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Zusammenfassung Einführung Der Fäkale Mikrobiota-Transfer (FMT) ist eine Behandlung zur Modulation der gastrointestinalen Mikrobiota. Der Einsatz bei rezidivierender Clostridioides-difficile-Infektion (rCDI) ist europaweit etabliert und wird in nationalen und internationalen Leitlinien empfohlen. Der FMT ist in Deutschland im Fallpauschalensystem der Krankenhäuser kodierfähig. Eine auf dieser Kodierung basierende umfassende Erhebung zur Häufigkeit des Einsatzes fehlt bislang. Material und Methodik Berichte des Instituts für das Entgeltsystem im Krankenhaus (InEK), des Statistischen Bundesamtes (DESTATIS) und Qualitätsberichte der Krankenhäuser 2015–2021 wurden auf FMT-Kodierung hin untersucht und im Rahmen einer strukturierten Expertenkonsultation bewertet. Ergebnisse Zwischen 2015 und 2021 wurden von 175 Krankenhäusern 1.645 FMT-Verfahren kodiert. Von 2016 bis 2018 waren dies jährlich im Median 293 (274–313) FMT, gefolgt von einem konstanten Rückgang in den folgenden Jahren auf 119 FMT im Jahr 2021. Patienten/-innen mit FMT waren zu 57,7% weiblich, im Median 74 Jahre alt und der FMT wurde zu 72,2% koloskopisch appliziert. Bei 86,8 % der Fälle wurde eine CDI als Hauptdiagnose genannt, gefolgt von 7,6% eine Colitis ulcerosa. Diskussion In Deutschland wird der FMT seltener eingesetzt als im europäischen Vergleich. Eine Anwendungshürde ist die behördliche Einordnung des FMT als nicht zugelassenes Arzneimittel, die zu erheblich höherem Aufwand bei Herstellung und Verabreichung führt und eine Erstattung erschwert. Die Europäische Kommission hat kürzlich eine Verordnung vorgeschlagen, den FMT als Transplantation einzuordnen. Dies könnte die regulatorische Situation des FMT in Deutschland perspektivisch verändern und so zu einem flächendeckenden Angebot eines in Leitlinien empfohlenen Therapieverfahrens beitragen.

There is a bidirectional interaction between the intestines and lungs, the so-called lung-intestinal axis.The review article reports on studies that deal with a possible influence of the intestinal microbiota on the immune response to a SARS-CoV-2 infection.Studies have shown that COVID-19 is accompanied by dysbiosis that persists even after successful virus conversion (negative PCR). One study found that the severity of COVID-19 is associated with the intestinal microbiota. A dysbiosis could thus favor the so-called cytokine storm. There is indication that pre- and probiotics could boost the immune response in both the guts and lungs.Hintergrund: Zwischen Darm und Lunge besteht eine bidirektionale Interaktion, die sogenannte Lungen-Darm-Achse.Methode: In der Übersichtsarbeit wird über Studien berichtet, die sich mit einem möglichen Einfluss der intestinalen Mikrobiota auf die Immunantwort auf eine SARS-CoV-2-Infektion befassen.Ergebnisse und Schlussfolgerungen: Untersuchungen haben gezeigt, dass COVID-19 von einer Dysbiose begleitet wird, die auch nach erfolgreicher Viruskonversion (negativer PCR) persistiert. Eine Studie fand heraus, dass der Schweregrad von COVID-19 mit der intestinalen Mikrobiota assoziiert ist. Eine Dysbiose könnte somit den sogenannten Zytokinsturm begünstigen. Es gibt Hinweise, dass Pre- und Probiotika die Immunantwort sowohl im Darm als auch in der Lunge verstärken könnten.Schlüsselwörter: Lungen-Darm-Achse, intestinale Mikrobiota, COVID-19, Zytokinsturm, ProbiotikaEingereicht am 19.5.2021 - Revision akzeptiert am 28.6.2021.

Intestinal dysbiosis remains the focus of research into the pathogenesis of chronic inflammatory bowel disease (IBD). The potential role of gut microbiota in the development of IBD includes interaction with the host genome and immune system, as well as various environmental factors, diet, drugs, industrialization, etc. Other organs are negatively affected by intestinal dysbiosis via gut-brain axis. The composition of microbiota and its metabolic activity has a significant impact on the effectiveness of anti-inflammatory therapies. Microbiome-based treatment for IBD includes the use of diet, antibiotics, pre-, pro- and synbiotics, and faecal transplantation (FMT). The development of effective therapies for IBD patients will only be possible once the interactions between the microbiota and its metabolites and the host immune system are better understood.Die intestinale Dysbiose steht weiterhin im Fokus der Erforschung der Pathogenese der chronisch-entzündlichen Darmerkrankung (CED). Die potenzielle Rolle der Darmmikrobiota bei der Entstehung einer CED umfasst eine Interaktion mit Genom und Immunsystem des Wirtes sowie mit verschiedenen Umwelteinflüssen, Ernährung, Medikamenten, Industrialisierung usw. Andere Organe beeinflusst die intestinale Dysbiose negativ über die Darm-Hirn-Achse. Die Zusammensetzung der Mikrobiota und deren metabolische Aktivität hat bedeutenden Einfluss auf die Wirksamkeit der antientzündlichen Therapien. Die mikrobiombasierte Behandlung bei CED umfasst u. a. den Einsatz von Diät, Antibiotika, Pre-, Pro- und Synbiotika sowie Stuhltransplantation (FMT). Die Entwicklung von effektiven Therapien für CED-Patienten wird erst dann möglich sein, wenn die Interaktionen zwischen der Mikrobiota und deren Stoffwechselprodukten und dem Immunsystem des Wirtes besser verstanden werden.Schlüsselwörter: Darmmikrobiom, Dysbiose, chronisch-entzündliche Darmerkrankung, Biologika, personenorientierte TherapieEingereicht am 6.12.2021 - akzeptiert am 14.12.2021.

Different mechanisms have a negative impact on the course of inflammatory bowel disease. Important mechanisms include amongst others an increased release of pro-inflammatory cytokines, intestinal dysbiosis, increased permeability of the intestinal barrier, increased release of corticotropin-releasing factor (CRF) in the brain, activation of mast cells in the intestinal mucosa and inadequate central pain processing with the consequences of anxiety and depression. All of these factors can increase the inflammatory response in the intestine and lead to acute flare-ups. For this reason, appropriate stress management is extremely important for the success of therapy.

