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ZusammenfassungDie Gastroenterologie bietet ein weites Feld für zukünftige „Klug-entscheiden-Empfehlungen“ (KEE), die nicht nur den gesicherten Einsatz diagnostischer Tests wie Laboruntersuchungen oder bildgebende Verfahren betreffen, sondern auch medikamentöse Therapien und die gastroenterologische Endoskopie. Dem zu häufigen Einsatz von Medikamenten wie Antibiotika und Protonenpumpenhemmern steht ihr zu seltener Einsatz bei gesicherten Indikationen gegenüber. Ähnliches trifft auf die abdominelle Bildgebung zu, insofern bei vielen Fragestellungen zu häufig der Computertomografie der Vorzug vor einer qualifizierten Sonografie gegeben wird. Laborwerte wie Lipase oder Amylase sind beim asymptomatischen Patienten nicht weiterführend und verursachen u. U. eine Vielzahl von unnötigen weiteren diagnostischen Maßnahmen. Bei akuter Pankreatitis bringt die Bestimmung beider Enzyme keinen additiven diagnostischen Nutzen. Ähnlich wenig hilfreich ist der unkritische Einsatz von weiteren für die Gastroenterologie relevanten Laborparametern wie CEA, Ammoniak oder Procalcitonin. In der Endoskopie ist eine „Vorsorgegastroskopie“ bei asymptomatischen Patienten ohne Risikofaktoren nicht sinnvoll, während die Koloskopie als Vorsorgeuntersuchung auf ein Kolonkarzinom zu selten von über 50-Jährigen wahrgenommen wird.Die sich dramatisch entwickelnde Adipositaspandemie und der damit einhergehende massive Anstieg an fortgeschrittenen nichtalkoholischen Fettlebererkrankungen mit entsprechender Morbidität und Mortalität machen KEE erforderlich, die nicht nur Empfehlungen für den einzelnen Patienten geben, sondern auch Maßnahmen zur Regulierung des Verkaufs hochverarbeiteter Lebensmittel oder zuckerreicher Softdrinks darlegen. Auch zukünftig werden sich die „Key Questions“ für KEE in der Gastroenterologie aus der Erstellung von Leitlinien heraus ergeben. Dennoch sind auch KEE für Situationen im klinischen Alltag wünschenswert, für die es keine Leitlinienempfehlungen gibt. Durch interdisziplinären Expertenkonsens und Berücksichtigung vorhandener wissenschaftlicher Daten kann diesen KEE eine sichere Basis verschafft werden.

ZusammenfassungDie portale Hypertension bei Patienten mit Leberzirrhose kann nicht nur durch interventionelle (TIPS: transjugulärer portosystemischer Stent-Shunt) oder operative Shuntanlagen, sondern auch medikamentös beeinflusst werden. Zahlreiche Studien beschäftigten sich mit der Frage, ob diese Substanzen bei dauerhafter Gabe zu einer Prognoseverbesserung bei Patienten mit Leberzirrhose führen können. Nicht selektive Betablocker (NSBB), Statine, Antibiotika, Enoxaparin und Albumin haben viele Angriffspunkte in der Pathogenese der portalen Hypertension oder bei Dekompensation der Leberzirrhose, sodass sie grundsätzlich als Kandidaten für eine Langzeittherapie infrage kommen. Während es für NSBB, Antibiotika und Albumin klare Indikationen in der Versorgung von Patienten mit dekompensierter Leberzirrhose gibt, ist dies weniger geklärt für den Einsatz von Statinen oder Antikoagulanzien. Neuere Untersuchungen ergaben widersprüchliche Ergebnisse, wenn der primäre Endpunkt einer Studie die Prognoseverbesserung oder die Vermeidung einer Dekompensation der Zirrhose durch eine dauerhafte medikamentöse Therapie war. Zum jetzigen Zeitpunkt ergibt sich aufgrund der aktuellen Studienlage keine Veranlassung, das bisherige, in Leitlinien abgesicherte Vorgehen im täglichen Alltag zu ändern. Diese Übersicht gibt einen Überblick zum Einsatz von NSBB, Antibiotika, Statinen, Antikoagulanzien und Albumin bei Komplikationen der portalen Hypertension insbesondere im Hinblick auf ihren dauerhaften Einsatz zur Verbesserung des Überlebens von Patienten mit Leberzirrhose.

ZusammenfassungDie Leitlinie Komplikationen der Leberzirrhose der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) ersetzt die Leitlinie aus dem Jahr 2011. Sie basiert auf den Empfehlungen der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) für eine evidenzbasierte Konsensus-Leitlinie der Entwicklungsstufe S2k und wurde interdisziplinär unter Beteiligung aller relevanten Fachgesellschaften und der Patientenvertretung erstellt. Neben den in der Vorgängerversion behandelten Kapiteln Aszites, spontan bakterielle Peritonitis, hepatorenales Syndrom, hepatischer Hydrothorax und hepatopulmonales Syndrom wurden die Kapitel Diagnostik und Therapie der Hepatischen Enzephalopathie neu aufgenommen.

