Loss of differentiation in intestinal metaplasia in cancerous stomachs. A comparative morphologic study.

229 stomachs resected for duodenal and gastric ulcer and carcinoma were examined with special regard to the morphological and histochemical pattern of intestinal metaplasia (IM). The results of qualitative and semiquantitative studies were analysed statistically. Whereas duodenal and gastric ulcer cases are best discriminated by the presence or absence of IM, the strongest discriminating factor between carcinoma and gastric ulcer is the content of goblet cells in metaplastic crypts. Metaplastic crypts lined exclusively with goblet cells producing sulfated acid glycoproteins could be identified in more than one third of the cancer cases. The increase in goblet cells coincides with a loss of the more differentiated cells in the metaplastic glands, such as enterocytes, APUD cells, or Paneth cells. This "enterocoli metaplasia" seems to be specific for cancer bearing mucosa and occurs more often in cancer of intestinal type; it may represent a form of a derepressive dedifferentiation. The significance of enterocoli metaplasia as a premalignant lesion remains to be elucidated.

[Adhesive (retractile) capsulitis of the hip joint in diabetes mellitus. An x-ray histomorphological synopsis]. / Adhäsive (retraktile) Kapsulitis des Hüftgelenkes bei Diabetes mellitus. Röntgenologisch-histomorphologische Synopsis.

Adhesive (retractile) capsulitis of the hip joint is a rare complication (association) of (juvenile) diabetes mellitus. The clinical features, plain radiographic and CT findings and histomorphological appearances of this condition are described and attention is drawn to changes in the elastic tissue in the fibrosed capsule. Three diagnostic radiological features have been defined; in their presence, arthrography or diagnostic arthroscopy need not be performed.

[Fat embolism--a too infrequently determined pathoanatomic diagnosis]. / Die Fettembolie--eine zu selten gestellte pathoanatomische Diagnose.

In 1993, pulmonary fat embolism occurred in 92 cases (17%) out of 527 clinical autopsies. It was found in 62% of patients who had suffered bone fractures, in 9% with soft tissue surgery and in 53% after resuscitation; non-traumatic fat embolism was present in 6% of the cases. The comparison group of 50 persons with lethal polytrauma revealed pulmonary fat embolism in 52% of the cases. Bone-marrow embolism and microthrombi accompanied fat embolism of the lungs; furthermore some of the persons with pulmonary fat embolism also expressed minor degrees of renal (55%) and cerebral (25%) fat emboli. A retrospective analysis of the clinical data revealed no specific symptoms: a so called fat embolism syndrome had not been discovered clinically in any of the cases with histologically proven fat embolism. The significance of pulmonary fat embolism as a cause of death with regard to histological and clinical findings is discussed.

Expression and function of protein phosphatase PP2A in malignant testicular germ cell tumours.

Testicular germ cell tumours (TGCT) represent the most common malignancy in young males. We reported previously that two prototype members of the mitogen-activated protein kinase (MAPK) family, the MAPK ERK kinase (MEK) and extracellular signal-regulated kinase (ERK), are inactive in malignant testicular germ cells and become active after drug stimulation, leading to apoptosis of tumour cells. In this study, we asked whether the protein phosphatase PP2A, a known inhibitor of the MEK-ERK pathway, participates in the proliferation and/or apoptosis of primary TGCT (n = 48) as well as two TGCT cell lines (NTERA and NCCIT). Quantitative RT-PCR, immunohistochemistry, western blot analyses and phosphatase assay indicate that primary TGCT as well as TGCT cell lines express PP2A and that PP2A is active in TGCT cell lines. The inhibition of PP2A by application of two PP2A inhibitors, cantharidic acid (CA) and okadaic acid (OA), results in a significant increase in caspase-3-mediated apoptosis of TGCT cell lines. Thereby, PP2A inhibition was accompanied by phosphorylation and activation of MEK and ERK. Functional assays using the MEK inhibitor PD98059 demonstrated that the phosphorylation of MEK and ERK was required for the induction of caspase-3-mediated apoptosis of malignant germ cells. Thus, our data suggest that inhibition of PP2A mediates its apoptosis-inducing effect on TGCT through activation of the MEK-ERK signalling pathway that leads to caspase-3-mediated apoptosis of tumour cells. In addition our results support previous observations that PP2A exerts an anti-apoptotic effect on malignant tumour cells.

[Cancer and age or: Cancer as a finite urn model]. / Krebs und Alter oder: Der Krebs als Ereignis in einem endlichen Urnenmodell.

The consideration is based on a finite urn model (drawn balls are not returned). One important conclusion is that increasing effects of selection on the surviving population are to be assumed only by selection of death. Inaccuracy of official death rates results from insufficiency in registration of the confidential part of death certificates. 57% (in females) and 58% (in males) of all malignant tumors (based on examinations in the presented autopsy material) are found beyond the age of 60. More rare than expected are multiple tumors: formal arguments for this are discussed, the phenomenon being explained by a considerably increased death rate. The spectrum of target organs for metastases in the age groups (over 60 years) is tabulated for the oesophagus, stomach, colon-rectum, lung, mamma and prostata as primary tumor localization. As it matastasizes each primary tumor localization shows a specific time course and a specific organ selection. The correlation between malignant tumors and concomitant non tumorous diseases is given special attention. The latter are regarded as indicator for the pathogenesis of tumor diseases. The conclusions are that the remaining population in the urn model is highly selected. This becomes more pronounced in the older and most advanced age groups.

