[Percutaneous endoscopic gastrostomy. Complications with and without anticoagulation]. / Perkutane endoskopische Gastrostomie. Komplikationen mit und ohne Antikoagulation.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) has been classified to date as a high-risk procedure (ASGE guidelines). Coagulopathies, thrombocyte aggregation inhibitors (Aspirin, clopidogrel etc.) and phenprocoumone or warfarin are considered to be contraindications. The study examined for the first time the risk factors in patients with and without concurrent anticoagulation. METHODS: Between 2001 and 2007 PEGs were placed in 450 patients with neurological diseases at the University Hospital for General and Visceral Surgery in Freiburg and studied prospectively during hospitalization. The patients were divided into 3 groups: group 1 controls (n=50, no anticoagulation), group 2 low-molecular-weight heparin (LMWH) prophylaxis (n=152) and group 3 therapeutic anticoagulation (unfractionated heparin, phenprocoumone, therapeutic LMWH, aspirin, clopidorel and combinations, n=248). Univariate analyses were performed to determine risk factors for the occurrence of infection, bleeding and peritonitis. The p-values (p), odds ratios (OR) and 95% confidence intervals (CI) are given. RESULTS: The average hospitalization time was 27.4 days (range 1-268 days) and hospital mortality was 6%. There were no cases of death due to the PEG. Complications included peristomal infections (n=30, 6.6%) and peritonitis (n=6, 1.3%). Post-PEG bleeding did not occur either with or without anticoagulation. The investigated risk factors showed no statistically significant values with respect to prognosis for these complications. Multivariate testing could not be carried out due to the low number of complications. CONCLUSION: Complications of PEG placement with the method used here are rare. An increased risk of bleeding during therapeutic anticoagulation was not observed. In our opinion the present data indicate that PEG placement can be carried out in selected patients with increased risk of thromboembolism without discontinuation of anticoagulation.

Ingroup perception and responses to stigma among persons with mental illness.

OBJECTIVE: Mental illness stigma is common, but it is unclear why it affects some individuals more than others. We tested the hypothesis that the way persons with mental illness perceive their ingroup (people with mental illness) in terms of group value, group identification and entitativity (perception of the ingroup as a coherent unit) shapes their reaction to stigma. METHOD: Ingroup perceptions, perceived legitimacy of discrimination and reactions to stigma (educating or helping others, social performance, secrecy, social distance, hopelessness) were assessed among 85 people with mental illness using questionnaires and a standardized role-play test. RESULTS: Controlling for depression and perceived discrimination, high group value and low perceived legitimacy of discrimination predicted positive reactions to stigma. High group identification and entitativity predicted positive reactions only in the context of high group value or low perceived legitimacy of discrimination. CONCLUSION: Group value and perceived legitimacy of discrimination may be useful targets to help people with mental illness to better cope with stigma.

CpG-island methylation of the ER promoter in colorectal cancer: analysis of micrometastases in lymph nodes from UICC stage I and II patients.

Patients with UICC stage II colorectal cancer (CRC) have a risk of approximately 20% to develop disease recurrence after tumour resection. The presence and significance of micrometastases for locoregional recurrence in these patients lacking histopathological lymph node involvement on routine stained HE sections is undefined. Oestrogen receptor (ER) promoter methylation has earlier been identified in CRC. Therefore, we evaluated the methylation status of the ER promoter in lymph nodes from 49 patients with CRC UICC stage I and II as a molecular marker of micrometastases and predictor of local recurrence. DNA from 574 paraffin-embedded lymph nodes was isolated and treated with bisulphite. For the detection of methylated ER promoter sequences, quantitative real-time methylation-specific PCR was used. Of the 49 patients tested, 15 (31%) had ER methylation-positive lymph nodes. Thirteen of those (86%) remained disease free and two (14%) developed local recurrence. In the resected lymph nodes of 34 of the 49 patients (69%), no ER promoter methylation could be detected and none of these patients experienced a local relapse. The methylation status of the ER promoter in lymph nodes of UICC stage I and II CRC patients may be a useful marker for the identification of patients at a high risk for local recurrence.