Gastroenterology offers a wide field for future "choosing wisely" recommendations (CWR). They should refer not only to an under- or overuse of diagnostic tools like laboratory or imaging tests but also to an evidence-based application of drug therapies und endoscopic interventions. Drugs like antibiotics or proton pump inhibitors are both often prescribed in the absence of clearly defined underlying diseases and not given when an indication is clear. Similar is true for the ordering of abdominal imaging methods. Computerized tomography of the abdomen too often is preferred over a qualified ultrasound study. Laboratory tests like amylase or lipase should not be ordered for asymptomatic patients since false positive values often end up with further useless and occasionally invasive examinations. Ordering both enzymes in acute pancreatitis will not provide any additional information. Similarly, CEA, ammonia or procalcitonin have either limited or no value in gastroenterology. Upper gastrointestinal endoscopy should not be performed in asymptomatic people without any risk factors. On the other hand, colonoscopy is still underused as a valuable screening tool for detection and secondary prevention of colorectal carcinomas in people over 50 years old.The dramatic rise in people suffering from obesity is paralleled by an enormous increase in severe cases of non-alcoholic fatty liver disease associated with high morbidity and mortality. This calls for CWRs addressing this causal relationship and offering not only patient centered therapeutic solutions but also calling for effective measures to regulate the marketing of highly processed food or sugar enriched soft drinks. Published guidelines in Gastroenterology will continue to be a rich source for delineating new CWRs. Nevertheless, CWRs are also needed in daily practice offering solutions for clinical problems not covered by guidelines. These, however, have to be based both on a broad interdisciplinary consent of experts in the field and on scientific evidence.Die Gastroenterologie bietet ein weites Feld für zukünftige „Klug-entscheiden-Empfehlungen“ (KEE), die nicht nur den gesicherten Einsatz diagnostischer Tests wie Laboruntersuchungen oder bildgebende Verfahren betreffen, sondern auch medikamentöse Therapien und die gastroenterologische Endoskopie. Dem zu häufigen Einsatz von Medikamenten wie Antibiotika und Protonenpumpenhemmern steht ihr zu seltener Einsatz bei gesicherten Indikationen gegenüber. Ähnliches trifft auf die abdominelle Bildgebung zu, insofern bei vielen Fragestellungen zu häufig der Computertomografie der Vorzug vor einer qualifizierten Sonografie gegeben wird. Laborwerte wie Lipase oder Amylase sind beim asymptomatischen Patienten nicht weiterführend und verursachen u. U. eine Vielzahl von unnötigen weiteren diagnostischen Maßnahmen. Bei akuter Pankreatitis bringt die Bestimmung beider Enzyme keinen additiven diagnostischen Nutzen. Ähnlich wenig hilfreich ist der unkritische Einsatz von weiteren für die Gastroenterologie relevanten Laborparametern wie CEA, Ammoniak oder Procalcitonin. In der Endoskopie ist eine „Vorsorgegastroskopie“ bei asymptomatischen Patienten ohne Risikofaktoren nicht sinnvoll, während die Koloskopie als Vorsorgeuntersuchung auf ein Kolonkarzinom zu selten von über 50-Jährigen wahrgenommen wird.Die sich dramatisch entwickelnde Adipositaspandemie und der damit einhergehende massive Anstieg an fortgeschrittenen nichtalkoholischen Fettlebererkrankungen mit entsprechender Morbidität und Mortalität machen KEE erforderlich, die nicht nur Empfehlungen für den einzelnen Patienten geben, sondern auch Maßnahmen zur Regulierung des Verkaufs hochverarbeiteter Lebensmittel oder zuckerreicher Softdrinks darlegen. Auch zukünftig werden sich die „Key Questions“ für KEE in der Gastroenterologie aus der Erstellung von Leitlinien heraus ergeben. Dennoch sind auch KEE für Situationen im klinischen Alltag wünschenswert, für die es keine Leitlinienempfehlungen gibt. Durch interdisziplinären Expertenkonsens und Berücksichtigung vorhandener wissenschaftlicher Daten kann diesen KEE eine sichere Basis verschafft werden.

Portal hypertension in patients with liver cirrhosis can be improved, not only by surgical or interventional shunt placements, but also by drug-only treatment. Many recent studies addressed the question whether any of these substances can improve survival of patients with liver cirrhosis when administered continuously for months and years. Non-selective beta-blockers (NSBB), statins, antibiotics, enoxaparin and albumin have been shown to possess many beneficial effects in the pathophysiology of portal hypertension or on events leading to decompensation of liver cirrhosis. Accordingly, they represent candidate drugs for long-term treatment to improve patient survival. In contrast to NSBB, antibiotics and albumin, which have clearly defined indications in the treatment of complications related to portal hypertension, the role of statins and anticoagulants in the management of these patients remains to be further elucidated. Recent studies came to opposing results when a permanent treatment was tested to improve patient prognosis or to prevent liver decompensation. At present, there is no reason to change our everyday practice beyond established management proposals published in practice guidelines. This paper gives an overview of present and future indications for treatment with NSBB, antibiotics, statins, anticoagulants and albumin with special reference to studies aiming at improving prognosis of patients with liver cirrhosis.Die portale Hypertension bei Patienten mit Leberzirrhose kann nicht nur durch interventionelle (TIPS: transjugulärer portosystemischer Stent-Shunt) oder operative Shuntanlagen, sondern auch medikamentös beeinflusst werden. Zahlreiche Studien beschäftigten sich mit der Frage, ob diese Substanzen bei dauerhafter Gabe zu einer Prognoseverbesserung bei Patienten mit Leberzirrhose führen können. Nicht selektive Betablocker (NSBB), Statine, Antibiotika, Enoxaparin und Albumin haben viele Angriffspunkte in der Pathogenese der portalen Hypertension oder bei Dekompensation der Leberzirrhose, sodass sie grundsätzlich als Kandidaten für eine Langzeittherapie infrage kommen. Während es für NSBB, Antibiotika und Albumin klare Indikationen in der Versorgung von Patienten mit dekompensierter Leberzirrhose gibt, ist dies weniger geklärt für den Einsatz von Statinen oder Antikoagulanzien. Neuere Untersuchungen ergaben widersprüchliche Ergebnisse, wenn der primäre Endpunkt einer Studie die Prognoseverbesserung oder die Vermeidung einer Dekompensation der Zirrhose durch eine dauerhafte medikamentöse Therapie war. Zum jetzigen Zeitpunkt ergibt sich aufgrund der aktuellen Studienlage keine Veranlassung, das bisherige, in Leitlinien abgesicherte Vorgehen im täglichen Alltag zu ändern. Diese Übersicht gibt einen Überblick zum Einsatz von NSBB, Antibiotika, Statinen, Antikoagulanzien und Albumin bei Komplikationen der portalen Hypertension insbesondere im Hinblick auf ihren dauerhaften Einsatz zur Verbesserung des Überlebens von Patienten mit Leberzirrhose.

