Therapeutic potential of active stent coating

Various clinical studies have shown the superiority of stent implantation as compared to conventional balloon angioplasty for the treatment of significant coronary stenosis. However, restenosis remains a major drawback of this interventional technique. Against the background of this serious problem, the concept of stent coating has been developed. In general, coatings can be classified into two types: passive coatings, which only serve as a barrier between the stainless steel, and the tissue and active coatings, which directly interfere with the process of intima proliferation. At this moment, primarily immunosuppressive and cytostatic substances are used as active coatings. Large randomised studies have shown that this novel concept can be successfully implemented into clinical practice. Beside these promising results, studies also revealed potential risks of this new approach. Not only the dosage of the drug but also an optimised kinetic of drug release seem to be essential in preventing restenosis. As with most drugs, the inhibition of neointima proliferation is not restricted to vascular smooth muscle cells but also affects the process of re-endothelialisation, thus we may face a new pitfall of late-stent thrombosis. Although this technique may harbour potential risks, the introduction of stent coating has the potential to dramatically reduce the incidence of restenosis and an exciting chapter in the field of cardiology has been opened.     

Metabolic evaluation of 94 patients 5 to 16 years after ileocecal pouch (Mainz pouch 1) continent urinary diversion

PURPOSE In continent urinary diversion metabolic disturbances may be encountered in long-term followup. We evaluated metabolic consequences in patients with a minimum followup of 5 years after Mainz pouch 1 urinary diversion. MATERIALS AND METHODS: At our institution continent urinary diversion using the ileocecal segment was performed between 1983 and 1995 in 458 patients. A total of 94 patients with an ileocecal pouch for a minimum of 5 years were reevaluated for metabolic changes. Median followup was 9.0 years. Routine laboratory parameters, blood gas analysis, vitamin B12, vitamin D25, cross-laps, bone specific alkaline phosphatase, osteocalcin and propeptide of type I collagen were obtained. Bone density was measured in 18 patients. Vitamin B12 changes could be followed longitudinally in 24 patients. RESULTS: Medians of all parameters were in normal ranges. Clinical examinations revealed no signs of megaloblastic anemia, funicular myelosis or osteoporosis. There was no significant decrease of vitamin B12 in the long run. After followup examination we recommended vitamin B12 supplementation in 32% of patients because levels were in the lower normal range or below. A total of 37% of patients continue to take Na+/K+-citrate for prevention of metabolic acidosis. CONCLUSIONS: Patients with an ileocecal pouch and a followup of more than 5 years did not present with clinical symptoms caused by metabolic disturbances. Nevertheless, systematic followup of blood gases in particular and alkali supplementation may have prevented bone demineralization. Followup of vitamin B12 is of concern because about a third of these patients need supplementation.     

Biochemische Marker bei isch?mischen und nicht isch?mischen Myokardsch?digungen

Zusammenfassung Hintergrund: Biochemische Marker sind seit fast 50 Jahren integrativer Bestandteil der nicht invasiven kardialen Diagnostik und haben mit den kardialen Troponinen angesichts ihres prognostischen Potentials bei akutem Koronarsyndrom eine Renaissance erfahren. Diagnostik: Nach den Empfehlungen der National Acadamy of Clinical Biochemistry und der International Federatuion of Clinical Chemistry stellen das kardiale Troponin T und das kardiale Troponin I den neuen Goldstandard in der biochemischen kardialen Ischämiediagnostik dar. Charakteristikum dieser neuen Marker ist zum einen das verbesserte diagnostische Potential, das sich in der Wahl zweier Grenzwerte zur Differenzierung einer minimalen Myokardschädigung vom definitiven akuten Myokardinfarkt widerspiegelt. Zum anderen erlauben die neuen kardiospezifischen Marker eine Risikostratifizierung in dem klinisch bedeutsamen Szenario des akuten Koronarsyndroms (zwei- bis dreifach erhöhte Mortalitätsrate für Patienten mit ST-Strecken-Hebung oder Ruhe-Angina pectoris und kardialer Troponinerhöhung zum Zeitpunkt der Aufnahme). Eine weitere Indikation für die Bestimmung karidaler Marker liegt in der Beurteilung des Therapieerfolgs invasiver und nicht invasiver Reperfusionsstrategien und in der nicht invasiven Diagnostik von nicht ischämischen Myokardschädigungen (Myokarditis, Herzkontusion und Chemotherapie). Schlussfolgerung: Biochemische kardiale Marker sind zur Diagnostik ischämischer und nicht ischämischer Myokardschädigungen einsetzbar. Die kardialen Troponine scheinen sich dabei als Goldstandard für das neue Millennium zu etablieren. Abstract Background: Biochemical markers have been an integrative part of non-invasive diagnostic strategies in cardiology for nearly 50 years, experiencing a renascence by the recently acknowledged prognostic potential of cardiac troponins in acute coronary syndromes. Diagnosis: According to the guidelines of the National Academy of Clinical Biochemistry and the International Federation of Clinical Chemistry cardiac troponin T and cardiac troponin I should be considered as the new "gold markers" of ischemic myocardial injury. One characteristic feature of these new markers is the improved diagnostic potential, reflected by the choice of two cut-off values to distinguish minor myocardial injury from acute myocardial infarction. In addition, cardiac troponins allow risk stratification in the clinical setting of acute coronary syndromes: approximately threefold higher mortaligy rate for patients with rest angina or ST segment elevation and cardiac troponin elevation on admission. Other indications for cardiac marker analysis are monitoring of therapeutic success in case of invasive and non-invasive reperfusion strategies and non-invasive diagnosis of non-ischemic myocardial injury (myocarditis, cardiac contusion and chemotherapy). Conclusion: Biochemical cardiac markers are a useful tool in the diagnosis of both ischemic and non-ischemic myocardial injury. Among these, cardiac troponins seem to become the gold markers for the new millennium.     