Magnetic resonance imaging contrast agent targeted toward activated platelets allows in vivo detection of thrombosis and monitoring of thrombolysis.

BACKGROUND: Platelets are the key to thrombus formation and play a role in the development of atherosclerosis. Noninvasive imaging of activated platelets would be of great clinical interest. Here, we evaluate the ability of a magnetic resonance imaging (MRI) contrast agent consisting of microparticles of iron oxide (MPIOs) and a single-chain antibody targeting ligand-induced binding sites (LIBS) on activated glycoprotein IIb/IIIa to image carotid artery thrombi and atherosclerotic plaques. METHODS AND RESULTS: Anti-LIBS antibody or control antibody was conjugated to 1-microm MPIOs (LIBS MPIO/control MPIO). Nonocclusive mural thrombi were induced in mice with 6% ferric chloride. MRI (at 9.4 T) was performed once before and repeatedly in 12-minute-long sequences after LIBS MPIO/control MPIO injection. After 36 minutes, a significant signal void, corresponding to MPIO accumulation, was observed with LIBS MPIOs but not control MPIOs (P<0.05). After thrombolysis, in LIBS MPIO-injected mice, the signal void subsided, indicating successful thrombolysis. On histology, the MPIO content of the thrombus, as well as thrombus size, correlated significantly with LIBS MPIO-induced signal void (both P<0.01). After ex vivo incubation of symptomatic human carotid plaques, MRI and histology confirmed binding to areas of platelet adhesion/aggregation for LIBS MPIOs but not for control MPIOs. CONCLUSIONS: LIBS MPIOs allow in vivo MRI of activated platelets with excellent contrast properties and monitoring of thrombolytic therapy. Furthermore, activated platelets were detected on the surface of symptomatic human carotid plaques by ex vivo MRI. This approach represents a novel noninvasive technique allowing the detection and quantification of platelet-containing thrombi.

Analysis of muscle microcirculation in advanced diabetes mellitus by contrast enhanced ultrasound.

AIMS: Contrast enhanced ultrasound (CEUS) was recently established to quantify perfusion deficits in peripheral arterial disease (PAD). However, this approach was not suitable to assess microangiopathy of skeletal muscle, a major contributor to PAD in diabetic patients. We hypothesized that an optimized methodology would detect impaired microcirculation. METHODS: Ten patients with advanced diabetes mellitus (mean diabetes duration 21 years), 10 PAD patients, and 10 control subjects were enrolled consecutively. The arrival times of the contrast agent Sonovue after intravenous injection were assessed selectively in a small artery, muscle tissue and a muscle vein of the calf muscle. Contrast transit times (CTTs) were calculated as the differences between arrival times. RESULTS: The median CTT for artery-vein was significantly higher in the diabetes group (43 s) than in the PAD (22 s, p=0.007) and control groups (11 s, p<0.001, no value overlap). CTTs for artery-muscle and muscle-vein were shorter with highest median values in the diabetes group. CONCLUSIONS: We validated improved CEUS as consistent method to detect changes in the microvascular bed. This method may become a valuable tool to quantify impaired microcirculation in diabetes and help to improve patient care.

Heart-type fatty acid-binding protein for risk assessment of chronic thromboembolic pulmonary hypertension.