This guideline provides evidence-based key recommendations for diagnosis and therapy of complications of liver cirrhosis and upgrades the 2011 version. An interdisciplinary team of medical experts and patient support groups developed the guideline following the AWMF recommendations for evidence based consensus guidelines. New chapters concerning diagnosis and therapy of hepatic encephalopathy were added.Die Leitlinie Komplikationen der Leberzirrhose der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) ersetzt die Leitlinie aus dem Jahr 2011. Sie basiert auf den Empfehlungen der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) für eine evidenzbasierte Konsensus-Leitlinie der Entwicklungsstufe S2k und wurde interdisziplinär unter Beteiligung aller relevanten Fachgesellschaften und der Patientenvertretung erstellt. Neben den in der Vorgängerversion behandelten Kapiteln Aszites, spontan bakterielle Peritonitis, hepatorenales Syndrom, hepatischer Hydrothorax und hepatopulmonales Syndrom wurden die Kapitel Diagnostik und Therapie der Hepatischen Enzephalopathie neu aufgenommen.

Background The objectives of follow-up care for cancer patients include psycho- social assistance and the detection of health problems. The concept of follow-up care rests on the assumption that the early detection of cancer recurrences and disease- or treatment-related complications is beneficial to patients. In this article, we provide an overview of the scientific evidence supporting current recommen- dations for the follow-up care of patients with colorectal cancer, lung cancer, and lymphoma. Methods This review is based on pertinent publications that were retrieved by a selective search in PubMed, supplemented by the authors' own experience in patient care and guideline creation. Results As recurrences usually arise soon after initial treatment, the recommended follow-up interval is shorter in the first two years (3-6 months) and longer thereafter (6-12 months). The question of which particular follow-up studies should be per- formed has only been systematically analyzed in a few cases. For patients with colorectal cancer, colonoscopy is the most important study. Intensive follow-up care is associated with a statistically non-significant increase in the survival rate compared to minimal follow-up care (77.5% versus 75.8%). Intensive diagnostic follow-up studies have been found to lead to a doubling of the frequency of operations for recurrence with curative intent, yet without any effect on the average survival time. The findings in lung cancer are similar. However, after tumor resection with curative intent, regularly repeated CT scanning leads to a survival advantage. In lymphoma patients, the longer the interval from primary treatment, the greater the likelihood of treatment-related secondary illnesses. It is not yet known how follow-up care should be provided to these patients in order to help them best. Conclusion The evidence supporting the efficacy of currently recommended modalities of follow-up care for cancer patients is weak. Until more data from clinical studies become available, the current guidelines should be followed.

Anamnese und Befund | Eine 79-jahrige Patientin litt seit Jahren unter Schmerzen der Halswirbelsaule (HWS) mit Ausstrahlung in beide Schultern. Eine Rezidivstruma war bekannt, eine Behandlung geplant. Seit 8 Monaten bemerkte die Patientin zunehmende Atemnot. Es kam zur notfallmasigen, stationaren Aufnahme mit inspiratorischem Stridor und Attacken hochster Luftnot. Die Betroffene konnte nur unter Tragen einer Halsorthese ausreichend atmen. Es fand sich ein erheblicher, inspiratorischer Stridor. Neurologische Defizite bestanden nicht. Untersuchungen | Die Tracheoskopie zeigte eine dorsale Raumforderung. Die darauf hin organisierte zervikale Diagnostik mittels Nativaufnahmen, MRT und Computertomografie der HWS bestatigte eine ausgepragte Spondylophytenbildung an den Vorderkanten mit Ventralisierung des Osophagus und einer uber 50 %igen, dorsalen Einengung des Tracheallumens. Therapie und Verlauf | Es erfolgte eine Thyreoidektomie unter Monitoring des N. vagus. In gleicher operativer Sitzung wurde anschliesend die mikrochirurgische Resektion der Spondylophyten durchgefuhrt. Ein Jahr nach Operation ist die Dyspnoe nicht mehr aufgetreten. Folgerungen | Bemerkenswert war die Koinzidenz von Struma und ventraler HWS-Spondylose mit erheblicher Dyspnoe. Die Krankenvorgeschichte stellte das eigentliche Problem dar: Die Patientin war zur Operation der grosen Struma bereits geplant und zunachst als internistischer Notfall aufgenommen worden. Uber die Tracheoskopie wurde dann die HWS-Spondylose erkannt. Der Fallbericht mahnt dazu, gerade bei der Kombination aus Struma und Dyspnoe an zusatzliche HWS-Veranderungen zu denken. Es besteht immer die Moglichkeit, die Situation mit einer HWS-Nativaufnahme schnell zu klaren. Das Ubersehen der komprimierenden HWS-Stenose kann dramatisch werden, es wurden Falle beschrieben, die in einer notfallmasigen Tracheotomie endeten.