Zusammenfassung Hintergrund Die Existenz der Histaminintoleranz (HIT) ist umstritten. Als Ursache wird ein gestörter Histaminabbau infolge einer Diaminooxidase(DAO)-Defizienz vermutet. Doch auch andere Faktoren, z. B. eine erhöhte Histaminproduktion durch Darmbakterien, können zu erhöhten Histaminspiegel beitragen. Ziel dieser Untersuchung war es, eine mögliche Veränderung der Darmbakterien in histaminintoleranten Patienten im Vergleich zu gesunden Personen zu detektieren. Material und Methodik Bei allen Studienprobanden erfolgte die Bestimmung von Gesamt-IgE, nahrungsmittelspezifischen IgEs, TNF-α, Plasmahistamin sowie der Serum-DAO-Aktivität. Anhand von Stuhlproben wurde die Histamin- und Zonulinkonzentration sowie die bakterielle Zusammensetzung mittels 16S-rRNA-Sequenzierung unter Verwendung der Illumina Plattform analysiert. Ergebnisse Insgesamt 18 Probanden (30,2 ± 12,5 Jahre, 94,4 % weiblich) wurden in die Studie eingeschlossen. Diese umfassten Patienten mit HIT (n = 8; 28,9 ± 11,2 Jahre) und gesunde Kontrollen (n = 10; 31,3 ± 13,9 Jahre). Innerhalb der Studiengruppen wurden keine signifikanten Unterschiede in der Histaminkonzentration im Stuhl festgestellt, wohingegen die HIT-Patienten tendenziell erhöhte Zonulinkonzentration im Stuhl aufwiesen. Die Mikrobiomanalyse zeigte eine erniedrigte bakterielle α-Diversität (p = 0,05) und ein erhöhtes Vorkommen von Proteobacteria in der HIT-Gruppe. Weiterhin wiesen die HIT-Patienten ein signifikant geringeres Vorkommen der Butyrat-produzierenden Bakteriengattungen Faecalibacterium (p = 0,045) und Butyricimonas (p = 0,003) auf. Zudem waren die Anteile an Sutterella (p = 0,043) und Hespellia (p = 0,043) erniedrigt. In keiner Studiengruppe wurden vermehrt histaminproduzierende Bakterien detektiert. Schlussfolgerung Unsere Ergebnisse deuten auf eine veränderte Darm-Mikrobiota in Patienten mit HIT hin. Der erhöhte Anteil von Proteobacteria und der erniedrigte Anteil an Butyrat-produzierenden Bakterien sowie höhere Zonulinwerte im Stuhl weisen dabei auf eine mögliche Dysbiose oder eine gestörte Darmbarriere hin. Eine erhöhte intestinale Histaminexposition durch Darmbakterien scheint in der Pathogenese der Histaminintoleranz hingegen unwahrscheinlich.

The risk for an unfavourable course of SARS-CoV-2 pneumonia rises with age and comorbidities. We report the case of an elderly female where the sum of such factors – together with massive findings in the computed tomography of the lung – led us to a therapy with hydroxychloroquine as a compassionate use. The unfavourable outcome demonstrates that – despite the enthusiasm of some authors – hydroxychloroquine is no miracle drug. The worldwide SOLIDARITY trial will help clinicians to assess the potential of the repurposed antimalarial drugs better.

The SARS-CoV-2 infection has recently been declared a pandemic by the WHO. Most fatalities occur in elderly people with comorbidities. However, SARS-CoV-2 pneumonias do also occur in younger patients with no comorbidities or risk factors at all. We report here on one of the “early” cases that occurred in Germany. A 57-year-old man was infected and developed pneumonia after a skiing vacation in Northern Italy. Other members of the travel group also fell ill, but only showed flu-like symptoms. Only a few if any infections originated from the affected person; at this point in time the infection situation in the region could still be grasped. Under supportive measures, the disease developed positively despite impressive radiological findings. The positive course is likely also due to the age of the person affected and the lack of any risk factors. The case does also exemplify thata good health condition does not necessarily protect from acquiring a moderately severe SARS-CoV-2 infection.

Introduction The prevalence of patients with food intolerance (FI) has increased significantly. Immunoglobulin (Ig)E-mediated food allergies (FAs) are detected by determining IgE antibodies and skin prick test. Carbohydrate malabsorptions are clarified with breath tests. However, these diagnostic measures cannot capture all intolerances and have limitations in case of gut-mediated FI. The aims of this pilot study were to evaluate different methods to determine intestinal mucosal IgE in patients with FA and to characterize the intestinal mucosa in patients with FI of unknown origin (FH). Methods Patients with FA and FH were compared with healthy controls. To determine the IgE antibodies and the cytokines tumor necrosis factor (TNF)-α and interferon (IFN)-γ of the intestinal mucosal, a lavage was performed as part of an ileocolonoscopy and samples were taken using the cytobrush and biopsy forceps. In a subgroup, mucosal samples were also taken from the duodenum. Results Data in homogenates of intestinal mucosal samples yielded the highest sensitivity for IgE antibody titers compared with lavage and cytobrush. Patients with FA presented increased intestinal TNF-α and low IFN-γ values. This was in contrast to FH patients, who showed low intestinal IgE antibodies and TNF-α levels, but increased IFN-γ values. Discussion The determination of IgE antibodies to diagnose intestinal IgE-mediated FA is most reliable in intestinal mucosal samples. Increased TNF-α and low IFN-γ levels in patients with FA characterize an allergic reaction. Decreased TNF-α and increased IFN-γ levels in patients with FH indicate an inflammation-related intolerance reaction (see Visual Abstract, Supplementary Digital Content 1, http://links.lww.com/CTG/A520).

Turner syndrome can be manifest with a considerable genetic and phenotypic variability. This merely accounts for about 50% of patients who do not have the “classic” 45 X genotype. We report the case of a 42-year-old female patient with a 46, X, del (X) q 21 genotype (deletion on the second X chromosome on the long arm). As the patient displayed a non-typical phenotype and was infertile, a diagnosis was established at the age of 24 with no follow-up treatment. As part of our therapy of the individual due to newly manifested diabetes mellitus, our diagnostic workup revealed a severe metabolic syndrome encompassing fatty liver disease, obstructive sleep apnea syndrome and hyperuricemia. Our observations should sensitize physicians treating female patients for one or more aspects of the metabolic syndrome and its presence in Turner syndrome. These patients have an unfavorable cardiovascular profile, in part due to the metabolic syndrome, but also due to factors intrinsic to Turner syndrome.