Heart-type fatty acid-binding protein (H-FABP) is a reliable marker of myocardial injury and was recently identified as a predictor of outcome in acute pulmonary embolism. The aim of the present study was to investigate the prognostic value of H-FABP in chronic thromboembolic pulmonary hypertension (CTEPH). In total, 93 consecutive patients with CTEPH were studied. During long-term follow-up (median duration 1,260 days, interquartile range (IQR) 708-2,460 days), 46 (49%) patients had an adverse outcome, defined as CTEPH-related death, lung transplantation or persistent pulmonary hypertension after pulmonary endarterectomy (PEA). Baseline H-FABP levels in plasma ranged from 0.69-24.3 ng x mL(-1) (median (IQR) 3.41 (2.28-4.86) ng x mL(-1)). Cox regression analysis revealed a hazard ratio of 1.10 (95% confidence interval 1.04-1.18) for each increase of H-FABP by 1 ng x mL(-1), and continuous elevations of H-FABP emerged as an independent predictor of adverse outcome by multivariable analysis. PEA was performed in 52 patients and favourably affected the long-term outcome. Kaplan-Meier analysis revealed that patients with baseline H-FABP concentrations >2.7 ng x mL(-1), the median value of the biomarker in the surgically treated population, had a lower probability of event-free survival after PEA. Heart-type fatty acid-binding protein is a promising novel biomarker for risk stratification of patients with chronic thromboembolic pulmonary hypertension.

The Ki67+ proliferation index correlates with increased cellular retinol-binding protein-1 and the coordinated loss of plakophilin-1 and desmoplakin during progression of cervical squamous lesions.

AIMS: To investigate the modulation of cellular retinol-binding protein (CRBP)-1 and the desmosomal plaque proteins plakophilin (PKP)-1 and desmoplakin (DP) in correlation with the Ki67+ proliferation index (PI) during the progression of cervical squamous intraepithelial lesions (SIL) to squamous cell carcinoma (SCC). METHODS: Using in situ imaging by brightfield and confocal laser scanning microscopy, the expression of CRBP-1 protein and transcripts, PKP-1, DP and the Ki67 PI were analysed in 38 low-grade (L) SIL, 56 high-grade (H) SIL, 49 SCC, 30 control cervices and 10 human papillomavirus-positive condylomatous lesions. RESULTS: CRBP-1+ cells increased from 11.4% in the normal cervix to 80.3% in LSILs, 92.3% in HSILs and slightly decreased to 78.3% in invasive SCCs (P = 0.0001) in close association with the Ki67 PI (r =0.41; P < 0.0001). PKP-1+ and DP+ cells were correlated (0.32; P < 0.0001) and decreased from normal (81% versus 92.3%) to LSIL (53.1% versus 85.3%), to HSIL (46.4% versus 67.5%) and SCC (35.1% versus 35.9%). The Ki67+ PI was inversely correlated with DP (-0.20, P = 0.0014) and PKP-1 (-0.19, P = 0.015). Condylomata retained low CRBP-1 and high expression of PKP-1 and DP. CONCLUSIONS: The gain of CRBP-1 and the loss of desmosomal proteins occur early in cervical carcinogenesis.

[Palliative medicine content in German-language medical textbooks]. / Palliativmedizinische Inhalte in deutschsprachigen medizinischen Lehrbüchern.

BACKGROUND: There is a need for improved end-of-life care, especially in the light of demographic changes with an increased incidence of cancer. Although medical textbooks are central to the training of medical students and also serve as a reference for more experienced clinicians, only few data exist on the extent to which medical textbooks address end-of-life care. We analysed the quantity and quality of information on end-of-life care given in German textbooks on different medical disciplines. MATERIAL AND METHODS: 26 top-selling German medical textbooks were analysed for the presentation of end-of-life care in chapters that address the 13 most common causes of death worldwide RESULTS: In the 159 chapters analysed for information on traditional topics, like risk factors or early diagnosis (group A), such information was provided in 52% compared with only 9% on end-of-life topics, such as symptom management or manner of death (group B) (p=0.0001). There was no statistically significant difference between the different medical specialities (p=0.22). Line-by-line analysis showed that the phrase death or related terms was mentioned in only 57 of 159 chapters dealing with the most common causes of death worldwide. CONCLUSION: The top-selling German textbooks that were analysed generally offer little helpful information on end-of-life care of patients.

The use of a polytetrafluoroethylene-covered stent graft for transjugular intrahepatic portosystemic shunt (TIPS): Long-term follow-up of 100 patients.

