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Zusammenfassung: Zahlreiche Erkenntnisse in der Prostatakarzinomforschung basieren auf Zellkulturergebnissen. Neuere genomische Untersuchungen zeigen jedoch, dass verwendete permanente Prostatakarzinomzelllinien sich deutlich von dem klinisch relevanten, primären Prostatakarzinom unterscheiden und damit die Übertragbarkeit dieser Zellkulturergebnisse auf die Klinik nur bedingt gegeben ist. Das Arbeiten mit Primärzellkulturen aus Gewebestückchen von Prostatektomiepräparaten bietet eine sehr gute Alternative, doch die Etablierung von Primärkulturen gestaltet sich schwierig und recht aufwändig. In dieser Arbeit wurde ein Primärzellkulturmodell mit einem Invasionssystem kombiniert. Hiermit gelang es nicht nur invasiv wachsende Zellpopulationen aus Primärkulturen zu selektionieren, sondern auch diese Zellen in einem 3D-Modell unter der Ausbildung von Sphäroiden weiter zu kultivieren. Zur Charakterisierung dieser Zellpopulation haben wir vergleichende genomische Hybridisierungen durchgeführt, die zahlreiche genetische Alterationen aufzeigen. Das hier dargestellte Modell ermöglicht es erstmalig, invasive Zellklone aus primärem Prostatakarzinomgewebe zu gewinnen und durch Kultivierung für weitere Untersuchungen zu verwenden.

Abstract: Background: Several new techniques have recently been described that allow the endoscopic mucosal resection even of broad-based flat lesions in the gastrointestinal tract. The technique recently described by us of using a water jet dissector (Helix HydroJet®) for a selective deposition of liquid in the submucosal lamina has now been combined with different substances, and their effects have been compared. Material and Methods: Gastroscopies were carried out in 8 pigs under intubation anesthesia, and 2 submucosal cushions each were created in the stomach using one out of 4 test substances (gelatin, glucose 50, hydroxyethyl starch [HES] 10%, dextran 40), as well as one cushion of isotonic saline solution placed in each area via the Helix HydroJet®. The height of the submucosal cushions was intermittently measured over a period of 40 or 20 min, respectively, by miniprobe endosonography. In 7 of the animals the stomach was subsequently subjected to mucosal resection. The specimens and the gastric wall were histologically assessed to evaluate the localization of the liquid cushion and the effect on adjacent layers of the gastric wall. Results: All test substances produced strictly selective liquid cushions in the submucosa. With HES 10% and dextran the maximum height of the cushions initially increased and then decreased during the further course to an average of 90% of the initial height within 40 min. Isotonic saline solution showed the most rapid decrease in height (72% after 20 min). The histological assessment confirmed the selective nature of the liquid deposit in the submucosa. Discussion: Plasma expanders produced cushions that initially increased in height but then remained constant for a longer period than cushions produced using glucose 50, gelatin, or isotonic saline solution. The combination of transmucosal jet application for elevation of the mucosa with plasma expanders is therefore an interesting approach to optimize endoscopic mucosal resections.

Two isoforms of facilitative glucose transporters (GLUT), namely the erythroid/brain-type GLUT 1 and the liver-type GLUT 2, were demonstrated in native cryostat sections of normal rat liver and brain by immunofluorescence and a very sensitive immunoalkaline phosphatase reaction. Fixation with 0.1% alcoholic periodic acid resulted in an excellent localization of GLUT 2 in liver and GLUT 1 in brain. GLUT 1 in liver, however, could successfully be demonstrated after fixation with 1% alcoholic formaldehyde. GLUT 2 occurred in all hepatocytes as a basolateral membrane protein with a gradient of high expression in the periportal area and a lower one in the perivenous part. The first layer of hepatocytes adjacent to the hepatic vein coexpressed GLUT 1. In addition, GLUT 1 could be detected in the smooth muscle layer of the portal vein and in the apical and lateral plasma membrane of the bile duct epithelium. In brain, GLUT 1 showed a high expression in the microvessels, the ependym and in the basal plasma membrane of choroid plexus epithelial cells. The blood capillaries associated with the choroidal epithelium were, however, negative for GLUT 1. The importance of the new findings in this study for the physiological role of the respective facilitative glucose transport proteins is discussed.

•What is already known on this subject? NTCP deficiency is associated with hypercholanemia.•What are the new findings?Upon review of the literature, serum bile acid levels may be related to the mutation.•How might it impact on clinical practice in the foreseeable future?NTCP deficiency should be considered as part of the differential diagnosis of unexplained failure to thrive, anicteric cholestasis, fetal demise, or unexplained histological liver abnormalities associated with hypercholanemia.

Extended sleeve pneumonectomy including removal of the superior vena cava, right atrium and parts of left atrium on cardiopulmonary bypass was successfully performed in a 40-year-old man. The tumour was histologically proven a T4 N1 stage with margins free from tumour. Adjuvant radiochemotherapy was administered postoperatively on an outpatient base. The patient did well for 7 months then he died from myocardial infarction due to metastatic infiltration of the right coronary artery. Other metastatic deposits were not found at autopsy. More data from extended pulmonary resections are required to demonstrate a benefit.

A 71-year-old woman was admitted with angina pectoris. During hospitalization she developed a myocardial infarction (NSTEMI). Laboratory results revealed a mild elevated troponin and an elevated calcium level (3.35 mmol/l). Subsequently, there was a decreased phosphate (0.36 mmol/l [normal 0.81-1.62 mmol/l]) as well as 16-fold elevated serum level of parathyroid hormone (PTH, 1156 ng/l [normal 10-73 ng/l]), indicating a primary hyperparathyroidism. Sonographically a thyroidal node was detected, not clearly demarcated (TIRADS 5). FNA showed a monomorphic, partial follicular cell population with an immunohistochemical positivity for PTH. Magnetic resonance imaging (MRI) showed a 5 cm large tumor at the right caudal pole of the thyroid with compression of the dorsolateral trachea without infiltration. Surgical removal with en bloc resection of the right hemithyroid with parathyroidectomy was performed. Postoperatively the PTH level dropped to 12.1 ng/l. Pathological examination revealed a 5 cm tumor with infiltration of the thyroid and a perineural invasion. The diagnosis of a presymptomatic parathyroid carcinoma could be established. The affirmative histopathological diagnosis of a parathyroid carcinoma can be challenging and is limited to tumors with evidence of invasive growth in adjacent structures such as the thyroid and/or soft tissue, perineural spaces, angioinvasion of capsular and/or extracapsular vessels, and/or documented metastases.