Eine SARS-CoV-2-Infektion verursacht in bis zu 20% der Fälle nur gastroenterologische Symptome wie Diarrhö, Bauchschmerzen, Übelkeit oder Appetitlosigkeit. Auch konnte gezeigt werden, dass die Viren mit dem Stuhl ausgeschieden werden. Das Coronavirus ist zudem ein neuer Faktor in der Behandlung chronisch entzündlicher Darmerkrankungen (CED) — und bei Endoskopien.

Coronavirus disease 2019 (COVID 19) is an emerging infectious disease caused by a novel coronavirus SARS-CoV2 that was first identified in Wuhan, China 2019 and that led to a worldwide pandemia. In addition to typical respiratory signs (dry cough, shortness of breathing), some patients may develop gastrointestinal and hepatological complications including diarrhea or acute hepatitis, respectively. Due to the close contact to the patient’s secretion, the gastroenterologists are at increased risk of getting the infection. Therefore, a proper individual risk stratification before every endoscopic procedure is highly recommended. Endoscopy personnel should reduce exposure hazards by keeping a distance from the patient and using gloves, face masks, face shields and gowns. Taking into the consideration the fact that the virus proliferates in the gastrointestinal (GI) tract, special attention should be given to handling with stool specimens. In patients obtaining FMT for recurrent C. difficile infection, recommended screening measures include donor’s medical history and testing for SARS-CoV-2 presence in pharyngeal and stool specimens.

Leber und Darm stehen in engem Austausch miteinander. Das Risiko fur eine Schadigung der Leber steigt, wenn die Darmbarriere geschadigt ist („leaky gut“). In der Ubersichtsarbeit wird dargestellt, wie Darmbakterien die Pathogenese chronischer Lebererkrankungen beeinflussen und welche Therapiemoglichkeiten es gibt. Die Dysbiose im Darm spielt eine wichtige Rolle bei der Entstehung chronischer Lebererkrankungen wie der alkoholischen Leberkrankheit, der nichtalkoholischen Fettlebererkrankung, der primar biliaren Cholangitis, der primar sklerosierenden Cholangitis und der Leberzirrhose. Eine Darmmikrobiom-modulierende Therapie mit Probiotika, Prebiotika oder Synbiotika zeigt positive Effekte. Die genauere Bedeutung dieses Therapieansatzes mussen weitere Studien klaren.

ZusammenfassungKohlenhydratmalassimilationen als häufige Nahrungsmittelunverträglichkeiten spielen im klinischen Alltag eine zunehmende Rolle. Aus klinischer Sicht ist es wichtig, Intoleranzen von anderen Nahrungsmittelunverträglichkeiten, vor allem Nahrungsmittelallergien, zu differenzieren. Die Symptome der Kohlenhydratintoleranz manifestieren sich durch postprandiale Bauchschmerzen mit Übelkeit, Flatulenz und Meteorismus, gashaltige Diarrhöen und in seltenen Fällen extraintestinale Beschwerden (Fatigue, Arthralgien, Myalgien etc.). Typisch für die Kohlenhydratintoleranzen ist das Fehlen von erhöhten Entzündungsparametern, wie CrP im Blut oder Calprotectin im Stuhl. Die Kohlenhydratintoleranzen werden mit dem H2-Atemtest diagnostiziert. Die Therapie besteht in erster Linie darin, die verantwortlichen Zucker zu meiden. In letzter Zeit konnte eine pathophysiologische Verbindung zwischen Kohlenhydratmalabsorption und Reizdarmsyndrom festgestellt werden. Dafür ist in erster Linie die Störung der Zusammensetzung des Darmmikrobioms (Dysbiose) verantwortlich. Therapeutisch wird bei diesen Patienten eine Reduktion von Mono- und Disacchariden und Polyolen (FODMAP-Prinzip) empfohlen.

Durch die weltweit zunehmende Pravalenz der Adipositas erkranken immer mehr Menschen an einer nichtalkoholischen Fettlebererkrankung (NAFLD). Bei ca. 30% entwickelt sich daraus eine nichtalkoholische Steatohepatitis (NASH). Wird diese nicht rechtzeitig erkannt und behandelt, drohen irreversible Schaden bis hin zu Karzinomen.

BACKGROUND Pancreatic intraductal papillary mucinous neoplasms (IPMNs) present a clinical challenge. Evidence-based guidelines are lacking. The so-called "Fukuoka criteria" were developed to assess the risk of malignancy in IPMNs upon imaging. However, little is known about their diagnostic value and the natural course of IPMNs. Thus, the aim of this study was the assessment of Fukuoka criteria and patient management in pancreatic IPMNs -during follow-up. MATERIAL AND METHODS IPMNs were identified via retrospective survey of endoscopic ultrasound (EUS) examinations. Fukuoka criteria were assessed on EUS findings and additional imaging (CT, MRI, ultrasound). Patients' symptoms and comorbidities were recorded. Dynamics of Fukuoka criteria and patient management were compared at first presentation and during follow-up. RESULTS We screened 1324 EUS examinations. Sixty-five patients (male/female, 14/37; mean age, 68.8 years; range, 48-85 years) with IPMNs were identified (57 branch duct (BD-)IPMNs, 3 main duct (MD-) IPMNs, 5 mixed-type (MT)-IPMNs). Seven patients received surgical resection (4 BD-IPMNs, 2 MD-IPMNs, 1 MT-IPMN). Nine BD-IPMNs had neither surgery nor follow-up. Fifty-one patients (44 BD-IPMNs, 2 MD-IPMNs, 5 MT-IPMNs) underwent follow-up (mean duration, 18.7 months; range, 3-139 months). There were 15/51 patients who were initially Fukuoka-positive. One MD-IPMN, 4/5 MT-IPMNs, and 13/44 BD-IPMNs showed progressive changes but were not resected due to patients' refusal or comorbidities. Four BD-IPMNs converted to Fukuoka-positive. CONCLUSIONS Evidence-based guidelines for non-invasive dignity assessment of IPMNs are lacking. In our study, MD-IPMNs displayed greater dynamics than BD-IPMNs and MT-IPMNs concerning Fukuoka criteria. Prospective long-term studies are needed to clarify prognostic significance of the single Fukuoka criteria and sensible duration of follow-up.

Eine SARS-CoV-2-Infektion verursacht in bis zu 20% der Falle nur gastroenterologische Symptome wie Diarrho, Bauchschmerzen, Ubelkeit oder Appetitlosigkeit. Auch konnte gezeigt werden, dass die Viren mit dem Stuhl ausgeschieden werden. Das Coronavirus ist zudem ein neuer Faktor in der Behandlung chronisch entzundlicher Darmerkrankungen (CED) — und bei Endoskopien.