Elevated liver enzymes are a frequent finding in both symptomatic and asymptomatic patients necessitating further evaluation to clarify the underlying disease. Three different patterns of increased liver enzymes can be defined to allow for a more precise and rational further diagnostic approach. A predominant increase in transaminase activities reflects a disturbance of hepatocellular integrity which can be found in patients with viral hepatitis, genetic liver diseases like Wilson`s disease or hemochromatosis, and drug-induced liver diseases. A second pattern is characterized by high serum alkaline phosphatase and γ-glutamyltranspeptidase activities indicating cholestatic liver diseases. The next important diagnostic measure in this group is an ultrasound study discerning intra- from extrahepatic cholestasis. Intrahepatic cholestatic diseases include primary and secondary sclerosing cholangitis, genetic disturbances of canalicular membrane transporters or drug-induced liver dieseases. Extrahepatic cholestasis involves obstruction of the large bile ducts by gall stones or tumors. The third enzym pattern is defined by a predominant rise in γ-glutamyl transpeptidase which is observed in alcoholic or non-alcoholic fatty liver disease and infiltrating liver diseases. A rise in liver enzymes is not necessarily indicative of a primary hepatic origin. Extrahepatic diseases often cause similarly increased serum activities. In addition even higher values can be observed under normal conditions during pregnancy or in adolescens. Lower values in asymptomatic patients should only be controlled since more than 30% of elevated transaminases spontaneously normalize during follow-up.

History and findings A 45-year-old woman sustained an ankle fracture in an accident. At examination she was found to have marked pallor of skin and mucosae. There was no hint for melaena or haematemesis. Investigations Biochemical tests showed marked iron deficiency anaemia (haemoglobin 7.5 g/dl) and raised serum bilirubin and C-reactive protein levels (1.94 mg/dl and 85.2 mg/l, respectively). Abdominal sonography revealed a cystic space-occupying mass (8 x 4.5 cm) projecting onto the gallbladder, interpreted as a choledochal cyst of unknown origins without bleeding. After treatment of the ankle fracture an endoscopic retrograde cholangiopancreatography was performed. This showed a large cyst of the choledochal duct into which the cystic and choledochal ducts entered, without evidence of tumour or haematoma. There was also a 1 cm prepapillary common choledochal and Wirsung duct. Treatment and course With these findings, the diagnosis of a congenital choledochal cyst (type Ia of Todani) could be made. After healing of the ankle fracture the cyst was removed and a Roux Y-anastomosis created. The cystic tissue was benign. At follow-up 6 months later the patient was symptom-free and no longer anaemic. Conclusions Congenital choledochal cysts are very rare in Europeans. The symptom-free course with anaemia and no manifestation until adulthood is also very unusual.

Anamnese und klinischer Befund: Bei einem 57jahrigen Patienten mit chronischer Diarrhoe war seit Jahren keine Diagnose gefunden worden. Die bis zu 15 wasrigen Stuhle pro Tag waren unabhangig von der Nahrungsaufnahme und ohne Blutbeimengung. Begleitend waren Muskelkrampfe vor allem in den Beinen aufgetreten. Seit 15 Jahren waren rezidivierende Ulcera ventriculi et duodeni bekannt, deswegen war vor 13 Jahren eine selektive proximale Vagotomie durchgefuhrt worden. Der korperliche Untersuchungsbefund war unauffallig. Untersuchungen: Leicht erhoht war die Aktivitat der alkalischen Phosphatase (182 U/l) und der Spiegel des C-reaktiven Proteins (9,3 mg/l); der Serumeisenspiegel betrug 42 µg/dl. Alle anderen Parameter des Routinelabors einschlieslich Eiweiselektrophorese, Blutbild und Differentialblutbild, lagen im Normbereich. Eine Gastroskopie erbrachte eine ulzerierende Duodenitis, eine erosive Gastritis mit zahlreichen Ulcera und eine Refluxosophagitis III°-IV°. Endosonographisch fiel ein vergrobertes Schleimhautrelief des Magens auf als Zeichen der foveolaren Hyperplasie und ein etwa 4 × 3 cm groser Tumor neben dem Bulbus duodeni. Der daraufhin bestimmte Gastrinspiegel war auf 7537 pg/ml erhoht (Normwert

The pattern of elevated serum liver enzymes in symptomatic or asymptomatic patients allows for an initial classification of liver diseases into cholestatic or hepatocellular diseases. A female patient with extrahepatic cholestasis due to segmental bile duct strictures and a localized mass lesion within the pancreas is presented. Although many diagnostic procedures were performed in this case the diagnosis was not obtained before surgical laparotomy was initiated with bioptic sampling from bile ducts, lymph nodes and pancreatic tissue. Microscopic examination of the specimen revealed extensive biliary and pancreatic scarring together with periductal infiltrates composed of lymphocytes and plasma cells consistent with sclerosing cholangitis in systemic autoimmune pancreatitis. The patient completely recovered upon treatment with prednisone and azathioprine. The difficult approach to the final diagnosis is discussed in light of established and modern diagnostic tools.

