Ulcerative Colitis: Kroesen AJ

Hoffmann JC, Zeitz M, Bischoff SC, Brambs HJ, Bruch HP, Buhr HJ, Dignass A, Fischer I, Fleig W, Fölsch UR, Herrlinger K, Höhne W, Jantschek G, Kaltz B, Keller KM, Knebel U, Kroesen AJ, Kruis W, Matthes H, Moser G, Mundt S, Pox C, Reinshagen M, Reissmann A, Riemann J, Rogler G, Schmiegel W, Schölmerich J, Schreiber S, Schwandner O, Selbmann HK, Stange EF, Utzig M, Wittekind C. · Medizinische Klinik I mit Schwerpunkt Gastroenterologie/Infektiologie/Rheumatologie, Charité, Universitätsmedizin Berlin. · Z Gastroenterol. · Pubmed #15455267 No free full text.

This publication has no abstract.

Kroesen AJ, Schreiber S, Buhr HJ. · Chirurgische Klinik und Poliklinik I, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Germany. · Zentralbl Chir. · Pubmed #12476363 No free full text.

Abstract: Ulcerative colitis can be cured with a reasonable quality of life by the complete excision of the colorectum and construction of an ileoanal pouch. The cure is incomplete since there is a certain incidence of a so called pouchitis. Pouchitis occurs with a frequency of 36 %. A single episode of a pouchitis can be cured easily, but in 8-32 % the concerned patients develop a chronic pouchitis. There are many signs that pouchitis might be a remanifestation of ulcerative colitis. This article gives an overview on the actual state of pathophysiology, pathogenesis and therapy of this disease. Apart of that the surgical aspects of the disease are described.

Kroesen AJ, Dullat S, Schulzke JD, Fromm M, Buhr HJ. · Department of Surgery, Charité-Universitatsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany. · Scand J Gastroenterol. · Pubmed #18569988 No free full text.

Abstract: OBJECTIVE: Backwash ileitis (BI) has not been identified as a risk factor for pouchitis. The aim of this study was to investigate the barrier function of the ileoanal pouch depending on the presence of BI. The incidence of pouchitis in a population of ulcerative colitis patients with BI is also reported. MATERIAL AND METHODS: Biopsies were taken from 80 patients with ulcerative colitis: a) terminal ileum prior to pouch creation (pre-IAP); b) 16 months after ileostomy closure (intact pouch); and c) during pouchitis. Patients were stratified into the BI group and the non-BI (ØBI) group. Barrier function was determined in Ussing-chambers as epithelial resistance by impedance analysis and as mannitol permeability from (3)H-mannitol fluxes. Na(+)-glucose co-transport was measured as a change in short-circuit current (I(SC)) after addition of glucose. Relative risk of developing pouchitis was calculated by corrected chi(2) test. RESULTS: In 13/21 (BI/ØBI) pre-IAP patients, 23/37 (BI/ØBI) with an intact pouch, and 35/7 (BI/ØBI) with pouchitis, epithelial resistance in BI/ØBI was 13.5+/-1.6/14.3+/-0.9 Omega.cm(2) for pre-IAP, 12.7+/-1.3/16.8+/-1.2 Omega x cm(2) (p<0.05 BI versus ØBI) for the intact pouch, and 10.1+/-1.1/9.9+/-1.8 Omega x cm(2) for pouchitis (p<0.05 BI versus ØBI with an intact pouch). No differences were found for electrogenic chloride secretion and active Na(+)-glucose co-transport between BI/ØBI in the three groups. In patients with BI, pouchitis was more common (35 versus 7 patients, odds ratio 33.0 (95% CI 8.3-143.9; p<0.0001)). CONCLUSIONS: Ulcerative colitis patients with BI show impaired barrier function in the further course of the ileoanal pouch. Thus, BI has a long-term impact on epithelial barrier function.

Zurbuchen U, Kroesen AJ, Buhr HJ. · Abteilung für Viszeral- und Thoraxchirurgie, Chirurgischen Klinik I, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Deutschland. · Urologe A. · Pubmed #18210064 No free full text.

Abstract: The optimization of surgical techniques has made it possible to now treat patients with deep-seated rectal cancer by performing deep anterior rectal resection with coloanal anastomosis while avoiding a permanent stoma. To prevent a high bowel movement frequency and limited continence with an imperative need to empty the bowel, the coloanal pouch operation was developed to construct a rectal substitute. Nowadays, patients with ulcerative colitis or familial adenomatous polyposis of the colon undergo proctocolectomy as the definitive treatment for their underlying disease. Continuity is restored by creating an ileoanal reservoir. This contribution describes the surgical indications and pathophysiological changes for the colon J-pouch and ileoanal reservoir. In addition, explanations of the surgical techniques for both procedures are presented. The functional results are compared with those of other reconstruction options and discussed, taking our own results into consideration.

Kroesen AJ, Leistenschneider P, Lehmann K, Ransco C, Dullat S, Blaut M, Schulzke JD, Fromm M, Buhr HJ. · Department of Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany. · Inflamm Bowel Dis. · Pubmed #16917229 No free full text.