PURPOSE: To retrospectively evaluate results and clinical outcome of transjugular intrahepatic portosystemic shunt (TIPS) after implantation of a polytetrafluoroethylene (PTFE)-covered stent graft. MATERIAL AND METHODS: The stent graft was used in 112 patients with higher risk of primary (i.e. patients with Budd-Chiari syndrome) or secondary shunt failure (patients with occlusion of a previous uncovered stent), or a complicated TIPS procedure with an imminent technical complication requiring covered stent. Patients were scheduled at 3- to 6-month intervals for duplex-sonographic control of shunt function. Radiological revision was performed in patients with a decrease in shunt function by >25%, primary non-response, or relapse of the index symptom. RESULTS: Twelve patients were lost to follow-up, and 100 patients were followed for 22+/-15 months. The actuarial rates of shunt patency were 90, 84, and 74% at 1, 2, and 3 years of follow-up, respectively. Two patients developed early (within 1 month) and 14 patients late shunt failure. Except for one transient rise in liver enzymes due to outflow obstruction by the stent graft, no technical complications were seen. Primary response to treatment was seen in 97% of patients treated for variceal bleeding and 84% of patients treated for refractory ascites. A relapse of the index symptom was seen in 13% of bleeders and 9% of patients treated for refractory ascites. CONCLUSION: TIPS created with a PTFE-covered stent graft showed favorable long-term results.

Primary CNS lymphoma in immunocompetent patients from 1989 to 2001: a retrospective analysis of 164 cases uniformly diagnosed by stereotactic biopsy.

BACKGROUND: We present outcome data of a cohort of 164 immunocompetent PCNSL patients uniformly diagnosed at a single center for stereotactic neurosurgery, and evaluate the acceptance and impact of combination radiotherapy (RT) and chemotherapy (CHT) with high-dose methotrexate (HD-MTX) over time. METHOD: We assessed choice of treatment and patient survival in a series of 164 PCNSL cases diagnosed from 1989 to 2001, and performed a re-evaluation of histopathology and pre-operative clinical data. FINDINGS: From 1989 to 1993, RT was the predominant therapy, and additional CHT did not improve survival. After 1994, the use of combination CHT/RT increased continuously, consistently contained MTX, and was associated with longer survival than RT only: median survival was 14 months after CHT/RT (2-year survival 35.7%) and 10 months (2-year survival 26.2%) after RT only (not significant). Overall median survival remained poor, increasing from six (1989-1993) to nine months (1994-2001) (p = 0.008). Survival was variable, with a few patients surviving >4 years after diagnosis in the CHT/RT as well as in the RT only group. CONCLUSIONS: Despite considerable improvement of PCNSL therapy, the overall benefit of combined CHT/RT versus RT only was lower than that expected from previous phase II clinical trials. The striking variability of survival in either treatment group may suggest a yet undefined biological heterogeneity of PCNSL, which may also include a more aggressive PCNSL subtype in the group of patients with rapidly progressive disease and not eligible for standard therapy.

Do stroke patients with normal carotid arteries require TEE for exclusion of relevant aortic plaques?

OBJECTIVES: This study investigated (a) the hypothesis that stroke patients with aortic atheroma would show comparable atherosclerotic changes in the carotid arteries, which are easily accessible for ultrasound evaluation and (b) the possibility of carotid duplex sonography as a replacement for transoesophageal echocardiography (TEE) for the exclusion or prediction of relevant aortic plaques. METHODS: In 301 consecutive patients (mean age 62 years) with acute cerebral ischaemia, two dimensional ultrasound measurements were taken of common carotid artery intima media thickness (IMT) and maximal plaque area (PA) and the local degree of internal carotid artery (ICA) stenosis were determined. Maximal aortic wall thickness (AWT) was assessed by TEE. RESULTS: An IMT < or =0.9 mm yielded a negative predictive value (NPV) of 95.8% for exclusion of aortic atheromas > or =4 mm and an NPV of 100% for the exclusion of aortic thrombi. However, positive predictive value of IMT >0.9 mm was low (29.6%), increasing only slightly in the presence of carotid plaques (33%). Incidence of aortic thrombi was significantly higher with > or =50% compared with <50% ICA stenosis (11.3% v 3.9%, respectively). IMT and PA correlated moderately with AWT (r = 0.47, r = 0.53, respectively; p<0.001). Systolic blood pressure, coronary heart disease and peripheral artery disease, increased IMT, and ICA stenosis > or =50% were independently related to AWT > or =4 mm. CONCLUSIONS: A high NPV of normal carotid ultrasound does not support routine TEE for the exclusion of complex aortic plaques as a high risk source of cerebral embolism. However, in patients with carotid atherosclerosis, particularly in those with ICA stenosis > or =50%, TEE should be performed to exclude an additional high risk source for stroke.

