Nachsorge,Rezidivtherapie, psychoonkologische Versorgung und Palliativmedizin des Endometriumkarzinoms

In April 2018 the first German interdisciplinary S3 guideline for the diagnostics, treatment, and follow-up of patients with endometrial cancer was published. This article is a summary of Chap. 9 on “Surveillance/Recurrence/Metastases of Endometrial Cancer” and is a clinically oriented abbreviated version, which includes recommendations for investigation modalities in aftercare and treatment options in cases of recurrence. Also included are aspects of psycho-oncological support and palliative medical care from the S3 guideline.     

CDw60 glycolipid antigens of human leukocytes: structural characterization and cellular distribution

Monoclonal CDw60 antibodies recognize glycolipid antigens with restricted surface expression on human leukocytes. They allow us to define new functional subpopulations of T lymphocytes and are able to induce costimulatory signals. In this report, we describe the molecular composition of CDw60 glycolipid antigens derived from different human leukocyte subpopulations. The glycolipids were isolated and their structures were identified by immunochemical methods. All molecules containing the CDw60 determinant were found in the disialoganglioside fraction. They were O-acetylated derivatives of the gangliosides II3 (Neu5Ac)2-LacCer (GD3), IV3 (Neu5Ac)2-nLc4Cer (DSPG), and VI3 (Neu5Ac)2- nLc6Cer (DSnHC), respectively. The most common CDw60 glycolipid antigen in human leukocytes was 9-O-acetyl GD3. In a comparison of various cell types, the highest concentration of 9-O-acetyl GD3 on a per cell basis was determined in granulocytes and in blood T lymphocytes, whereas B lymphocytes, thymus cells, and monocytes contained considerably smaller amounts of this molecule. Polar CDw60 antigens such as 9-O-acetyl DSPG and 9-O-acetyl DSnHC were only detected in granulocytes.     

Different capacities for amino acid transport in periportal and perivenous hepatocytes isolated by digitonin/collagenase perfusion

Periportal and perivenous hepatocytes were isolated from rat liver by digitonin/collagenase perfusion for investigating the acinar heterogeneity of amino acid transport activities related to glutamine and ammonia metabolism. Immunocytochemical staining of the respective subpopulations for glutamine synthetase demonstrated that periportal subpopulations were essentially free of glutamine synthetase-positive cells, whereas perivenous subpopulations showed a 2- to 3-fold enrichment of glutamine synthetase-positive hepatocytes. The high perivenous/periportal ratio of 59 found for glutamine synthetase activity as well as the perivenous/periportal ratios of other marker enzymes further indicated the good separation of periportal and perivenous cells. alpha-Aminoisobutyric acid, histidine and glutamate were used to determine the distribution pattern of amino acid transport systems A, N and G-, as well as of the sodium-independent uptake of these compounds 1 hr after isolation and after maximal hormonal stimulation during primary culture. The strong heterogeneity of the sodium-independent transport of histidine, characterized by higher perivenous transport rates [perivenous/periportal ratio: 1.5 (1 hr) to 3.5 (48 hr)], suggests a significant role of facilitated diffusion, presumably in glutamine export. Conversely, the strong heterogeneity of the sodium-dependent glutamate transport (System G-) characterized by higher uptake rates in nonstimulated [perivenous/periportal ratio: 6.6 (1 hr)] and in hormonally treated perivenous hepatocytes (perivenous/periportal ratio: 2.2) reflects its possible significance with respect to the substrate availability for glutamine synthesis. The observed heterogeneities provide a basis for understanding how substrate fluxes related to glutamine metabolism might be established and regulated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dopamine: its potential for inducing ischemic left ventricular dysfunction

As an agent potentially capable of inducing ischemia in patients with coronary artery disease, dopamine administered intravenously was evaluated as a pharmacologic stress agent by supine radionuclide angiography, and the results were compared with ergometer exercise. In a preliminary group of 11 subjects (4 normal subjects and 7 patients with coronary disease), dopamine alone was administered in increments of 2.5 micrograms/kg per min to a maximum of 15 micrograms/kg per min. There were significant differences between exercise and dopamine in maximal stress heart rates, 129.3 +/- 30.0 versus 88.0 +/- 35.8 beats/min (p less than 0.05) in normal subjects and 118.9 +/- 21.1 versus 87.6 +/- 22.6 beats/min (p less than 0.05) in patients with coronary disease, as well as in maximal stress rate-pressure products, 213.3 +/- 51.4 versus 155.0 +/- 52.5 mm Hg/min X 10(2) (p less than 0.02) in normal subjects and 216.0 +/- 45.6 versus 161.0 +/- 48.6 mm Hg/min X 10(2) (p less than 0.003) in patients with coronary disease. As a result, in these patients the ejection fraction response was significantly different: -3.3 +/- 4.5% with exercise versus + 6.3 +/- 4.6% with dopamine (p less than 0.05). In a second group of 41 subjects (9 normal subjects and 32 patients with coronary disease), atropine (0.6 mg) was administered intravenously before and after every second dopamine dose increment. This produced statistically similar maximal stress heart rates as compared with exercise in all subjects, rate-pressure products in normal subjects and slightly higher values with dopamine in patients with coronary disease: 200.3 +/- 47.2 versus 183.1 +/- 43.0 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Frequency and Late Results of Local Recurrence and Metachronous Distant Metastases in Rectal Cancer

