[Clinical experience with percutaneus large-core needle biopsies of the breast and evaluation of cytopathological and histopathological results]. / Klinische Erfahrungen mit einer kombinierten imprintzytologischen und histopathologischen und Begutachtung von perkutanen Stanzbiopsien der Mamma.

OBJECTIVE: Core needle biopsy (CNB) allows a microinvasive diagnosis of breast lesions. We investigated whether imprint cytology of CNB specimens is a useful method of rapidly obtaining additional diagnostic information. MATERIAL AND METHOD: During five years 46 218 breast examinations for 23 300 patients were performed. 563 patients were examined by CNB. The results of imprint cytology were compared with the histopathological results. Statistical analysis was done for all patients who underwent subsequent surgery. RESULTS: 195 of 563 patients were treated surgically. 155 patients exhibited malign lesions. 40 patients showed benign breast lesions. Four patients with malign findings in imprint cytology and histopathology of CNB were treated conservatively. Imprint cytology had a sensitivity of 0.89, specificity of 0.88, positive predictive value of 0.96 and negative predictive value of 0.67. Histopathology revealed a sensitivity of 0.90, specificity of 0.95, positive predictive value of 0.98 and negative predictive value of 0.70. 364 patients with benign findings in imprint cytology and histopathology were controlled subsequently. One of these patients developed five month later an invasive ductal tumor. CONCLUSION: Imprint cytology of CNB is a reliable method to obtain additional diagnostic information. Inadequate and suspicious cases should be evaluated based on complementary diagnostic procedures for breast lesions.

In vitro corrosion of titanium.

Titanium is used in dentistry for implants and frame work because of its sufficient chemical, physical and biological properties. The corrosion behaviour is from high interest to value biocompatibility. A static immersion test was undertaken with a titanium test specimen (30 mm x 10 mm x 1 mm, immersion time = 4 x 1 w, n = 3 for each series). The following parameters were investigated: specimen preparation, grinding, pH-value, different casting systems, comparison with CAD/CAM, influence of: chloride, thiocyanate, fluoride, lactate, citrate, oxalate, acetate. Atomic absorption spectroscopy was used to analyse the solutions weekly. The course of corrosion was investigated photometrically. Titanium reveals ion releases [(0.01-0.1) microg/(cm2 x d)] in the magnitude of gold alloys. There is little influence of grinding and casting systems in comparison with organic acids or pH value. The ion release increases extreme (up to 500 microg/(cm2 x d)) in the presence of fluoride. Low pH values accelerate this effect even more. Clinically, no corrosion effects were observed. Nevertheless it is recommended that it is best to avoid the presence of fluoride or to reduce contact time. In prophylactic fluoridation of teeth, a varnish should be used.

Carcinoembryonic antigen as differentiation marker for small cell lung cancer in vitro and its clinical relevance.

Fifteen small cell lung cancer (SCLC) cell lines and 249 histopathological specimens from patients with SCLC were investigated for carcinoembryonic antigen (CEA) expression. Quantitative determinations of CEA in cell line homogenates correlated significantly (p less than 0.001) with L-DOPA decarboxylase (DDC) activities and population doubling times (PDT). Using monoclonal antibodies specific for CEA (BW 431/31) and crossreactive with non-specific crossreacting antigens (NCA) 55 and 95 (BW 250/183 and BW 374/14), the CEA-reactive moiety in SCLC was immunologically identified as CEA. In vivo studies demonstrated CEA by immunohistochemistry in 57% (141/249) of newly diagnosed SCLC. The presence of CEA and the degree of immunostaining did not correlate with clinical parameters.

Clinical relevance of histologic subtyping in small cell lung cancer.

