[Treatment of chronic mediastinitis]. / Therapie der chronischen Mediastinitis.

BACKGROUND: Chronic mediastinitis is a rare disorder characterized by the proliferation of fibrous tissue within the mediastinum resulting in compression of mediastinal structures. OBJECTIVE: This article gives an overview of the treatment options for chronic mediastinitis. MATERIAL AND METHODS: A literature search was carried out regarding treatment options for chronic mediastinitis RESULTS AND CONCLUSION: Little is known about the pathogenesis of chronic mediastinitis, which has hampered the development of novel therapeutic approaches. There is no convincing evidence for the success of medicinal (antifungal or conventional anti-inflammatory) therapy and it is not recommended. In cases of clinical symptoms procedures for decompression, such as endovascular or endobronchial stents or surgical procedures, such as decompression interventions or extra-anatomic bypasses should be considered. The prognosis for unilateral involvement is better than for bilateral involvement if performed in specialized centers.

[Anticoagulants in thoracic surgery]. / Blutgerinnungsbeeinflussende Medikamente in der Thoraxchirurgie.

BACKGROUND: Many patients undergoing thoracic surgery are treated with anticoagulants or platelet aggregation inhibitors because of different comorbidities. Additionally the risk of thromboembolic events is increased perioperatively; therefore, a perioperative thrombosis prophylaxis is necessary. On the other hand the risk of intraoperative or postoperative bleeding is increased because of the volume of the thoracic cavity and the partially negative intrathoracic pressure. OBJECTIVES: This article gives an overview of the perioperative management of anticoagulant therapy in thoracic surgery and presents an appropriate approach in cases of severe bleeding. MATERIAL AND METHODS: A literature search was carried out regarding currently used anticoagulants. RESULTS AND CONCLUSION: For the correct perioperative application of vitamin K antagonists, platelet aggregation inhibitors, new oral anticoagulants and drugs for thrombosis prophylaxis, it is of major importance to conceive an individual risk profile of thoracic surgery patients. However, there are not enough evidence-based data referring to the correct perioperative management for new oral anticoagulants.

Intraoperative sRAGE kinetics. A new age-related outcome predictor of cardiac surgery.

BACKGROUND: Glycated proteins (advanced glycation endproducts, AGE) in tissue are associated with degenerative diseases. This study evaluated the role of sRAGE (soluble receptor for advanced glycation endproducts), a decoy receptor of AGEs in blood, for the outcome of patients after coronary artery bypass grafting (CABG). METHODS: A total of 90 patients undergoing CABG were analysed in two centres. Perioperative blood samples were collected before surgery up to 1 week postoperatively. sRAGE was measured by ELISA. Patients were subdivided regarding age (< 64 versus > 70 years, 14 % versus 35 % female), euroSCORE (< 3 versus > 4, 14 % versus 29 % female) and sRAGE changes between sternotomy and end of the operation (< 30 % versus > 45 %, 33 % versus 33 % female) and subsequently analysed with respect of postoperative outcome parameters. RESULTS: Preoperative sRAGE values did not correlate with the outcome of the patients. sRAGE levels increase within 10 min from 1,539 ± 96 to 5,311 ± 187 pg/ml after sternotomy, then returning to baseline levels within 2 days after surgery. Comparing the analysed possible risk factors age, euroSCORE and sRAGE changes, no difference was observed regarding 30-day mortality. Age and the euroSCORE are superior with respect of tachyarrythmia, whereas sRAGE kinetics seems to be superior with respect of prolonged postoperative respiration time/stay in the intensive care unit or catecholamine support. CONCLUSION: A prolonged, increased intraoperative sRAGE level is a new outcome predictor for patients undergoing CABG surgery, mutually complementary to the euroSCORE.

Inflammatory response in on- versus off-pump myocardial revascularization: is ECC really the culprit?