Die intestinale Mikrobiota muss als ein elementarer Baustein unserer Gesundheit betrachtet werden. Ubersichtsarbeit Eine gestorte Darmmikrobiota (Dysbiose) spielt eine zentrale Rolle in der Pathogenese funktioneller und entzundlicher Darmerkrankungen. Sie ist daruber hinaus auch haufig mit Erkrankungen auserhalb des Darmes vergesellschaftet. Die genaue Kausalitat bleibt unklar („Henne-Ei-Problematik“). Mit Hilfe von Prebiotika, Probiotika oder fakaler Mikrobiota-Therapie konnen bei chronischen, dysbioseassoziierten Erkrankungen relevante therapeutische Effekte erzielt werden. Die Wahl des Praparates sollte sich nach der klinischen Symptomatik ausrichten, die Dauer der Behandlung hangt vom jeweiligen Krankheitsbild ab.

Patient: Male, 65 Final Diagnosis: Humoral hypercalcemia Symptoms: Syncope Medication: — Clinical Procedure: Establishing diagnosis • lowering hypercalcemia with denosumab Specialty: Endocrinology and Metabolic Objective: Educational purpose (only if useful for a systematic review or synthesis) Background: Hypercalcemia in cholangiocellular carcinoma is a highly uncommon event, mainly reported in Asian patients. In the absence of bone metastases, humoral hypercalcemia of malignancy (HHM) can be assumed. This is mostly the consequence of an elevated parathormone-related peptide (PTHrP) level. The standard therapeutic options in HHM are sometimes limited by the underlying disease or concomitant diseases. Case Report: We report the case of a 65-year-old Caucasian male. A syncope due to a hypercalcemia of 4.16 mmol/L (normal range, 2.19–2.54 mmol/L) was the initial symptom that eventually led to the diagnosis of cholangiocellular carcinoma. He had no metastatic bone disease; HHM was suspected. PTHrP was moderately elevated. Since there were contraindications for the standard therapeutic options, a therapy with 120 mg denosumab was initiated and proved effective, safe, and restored the patient’s quality of life for 11 months. Conclusions: The moderate elevation of parathyroid hormone-related peptide (PTHrP) in this case is addressed in context with the recent insights of a substantial underestimation of this parameter by many commercial assays which can explain our observation. Denosumab, a human monoclonal antibody which acts as a RANKL-inhibitor (receptor activator of nuclear factor kappaB ligand) was recently suggested as a therapeutic alternative. In this case, the therapy of the hypercalcemia with denosumab due to contraindications for other therapies led to an effective and long-standing remission of hypercalcemia. Its effectivity should be studied in larger case samples.

Das Konzept der Hirn-Darm-Achse beschreibt die Kommunikation zwischen zentralem und enterischem Nervensystem. Der Austausch von Informationen erfolgt dabei in beiden Richtungen. Die grosen Fortschritte in der Molekularmedizin in den letzten Jahren fuhrten zur Entdeckung einer enormen Zahl von Mikroorganismen im Darm (Darmmikrobiom), die die Funktion der Hirn-Darm-Achse stark beeinflussen. Ubersichtsarbeit Zahlreiche Studien weisen darauf hin, dass eine Dysfunktion der Hirn-Darm-Achse sowohl entzundliche als auch funktionelle Erkrankungen des Gastrointestinaltrakts zur Folge haben konnte. Daruber hinaus konnte gezeigt werden, dass die Storung der Zusammensetzung des Darmmikrobioms in der Kindheit die Reifung des zentralen Nervensystems beeinflusst und somit moglicherweise die Entstehung von psychischen Erkrankungen wie Autismus, Depression oder anderen begunstigt. Ein genauer kausaler Zusammenhang zwischen Psyche und Mikrobiom muss im Hinblick auf neue Therapiemoglichkeiten durch weitere Studien geklart werden.

Fecal microbiota transplantation (FMT) is a novel strategy for the therapy of dysbiosis-associated disorders via modulation of the gut microbiota. Intestinal dysbiosis is associated not only with digestive disorders, but also with a variety of extra-digestive disorders. A worldwide increasing number of FMT can be expected in the future as well as an increase in adverse events. We describe the case of a patient with chronic radiation colitis that developed adhesion ileus 2 days after FMT. Since these problems never occured before and the short time interval favours a causality, we speculate about FMT-induced alterations in gut motility causing a “trapping” of the small intestine in an adhesion and other mechanisms beyond “pure” coincidence.

Chronic liver diseases are a major cause of morbidity and mortality worldwide. Recently, gut dysbiosis was identified as an important factor in the pathogenesis of liver diseases. The relationship between gut microbiota and the liver is still not well understood; however, dysfunction of the gut mucosal barrier (“leaky gut”) and increased bacterial translocation into the liver via the gut–liver axis probably play crucial roles in liver disease development and progression. The liver is an important immunological organ, and, after exposure to gut-derived bacteria via portal circulation, it responds with activation of the innate and adaptive immune system, leading to hepatic injury. A better understanding of the pathophysiological links among gut dysbiosis, the integrity of the gut barrier, and the hepatic immune response to gut-derived factors is essential for the development of new therapies to treat chronic liver diseases.

Liver and intestine are in close contact with each other. The risk of damage to the liver increases, when the intestinal barrier is damaged ("leaky gut") .The review article describes how intestinal bacteria influence the pathogenesis of chronic liver diseases and what treatment options are available.Intestinal dysbiosis plays an important role in the development of chronic liver diseases such as alcoholic liver disease, nonalcoholic fatty liver disease, primary biliary cholangitis, primary sclerosing cholangitis, and cirrhosis. Intestinal microbial modulating therapy with probiotics, prebiotics or synbiotics shows positive effects. The more precise meaning of this therapeutic approach needs to be clarified in further studies.

Objective: To investigate a potential cause of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Clinical Presentation and Intervention: A 70-year-old female patient had nausea and collapsed. Although euvolemic, pathological laboratory findings showed hyponatremia and hypoosmolality, and cerebral magnetic resonance imaging showed hypertrophic pachymeningitis. Secondary hypertrophic pachymeningitis was excluded. Other nonneurological reasons for SIADH were also excluded. Moderate fluid restriction restored an almost normal serum osmolality and sodium. Conclusion: This case of SIADH was conservatively treated with moderate fluid restriction that almost restored normal serum osmolality and sodium levels.