Prognostic value of the ECG on admission in patients with acute major pulmonary embolism.

A number of ECG abnormalities can be observed in the acute phase of pulmonary embolism (PE). Their prognostic value has not yet been systematically studied in large patient populations. In 508 patients with acute major PE derived from a large prospective registry, the current authors assessed, on admission, the impact of specific pathological ECG findings on early (30-day) mortality. Atrial arrhythmias, complete right bundle branch block, peripheral low voltage, pseudoinfarction pattern (Q waves) in leads III and aVF, and ST segment changes (elevation or depression) over the left precordial leads, were all significantly more frequent in patients with a fatal outcome. Overall, 29% of the patients who exhibited at least one of these abnormalities on admission did not survive to hospital discharge, as opposed to only 11% of the patients without a pathological 12-lead ECG. Multivariate analysis revealed that the presence of at least one of the above ECG findings was, besides haemodynamic instability, syncope and pre-existing chronic pulmonary disease, a significant independent predictor of outcome. In conclusion, ECG may be a useful, simple, non-costly tool for initial risk stratification of patients with acute major pulmonary embolism.

[Completion pneumonectomy. Indications and results]. / Sekundäre Pneumonektomien. Indikationen und Langzeitergebnisse.

Completion pneumonectomy (CP) is widely known to be associated with high morbidity and lethality. However, in certain instances, it offers the only chance for cure. The results of the following CPs (N=86) were investigated: progressive or recurrent benign disease (N=6, group I), recurrence of a malignant tumor (N=41, group II), and complication after lung resection (N=39, group III). Right completion pneumonectomy was carried out in 48 cases and left completion pneumonectomy in 38. The overall 30-day lethality of CP was 20.2%, 0% in group I, 10% n group II, and 33.3% n group III. This lethality was significantly higher on the right side (29.8%) than on the left (7.7%; P=0.014). Differentiation between emergency and urgent indications resulted in 30-day lethalities of 54% and 23%, respectively. This difference is significant (P=0.002). The 30-day lethality for patients with anastomotic or stump insufficiency was 41% (P=0.002). Five-year survival was 26% in the group of patients with malignant disease and 32% in those with complications after lung resection. The results show: the lethality of CP remains high, especially after complications from operating in emergency conditions. However, considering the long-term survival, CP is certainly justified.

The Impella Recover microaxial left ventricular assist device reduces mortality for postcardiotomy failure: a three-center experience.