A review of inflammatory mediators in on- versus off-pump surgery reveals that parameters of systemic inflammation differ quantitatively, not qualitatively between these approaches. Mediator system and cellular activation is observed after surgical trauma and following ischemia/reperfusion. Such activation is also modulated by genetic factors. The available literature does not permit definitive conclusions to be made on the advantages of off-pump surgery with respect to the systemic inflammatory response. The relationship between mediator systems and clinical course needs to be assessed in large patient populations to demonstrate to what extent off-pump surgery is more than just theoretically superior to on-pump surgery.

Advanced glycation end products, diabetes and ageing.

Advanced glycation end products (AGEs) are formed in vivo by a non-enzymatic reaction of proteins with carbohydrates and accumulate in many tissues during ageing. They are discussed as being responsible for many age- and diabetes-related diseases. On the other hand, AGEs are formed by the heating of food and are taken up by the nutrition. The contribution of endogenously formed versus exogenous intake of AGEs to age-related diseases is still under discussion.

Can an endocytoscope system (ECS) predict histology in neoplastic lesions?

BACKGROUND AND STUDY AIMS: An endocytoscope system (ECS) has recently been developed with the possibility of super-high magnification of gastrointestinal mucosa, thus allowing in vivo imaging of living cells. The aim of the present study was to assess the potential of ECS in the prediction of histology in both normal gastrointestinal mucosa and neoplastic lesions. PATIENTS AND METHODS: In total, 76 patients (57 men, 19 women; age range 37-86 years) with neoplastic lesions in the esophagus, stomach, or colon were enrolled into the study and underwent esophagogastroduodenoscopy or colonoscopy. After staining with 1% methylene blue, the mucosa was examined with the ECS probe (x 450 and x 1100 magnification), and video sequences were recorded on video disk. Biopsies from the examined areas were taken for histology and served as the gold standard. The endocytoscope video sequences were evaluated by two blinded pathologists. Finally the results were compared with those resulting from the evaluation of an experienced endoscopist who was aware of the macroscopic endoscopic pictures and the endocytoscope image results. RESULTS: A total of 25 patients with esophageal lesions, 28 patients with colonic lesions, and 23 patients with gastric lesions were examined. The sensitivity and specificity for the evaluation of the blinded pathologists was 81% and 100%, respectively, in the esophagus, 56% and 89% in the stomach, and 79% and 90% in the colon. If an endoscopist evaluated the endocytoscopic pictures in combination with the macroscopic endoscopic images sensitivity and specificity increased significantly. CONCLUSIONS: First experiences with ECS show good sensitivity rates even by blinded assessment for esophageal and colonic lesions. Sensitivity for neoplastic lesions in the stomach is lower because of gastric mucous secretion. Combining the endoscopic and cytoscopic appearance of the lesion may further enhance the diagnostic value of the method.

Advanced glycation endproducts: a biomarker for age as an outcome predictor after cardiac surgery?

OBJECTIVE: A decline in the function of all organs can be detected during ageing. Although the trend appears to be stable, deviation within the elderly population is much greater in comparison to young controls. The aim of the study was to identify a marker of senescence which correlates to heart function. Advanced glycation endproducts (AGEs) accumulate with age and are associated with degenerative diseases. METHODS: Carboxymethyllysine (CML) concentrations in the pericardial fluid (as a measure of AGEs) were analysed with ELISA technique in 75 patients undergoing cardiac surgery and correlated with clinical parameters and outcome of these patients. RESULTS: CML content of pericardial fluid increases significantly with age. AGEs show an inverse correlation to left ventricular ejection fraction. High CML levels correlate with poor outcome of patients as shown by adverse cardiac events, prolonged ventilation time and prolonged stay within the Intensive Care Unit. Within all parameters, AGE concentration of the pericardial fluid fits better with the outcome of the patients in comparison to age alone. Interestingly, medical treatment with nitrates correlates with increased CML content. CONCLUSION: AGEs, in addition to being a marker of senescence, appear to represent a prognostic factor in cardiac surgery, which can be used as a predictor of patient outcome.