CASE HISTORY PHYSICAL EXAMINATION: A 79-years-old female suffered from cervical pain for several years which radiated in both shoulders. A nodular goiter was already known and therefore a radio iodine treatment had been planned. Eight months ago the patient noticed a progressing breathlessness. Emergency admission happened due to inspiratory stridor and severe attacks of dyspnoea. Sufficient breathing was only possible by wearing a rigid cervical collar. There were no neurological deficits.Tracheoscopy showed a mass in the dorsal cervical region. The cervical x-ray, computed tomography and magnet resonance imaging conformed a distinct spondylopathy at the leading edge of the cervical vertebral bodies including ventralisation of the oesophagus and narrowing of the trachea (50%).Simultaneously a total thyroidectomy, including neuromonitoring of the N. vagus, and ventral microsurgical resection of the spondylopathy was performed. There was no relapse of dyspnoea in the following year.The coincidence of a goiter and ventral cervical spondylopathy accompanied by significant dyspnoea is remarkable. The order of diagnostic steps in this emergency case displays a major problem. The patient was scheduled for goiter surgery and admitted as emergency due to a stridor. The cervical spondylopathy was diagnosed by tracheoscopy and cervical x-ray. This case report emphasizes the importance to think about cervical lesions in the presence of a goiter and dyspnoea. To find out quickly whether there is a cervical lesion or not a x-ray should be obtained. Missing these lesions can result in a fatal course.

Purpose To compare the effectiveness and tolerability of gemcitabine plus cisplatin with single-agent gemcitabine as first-line chemotherapy for locally advanced or metastatic pancreatic cancer. Patients and Methods Patients with advanced adenocarcinoma of the pancreas were randomly assigned to receive either gemcitabine 1,000 mg/m2 and cisplatin 50 mg/m2 given on days 1 and 15 of a 4-week cycle (GemCis arm) or gemcitabine alone at a dose of 1,000 mg/m2 on days 1, 8, and 15 of a 4-week regimen (Gem arm). The primary end point was overall survival; secondary end points were progression-free survival, response rate, safety, and quality of life. Results One hundred ninety-five patients were enrolled and showed baseline characteristics well balanced between treatment arms. Combination treatment in the GemCis arm was associated with a prolonged median progression-free survival (5.3 months v 3.1 months; hazard ratio [HR] = 0.75; P = .053). Also, median overall survival was superior for patients treated in the GemCis arm as compared with the Gem arm (7.5 v 6.0 months), an advantage which did not, however, reach statistical significance (HR = 0.80; P = .15). Tumor response rates were comparable between treatment arms (10.2% v 8.2%). The rate of stable disease was, however, greater in the combination arm (60.2% v 40.2%; P < .001). Grade 3 to 4 hematologic toxicity did not exceed 15% in both treatment arms. Conclusion These results support the efficacy and safety of an every-2-weeks treatment with gemcitabine plus cisplatin. Median overall survival and progression-free survival were more favorable in the combination arm as compared with gemcitabine alone, although the difference did not attain statistical significance.

BACKGROUND AND AIMS Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, improves biochemical, immunopathological and histological parameters in chronic cholestatic liver diseases. The immunomodulatory properties of UDCA show interesting similarities with the effects of glucocorticoids. We investigated the activation of the glucocorticoid receptor by UDCA and the glucocorticoid receptor dependent gene expression in primary rat hepatocytes as well as binding of radiolabelled UDCA to the glucocorticoid receptor ligand binding site expressed in a glucocorticoid receptor fusion protein. METHODS Primary rat hepatocytes in culture were co-transfected with a luciferase reporter gene construct (GRE-luc) containing a glucocorticoid receptor responsive element (GRE) and a glucocorticoid receptor expression vector (6RGR) followed by stimulation with dexamethasone or UDCA. Luciferase activity was determined and specific binding of glucocorticoid receptor to the GRE was confirmed by an electrophoretic mobility shift assay (EMSA). The glucocorticoid receptor binding site was expressed in a GR-myc fusion protein and binding of radiolabelled UDCA to the fusion protein was determined. RESULTS Incubation of co-transfected hepatocytes with 0.1-1.000 microM dexamethasone or 0.1-1.000 microM UDCA led to an 11.9- to 20.85-fold (dexamethasone) and 2.6- to 4.3-fold (UDC) increase of luciferase activity. Mobility shift assays using nuclear extracts from transfected and stimulated hepatocytes also showed a dose dependent increase of DNA binding after stimulation with UDCA. However, incubation of the GR-myc fusion protein with radiolabelled UDCA yielded no specific binding of UDCA to the glucocorticoid receptor binding site, whereas dexamethasone showed specific binding of the fusion protein. CONCLUSIONS UDCA activates the intracellular glucocorticoid receptor in a dose-dependent manner. Direct binding of the glucocorticoid receptor by radiolabelled UDCA at the glucocorticoid receptor binding site could be excluded as the mechanism of activation. The mechanisms involved in UDCA-mediated glucocorticoid receptor activation and possible targeted glucocorticoid receptor activation due to partial UDCA tissue specificity warrant further elucidation.