BACKGROUND: We evaluated patient outcomes and complications associated with the microaxial Impella Recover left ventricular assist device (Impella Cardiosystems AG, Aachen, Germany) for postcardiotomy low-output syndrome. This low-cost device is inserted across the aortic valve through a 10-mm vascular graft sewn to the ascending aorta. METHODS: Impella patients were compared with 198 patients treated with an intraoperative intra-aortic balloon pump between January 2000 and December 2002. Three risk scores were used: the Hausmann score, the Texas Heart Institute score, and the Cleveland intensive care unit score. Between September 2001 and March 2003, 24 patients were treated with the Impella Recover for low-output syndrome. Before device insertion, 21 could not be separated from cardiopulmonary bypass, and 3 had postoperative hemodynamic instability despite high-dose catecholamines. Sixteen were treated with the Impella and intra-aortic balloon pump and 8 with the Impella alone (no intra-aortic balloon pump because of peripheral vascular disease or because deemed unnecessary). RESULTS: No technical problems with device insertion occurred. Pump flow was 3.3 +/- 0.7 L/min at 28,000 +/- 4500 RPM. Support time was 61 +/- 56 hours (range, 7-228 hours). Four devices required repositioning. One device failed (leaking purge line) and was removed. Hemolysis was minimal (lactate dehydrogenase levels of 540 +/- 260 U/dL for Impella survivors). Mortality for Impella patients was 54% (13/24), similar to that for high-risk intra-aortic balloon pump patients (Hausmann score > or =2 [57%], intensive care unit score > or =2 [51%], Texas Heart Institute score > or =0.75 [55%], and cardiac index < or =2.3 [45%]). Cardiac output data were available in 19 Impella patients. Impella patients able to increase their cardiac output to 1 L/min or more above the pump flow of the Impella Recover had a 10% (1/10) mortality, versus 88% (8/9) in patients with a residual cardiac function of 1 L/min or less (P =.001). Comparison of high-risk intra-aortic balloon pump patients with Impella patients with residual cardiac function of 1 L/min or more showed a significant reduction in mortality, regardless of the high-risk definition used. Residual cardiac function was the strongest predictor of survival in Impella patients. CONCLUSIONS: The Impella Recover device provides 3 to 4 L/min flow. It improves survival in patients with low-output syndrome if the heart is able to pump 1 L/min or more above device flow.

Quality of life in goserelin-treated versus cyclophosphamide + methotrexate + fluorouracil-treated premenopausal and perimenopausal patients with node-positive, early breast cancer: the Zoladex Early Breast Cancer Research Association Trialists Group.

PURPOSE: To compare quality of life (QoL) in premenopausal and perimenopausal patients with node-positive, early breast cancer treated with the endocrine agent goserelin (Zoladex; AstraZeneca Pharmaceuticals LP, Wilmington, DE) or cyclophosphamide + methotrexate + fluorouracil (CMF). PATIENTS AND METHODS: Patients from 86 centers worldwide were randomly assigned to receive either goserelin (3.6 mg every 28 days for 2 years; n = 514) or CMF (six 28-day cycles; n = 496), and were included in the QoL study. QoL was assessed using a self-administered patient questionnaire that consisted of 39 items from the Rotterdam Symptom Checklist, including dimensions evaluating physical and psychological symptom distress, activities of daily living, hormonal effects, and an assessment of overall QoL. RESULTS: Early benefits were noted during months 3 to 6 of treatment, for goserelin compared with CMF. Significant differences were found for changes in overall QoL (eg, 6.96 +/- 0.88 v 0.69 +/- 0.92 at 6 months; P <.0001) and for physical symptom distress, activity levels, and "effort to cope with illness" dimensions. At 1, 2, and 3 years, there were no significant differences in overall QoL or specific QoL dimensions. Scores for hormonal symptoms were worse with goserelin during the 2-year goserelin treatment period; however, this trend was reversed at 3 years. CONCLUSION: Goserelin offers improved overall QoL during the first 6 months of therapy compared with CMF chemotherapy in premenopausal and perimenopausal patients with early breast cancer. Coupled with equivalent efficacy in estrogen receptor-positive patients, these data support the use of goserelin as an alternative to CMF in premenopausal and perimenopausal patients with estrogen receptor-positive, node-positive early breast cancer.

Regional myocardial perfusion defects during exercise, as assessed by three dimensional integration of morphology and function, in relation to abnormal endothelium dependent vasoreactivity of the coronary microcirculation.