Histopathologic specimens from 249 patients with small cell lung cancer (SCLC) were reviewed and classified into oat cell-type, pure intermediate cell-type (excluding specimens with mixed small cell/large cell features), and small cell/large cell-type. One hundred seventy (68%) specimens displayed oat cell features (including 30 with mixed oat cell/intermediate cell features), 66 (27%) displayed intermediate cell features, and 13 (5%) displayed mixed small cell/large cell features. No differences among these subtypes were found with respect to stage of disease, sex, age, performance status, and number and distribution of metastases. Complete and partial remission rates for the oat cell-type were, respectively, 31% and 38%, for the intermediate cell-type 20% and 45%, and for the small cell/large cell-type 38% and 31%. Two-year survival rates were 7%, 11%, and 15%, respectively. These data were all statistically insignificant, and comparisons of log-rank analyses of survival curves for these SCLC subtypes also showed no statistically significant differences. We thus conclude that histologic subtypes of SCLC are not distinct entities of clinical relevance, and that prognostic as well as therapeutic decisions cannot be based on histologic subtyping.

Nipple involvement and multicentricity in breast cancer. A study on whole organ sections.

Our study examined 166 patients with breast cancer with a mean age of 63 years. Each patient underwent mastectomy with the organ being investigated by histological giant sections and additional small sections from the nipple. Nipple involvement was found in 64 cases (38%). Multifocal carcinoma occurred in 76 patients. Further multicentric carcinomatous foci (36 cases) demonstrated a significant increase in affected nipples. Additional atypical ductal or lobular hyperplasia was observed in 53 cases and showed involvement in 34. Nine carcinomas of ductal origin were combined with lobular carcinoma in situ, all cases proved to have carcinomatous changes in the nipple. It is concluded that apart from the well-known influence of advanced tumor stages and tumor localization, nipple involvement correlates with multicentricity and multifocality of breast cancer as a disease of the whole organ.

[Erythrodermic sarcoidosis (a clinical, light and electron microscopy study)]. / Zur Frage der erythrodermischen Sarkoidose (Eine klinische, licht- und elektronenmikroskopische Untersuchung).

We report on a 50-year-old patient suffering from erythrodermic sarcoidosis accompanied by visible enlargement of the peripheric lymph nodes. Histologic examination revealed epithelioid granulomas in the skin, in a lymph node, and in a liver biopsy. Ultrastructurally, we found a focal presence of cells with Langerhans' granules sometimes in a spatial relation to lymphoid cells within the corial granulomas.

Human low density lipoproteins (LDL) in combination with cholesterol or cholesteryl linoleate as precursors for progesterone synthesis of human placenta in organ culture.

After preincubation of term placental tissue in organ culture for 24 h, progesterone synthesis is 2-3 fold lower than without preincubation. By adding human male serum proteins (MW less than 12,400), we obtained 2-3.5 fold lower tissue levels of progesterone. Serum proteins with high molecular weight (MW greater than 12,400) are postulated to facilitate progesterone release by binding free medium progesterone. In test series without preincubation, there are no significant (p less than 0.05) differences in progesterone formation in the presence of cholesterol (C), cholesteryl linoleate (CL), and LDL. In test series with preincubation, LDL causes a twofold increase in medium progesterone with C (0.1 and 1 mM) and CL (0.1 mM) in the presence of the low molecular weight serum protein (MW less than 12,400) solution. A decrease of 50% was obtained by 1 mM CL with/and without LDL. In culture medium containing high molecular weight serum proteins (MW greater than 12,400), 0.1 and 1 mM C and CL induce a twofold increase in progesterone production without any significant (p less than 0.05) differences between the single values. No further stimulation could be observed by LDL because there was sufficient LDL for maximal progesterone formation. In conclusion, LDL enhances the utilization of cholesterol and cholesteryl linoleate for progesterone production in term placenta. A lipoprotein cholesterol receptor is suspected.

[Unusual malignancies of the breast region]. / Seltene Malignome im Bereich der Mamma.

Three cases of rare sites of malignomas in the human breast are reported: malignant lymphoma (centrocytic - centroblastic) with generalised lymph node involvement, metastasis of a malignant melanoma, and a metastatic angiosarcoma. Problems of preoperative diagnosis are discussed.

Influence of human lipoproteins on the progesterone synthesis of human term placenta in organ culture.