Background Malnutrition is an under-recognized problem in hospitalized patients. Despite systematic screening, the prevalence of malnutrition in the hospital did not decrease in the last few decades. The aim of our study was to evaluate the prevalence of malnutrition and to determine the explicit daily calorie intake of hospitalized patients, to identify the risk factors of developing malnutrition during hospitalization and the effect on the financial reimbursement according to the German DRG-system. Material/Methods 815 hospitalized patients were included in this study. The detection of malnutrition was based on the nutritional-risk-screening (NRS) and subjective-global-assessment (SGA) scores. A trained investigator recorded the daily calorie and fluid intake of each patient. Furthermore, clinical parameters, and the financial reimbursement were evaluated. Results The prevalence of malnutrition was 53.6% according to the SGA and 44.6% according the NRS. During hospitalization, patients received on average 759.9±546.8 kcal/day. The prevalence of malnutrition was increased in patients with hepatic and gastrointestinal disease and with depression or dementia. The most important risk factors for malnutrition were bed rest and immobility (OR=5.88, 95% CI 2.25–15.4). In 84.5% of patient records, malnutrition was not correctly coded, leading to increased financial losses according to the DRG-system (94.908 Euros). Conclusions Hospitalized patients suffer from inadequate nutritional therapy and the risk for developing malnutrition rises during the hospital stay. The early screening of patients for malnutrition would not only improve management of nutritional therapy but also, with adequate coding, improve financial reimbursement according to the DRG-system.

Helicobacter pylori is a major risk factor for peptic ulcer, but studies on the role of H. pylori infection in gastric pathology are limited due to lack of convenient models resembling H. pylori infection in humans. We studied the effects of inoculation of conventional BALB/c mice with a toxigenic (cytotoxin associated gene A (cagA)+ and vacuolating cytotoxin gene A (vacA+) H. pylori strain on the course of healing of gastric ulcers. Following inoculation of toxigenic H. pylori or vehicle, gastric ulcers were produced in mice, which were then killed either at day 0 or after 2, 4, 7, 14 or 28 days and ulcer area and gastric blood flow (GBF) were determined. Gastric secretions from mice with chronic gastric fistulae were studied before and after inoculation with toxigenic H. pylori or vehicle (saline). The area (7 mm2 ) of ulcers in control mice decreased gradually and disappeared almost completely after 14 or 28 days. The ulcers in H. pylori-infected mice were present at all test days, showing a larger area than in vehicle control animals. The GBF in control mice rose gradually with decreasing ulcer size, being significantly higher at the ulcer margin than the ulcer crater. In contrast, the GBF in H. pylori-infected mice was significantly lower at the ulcer area than that in the vehicle controls but, again, the GBF at the ulcer margin was always higher than at the ulcer crater. Gastric acid output was reduced by more than 50% immediately after H. pylori inoculation and was accompanied by a significant increase in plasma gastrin release and a fall in gastric luminal somatostatin content. These secretory changes persisted at all test days. Oedema/congestion of surface epithelium appeared after 7 days and mucosal inflammatory infiltration appeared after 14 days, to further increase after 28 days, upon the induction of ulcer. Plasma interleukin (IL)-Is and IL-12 were significantly elevated above the initial values compared with controls. Conventional mice with gastric ulcers can be successfully infected with an H. pylori strain expressing cagA and vacA cytotoxin and this infection markedly delays healing of the ulcers, probably due to the fall in GBF in the ulcer area, mucosal inflammation, cytokine release and impairment of the gastrin-somatostatin link.

We examined the outcome and the complications of endoscopic balloon dilatation (EBD) of ileocaecal and colonic strictures due to Crohn’s disease. We examined 237 dilatation procedures in 77 patients with symptomatic ileocaecal and colonic stenosis regarding outcome, individual perforation risk, the need for further interventions, and other complications within a 10 years observation period. In 50 of 77 patients (64.9 %), endoscopic dilatation procedures were successful within a median follow-up period of 24 months (25th and 75th percentile 10–38.5 months). Thirty five patients (45.5 %) were successfully dilated with only one endoscopic procedure, while the remaining patients required two or more EBDs. Albeit the EBD, 27 patients of the whole cohort (35.1 %) underwent surgical repair of the stenosis in due course. Overall complication rate was 7.6 %, with postdilatation bleeding in 1.7 % and abdominal pain longer than 24 h in 4.2 %. Perforation occurred in 4 of 77 patients (5.2 %), resulting in a perforation rate of 1.7 % per intervention, or, more importantly, for the individual patient in a long-term perforation rate of 5.2 % per patient, respectively. Endoscopic balloon dilatation (EBD) is a safe and effective approach to ileocaecal and colonic stenosis in approximately 65 % of Crohn’s disease patients. Even in case of recurrence, further endoscopic treatments can be undertaken. The perforation rate depending on the number of interventions is low, but for the individual patient a cumulative per patient perforation risk of 5.2 % in the long-term should be considered during patient information and decisions for or against surgical interventions.

Mit einer Frequenz von etwa 1 : 500 stellt die Zoliakie (fruher Sprue) eine wichtige Differenzialdiagnose bei Personen mit Malabsorption, Abdominalbeschwerden, Diarrhoen und Nahrungsmittelunvertraglichkeiten dar. Die Zoliakie kann ein breites Spektrum gastrointestinaler Symptome, aber auch extraintestinaler Krankheitserscheinungen (z. B. Dermatitis herpetiformis Duhring), verschiedener oligo- oder asymptomatischer Verlaufe (z. B. Anamie, Osteoporose, Depression) bis hin zur refraktaren kollagenen Zoliakie induzieren. Die Zoliakie wird bei HLA-DQ2- und -8-pradisponierten Personen (HLA: humanes Leukozytenantigen) durch den Kontakt mit Gliadinen des Weizens uber eine pradominante Th1-Immunreaktion und eine begleitende humorale Th2-Antwort hervorgerufen, die schlieslich bis zur Zottenatrophie fuhren kann. Mit geeigneten serologischen Tests (Bestimmung der Immunglobulin[Ig]A-Antikorper gegen Gewebstransglutaminase, Endomysium und deamidierte Gliadinpeptide kann bei ausreichender Glutenzufuhr die Diagnose heute zuverlassiger als in fruheren Jahren gestellt werden. Bei IgA-Mangel muss auf die IgG-basierte Serologie gegenuber obigen Antigenen ausgewichen werden. Die Diagnosestellung kann entweder im Kindes- und Jugendalter bei Antitransglutaminasetitern uber dem Zehnfachen der Norm durch zwei der oben genannten Antikorpertests bei HLA-Ubereinstimmung gestellt werden oder sie wird bei weniger eindeutiger Serologie bzw. bei Erwachsenen durch die Endoskopie und histologische Marsh-Klassifizierung gesichert. Glutenprovokationen sind — soweit vom klinischen Zustand aus vertretbar — bei Personen mit bereits reduzierter Glutenaufnahme, bei grenzwertiger Serologie, Diskordanz zwischen Serologie und Histologie oder bei einem Verdacht auf Nahrungsmittelallergie angezeigt. Die Diagnose der Zoliakie muss vor Einleitung einer glutenfreien Kost definitiv und sicher gestellt sein. Denn es ist eine lebenslange Diat mit Karenz von Gluten (Gliadin; < 20 mg/kg Lebensmittel), Getreideprodukten (Weizen, Roggen, Gerste, Dinkel) sowie glutenhaltigen Zubereitungen und Getranken erforderlich. Bei effektiver Elimination von Gluten liegt eine gute Prognose bezuglich der kompletten Abheilung der Dunndarmentzundung vor. Nur in seltenen Fallen finden sich therapierefraktare Verlaufe, die mit einem enteropathieassoziierten T-Zell-Lymphomrisiko einhergehen. Zitierweise: Hahn M, Hagel AF, Hirschmann S, Bechthold C, Konturek P, Neuratz M, Raithel M. Modern diagnosis of celiac disease and relevant differential diagnoses in the case of cereal intolerance. Allergo J Int 2014; 23: 67–77 DOI 10.1007/s40629-014-0006-4