Regulation of cytokine synthesis in cardiac surgery: Role of extracorporeal circuit and humoral mediators in vivo and in vitro.

OBJECTIVE AND DESIGN: Cardiopulmonary bypass (CPB) impairs monocyte and neutrophil proliferation, cytokine synthesis, and antigen presentation. This study compares in vivo data with results from an extracorporeal circulation (ECC) model, distinguishing direct effects on cytokine synthesis from regulatory mechanisms. PATIENTS AND METHODS: Whole blood from 18 patients prior to, during and after CPB was stimulated with lipopolysaccharide (LPS). Tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 levels were measured. Additionally, blood from 4 volunteers was circulated in an ECC model. Cytokine levels were measured before and during mock ECC. RESULTS: LPS-induced cytokine synthesis was reduced after CPB (TNF-alpha: 11 %; IL-6: 29 %; IL-8: 48 % of preoperative values, all p < 0.001). In mock ECC, cytokine production (except IL-8) was suppressed: TNF-alpha production was lowest 60 min after starting ECC, IL-6 synthesis was lowest at 90 min (33 % and 15 % vs. pre-ECC levels; both p < 0.001). Patient sera contained cytokine-inhibitory activity after CPB, an activity not found in mock ECC. CONCLUSIONS: (1) In patients, CPB induces early transient LPS hyporesponsiveness; (2) blood contact with foreign surfaces induces LPS hyporesponsiveness; (3) serum cytokine-inhibitory activities are released after CPB, but not in mock ECC. Impaired leukocyte function may explain increased susceptibility to infections after CPB.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) restores decreased monocyte HLA-DR expression after cardiopulmonary bypass.

OBJECTIVES: Cardiopulmonary bypass (CPB) is associated with a disturbed immune response, e.g., impaired HLA-DR expression on monocytes and the release of pro- and anti-inflammatory cytokines. Cytokine release plays a role in the pathogenesis of postoperative systemic inflammatory response syndrome (SIRS) and immune system deterioration, e.g., impaired monocyte and polymorphonuclear neutrophil (PMN) function, factors that ultimately lead to an increased susceptibility to infections. To gain a further understanding, we investigated HLA-DR expression on monocytes and on B- and T-lymphocytes. In addition, we investigated the IN VITRO effect of the immunostimulating hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) on HLA-DR expression of these cell types. Neither HLA-DR expression on B- and T-lymphocytes nor the effects of GM-CSF in cardiac surgical patients have been studied before. METHODS: In 16 patients undergoing elective cardiac surgery with CPB, counts of circulating leukocyte subsets as well as HLA-DR expression on monocytes, B- and T-lymphocytes were measured by flow cytometry before, immediately after CPB, and on the 2nd and 10th postoperative days. Treatment with GM-CSF was performed IN VITRO in whole blood cultures with 100 ng/ml recombinant human GM-CSF for 20 h. RESULTS: Monocyte HLA-DR expression was attenuated immediately after CPB (125 +/- 4 mean channel fluorescence [MCF] vs. 143 +/- 2 MCF preoperatively, mean +/- SEM, P < 0.001). HLA-DR expression further decreased on the 2nd day after CPB and did not normalize until the 10th day after the operation. In contrast, HLA-DR expression on T-cells was unchanged, whereas HLA-DR expression on B-cells did not decrease before the 2nd day after CPB (152 +/- 3 MCF vs. 170 +/- 2 MCF preoperatively, P < 0.001). IN VITRO GM-CSF treatment increased HLA-DR expression on monocytes prepared after CPB to a degree comparable to preoperative values. HLA-DR expression on B-lymphocytes could not be restored by GM-CSF. CONCLUSIONS: Immune system suppression after cardiac surgery is reflected in prolonged diminished HLA-DR expression on monocytes and B-lymphocytes. Suppression is not irreversible but can - at least IN VITRO - be overridden by the immunostimulating compound GM-CSF.