OBJECTIVE: To test the hypothesis that scintigraphic regional myocardial perfusion defects during exercise in patients with normal coronary angiography may be related to abnormal endothelium dependent vasoreactivity of the corresponding myocardial territory in response to cold pressor testing. METHODS: 38 patients were classified into two groups according to the presence or absence of exercise induced scintigraphic myocardial perfusion defects. A cold pressor test was done in all patients during routine coronary angiography, followed by dynamic positron emission tomography to establish coronary blood flow mediated vasoreactivity of the epicardial coronary artery and the myocardial territories supplied by the left anterior descending, left circumflex, and right coronary arteries. RESULTS: 28 patients had regional myocardial perfusion defects while 10 had normal scintigraphic imaging. The three dimensional scintigraphic fusion image revealed 49 regional myocardial perfusion defects with a mean (SD) reversibility of the original stress defect of 20 (3)%. In patients with exercise induced regional myocardial perfusion defects, the responses of epicardial luminal area and regional myocardial blood flow (RMBF) to cold pressor testing were reduced compared with patients with normal perfusion imaging (epicardial luminal area: 5.2 (1.2) to 4.2 (0.86) mm2 v 4.7 (0.5) to 5.8 (0.5) mm2; RMBF: 0.75 (0.16) to 0.78 (0.20) ml/g/min v 0.75 (0.15) to 1.38 (0.26) ml/g/min; p < or = 0.03, respectively). In patients with regional abnormal scintigraphic perfusion, the corresponding RMBF response to cold pressor testing was more severely impaired than the mean myocardial blood flow in the remaining two vascular territories, but the difference was not significant (0.75 (0.16) to 0.78 (0.20) ml/g/min v 0.75 (0.10) to 0.87 (0.12) ml/g/min; NS). The endothelium independent increase in RMBF induced by glyceryl trinitrate did not differ between patients with exercise induced myocardial perfusion defects and those with normal perfusion images (0.75 (0.16) to 0.94 (0.09) ml/g/min v 0.75 (0.15) to 0.94 (0.09) ml/g/min; NS). There was a highly significant correlation between the endothelium dependent responses of RMBF to cold pressor testing and the severity of exercise induced scintigraphic regional myocardial perfusion defects (r = 0.95, p = 0.001). CONCLUSIONS: Exercise induced scintigraphic regional myocardial perfusion defects in patients with angina but normal coronary angiography may be related to abnormal endothelium dependent vasoreactivity of the corresponding myocardial territory.

[Nonsurgical therapy of hepatocellular carcinoma]. / Nicht-chirurgische Therapie des hepatozellulären Karzinoms.

Several non-surgical local ablation methods for the treatment of hepatocellular carcinoma (HCC) have been developed. Among them, percutaneous ethanol injection is worldwide an accepted alternative to surgery in patients with small HCCs. Other local minimal-invasive treatment options, like one time radio-frequency thermal ablation seem to result in more effective tumor control. Randomized controlled trials showed no survival benefit after transarterial chemoembolization and its variants for the treatment of local advanced HCCs. Combined therapeutic strategies may play an increasing role in future in these cases. Effective chemotherapy is not available for metastasized or advanced HCCs. The role of novel techniques for the treatment of HCC has to be carefully determined in large controlled clinical studies.

Long-term follow-up of patients in four prospective studies of the German Breast Cancer Study Group (GBSG): A summary of key results.

Evaluation of treatment modalities and prognostic factors in early breast cancer requires a long-term follow-up of patients in prospective studies. The German Breast Cancer Study Group (GBSG) started four nationwide studies in 1983 in which a total of 2,746 patients have been enrolled and followed for about 10 years. Questions that have been addressed in these studies are still relevant today and comprise the role of breast-conserving therapy, the duration of adjuvant chemotherapy, and whether adjuvant radiotherapy is needed. The key results of these studies are highlighted including some important findings on prognosis, e.g., the role of isolated locoregional recurrence and the prognosis of patients with 10 or more positive lymph nodes. The data of all randomized patients were regularly included into the overviews of the Early Breast Cancer Trialists' Collaborative Group; the data of the nonrandomized patients have been used to examine the external validity of treatment comparisons. Overall, it can be concluded that the GBSG studies have made valuable and internationally recognized contributions to the prognosis and treatment of patients with early breast cancer.

