Acetylcholine released by efferent vagus nerves inhibits macrophage activation. Here we show that the anti-inflammatory action of nicotinic receptor activation in peritoneal macrophages was associated with activation of the transcription factor STAT3. STAT3 was phosphorylated by the tyrosine kinase Jak2 that was recruited to the alpha7 subunit of the nicotinic acetylcholine receptor. The anti-inflammatory effect of nicotine required the ability of phosphorylated STAT3 to bind and transactivate its DNA response elements. In a mouse model of intestinal manipulation, stimulation of the vagus nerve ameliorated surgery-induced inflammation and postoperative ileus by activating STAT3 in intestinal macrophages. We conclude that the vagal anti-inflammatory pathway acts by alpha7 subunit-mediated Jak2-STAT3 activation.

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INTRODUCTION: Despite enormous efforts during the past decades, pancreatic adenocarcinoma (PAC) remains one of the most deleterious cancer entities. A useful biomarker for early detection or prognosis of PAC does not yet exist. The goal of our study was the characterization of β 6 -integrin (ITGB6) as a novel serum tumor marker for refined diagnosis and prognosis of PAC. Serum ITGB6 levels were analyzed in 3 independent PAC cohorts consisting of retrospectively and prospectively collected serum and/or (metastatic) PAC tissue specimens. METHODS: Using 2 independent cohorts, we measured serum ITGB6 concentrations in 10 chronic pancreatitis patients, 10 controls, as well as in 27 (cohort 1) and 24 (cohort 2) patients with PAC, respectively. In these patients, we investigated whether ITGB6 serum levels correlate with known clinical and prognostic markers for PAC and whether they might differ between patients with PAC or benign inflammatory diseases of the pancreas. RESULTS: We found that elevated serum ITGB6 levels (≥0.100 ng/mL) in patients suffering from metastasizing PAC presented an unfavorable prognostic outcome. By correlating the ITGB6 tissue expression in primary and metastatic PAC with clinical parameters, we found that positive ITGB6 expression in the tumor tissue is linked to increased serum ITGB6 levels in nonmetastatic PAC and correlates with carbohydrate antigen 19-9 and clinical outcome. DISCUSSION: Our findings suggest that ITGB6 might serve as a novel serum biomarker for early diagnosis and prognosis of PAC. Given the limited specificity and sensitivity of currently used carbohydrate antigen 19-9–based assays, ITGB6 may have the potential to improve the diagnostic accuracy for PAC.

For patients after bariatric surgery, diagnosis of gastric cancer is a challenge. We present a patient after Roux-en-Y gastric bypass with upper abdominal pain and abnormal computed tomography scan with diffuse wall thickening of the gastric antrum. Various biopsy techniques have been described, with surgical (laparoscopic) exploration being the most common. We were able to successfully diagnose gastric cancer in the excluded stomach by biopsy using a jejunogastrostomy, which proved to be safe and effective.

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Zusammenfassung Die Endosonographie (EUS) in der Gastroenterologie hat sich von der rein diagnostischen Modalität zur vielversprechenden therapeutischen Disziplin gewandelt. Erster Schritt in diese Richtung war das EUS-gesteuerte Entnehmen von Gewebsproben an schwierig zugänglichen Lokalisationen; hier ist die Feinnadelpunktion von Pankreasläsionen an vorderster Stelle zu nennen. Mit dem EUS-gesteuertem Punktieren werden aber auch Gefässe erreicht, sodass Varizen gezielt verödet werden können. Kollektionen nach einer Pankreatitis werden ebenfalls minimal-invasiv angegangen und werden so nach luminal drainiert, statt eine chirurgische Intervention nötig zu machen. Durch das Einbringen von Führungsdrähten über die Hohlnadel sind zudem verschiedene Zugänge der Gallenwege intra- und extrahepatisch möglich, sodass interne Drainagen bei frustraner ERCP (endoskopische retrograde Cholangiopankreatikographie) möglich werden. Durch das Einbringen von speziell konfigurierten beschichteten Stents wiederum werden mit der interventionellen EUS neue Zugänge in Hohlorgane minimal-invasiv als Alternative zu chirurgischen Eingriffen geschaffen. Als Beispiel ist hier die endoskopische Gastroenterostomie bei maligner Magenausgangsstenose zu nennen.