Over a 5-year period (1990 to 1995) 425 patients were operated on for rectal cancer. There were 48 local recurrences, 15 with additional distant metastases, 61 patients only had distant metastases. In our patients we found as a well known fact an increasing number of local recurrences and distant metastases with an increasing T- or N stage, no metastases in cases of low tumor grading (28/425 G1), but a high increase comparing patients with or without blood vessel invasion (V 12.3%, V1 42.9%). Lymphatic vessel invasion also shows a higher rate of local recurrences and distant metastases, even in nodal and blood vessel negative patients (L0, N0, V0, L1, N0, V0 60%).L- and V-positive patients should be included in a postoperative adjuvant therapy regime as well (together with all cases Stage II and III UICC), even in nodal negative cases.     

Duodenal pancreatectomy with occlusion of the pancreatic duct

In 1978 partial duodenopancreatectomy with Ethibloc duct occlusion of the pancreatic remnant was introduced for use in patients with severe chronic cephalic pancreatitis. Our intention was to remove the largely destroyed part of the gland, and to induce controlled glandular atrophy in the residual portion in order to prevent further recurrence of pancreatitis. Since then this surgical procedure has been performed in 328 patients. The perioperative mortality was 1.2%, the complication rate requiring relaparotomy 7.1%. So far pancreatitis has recurred in only 2.2% of cases, due, we believe, to incomplete ductal block. Some 53% of the patients remained free of pain and symptoms, while 35% have occasional minor complaints. In a prospective follow-up study of 23 patients, Ethibloc duct occlusion was shown to be highly effective in inducing controlled atrophy of the gland and thereby terminating the inflammatory process. Endocrine function was preserved at the post-resectional level.     

p38丝裂原活化蛋白激酶信号途径在鼠破骨细胞生成和骨吸收中的作用

目的研究p38丝裂原活化蛋白激酶(p38MAPK)信号途径在甲状旁腺素相关肽(PTHrP)诱导的破骨细胞生成和骨吸收中的作用。方法取小鼠骨髓细胞,在PTHrP(45ng/ml)的刺激下,在不同试验组中分别入0.1、1.0及10μmol/L的p38MAPK抑制剂Fr167653,继续培养6d。抗酒石酸染色,进行破骨细胞计数。在小鼠颅骨部位注射PTHrP建立骨吸收和高钙血症动物模型。每日给予p38MAPK抑制剂Fr16765330mg/kg,每日2次,X线片观察骨吸收面积,组织学检查计算单位面积内破骨细胞数目,采集血样观察全血内游离钙水平。结果PTHrP刺激下,大量破骨细胞生成(118.9±28.3)个/孔;加入0.1μmol/LFr167653可以部分抑制破骨细胞的生成(79.6±28.0)个/孔,加入10μmol/LFr167653几乎全抑制了破骨细胞生成(7.4±0.4)个/孔,每日给予Fr16765330mg/kg,每日2次,可以明显抑制骨吸收,表现为X线片上骨吸收面积减少,单位面积内破骨细胞数目减少,但是并不能有效地抑制高钙血症。结论抑制p38MAPK信号途径可以抑制破骨细胞的分化和局部骨吸收。     

Hedgehog signalling pathway in adult liver: A major new player in hepatocyte metabolism and zonation?

Metabolic Zonation, i.e. the heterogeneous distribution of different metabolic pathways in different zones of the lobules, forms the basis of proper function of the liver in metabolic homeostasis and its regulation. According to recent results, Metabolic Zonation is controlled by the Wnt/β-catenin signalling pathway. Here, we hypothesize that hedgehog signalling via Indian hedgehog ligands plays an equal share in this control although, up to now, hedgehog signalling is considered not to be active in healthy adult hepatocytes. We provide broad evidence taken mainly by analogy from other mature organs that hedgehog signalling in adult hepatocytes may particularly control liver lipid and cholesterol metabolism as well as certain aspects of hormone biosynthesis. Like Wnt/β-catenin signalling, it seems to act on a very low level forming a porto-central gradient in the lobules opposite to that of Wnt/β-catenin signalling with which it is interacting by mutual inhibition. Consequently, modulation of hegdehog signalling by endogenous and exogenous agents may considerably impact on liver lipid metabolism and beyond. If functioning improperly, it may possibly contribute to diseases like non-alcoholic fatty liver disease (NAFLD) and other diseases such as lipodystrophy.