VHL c.505 T>C mutation confers a high age related penetrance but no increased overall mortality.

BACKGROUND: Germline mutations of the VHL gene cause von Hippel-Lindau syndrome (VHL). In southern Germany, a specific mutation in this gene, c.505 T>C, is one of the most frequent alterations owing to a founder effect. METHODS: This study was conducted to evaluate morbidity, specific clinical risk profile, and mortality among a series of VHL c.505 T/C mutation carriers. A total of 125 eligible subjects carrying VHL c.505 T/C underwent ophthalmoscopy and gadolinium enhanced magnetic resonance imaging of the brain, the spinal cord, and the abdomen. Age related penetrance, morbidity, and mortality were assessed. RESULTS: Frequently observed lesions were phaeochromocytoma (47%), retinal angiomas (36%), haemangioblastoma of the spine (36%), and haemangioblastoma of the brain (16%). Four patients developed renal cell carcinoma. VHL was symptomatic in 47% of subjects; 30% were asymptomatic despite the presence of at least one VHL related tumour and 23% of the carriers had no detectable VHL lesion. Of the 19 patients who had died (15%), 10 died of symptomatic VHL lesions. Overall penetrance by cumulative incidence functions is estimated at 48% by 35 years and 88% by 70 years. In contrast to the only existing published report based on patients with presumably unselected VHL germline mutations, the mortality rate for c.505 T/C mutation carriers is comparable to that of the general population of Germany. CONCLUSIONS: Our results are an important example that a specific genotype, at least in the case of VHL c.505 T/C, can favourably impact on mortality despite a high age related penetrance. Our study also indirectly provides objective data which might be useful to the life and health insurance industry; it would appear that c.505 T>C mutation positive subjects have similar disease specific mortality to that of the general population owing to a combination of phenotype and timely detection of mutation carrier status followed by aggressive clinical screening and, if necessary, treatment.

Treatment of refractory hepatic hydrothorax with transjugular intrahepatic portosystemic shunt: long-term results in 40 patients.

BACKGROUND/AIMS: Hepatic hydrothorax is a complication of portal hypertension secondary to ascites. In this study, we investigated retrospectively the effects of the transjugular intrahepatic portosystemic shunt (TIPS) on hepatic hydrothorax refractory to diuretic treatment. METHODS: Forty patients (Child-Pugh class B, 24 patients; Child-Pugh class C, 16 patients) with hydrothorax refractory to diuretic treatment, pleurocenteses or pleurodesis were included. The TIPS implantation was successful in all patients, who were then followed for 16 +/- 14 months (range 1 day-54 months). RESULTS: TIPS reduced the portosystemic pressure gradient from 26 +/- 6 to 10 +/- 5 mmHg. In the 17 patients whom we followed for 12 months or longer, improvements were found for the Child--Pugh score (8.6 +/- 1.8 v. 6.7 +/- 1.5), serum albumin concentration (3.1 +/- 0.5 v. 3.6 +/- 0.5 g/l), and urinary sodium excretion (22 +/- 29 v. 89 +/- 43 mmol/24 h) (P< 0.05). Two patients developed severe hepatic encephalopathy requiring shunt occlusion. Hydrothorax improved in 82% of patients and resolved in 71% of patients. Fifty per cent of patients developed shunt insufficiency within 7 +/- 9 months, contributing to a probability of relapse-free 1-year survival of 35%. In these patients, shunt revision resulted in a secondary response rate of 82.3%. The 1-year survival was 64%. Both hydrothorax response and survival showed a significant inverse correlation with age over 60 years (P< 0.01 and P< 0.003, respectively) but not with other biomedical variables. CONCLUSION: TIPS is effective for hydrothorax refractory to diuretic treatment and other standard interventions to bridge the time to transplantation. Patients older than 60 years have a poor response and short survival.