[Nonsense--and sense?--in cause-of-death statistics. A validation study to test cancer mortality figures]. / Unsinn--und Sinn?--der Todesursachenstatistik. Eine Validitätsstudie zur Prüfung der Krebssterblichkeitsziffern.

Death certificates for all clinics of the University of Heidelberg are centrally filled in at the University Pathology Institute. The certificate which accompanies the body gives the information for the official death certificate. There were 6263 autopsies between 1974 and 1978. The entry in the death certificate was compared with the complete morbid-anatomical diagnosis. Sensitivity and positive correctness showed many errors, the proportion of false-negative diagnoses being nearly three times higher than false-positive ones.

Scanning electron microscopic comparison between the thrombogenic properties of heparinized and non-heparinized vena cava catheters. A long-term study.

In an experimental comparative study on rabbits, the efficacy of the reduction of surface thrombus formation was investigated using heparinized central venous catheters compared with non-heparinized. Up to a central indwelling period of ten days, there was a reduction of the thrombus layer thickness on the heparinized catheters of 80% (with a trial duration of three days this was as much as 90%). The action of the stabilized surface heparin, which leads to a substantial thromboresistance, is complex in nature. 1) By intensified adsorption of plasma proteins in the early phase (proteins consist of antithrombin III, factor IX, X and XI), there is very much less thrombocyte adhesion and aggregation on the heparinized catheter surfaces. 2) The externally orientated negative net charge of the heparin shows a similar effect. 3) If there is thrombocyte adhesion despite this, further heparin effects become more prominent. Thus the release of ThF 3 and ADP, which leads to aggregation, is markedly inhibited. On the other hand, this leads to easier dissolution of already aggregated thrombocytes and on the other to a reduction of the catalytic thrombocyte surface for the plasma clotting factors. 4) This effect is supported by the increased adsorption of antithrombin III onto the control surface. 5) Finally there is also an inhibitory effect of heparin on the activated Stuart-Prower factor. Local thrombosis on the venous catheter surface can thus be effectively reduced by local therapy, without greater risks for the intensive care patient.

Histologic differential diagnosis of focal liver lesions by ultrasonically guided fine needle biopsy.

Ultrasonically guided fine needle biopsies were carried out in 84 patients with focal liver lesions and were subsequently evaluated histologically. A correct diagnosis of malignancy was made in 46 of 52 patients with proven hepatic malignancy, showing an overall accuracy of 93%. The specificity of the procedure was 100%. Such histological examination not only enables the differentiation between primary and secondary hepatic malignancy; it has the additional advantage of making a more precise tumour description and at the same time it pinpoints the primary site of the tumour.

[Ectopic meningioma of the tonsil]. / Ektopes Meningeom in der Tonsille.

To our knowledge this is the first reported case of a primary extracranial meningioma located in the palatine tonsil. Immunohistochemical investigation of the tumour showed coexpression of vimentin and neuron-specific enolase (NSE). No staining was found with antibodies against cytokeratins KL1, 13/10, 8 and 18, epithelial membrane antigen EMA and melanoma protein (HMB-45). It seems justifiable to classify this tumour as an atypical meningioma because of the local increased mitotic activity.

[Colon carcinoma pathogenesis. An epidemiological study (author's transl)]. / Epidemiologische Untersuchungen zur Pathogenese des Dickdarmkarzinoms.

The mean incidence age for rectal carcinoma in women rose significantly in the township of Karlsruhe between 1971-1975 from 61,5 to 70,9 years, while the incidence age for colon carcinoma in men decreased significantly from 67,5 to 65,0 years. In the world incidence statistics of colon carcinoma in males, Karlsruhe ranks 16th (13,2 cases per 100 000 inhabitants), whereas the city ranks second for rectal carcinoma in males (18,5 cases/100 000). Prevalence patterns of gastric, colonic, and rectal carcinoma differ between individual districts of Karlsruhe. Time-related pathogenetic influence factors are discussed in extenso.

The reaction of the cornea in vivo and in vitro to thermal stimulation: a contribution to the thesis by Busse-Grawitz.

In a test series with 15 rabbits a so-called central keratitis by means of a redhot needle was set in the left and right eye. The cornea of the left eye was immediately extirpated under sterile conditions and was observed in the tissue culture for 6 days. The corresponding right eye of the first rabbit was left within the animal's body, later it was extirpated after 1/2, 1, 1 1/2, 2 hours etc. up to 11 days histologically examined. In the explants following results were obtained. After the lesion is set the puncture site is devoid of epithelium. A double wall of cells lies closely around the crater. One-and-one-half hours later these large cells with more or less variably segmented nuclei demonstrate a strong proliferation. The characteristic nucleus form, the weakly positive naphthol-ASD-chloracetateesterase-reaction and the variable peroxydase-reaction of these cells resemble quite closely leucocytes in phenomenology and ferment-histochemistry. We have therefore chosen the description leucocytoid cells. They are not leucocytes, but cells which originate from basal pluripotent epithelia of the cornea. The so-called central keratitis is not an inflammation in the sense of Marchand, it is rather a regenerative process. The thesis of Busse-Grawitz, that leucocytes in the cornea originate from collagen and elastic fibers or less than coccisized transitional forms, cannot be verified.