Zusammenfassung Das akute Leberversagen stellt einen seltenen Notfall vergleichbar der akuten Herzinsuffizienz mit kardiogenem Schock oder dem akuten Nierenversagen dar. Die Ursachen für ein akutes Leberversagen sind je nach geographischer Region verschieden und variieren in ihrer Häufigkeit. In unseren Breiten finden sich häufig Viren, Medikamente und Toxine als ätiologisches Agens. Die Einwirkung der Noxe führt zur Nekrose und/oder gesteigerten Apoptose der Hepatozyten mit Ausfall leberspezifischer Funktionen, sobald die Zahl funktionstüchtiger Zellen eine kritische Grenze unterschreitet. Klinisch äußert sich dies Syndrom durch das rasche Auftreten einer hepatischen Encephalopathie innerhalb von 7 Tagen nach Beginn der Lebererkrankung (fulminantes Leberversagen). Bei vorbestehender chronischer Leberschädigung definiert sich das Leberversagen über die Zeit, innerhalb der eine hepatische Encephalopathie nach Beginn eines Ikterus auftritt (hyperakutes, akutes und subakutes Leberversagen). Der Ausfall der Leberfunktion löst zahlreiche extrahepatische lebensbedrohliche Komplikationen aus, wie Hirnödem, Kreislaufversagen, Infektionen, Gerinnungsstörungen und Nierenversagen. Intensivmedizinische und hepatologische Kenntnisse und eine enge Kooperation mit einem Lebertransplantationszentrum sind wesentliche Voraussetzungen für eine erfolgreiche Therapie. Der permanente oder auxiliäre vorübergehende Leberersatz durch Implantation einer gesunden menschlichen Leber ermöglicht in 60–70% der Fälle ein dauerhaftes Überleben. Fortschritte wurden durch den temporären extrakorporalen Ersatz bestimmter Leberfunktionen erreicht. Hierdurch kann möglicherweise zukünftig die Zeit bis zur Regeneration der eigenen Leber oder bis eine Spenderleber zur Verfügung steht überbrückt werden. Diese Systeme sind für einen Einsatz in der täglichen Routine jedoch noch nicht ausreichend evaluiert.

We studied the role of brain electrical activity mapping (BEAM) in the assessment of neuropsychiatric disturbances in 48 cirrhotic patients without clinical evidence of hepatic encephalopathy (no HE, n = 19), with subclinical HE (grade 0, denoting pathological psychometric tests, n = 13) and mild-to-moderate HE (grade I, n = 6; grade II, n = 10). Results were compared with 23 healthy controls. BEAM variables quantified were: (i) the peak frequency (PF); (ii) the amplitude of PF; and (iii) the topographic localization of the maximum peak amplitude digitized for quantification by using a coordinate system. Mean amplitudes and their topographic localization in the following frequency-bands were analysed: delta (1.0-3.5 Hz), theta (4.0-7.5 Hz), alpha 1 (8.0-9.5 Hz), alpha 2 (10.0-11.5 Hz), beta 1 (12.0-15.5 Hz), beta 2 (16.0-19.5 Hz), and beta 3 (20.0-23.5 Hz). The PF was significantly slower in all HE patients than in healthy controls (8.5 +/- 2.0 Hz v. 10.1 +/- 1.0 Hz, P< 0.001). Even in no HE, the PF was significantly slower than in controls (8.6 +/- 1.5 Hz v. 10.1 +/- 1.0 Hz, P< 0.01). No relevant topographic differences of PF were observed. The mean amplitudes of the following bands differed significantly between controls and patients: theta (increased in HE, P< 0.05), alpha 2 (decreased in HE, P< 0.05), and beta 2 and beta 3 (increased in HE, (P < 0.05). In HE patients, the topographic localization of all beta bands showed a significant shift from parieto-occipital areas to central areas of the cortex. We conclude that BEAM is a sensitive tool for detecting neuropsychiatric disturbances in cirrhotics with no HE and with subclinical HE. The combination of PF in the theta band, increased mean amplitude in the beta 2 band, and the localization of the latter band in the frontocentral area of the cortex is an objective and sensitive tool for identifying neuropsychiatric disturbances in 85% of cirrhotic patients with no HE. Further studies are required to determine the clinical implications of these abnormal findings in the absence of overt clinical symptoms.

The prevalence of hepatitis B virus markers was investigated in 5305 individuals considered to be representative for the adult German population. After adjustment of the data according to the age and sex distribution in the whole German population an anti-HBc prevalence of 8.71% (95% confidence interval, 7.94-9.48%) and an HBsAg carrier rate of 0.62% (95% confidence interval, 0.40-0.84%) were calculated. Anti-HBc prevalence increased with age from 4.12% in the youngest group to 15.66% in the 61-70-year-old. The percentage of HBsAg carriers showed a maximum of 1.12% in the 41-50-year-old individuals and decreased significantly in the older age groups. 1.40% (95% confidence interval, 1.08-1.72%) of individuals had anti-HBc only. There was a trend to higher rates of this pattern in males than in females; a significantly higher percentage of persons with anti-HBc only was found in anti-HBc-positive individuals below 31 years than in older individuals. Five participants with anti-HBc only (7.7%, or about 0.1% of the whole population) showed HBV-DNA despite the absence of HBsAg. 3.1% of anti-HBc positive individuals where also positive for anti-HCV, that was significantly higher than the percentage of anti-HCV-positives among persons without any HBV marker (0.46%). This study provides a comprehensive picture of the current hepatitis B situation in Germany, showing new data especially on the distribution of HBsAg in the general population and on the subgroup of individuals with anti-HBc only.