Neue Konzepte der Prim?rpr?vention erfordern Umdenken

Zusammenfassung Die bisherigen Erfolge in der Senkung der Sterblichkeit an koronarer Herzkrankheit sind vor allem auf Verbesserungen in der Therapie der klinisch apparenten, akuten Ereignisse zurückzuführen und haben als Ergebnis, dass die Zahl von Patienten mit chronischer koronarer Herzkrankheit ansteigt. Nur die Vermeldung zukünftiger kardialer Ereignisse ermöglicht weitere Fortschritte in der Bekämpfung dieser Volkskrankheit. Die effektiven Therapiemöglichkeiten müssen bei geeigneten Patienten eingesetzt werden. Die neuen Konzepte der Primärprävention zielen darauf ab, die präventive Therapie zu individualisieren. Das Risiko soll durch den Einsatz von nicht invasiven Tests präzisiert werden, die eine präklinische Atherosklerose erkennen. Es wird eine quantitative Risikoabschätzung mittels Anamnese, körperlicher Untersuchung und Labortests vorgenommen. Dies wird durch Tabellen und einfache Risikoalgorithmen erleichtert, welche die mittels-, aber auch die langfristige (Lebenszeit-)Wahrscheinlichkeit nach kardialen Ereignisse angeben. Einzelne Risikofaktoren erfahren eine graduelle Neubewertung hinsichtlich ihrer Bedeutung, besonders der Diabetes mellitus und die arterielle Hypertonie. Mit den bildgebenden Verfahren, dem Knöchel-Arm-Index und der Messung des C-reaktiven Proteins stehen neue Methoden zur weiteren Risikostratifizierung zur Verfügung. Sie sollen es erleichtern, die therapeutische Entscheidung bei Patienten mit mittlerem Risiko auf eine rationale Grundlage unter Berücksichtigung der Pathophysiologie von Atherosklerose und koronarer Herzkrankheit zu stellen. Es sollen Patienten identifiziert werden, die ein ähnlich hohes Risiko aufweisen wie bei klinisch bereits fassbarer atherosklerotischer Erkrankung. Solche Patienten können gezielt therapiert werden, und die strikte Unterscheidung zwischen Primär- und Sekundärprävention wird abgelöst. Abstract The decline in cardiovascular mortality over the past decades is due to improved survival of patients with clinical events rather than to a declining incidence of these events. As a result, an increased prevalence of chronic coronary artery disease and especially congestive heart failure has been described. Further substantial reductions in coronary artery disease morbidity and mortality can only be anticipated if coronary artery disease is treated before the manifestation of clinical disease. Modern concepts of primary prevention incorporate and individualized approach to risk assessment. Medical history, physical examination, and established laboratory tests are the basic instruments which allow for quantitative risk assessment. Tables and simplified algorithms derived from large clinical trials enable the calculation of intermediate and long-term ("life-time") probability of cardiac events. In this setting of quantitative risk assessment, the importance of some risk factors is increasingly recognized, namely diabetes. Noninvasive diagnostic testing is used to detect preclinical atherosclerotic plaque disease. Direct imaging of coronary and peripheral arteries, the ankle-brachial index, and measurements of C-reactive protein represent novel methods which have become available for further risk stratification. Because they consider the pathophysiology of atherosclerosis and coronary artery disease, these methods may facilitate decision-making regarding preventive treatment in patients who have an intermediate risk on the basis of the traditional risk factors. The modern concept of primary prevention is aimed at identifying subjects whose risk is similarly high as that of patients with clinically established cardiovascular disease. These subjects can then be treated efficiently, and the strict distinction between primary and secondary prevention is blurred.     