Age-dependent myocardial reinduction of apoptosis inhibitors under VAD in heart failure.

Hemodynamic unloading using the ventricular assist device [VAD] results in partial functional recovery of failing hearts that show increased susceptibility to cardiomyocyte apoptosis. The caspase cascade is the central element of the apoptotic process in cells. We therefore tested expression shifts of left ventricular mRNA of caspases and their endogenous inhibitors from 15 patients with VAD support and successful bridging to transplantation using semiquantitative RT-PCR. Cardiac unloading was shown by the reduction in ventricular Pro-ANP mRNA under VAD. No alteration of mRNA expression under VAD could be observed for initiator caspases, for their selective inhibitors or for apoptotic signal molecules from the mitochondrial intermembrane space. Only two unselective cardiac IAPs (inhibitor of apoptosis protein) were increased under VAD with better recovery in younger patients. In conclusion, our findings indicate that successful hemodynamic unloading by VAD support causes only minor, age-dependent recovery in the expression of IAPs, while presumed alterations in antiapoptotic modulator systems upstream of the caspase cascade still remain to be identified.

Treatment of watermelon stomach (GAVE syndrome) by means of endoscopic argon plasma coagulation (APC): long-term outcome.

We report on 17 patients with GAVE-syndrome (gastric antral vascular ectasia) treated by means of endoscopic argon plasma coagulation (APC). 16 of 17 patients presented with iron deficiency anemia; transfusion-dependent anemia was noted in 11 patients (65%). Resolution of the gastric angiectasia could be achieved in all patients by endoscopic APC after 1-4 treatment sessions. Endoscopic follow-up revealed recurrence of GAVE in 5 patients (requiring further treatment sessions). Mean pretreatment hemoglobin level of 78 g/l improved to 115 g/l after treatment. Only one patient needed post-treatment transfusions; she had refused further endoscopy. The mean follow-up was 30.4 months (range 1-65). In one case circumferential scarring of the antrum led to asymptomatic stenosis 6 months after APC; at the same time early recurrence of extensive angiectasia occurred. Billroth I resection was performed. No other complications were observed. Our results show that argon plasma coagulation is an effective and safe treatment for gastrointestinal blood loss due to GAVE syndrome (watermelon stomach). Control endoscopies are indicated in order to recognize and treat recurrence of angiectasia on time.

Octreotide scintigraphy localizes somatostatin receptor-positive islet cell carcinomas.

Tyr-3-Octreotide is a synthetic derivative of somatostatin and a somatostatin-receptor analogue. The iodine-123-labelled compound localizes somatostatin-receptor-positive tumours. In this paper two patients are reported in whom somatostatin receptors were demonstrated in vitro. In a 60-year-old female with an islet cell carcinoma of the pancreas, multiple liver metastases and previously unrecognized bone metastases in the right acetabulum could be diagnosed as the reason for a persistent hypoglycaemia. In a 60-year-old male an islet cell carcinoma of the pancreas was localized with 123I-Tyr-3-octreotide. The somatostatin receptors were demonstrated in vitro and the tumour was successfully treated with somatostatin. These studies demonstrate that 123I-Tyr-3-octreotide offers the possibility of localizing somatostatin-receptor-positive tumours and their metastases. Moreover the method makes it possible to determine the receptor status of a tumour in vivo.

Electronic endoscopy--fibres or chips?

The video endoscope represents a new generation of endoscopic instruments. The main feature is an intragastric CCD-chip transforming the optical impulses into electronic signals. The latter are transmitted without any optical fibre bundle, transformed by a video processor and visualized on a television screen. The present experience show drawbacks in respect to mechanical properties of the endoscopes, to reproduction of colors (esp. red) and photographic documentation. On the other hand the excellent image quality guarantees convenient handling for investigator, information for attending persons (doctors, nurses, students), improved conditions for documentation and control of quality. Although the video-endoscope is not replacing fibre endoscopes at present, further improvement will promote its general acceptance.