Background Lipopolysaccharides (LPSs) are thought to be one of the triggers of organ reactions to sepsis, which causes hepatocellular dysfunction. This dysfunction can be demonstrated by a reduction of organic anion transport The aim of our study was to assess whether the transport of indocyanine green (ICG) is affected by LPS, and whether Kupffer cells are involved. Methods Single-pass liver perfusion with ICG at a concentration of 57.8 mg/kg/min was performed for 130 min. pH, oxygen tension and perfusion pressure were continuously measured in influent and effluent. Taurocholate was infused at 48.3 mg/kg/min to achieve a stable bile flow. LPS was added at concentrations of 0.45, 0.9 and 1.44 mg/kg/min for 30 min. ICG was determined photometrically in perfusate and bile. To depress the function of Kupffer cells male Wistar rats were treated with GdCl 3 24 h in advance. Primary cultured hepatocytes were used for studying the direct effect of LPS on the uptake rate of ICG. Results Forty-five minutes after administration of LPS a significant dose-dependent decrease of ICG uptake was seen in animals treated with LPS. Livers of animals pretreated with GdCl 3 did not show this decrease. LPS had no direct effect on the uptake of ICG into primary cultured hepatocytes, whereas treatment of these cells with 8-bromo-cGMP resulted in a significant increase of ICG uptake. Conclusion LPS has a rapid dose-dependent effect on the detoxification properties of the liver for ICG. The rapid effect of LPS on ICG uptake in hepatocytes is mediated by Kupffer cells.

Background: Triple therapy including two antibiotics and a proton pump inhibitor is a rational approach to the treatment of Helicobacter pylori induced peptic ulcer disease. The interaction of antimicrobial therapy and acid suppression is not yet well elucidated. Aims: To investigate the effects of proton pump inhibitors on roxithromycin levels in plasma and gastric tissue under steady-state conditions in volunteers. Methods: In two crossover studies omeprazole 20 mg b.d., lansoprazole 30 mg b.d., roxithromycin 300 mg b.d., and the combination of roxithromycin with either omeprazole or lansoprazole were administered to 12 healthy volunteers over 6 days. Blood plasma levels of the drugs were measured. In addition, roxithromycin concentrations were also determined in gastric juice and gastric tissue obtained during endoscopy. Results: The proton pump inhibitors and roxithromycin did not alter the blood plasma pharmacokinetics of each other. When compared to roxithromycin administered alone, its combination with a proton pump inhibitor significantly increased the roxithromycin concentrations in gastric juice (3.0–5.0 μg/mL vs. 0.3–0.4 μg/mL) and gastric tissue (antrum: 3.8–4.0 vs. 2.8 μg/g, fundus: 5.9–7.4 vs. 4.2–4.4 μg/g). Conclusions: Proton pump inhibitors and roxithromycin do not alter the systemic bioavailability of each other. However, proton pump inhibitors increase the local concentration of roxithromycin in the stomach which may contribute to the clinically proven synergic beneficial action in eradication therapy of H. pylori.

Objective The prevalence of anti-HCV in Germany has been determined for blood donors and certain risk groups, but the burden of disease in the general population remains unknown. The aim of this study was to determine the prevalence of anti-HCV in a study group representing the normal adult German population. Design A total of 5312 individuals aged 18-70 years were randomly selected from small, middle-sized and big cities in five different German states. Sera were tested for anti-HCV by enzyme immunoassay and immuno dot assay, as well as for anti-HBc and, in the case of a positive result, for anti-HBs and HBsAg. Serological typing was performed in anti-HCV-positive persons. Results Thirty-nine individuals were anti-HCV positive; indeterminate results (with antibodies against the viral core protein only) were obtained in 20. There was a tendency to higher prevalence rates with increasing age as well as to a higher prevalence in women. Serological typing revealed the presence of genotype 1 in the vast majority of participants (82%); only a minority showed genotype 3 (7.2%) or other genotypes (7.2%). Markers of HBV were seen in 43.6% of the anti-HCV positive individuals, with nearly one third (29.4%) of the double-infected showing anti-HBc as the only marker for HBV. Conclusions According to our data, an anti-HCV prevalence of 0.63% (95% confidence interval, CI, 0.42-0.84%) can be assumed in the general adult German population, with higher values in older people and women. Nearly half of the anti-HCV positive individuals also show markers of hepatitis B virus.

Lipid peroxidation is an autocatalytic mechanism leading to oxidative destruction of cellular membranes. In renal transplantation, this mechanism is triggered by ischemia/reperfusion and may be of relevance in graft failure.Using specific antibodies directed against malondialdehyde (MDA) and 4-hydroxynonenal (HNE) adducts, major aldehydic metabolites of lipid peroxidation, we investigated, in situ, by means of an immunohistochemical procedure, the occurrence of lipid peroxidation during different warm ischemic periods of 0, 15, 30, 45 and 60 minutes in rat kidneys prior to reperfusion. The same experiments included followup of the rats after nephrectomy and reperfusion for 10 days.We observed superficial and deep cortex immunostaining with both antibodies against MDA and HNE after 30 minutes of warm ischemia. This immunostaining was observed in the absence of any histological lesions, as assessed by routine staining. After 45 and 60 minutes of warm ischemia, lipid peroxidation byproducts were detected both in the cortex and in the medulla, which is associated with 33% and 66% of rat deaths respectively.This study confirms the involvement of the lipid peroxidation process in kidney damage during anoxia before reperfusion, and its extension to the whole organ. Lipid peroxidation byproducts were detectable in warm ischemic kidney, and the presence of medulla immunostaining was associated with the animals' death. Lipid peroxidation immunostaining might thus be useful as a sensitive tool to detect ischemic damage after warm ischemia prior to reperfusion, as well as in the decision to carry out kidney transplantation in humans.