In the presence of LDL (200 micrograms/ml) and HDL (400 micrograms/ml), the uptake of radioactive cholesterol by a human term placenta in organ culture was enhanced by about 1.5 and 2.5, respectively, after 24-h incubation. Using cholesterol linoleate, the ratio was 1.0 and 1.5, and the tissue concentration of progesterone was 5-fold higher in the presence of LDL (600 micrograms/ml) than in the presence of HDL (4.4 mg/ml). A dose-dependent increase in medium progesterone was found using either LDL or HDL in combination with cholesterol or cholesterol linoleate, respectively. In human term placenta in organ culture, the human lipoproteins LDL and HDL both have a carrier function for cholesterol and cholesteryl linoleate, stimulate the uptake of these steroids in the placental tissue, and enhance placental progesterone formation. Furthermore, the lipoproteins facilitate progesterone release from the placental tissue.

[Ultrasound tomography and guided fine needle biopsy of intrathoracic space occupying lesions]. / Ultraschalltomographie und gezielte Feinnadelbiopsie intrathorakaler Raumforderungen.

Pleural and pleural-based intrathoracic masses lead to a real sound transmission, thus allowing a sonomorphological diagnostic approach. Thoracic sonography is particularly helpful to evaluate the nature of pleural-based radiographic opacities. Moreover, fine needle biopsies guided by sonography permit cyto-histological diagnoses of intrathoracic masses. Ultrasound-guided fine needle biopsy was performed in 15 patients with pleural-based space-occupying pulmonary lesions. True positive results were obtained in 12 of the 15 patients with two true negative results and one false negative aspiration. The overall accuracy of aspiration cytology was 14 out of 15 (93.3%). In one patient a small pneumothorax occurred as a complication of the transthoracic needle approach.

Demonstration of immunoreactive calcitonin in sera and tissues of lung cancer patients.

In sera of 194 patients with lung carcinoma, calcitonin was estimated by radioimmunoassay with an antibody against human calcitonin. Increased levels of calcitonin-immunoreactive protein were found in 57% of the patients with small cell carcinoma, in 10% of the patients with squamous carcinoma and in only 2 patients with large cell carcinoma. In patients with small cell carcinoma, serial determinations of calcitonin were accomplished during therapy. Significantly decreased calcitonin levels were found in patients who responded to therapy with cytostatics and X-ray. Increased calcitonin levels were measured from 1 to 2 months before clinical symptoms of a relapse were detectable. Investigations on the biochemical nature of this calcitonin-immunoreactive protein were made on both serum of lung cancer patients and tumor tissue. Evidence for the production of calcitonin-immunoreactive protein directly by the tumor was given by immune histology and by determinations of calcitonin in tumor tissue. Three protein fractions, which were immunoreactive with anti-human calcitonin, with molecular weights of about 100,000, 48,000 and 20,000, were separated by gel filtration. The two higher molecular weight fractions were degraded to molecular weights of about 17,000 and about 3400--the molecular weight of physiological calcitonin--by incubation with sodium dodecyl sulphate under reducing conditions. These results led to the conclusion that it may be possible to characterize a tumor-specific calcitonin precursor molecule; in addition to its use in monitoring therapy it may be useful in the differential diagnosis of small cell carcinoma.

[Antidiuretic hormone in patients with bronchial carcinoma (author's transl)]. / Antidiuretisches Hormon bei Patienten mit Bronchialkarzinom.

Antidiuretic hormone (ADH) was determined by radioimmunoassay in 139 patients with bronchial carcinoma. Serum ADH levels, compared with a control group, were increased in 30% of patients with small-cell and 21% of patients with large-cell bronchial carcinoma. Patients with squamous carcinoma or adenocarcinoma had normal ADH values. There was no correlation between serum ADH levels and stage of tumour. Serial ADH measurements during chemotherapy provided good correlation between ADH and response to treatment. ADH was also demonstrable by immunohistology in the tumour cells of one patient with increased serum levels.

[Solid tumours of human primary hepatocellular carcinoma cell-lines in hypothymic mice: a model for biochemical and therapeutic studies (author's transl)]. / Solide Tumoren menschlicher primärer hepatozellulärer Karzinomzellinien in hypothymischen Mäusen: ein Modell für biochemische und therapeutische Studien.