At an incidence of 1:500, celiac disease (formerly sprue) is an important differential diagnosis in patients with malabsorption, abdominal discomfort, diarrhea and food intolerances. Celiac disease can induce a broad spectrum of both gastrointestinal and extraintestinal symptoms, e.g. dermatitis herpetiformis (Duhring’s disease). A variety of oligo- and asymptomatic courses (e.g. anemia, osteoporosis, depression) through to refractory collagenic celiac disease are seen. In HLA-DQ2 and -8 predisposed individuals, celiac disease is provoked by contact with wheat gliadin fractions through a predominantly Th1 immune response and an accompanying Th2 response, which can eventually lead to villous atrophy. Using appropriate serological tests (IgA antibodies against tissue-transglutaminase, endomysium and deamidated gliadin peptides) under sufficient gluten ingestion, the diagnosis can be made more reliably today than previously. The same IgG-based serological tests should be used in the case of IgA deficiency. Diagnosis can either be made in children and adolescents with anti-transglutaminase titers exceeding ten times the standard for two of the above-mentioned serological markers and HLA conformity or it is made by endoscopy and histological Marsh classification in adults and in cases of inconclusive serology. If clinically tolerated, gluten challenges are indicated in patients that already have reduced gluten intake, in borderline serological results, discordance between serological and histological results or in suspected food allergy. The diagnosis of celiac disease needs to be definitive and robust before establishing a gluten-free diet, since lifelong abstention from gluten (gliadin < 20 mg/kg foodstuffs), cereal products (wheat, rye, barley and spelt) as well as from preparations and beverages containing gluten, is necessary. With effective elimination of gluten, the prognosis regarding complete resolution of small bowel inflammation is good. Refractory courses are seen only in rare cases, accompanied by enteropathy-associated T-cell lymphoma.

Background Acoustic radiation force impulse (ARFI) elastography is a reliable diagnostic device for quantitative non-invasive assessment of liver fibrosis in patients with chronic liver disease. The aim of our prospective study was to evaluate the impact of ARFI in patients after orthotopic liver transplantation (OLT). Therefore, we compared ARFI shear wave velocities with clinical features, non-invasive markers, and the histology of patients following OLT. Material/Methods Post-transplant patients underwent a clinical examination and blood samples were taken. B-mode and Doppler ultrasound (US) of the portal vein and the hepatic artery were performed. Subsequently, a minimum of 10 valid ARFI values were measured in the left and right liver lobe. Liver biopsy was performed if indicated. Results Between May 2012 and May 2014, 58 Patients after OLT were included in the prospective study. Laboratory markers and aspartate aminotransferase-to-platelet ratio index (APRI) correlated with ARFI values (r=0.44, p

BACKGROUND Non-invasive procedures such as acoustic radiation force impulse imaging (ARFI) shear-wave elastography are currently used for the assessment of liver fibrosis. In the course of chronic hepatitis C, significant liver fibrosis or cirrhosis develops in approximately 25% of patients, which is a negative predictor of antiviral treatment response. Cirrhosis can be prevented by successful virus elimination. In this prospective study, a pretreatment ARFI cutoff value of 1.5 m/s was evaluated in relation to sustained virological response to anti-HCV therapy. MATERIAL AND METHODS In 23 patients with chronic hepatitis C, liver stiffness was examined with ARFI at defined times before and under antiviral triple therapy (peginterferon, ribavirin in combination with a first-generation protease inhibitor, and telaprevir or boceprevir). Patients were stratified into 2 groups based on pretreatment ARFI values (

Objective: The aim of this work was to describe the use of a combination of fidaxomicin and fecal microbiota therapy (FMT) in Clostridium difficile infection (CDI). Clinical Presentation and Intervention: A 78-year-old female, who was admitted for surgery due to acute diverticulitis caused by postoperative complications and broad antibiotic therapy, developed CDI-induced colitis. Despite the introduction of metronidazole and vancomycin therapy, her clinical condition continued to deteriorate. She was transferred to the intensive care unit where FMT followed by fidaxomicin were performed because her C-reactive protein and leucocyte levels remained elevated. Further clinical improvement and the resolution of colitis was observed. Conclusion: In this case, severe CDI colitis was successfully treated with the combination of FMT and fidaxomicin.

The caudal homeobox factor 1 (CDX1) is an essential transcription factor for intestinal differentiation. Its aberrant expression in intestinal metaplasia of the upper gastrointestinal tract is a hallmark within the gastritis-metaplasia-carcinoma sequence. CDX1 expression is influenced by certain pathways, such as Wnt, Ras, or NF-κB signaling; however, these pathways alone cannot explain the transient expression of CDX1 in intestinal metaplasia or the molecular inactivation mechanism of its loss in cases of advanced gastric cancer. In this study, we investigated the epigenetic inactivation of CDX1 by promoter methylation, as well as the functional link of CDX1 promoter methylation to the inflammatory NF-κB signaling pathway. We identified methylation-dependent NF-κB binding to the CDX1 promoter and quantified it using competitive electrophoretic mobility shift assays and chromatin immunoprecipitation. A methylated CDX1 promoter was associated with closed chromatin structure, reduced NF-κB binding, and transcriptional silencing. Along the gastritis-metaplasia-carcinoma sequence, we observed a biphasic pattern of tumor necrosis factor-α (TNF-α) protein expression and an inverse biphasic pattern of CDX1 promoter methylation; both are highly consistent with CDX1 protein expression. The stages of hyper-, hypo-, and hyper-methylation patterns of the CDX1 promoter were inversely correlated with the NF-κB signaling activity along this sequence. In conclusion, these functionally interacting events drive CDX1 expression and contribute to intestinal metaplasia, epithelial dedifferentiation, and carcinogenesis in the human stomach.