Background: Surveillance of patients with Barrett's esophagus or ulcerative colitis for dysplasia is confined to biopsy specimens taken randomly during endoscopy because dysplasia remains undetectable by visual inspection. We attempted to visualize dysplastic tissue during endoscopy after sensitization with 5-aminolevulinic acid (5-ALA) leading to accumulation and formation of protoporphyrin IX and induction of characteristic red fluorescence of the latter substance using blue light illumination. Methods: Six patients with histologically proven low- or high-grade dysplasia (Barrett's esophagus 2, ulcerative colitis 1, Billroth-II stomach 1, rectal polyps 2) were treated with oral administration of different concentrations of 5-ALA (10 to 20 mg/kg) or by local instillation of 3 gm 5-ALA in the rectum. Endoscopic fluorescence detection was performed 1 to 6 hours after sensitization using a blue light source and compared with conventional white light endoscopy. Biopsies of fluorescent and nonfluorescent areas were compared with histologic findings. Results: Normal duodenal mucosa and squamous epithelium showed more intense 5-ALA–induced background red fluorescence compared with normal mucosa in the stomach or Barrett's mucosa. Histologically, dysplasia was exclusively found in areas with red fluorescence. False-positive fluorescence was associated with microscopic inflammation of the mucosa or feces in the colon. Conclusions: 5-ALA–induced protoporphyrin IX fluorescence may be useful in the detection of dysplasia in the gastrointestinal tract by enhancement of endoscopic surveillance of patients at a high risk for dysplasia.

SUMMARY Objective. This study investigates the role of the air oesophagogram in conventional chest X-rays for the diagnosis of oesophageal dysmotility in patients with connective tissue diseases. Methods. Fifty-one patients with connective tissue diseases were studied by oesophageal manometry and lateral and posterior‐ anterior chest X-rays. The presence or absence of oesophageal air on chest X-rays were evaluated separately in the upper, middle and distal segment of the oesophagus. Forty-seven chest X-rays of patients without connective tissue diseases, who had undergone manometry for the evaluation of oesophagus-related symptoms and who had normal oesophageal function, were analysed as a control. Results. A total of 23/51 patients with connective tissue diseases showed oesophageal dysfunction in manometry; 16/51 patients (31%) had air in two or more oesophageal segments on the lateral chest X-ray. There was a significant association of manometrically proven oesophageal dysmotility and air in two or three oesophageal segments (P< 0.05; sensitivity 48%, specificity 82%). However, the prevalence of an air oesophagogram showed no significant diVerence between patients with connective tissue diseases and the control group (10/47; 21%). Conclusion. The radiological sign of an air oesophagogram is neither sensitive nor specific enough to omit oesophageal motility studies in patients with connective tissue diseases.

PURPOSE: This study was designed to compare esophageal and anorectal function parameters in patients with systemic sclerosis and to define the role of anorectal manometry in the diagnosis of gastrointestinal involvement of systemic sclerosis. PATIENTS AND METHODS: Twenty-six consecutive patients (22 females) with systemic sclerosis originally referred for assessment of esophageal function were evaluated by esophageal and anorectal manometry. Anorectal function parameters were compared between patients with normal and those with disturbed esophageal function. RESULTS: A total of 17 of 26 patients (65 percent) had severe esophageal dysfunction with aperistalsis of the lower two-thirds of the esophagus, whereas 9 patients (35 percent) had normal esophageal manometry. Only three patients (11.5 percent) suffered from occasional fecal incontinence. Anorectal function parameters (resting pressure, maximum squeeze pressure, perception threshold) were not significantly different between patients with normal and those with disturbed esophageal motility. Rectoanal inhibitory reflex was excitable in nearly 90 percent of patients. CONCLUSION: In an unselected group of patients with systemic sclerosis, fecal incontinence and abnormal anorectal function are rather rare findings. Anorectal manometry cannot differentiate between patients with and without gastrointestinal involvement of systemic sclerosis.

The predictive value of esophagus-related symptoms for the diagnosis of esophageal dysmotility induced by systemic sclerosis (SSc) was prospectively evaluated in 50 consecutive patients with SSc. Patients were classified as symptomatic when either dysphagia or repeated episodes of heartburn were present. All patients underwent esophageal manometry; SSc-induced esophageal dysfunction was diagnosed when there was aperistalsis or marked hypocontractility of the distal two-thirds of the esophageal body. Twenty-nine patients (58%) had a history of esophagus-related symptoms, while 21 patients (42%) were asymptomatic. Compared to esophageal manometry, esophagus-related symptoms had a sensitivity of 64%, a specificity of 52%, a negative predictive value of 50% and a positive predictive value of 62% for the diagnosis of SSc-induced esophageal dysfunction. In conclusion, the association of esophagus-related symptoms and esophageal motility pattern is poor. As clinical management strategies depend on proof of esophageal dysfunction, screening examinations are mandatory in all patients with SSc.

Ehlers-Danlos syndrome (EDS) type IV is an autosomal dominant connective tissue disease caused by mutations in the type III collagen gene resulting in extreme tissue fragility. Affected individuals are at risk of dramatic and often fatal complications, mostly spontaneous arterial, uterine, or colonic ruptures. Phenotypic expression of EDS type IV is variable and clinical signs are generally quite subtle, thus making a prompt diagnosis difficult. The case of a 33-year-old woman is described who presented with a wide range of clinical features and sequelae that eventually led to the diagnosis of EDS type IV. She presented with spontaneous liver rupture, renal infarction, and pneumothorax, all representing rare complications of EDS type IV. Prior history revealed a uterine rupture in advanced pregnancy associated with ischemic necrosis of the descending and sigmoid colon. EDS type IV should be suspected in young individuals who present with such unusual complications. Early diagnosis is essential if severe or even lethal complications are to be avoided in the diagnostic and therapeutic management of such patients.