HBsAg producing cell-lines of human primary hepatocellular carcinomas express a multitude of differentiated hepatocyte functions. They also grow in hypothymic (nude) mice as solid tumours. Here we describe the subcutaneous injection of cell-lines PLC/PRF/5, Hep 3B and Mahlavu (HBsAg negative) into hypothymic mice to produce a high tumour take without prior immunosuppressive treatment. Serial transplantation of tumour fragments into new animals allows the development of large homogeneous experimental groups and a substantial multiplication of tumour cell mass. The transplanted tumours from PLC/PRF/5 and Hep 3B cells continue to synthesize HBsAg and alpha-fetoprotein, and they secrete these proteins into the blood of their hosts. Fibrinogen and alpha 1-antitrypsin can be demonstrated in the cells of these two tumours but not in tumours originating from Mahlavu cells. This model offers experimental conditions to study the function of solid human primary liver cell carcinomas under the influence of an intact organism.

[Follicular lymphatic hyperplasia of the small intestine in antibody deficiency syndrome (author's transl)]. / Follikuläre lymphatische Hyperplasie des Dünndarmes bei Antikörpermangelsyndrom.

Selective serum IgA deficiency and follicular lymphatic hyperplasia of the terminal ileum were observed in a 30-year-old patient. Due to the relative ileal stenosis he complained of colicky abdominal pains particularly after flatulant food. There was no malabsorption syndrome or lambliasis. Although immunohistochemically IgA producing plasma cells were demonstrated in the intestinal wall, no immunoglobulin could be demonstrated in the intestinal juice, suggesting a secretory defect. The very high percentage of IgE producing plasma cells was noteworthy, these cells having led to the macroscopical picture of follicular hyperplasia. Due to the relative frequency of IgA deficiency (about 1 : 700) and the known increased incidence of malignant disease regular surveillance of these patients is indicated.

Occurrence of dysplastic epithelium in the murine vagina after transfer of cell-free extracts from carcinoma in situ of the human cervix uteri.

Cell-free extracts were prepared from tissue specimens of intraepithelial carcinoma of the cervix uteri of human patients and subsequently injected into newborn and juvenile mice of NMRI strain via several routes. Cytological controls of vaginal epithelium were carried out in periods of 8--12 wk. Groups of mice were killed at varying intervals for histological examination. After a latency of 4-8 mth dysplastic changes of the vaginal epithelium were found in 67.6% (48 out of 71) of the mice and were graded as hyperplasia, mild and severe dysplasia and carcinoma in situ. Antibody against herpes virus hominis was not detected in the sera of these mice. Only 1 out of 120 control mice had mild dysplasia 16 mth after inoculation of an extract from noninfected human embryo kidney cells. In 9 out of 10 human cases of histologically confirmed cervical carcinoma in situ, injection of extracts into mice was followed by the appearance of dysplastic epithelium in the murine vagina. In the one case in which no positive response was obtained, the observation time had been less than 6 mth.

[Modern postmortem coronary angiographic examination methods in the service of clinical cardiology (author's transl)]. / Neuere postmortale koronarangiographische Untersuchungsverfahren im Dienst klinischer Kardiologie.

The coronary vessels of the postmortal heart can be radiologically reproduced after being filled compactly with a contrast medium or by x-ray double contrast. All vessels are primarily filled by injecting contrast medium over the aorta, even when multiple orifices, ostiumstenoses, or artificial anastomoses exist. Further, the possibility is granted to reproduce the coronary ostia. A special process permits the radiological reproduction of postmortal coronary vessels in the same projection as used by clinical cardiologists intravitally. Stereoscopic x-ray pictures are easily produced, even when using an x-ray tube in fixed position. The radiological examination of horizontal heart slices combined with histological giant sections, allows an exact determination of the supplying areas of singular coronary vessels and their branches, as well as providing information about the relationship between coronary arterial and myocardial pathology. The double contrast x-ray method offers the advantage of a faultless reproduction of the coronary ostia and an estimation of the singular vessels, even with multiple overshadowing. In addition conclusions can be drawn from the changes of diameters of the coronary vessels under defined pressure as to the mechanical wall characteristics post-mortem. By means of these extended methods the postmortal radiological examination of coronary vessels can play an important role in the solution of scientific problems of clinical cardiology today.