Candida infection of local necrosis in severe acute pancreatitis is associated with increased mortality

The aim of this study was to evaluate the frequency of Candida infection of pancreatic necrosis in patients suffering from severe acute pancreatitis (SAP) and to analyze its impact on the outcome. Two-hundred and fifty consecutive patients with SAP from January 1986 to December 1998 were studied retrospectively. Their mean APACHE II score at the day of admission was in 16.1 (range 8-35). All patients were in need of operative therapy. Overall mortality was 38.8% (97 patients). One-hundred and eighty-two patients (72.8%) suffered from local infected necrosis. Among these patients, local Candida infection was observed in 31 patients, whereof 23 patients (74%) suffered from local fungal infection detected at first operation. During the course of disease, 12 patients (39%) also revealed fungemia. Local Candida infection as compared to no Candida infection was associated with an increased mortality rate (84% vs. 32%; P 0.0001). Multivariate logistic regression analysis identified APACHE II score (P < 0.0001), age of the patient (P < 0.003), extent of pancreatic necrosis (P < 0.002), and local bacterial (P < 0.04) and fungal infection (P < 0.004) as independent factors significantly contributing to mortality. SAP, requiring surgical treatment, is associated with high in-hospital mortality. Patients suffering from local Candida infection are at high risk of fatal outcome.     

Stand der chirurgischen Studien in der Onkologie, Teil 2

Zusammenfassung. Das optimale Resektionsausma? und diverse pr?operative zytostatische und strahlentherapeutische Strategien bildeten auch beim Pankreas-, Rektum- und Mammacarcinom – diese Tumore werden in Teil 2 der Literaturübersicht thematisiert – die zentrale Fragestellung rezenter prospektiver, randomisierter Studien. W?hrend beim Pankreaskarzinom bisher nach erweiterter Lymphadenektomie kein eindeutiger überlebensvorteil festzustellen war, hat die totale mesorektale Exzision die Rektumchirurgie revolutioniert. Unter definierten Bedingungen hat sich die brusterhaltende Chirurgie beim Mammacarcinom als gleichwertig zur Mastektomie best?tigt. Ob die Sentinel-Lymphadenektomie vertretbar ist, kann noch nicht definitiv beurteilt werden. Nach neoadjuvanter Chemotherapie ist der Anteil brusterhaltender Operationen signifikant h?her, das überleben ist in bisher ver?ffentlichten Studien jedoch nicht signifikant ver?ndert. Beim Rektumcarcinom kann die Lokalrezidivrate durch pr?operative Radiatio signifikant gesenkt werden; es scheint, da? multimodale pr?operative Therapieschemata die kurative Resektionsrate und Sphinktererhaltung beim lokal fortgeschrittenen Rektumcarcinom durch Tumorverkleinerung anzuheben imstande sind.      

Prognostic relevance of three histological grading methods in breast cancer.

Histological grading is an important parameter for the risk assessment in patients with breast cancer. However, up to now differing grading methods are used which have not been compared with respect to their prognostic significance. In the present study the prognostic significance of three different methods of histological grading (Elston, Contesso, Helpap) was determined in a sample of 292 patients. Furthermore, results obtained in needle biopsies were compared with those obtained in surgical resection specimens in 31 cases. The mitotic counts and the Contesso method were performed on two microscopes with different field areas (0.238 mm2 and 0.345 mm2). Univariate and multivariate analysis revealed that all three histological grading methods had a high prognostic value concerning overall survival (OS) and disease-free survival (DFS). Using univariate and multivariate analysis the Elston method performed best to determine OS and DFS (p<0.0001 and p<0.001). The field area of the microscope had a minor influence on the mitotic count and on the results of the Contesso method. The histological grading was reliable in needle biopsies: the best agreement to grading obtained in the definitive surgical specimen was achieved with the Elston method (kappa statistic 0.727). As a conclusion, we could show that determination of the histological grade is an important prognostic factor in breast cancer with the Elston method giving the best results. Also, we could demonstrate that histological grading in needle biopsies is reliable enough to allow a preoperative risk estimation.