Background Training simulators have been used for decades with success; however, a standardized educational strategy for diagnostic EGD is still lacking. Objective Development of a training strategy for diagnostic upper endoscopy. Study design Prospective, randomized trial. Settings A total of 28 medical and surgical residents without endoscopic experience were enrolled. Basic skills evaluations were performed following a structured program involving theoretical lectures and a hands-on course in diagnostic EGD. Subsequently, stratified randomization to clinical plus simulator training (group 1, n=10), clinical training only (group 2, n=9), or simulator training only (group 3, n=9) was performed. Ten sessions of simulator training were conducted for groups 1 and 3 during the 4-month program. Group 2 underwent standard training in endoscopy without supplemental simulator training. The final evaluation was performed on the simulator and by observation of 3 clinical cases. Skills and procedural times were recorded by blinded and unblinded evaluators. Main Outcome Measurements Time to reach the duodenum, pylorus, or esophagus. Results All trainees demonstrated a significant reduction in procedure time during a simple manual skills test ( P P = .006, P = .042 and P = .017) in the simulator independent of the training strategy. Group 1 showed shorter times to intubate the esophagus (61 ± 26 seconds vs 85 ± 30 seconds and 95 ± 36 seconds) and the pylorus (183 ± 65 seconds vs 207 ± 61 seconds and 247 ± 66 seconds) during the clinical evaluation. Blinded assessment of EGD skills showed significantly better results for group 1 compared with group 3. Blinded and unblinded evaluations were not statistically different. Limitations Small sample size. Conclusions Structured simulator training supplementing clinical training in upper endoscopy appears to be superior to clinical training alone. Simulator training alone does not seem to be sufficient to improve endoscopic skills.

Summary Background Recent studies suggest that adipose tissue hormones are involved in the pathogenesis of obstructive sleep apnoea syndrome (OSAS). The role of leptin, obestatin and apelin still needs to be established. Material/Methods Ten patients with newly diagnosed OSAS (AHI >10/h and ESS >10 points) were enrolled in the study as well as ten healthy volunteers as controls. All underwent measurements for Leptin, Obestatin and Apelin in four hour intervals during diagnostic polysomnography for 24 h and the patients also three months after onset of CPAP treatment. Furthermore the HOMA-index and body composition were quantified. Results Plasma apelin levels in the patients decreased under CPAP therapy, but showed no significant difference in patients and volunteers. We found a positive correlation to AHI, BMI in the therapy group at all observation points. Leptin plasma levels were higher in the patient group and decreased after onset of CPAP therapy. Leptin plasma levels were positively correlated to the BMI, min. 02 and AHI in the patient group before therapy. Plasma obestatin levels did not differ significantly in these three observation groups, but were partly correlated to AHI and weight in the newly diagnosed OSAS group. Conclusions In agreement with previous investigations, we could demonstrate a difference in leptin plasma levels between healthy volunteers and patients with newly diagnosed OSAS. Apelin decreases under CPAP therapy, but not significantly. Obestatin remains unchanged after onset of CPAP. We further found a linkage between leptin plasma levels and BMI, AHI and weight in the untreated patient group.

Summary Background The aim of this retrospective study was to evaluate the efficacy and safety of weekly high-dose 5-fluorouracil (5-FU)/folinic acid (FA) as 24-h infusion (AIO regimen) plus irinotecan in patients with histologically proven metastatic gastroesophageal adenocarcinoma (UICC stage IV). Material/Methods From 08/1999 to 12/2008, 76 registered, previously untreated patients were evaluable. Treatment regimen: irinotecan (80 mg/m2) as 1-h infusion followed by 5-FU (2000 mg/m2) combined with FA (500 mg/m2) as 24-h infusion (d1, 8, 15, 22, 29, 36, qd 57). Results Median age: 59 years; male/female: 74%/26%; ECOG ≤1: 83%; response: CR: 1%, PR: 16%, SD: 61%, PD: 17%, not evaluable in terms of response: 5%; tumor control: 78%; median OS: 11.2 months; median time-to-progression: 5.3 months; 1-year survival rate: 49%; 2-year survival rate: 17%; no evidence of disease: 6.6%; higher grade toxicities (grade 3/4): anemia: 7%, leucopenia: 1%, ascites: 3%, nausea: 3%, infections: 12%, vomiting: 9%, GI bleeding of the primary tumor: 4%, diarrhea: 17%, thromboembolic events: 4%; secondary metastatic resection after downsizing: 16 patients (21%), R-classification of secondary resections: R0/R1/R2: 81%/6%/13%, median survival of the 16 patients with secondary resection: 23.7 months. Conclusions Combined 5-FU/FA as 24-h infusion plus irinotecan may be considered as an active palliative first-line treatment accompanied by tolerable toxicity; thus offering an alternative to cisplatin-based treatment regimens. Thanks to efficient interdisciplinary teamwork, secondary metastatic resections could be performed in 16 patients. In total, the patients who had undergone secondary resection had a median survival of 23.7 months, whereas the median survival of patients without secondary resection was 10.1 months (p≤0.001).

Summary Background Metastatic insulinoma is a disease associated with a poor life expectancy. Case Report The case of a presently 68 year old female with malignant, metastatic insulinoma is reported. Due to severe clinical symptoms surgical tumor mass reduction was conducted. Furthermore the patient underwent a chemotherapy using streptozotocine and fluorouracil. After two years without any symptoms, the remaining hepatic metastases increased in size and again hypoglycemias occurred. To reachieve an asymptomatic state and further reduction in tumor mass, the decision was made for transarterial chemoembolization with streptozotocine. After the first treatment the patient was hypoglycemia – free for 3 months, after another more extensive chemoembolization the patient is presently symptom free for 8 months. Conclusions Since the diagnosis of extended disease was established, the patient has survived for 36 months. We regard this as the result of a multimodal approach and the extensive use of local tumor therapy. The different therapeutic options for local tumor therapy are reported and discussed.

