive lymphoid hyperplasia in the draining PLN. Both strains also showed a similar quartz content in the draining PLN but in BALB/c mice quartz particles were concentrated in the ASN, whereas in DBA/2 mice they were evenly dispersed over the PLN. Because the silicotic response of athymic BALB/c nu/nu mice was even stronger than that of euthymic BALB/c mice, T cells are not required for the development of silicotic nodules. This fits the notion that quartz is not an antigen and that high and low responder strains are MHC-identical. Because quartz-treated BALB/c, but not DBA/2 mice, showed a persistent expression of the macrophage differentiation markers MRP8 and MRP14, phenotypically the observed strain difference in silicotic responsiveness seems to be expressed at the level of macrophages.

Differential diagnosis of malignant tumours in the abdominal cavity of rats after intraperitoneal injection of crocidolite or benzo[a]pyrene.

In our investigation (i.p. test), crocidolite and benzo[a]pyrene, both caused a progression from initially reactive, then autonomously transformed proliferation of myofibroblasts and undifferentiated mesenchymal cells to malignant, multidirectionally differentiated (desmin and ED-1 positive) fibro-histiocytic tumours. Immunohistochemically these tumours showed no morphological characteristics (for example co-expression of vimentin and keratin in spindle-shaped tumour cells) of human asbestos-associated malignant mesotheliomas. On the other hand many tumour cells induced by crocidolite and benzo[a]pyrene had an ultrastructural appearance resembling fibroblasts and myofibroblasts. These have been demonstrated in only a few desmoplastic and sarcomatous mesotheliomas in human beings. None of the tumours revealed the typical ultrastructural features of epitheloid or transitional mesotheliomas. Apparently, both carcinogenic substances induce the transformation of undifferentiated pluripotent mesenchymal cells in rat peritoneum, regardless of their localization in the submesothelial compartment or perivascular connective tissue (preferentially after crocidolite application) or in the connective tissue pseudocapsule of major benzo[a]pyrene containing beeswax/tricaprylin depots in the mesometrium and mesenterial fatty tissue. In this way asbestos fibres in this animal experiment do not seem to induce an arrest in differentiation of intermediate or immature mesothelial cells as supposed formerly, but rather affect undifferentiated mesenchyme cells and myofibroblasts. This is an explanation for the immunohistochemical expression of markers of muscular differentiation in these tumour cells, which is known to occur in human malignant fibro-histiocytic tumours. If supplementary immunohistochemical investigations with different keratin antibodies also fail to confirm the mesothelial differentiation of the tumours induced in our i.p. test, the decision to call them "mesotheliomas" should be reconsidered. Further immuno-transmission-electron microscopical investigations with intermediate filament or macrophage antibodies are needed to clarify whether the term malignant "fibrohistiocytic sarcoma", "mesenchymoma" or "mesothelioblastoma" would be more correct from the morphological point of view.