Endocytosis and Recycling of Tight Junction Proteins in Inflammation

A critical function of the epithelial lining is to form a barrier that separates luminal contents from the underlying interstitium. This barrier function is primarily regulated by the apical junctional complex (AJC) consisting of tight junctions (TJs) and adherens junctions (AJs) and is compromised under inflammatory conditions. In intestinal epithelial cells, proinflammatory cytokines, for example, interferon-gamma (IFN-γ), induce internalization of TJ proteins by endocytosis. Endocytosed TJ proteins are passed into early and recycling endosomes, suggesting the involvement of recycling of internalized TJ proteins. This review summarizes mechanisms by which TJ proteins under inflammatory conditions are internalized in intestinal epithelial cells and point out comparable mechanism in nonintestinal epithelial cells

Der Endothelin-Rezeptorantagonist Bosentan reduziert die Leukozyten-Endothel-Interaktion und die Aktivität chronisch entzündlicher Darmerkrankungen:eine tierexperimentelle intravitalmikroskopische Studie

Einleitung: Die Wirkung des Endothelin-Rezeptor-Antagonisten Bosentan auf die Leukozyten-Endothel-Interaktion und die Entzündungsaktivität einer Dextran-Sodium-Sulphate (DSS) induzierten Colitis der Maus wurde untersucht. Methoden: Balb/c Mäuse wurden in 3 Gruppen (n=10) eingeteilt: gesunde Kontrolle, Colitis (DSS zyklisch oral für 30 Tage), Colitis + Therapie mit Bosentan intraperitoneal täglich an Tag 26-30. An Tag 30 wurde die histologische und klinische Entzündungsaktivität sowie intravitalmikroskopisch die Leukozytenadhäsion in Colon-Venolen untersucht. Ergebnisse: Die Colitis-Induktion führte zu einer hohen Zahl rollender und adhärenter Leukozyten. Die Therapie mit Bosentan senkte die Zahl adhärenter, nicht aber rollender Leukozyten, erhöhte die Leukozyten-Rollgeschwindigkeit, und senkte die klinische und histologische Entzündungsaktivität. Schlussfolgerung: Durch Reduktion der Leukozytenadhäsion könnte Bosentan bei chronisch entzündlichen Darmerkrankungen therapeutisch wirken.Introduction: The effect of Bosentan, an endothelin receptor antagonist, on endothelial leukocyte adhesion and on inflammation was studied in a dextran sodium sulphate induced murine colitis. Methods: Balb/c mice were divided into 3 groups (n=10): healthy control, colitis (cyclic oral application of DSS for 30 days), colitis + therapy with Bosentan intraperitoneally daily on days 26-30. On day 30 clinical and histological inflammation were examined, and leukocyte adhesion in colonic venules was assessed by in vivo microscopy. Results: Induction of colitis led to high numbers of rolling and firmly adherent leukocytes. Bosentan therapy reduced the number of adherent, but not rolling leukocytes, increased leukocyte rolling velocity, and reduced clinical and histological inflammation. Conclusion: By reducing leukocyte adhesion Bosentan could be a therapeutic option in inflammatory bowel disease

Single-Port Laparoscopic Surgery for Inflammatory Bowel Disease

Background. Single Port Laparoscopic Surgery (SPLS) is being increasingly employed in colorectal surgery for benign and malignant diseases. The particular role for SPLS in inflammatory bowel disease (IBD) has not been determined yet. In this review article we summarize technical aspects and short term results of SPLS resections in patients with Crohn's disease or ulcerative colitis. Methods. A systematic review of the literature until January 2012 was performed. Publications were assessed for operative techniques, equipment, surgical results, hospital stay, and readmissions. Results. 34 articles, published between 2010 and 2012, were identified reporting on 301 patients with IBD that underwent surgical treatment in SPLS technique. Surgical procedures included ileocolic resections, sigmoid resections, colectomies with end ileostomy or ileorectal anastomosis, and restorative proctocolectomies with ileum-pouch reconstruction. There was a wide variety in the surgical technique and the employed equipment. The overall complication profile was similar to reports on standard laparoscopic surgery in IBD. Conclusions. In experienced hands, single port laparoscopic surgery appears to be feasible and safe for the surgical treatment of selected patients with IBD. However, evidence from prospective randomized trials is required in order to clarify whether there is a further benefit apart from the avoidance of additional trocar incisions

Temporary Fecal Diversion in the Management of Colorectal and Perianal Crohn’s Disease

Aim. To evaluate the results of temporary fecal diversion in colorectal and perianal Crohn’s disease. Method. We retrospectively identified 29 consecutive patients (14 females, 15 males; median age: 30.0 years, range: 18–76) undergoing temporary fecal diversion for colorectal (n=14), ileal (n=4), and/or perianal Crohn’s disease (n=22). Follow-up was in median 33.0 (3–103) months. Response to fecal diversion, rate of stoma reversal, and relapse rate after stoma reversal were recorded. Results. The response to temporary fecal diversion was complete remission in 4/29 (13.8%), partial remission in 12/29 (41.4%), no change in 7/29 (24.1%), and progress in 6/29 (20.7%). Stoma reversal was performed in 19 out of 25 patients (76%) available for follow-up. Of these, the majority (15/19, 78.9%) needed further surgical therapies for a relapse of the same pathology previously leading to temporary fecal diversion, including colorectal resections (10/19, 52.6%) and creation of a definitive stoma (7/19, 36.8%). At the end of follow-up, only 4/25 patients (16%) had a stable course without the need for further definitive surgery. Conclusion. Temporary fecal diversion can induce remission in otherwise refractory colorectal or perianal Crohn’s disease, but the chance of enduring remission after stoma reversal is low

Segmental resection of the duodenum for gastrointestinal stromal tumor (GIST)

<p>Abstract</p> <p>Background</p> <p>Gastrointestinal stromal tumors (GIST) are the most frequent mesenchymal tumors of the gastrointestinal tract. The biological appearance of these tumors reaches from small lesions with benign appearance to aggressive sarcomas. Only 3–5% of GISTs are localized in the duodenum. There is a controversy, if duodenal GISTs should be treated by a duodenopancreatectomy or by a limited resection of the duodenum.</p> <p>Case presentation</p> <p>A 29-year-old man presented with an acute upper gastrointestinal bleeding from a submucosal tumor located in the proximal part III of the duodenum, 3 cm distal of the papilla of Vater. After an emergency laparotomy with ligation of tumor-feeding vessels in a primary hospital, definitive surgical therapy was performed by partial resection of the duodenum with a duodenojejunostomy. Histology revealed a GIST with a diameter of 2.5 cm and <5 mitoses/50 high power fields, indicating a low risk of malignancy. Therefore no adjuvant therapy with Imatinib was initiated.</p> <p>Conclusion</p> <p>GISTs of the duodenum are a rare cause of upper gastrointestinal bleeding. Partial resection of the duodenum is a warranted alternative to a duodenopancreatectomy, as this procedure has a lower operative morbidity, while providing comparable oncological results.</p