Summary Background Endoscopic treatment of advanced biliary disorders and their complications following surgical procedures is often difficult especially after Billroth II gastric resection. In such cases, endoscopic access to the papilla and neopapilla is often low, and access to the choledocho- or hepaticojejunostomy is often difficult. Thus, percutaneous cholangiodrainage or re-operation is therefore indicated when endoscopic access to the papilla failed. But both of those methods are much more invasive and more likely to be followed by complications than use of a purely endoscopic approach. Case Report The present case report describes endoscopic access to the papilla with both push enteroscopy and double-balloon enteroscopy (DBE, push-and-pull enteroscopy) in a female patient after Billroth II resection with bile leakage following cholecystectomy. Successful closure of the bile duct fistula could be achieved via an unusual abdominal-biliary-jejunal cannulation way after several attempts of modern enteroscopy and in this way re-operation was avoided. Conclusions Modern enteroscopy by experienced investigators using push-and-pull enteroscopes can provide access to the papilla even in complex postoperative anatomic rearrangements. Push-and-pull enteroscopes offer a further option for successful cannulation of the papilla and therapeutic interventions via additional stabilization with balloons and the modern enteroscopic approach by push-and-pull enteroscopy appears to provide more patient comfort, requires less analgo-sedation and examination time and in cases with intra-abdominal drainage this external access may be used as an additional aid for exploration and intervention in complex individual cases with extremely difficult treatable bile duct injuries.

Background: Percutaneous endoscopic gastrostomy (PEG) is considered the preferred route for long-term enteral feeding. The aim of this study was to determine predictors of an increased mortality risk after PEG insertion. Methods: A retrospective study was conducted during a 13-year period in the gastroenterology department of Erlangen University Hospital. The authors completed a questionnaire with details of demographic data, diagnosis, indication for PEG, type of tube, and cause of death. Patients were contacted regularly at scheduled appointments. Results: In total, 787 patients (574 male [72.9%]) underwent PEG placement by the pull technique. The main underlying disease was malignant (75.6%). By the end of the study period, 614 patients had died. The average survival time was 720 days. The 30-, 60-, 90-day and 1-, 3-, and 5-year mortality rates amounted to 6.5%, 9.8%, 13%, 32.1%, 59.3%, and 69.8%, respectively. Predictive factors of increased 30-day mortality were higher age, lower body mass index (BMI), and the presence of diabetes mellitus. The presence of all 3 variables served as an indicator to detect high-risk patients, with a sensitivity of 0.80 and a specificity of 0.64. Conclusion: Mortality predictors for patients after PEG insertion are higher age, lower BMI, and the presence of diabetes mellitus. To avoid unnecessary and dangerous examinations in high-risk patients, the above-mentioned predictive factors of mortality should be checked before PEG placement.

The investigation of the human microbiome is the most rapidly expanding field in biomedicine. Early studies were undertaken to better understand the role of microbiota in carbohydrate digestion and utilization. These processes include polysaccharide degradation, glycan transport, glycolysis, and short-chain fatty acid production. Recent research has demonstrated that the intricate axis between gut microbiota and the host metabolism is much more complex. Gut microbiota—depending on their composition—have disease-promoting effects but can also possess protective properties. This review focuses on disorders of metabolic syndrome, with special regard to obesity as a prequel to type 2 diabetes, type 2 diabetes itself, and type 1 diabetes. In all these conditions, differences in the composition of the gut microbiota in comparison to healthy people have been reported. Mechanisms of the interaction between microbiota and host that have been characterized thus far include an increase in energy harvest, modulation of free fatty acids—especially butyrate—of bile acids, lipopolysaccharides, gamma-aminobutyric acid (GABA), an impact on toll-like receptors, the endocannabinoid system and “metabolic endotoxinemia” as well as “metabolic infection.” This review will also address the influence of already established therapies for metabolic syndrome and diabetes on the microbiota and the present state of attempts to alter the gut microbiota as a therapeutic strategy.

Introduction The pathogenesis of Crohn's disease is unclear, but an abnormal immune response seems to play an important role. This study investigated whether serum tryptase could be shown in Crohn's disease as a marker of disease. Materials and methods Mast cell tryptase was detected in sera of 48 patients with active Crohn's disease, 31 patients with inactive Crohn's disease, 17 patients with mastocytosis, and 50 controls. Tryptase detection was carried out by UniCap System. Tryptase levels are given as U/I x m 2 body surface area to overcome variations of body weight, height, etc. between malnourished and normal persons. Results Serum tryptase levels (U/I x m 2 body surface area) of controls were 2.4 ± 1.0, of patients with Crohn's disease 2.5 ± 2.0. In contrast, serum tryptase values were significantly increased in untreated patients with mastocytosis (21.19 ± 18.55). Discussion Mast cell tryptase is not elevated in sera of Crohn's disease. It might thus be speculated that this highly mast cell associated mediator might only contribute to local symptoms of Crohn's disease such as diarrhea, abdominal pain, etc., but not to its systemic inflammatory effects (Th 1 cytokine pattern). Tryptase may be well used for the screening of patients with mastocytosis.

Some recent studies indicate that cannabis may induce acute pancreatitis in humans and administration of anandamide increases the severity of acute pancreatitis; whereas another study exhibits some therapeutic effects in acute pancreatitis. Aim of the present study was to discover what is the reason for these opposite confusing results and to determine the role of sensory nerves in this effect. Acute pancreatitis was induced in rats by cerulein. Anandamide, an endogenous cannabinoid, was administered i.p. (1.5 micromol/kg) before or 2 h after cerulein administration. Stimulation of sensory nerves was performed by capsaicin (0.5 mg/kg s.c.). In rats treated with combination of anandamide plus capsaicin, capsaicin was given 10 min after each dose of anandamide. After the last injection of cerulein or 4 h later, the study was terminated. In our study we observed that stimulation of sensory nerves by capsaicin, before administration of cerulein, reduced the severity of acute pancreatitis. Anandamide, administered alone before cerulein, increased pancreatic damage in acute pancreatitis. Anandamide administered in combination with capsaicin, before cerulein, abolished the capsaicin-induced protective effect on the pancreas. Opposite effects were observed when capsaicin and anandamide were administered after injection of cerulein. Capsaicin increased the severity of acute pancreatitis, whereas anandamide reduced pancreatic damage and reversed the deleterious effect of capsaicin. We conclude that the effect of anandamide on the severity of acute pancreatitis depends on the phase of this disease. Administration of anandamide, before induction of pancreatitis, aggravates pancreatic damage; whereas anandamide administered after induction of pancreatitis, reduces the severity of acute pancreatitis. Sensory nerves are involved in the mechanism of this biphasic effect of anandamide.