Abstract: BACKGROUND AND AIMS: Bacterial overgrowth appears to play an important role in the pathogenesis of ileoanal pouches. Therefore, the capability of bacterial permeation and its determinants is of great interest. The aim of this study was to examine bacterial permeation in the ileoanal pouch and to correlate the results with the degree of inflammation, the epithelial resistance, the mucosal transport function, and the age of the ileoanal pouches. MATERIALS AND METHODS: Biopsies were taken from 54 patients before colectomy (n = 13; preileal pouch-anal anastomosis [IPAA]), and closure of ileostomy (n = 7; deviation), <1 year after closure of ileostomy (n = 8; intact pouch I), >1 year after closure of ileostomy (n = 16; intact pouch II), in the case of pouchitis (n = 11), and in 11 controls. Tissues were mounted in a miniaturized Ussing chamber. Escherichia coli was added to the mucosal side of the Ussing chamber, and the permeation was proven by serosal presence of E. coli. Epithelial and subepithelial resistance was determined by transmural impedance analysis. Active Na-glucose cotransport and active Cl secretion were measured. Specimens were analyzed by fluorescent in situ hybridization with oligonucleotide probes targeting the bacterial 16s ribosomal RNA. The bacteria in and on the tissue were enumerated. RESULTS: Bacterial permeation occurred in 2 of 13 pre-IPAA, 2 of 7 deviations, 0 of 8 intact pouch I, 9 of 16 intact pouch II, 5 of 11 pouchitis specimens, and 0 of 11 ileum controls. The frequency of bacterial permeation in the intact pouch II group is higher than in the intact pouch I group (P < 0.001). Epithelial resistance, mannitol fluxes, electrogenic chloride secretion, sodium-glucose cotransport of the bacterially permeated specimens versus nonpermeated of the intact pouch II group, and the pouchitis group and subepithelial resistance remained unchanged. Intramural bacteria could be detected by fluorescence in situ hybridization mainly in long-lasting pouches, but there was no correlation with bacterial permeation. CONCLUSIONS: The long-lasting ileoanal pouch is associated with increased bacterial permeability. This is not correlated with a disturbed function of the pouch mucosa but could be a precursor of pouchitis.

Zeissig S, Bürgel N, Günzel D, Richter J, Mankertz J, Wahnschaffe U, Kroesen AJ, Zeitz M, Fromm M, Schulzke JD. · Department of Gastroenterology, Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. · Gut. · Pubmed #16822808 No free full text.

Abstract: BACKGROUND: Epithelial barrier function is impaired in Crohn's disease. AIM: To define the underlying cellular mechanisms with special attention to tight junctions. METHODS: Biopsy specimens from the sigmoid colon of patients with mild to moderately active or inactive Crohn's disease were studied in Ussing chambers, and barrier function was determined by impedance analysis and conductance scanning. Tight junction structure was analysed by freeze fracture electron microscopy, and tight junction proteins were investigated immunohistochemically by confocal laser scanning microscopy and quantified in immunoblots. Epithelial apoptosis was analysed in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling and 4',6-diamidino-2-phenylindole staining. RESULTS: Patients with active Crohn's disease showed an impaired intestinal barrier function as indicated by a distinct reduction in epithelial resistance. As distribution of conductivity was even, focal epithelial lesions (eg, microerosions) did not contribute to barrier dysfunction. Instead, freeze fracture electron microscopy analysis showed reduced and discontinuous tight junction strands. Occludin and the sealing tight junction proteins claudin 5 and claudin 8 were downregulated and redistributed off the tight junction, whereas the pore-forming tight junctions protein claudin 2 was strongly upregulated, which constitute the molecular basis of tight junction changes. Other claudins were unchanged (claudins 1, 4 and 7) or not detectable in sigmoid colon (claudins 11, 12, 14, 15 and 16). Claudin 2 upregulation was less pronounced in active Crohn's disease compared with active ulcerative colitis and was inducible by tumour necrosis factor alpha. As a second source of impaired barrier function, epithelial apoptosis was distinctly increased in active Crohn's disease (mean (SD) 5.2 (0.5)% v 1.9 (0.2)% in control). By contrast, barrier function, tight junction proteins and apoptosis were unaffected in Crohn's disease in remission. CONCLUSION: Upregulation of pore-forming claudin 2 and downregulation and redistribution of sealing claudins 5 and 8 lead to altered tight junction structure and pronounced barrier dysfunction already in mild to moderately active Crohn's disease.

Kroesen AJ. · Department of Surgery I, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12200 Berlin, Germany. · Int J Colorectal Dis. · Pubmed #16496162 No free full text.

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Amasheh S, Barmeyer C, Koch CS, Tavalali S, Mankertz J, Epple HJ, Gehring MM, Florian P, Kroesen AJ, Zeitz M, Fromm M, Schulzke JD. · Department of Clinical Physiology, Campus Benjamin Franklin, Charité-University Medicine Berlin, Hindenburgdamm 30, 12200 Berlin, Germany. · Gastroenterology. · Pubmed #15188166 No free full text.

Abstract: BACKGROUND & AIMS: The main limiting factor for sodium absorption in distal colon is the amiloride-sensitive epithelial sodium channel (ENaC). This study aimed to characterize mechanisms involved in the dysregulation of ENaC expression in ulcerative colitis (UC). METHODS: Epithelial preparations from surgically removed inflamed and control sigmoid colons were used. Active electrogenic Na(+) transport (J(Na)) was determined after 8-hour aldosterone stimulation in Ussing-chambers (corrected for the altered epithelial/subepithelial resistance ratio). Subsequently, ENaC alpha-, beta-, and gamma-subunits were analyzed immunohistochemically and in Western and Northern blots (corrected for the inflammatory increase in subepithelial protein content). To study gene regulation, the promoters of beta- and gamma-ENaC were analyzed in reporter gene assays. RESULTS: In controls, aldosterone stimulated J(Na) and induced ENaC beta- and gamma-subunit expression, whereas this response was virtually abolished in UC. Preservation of surface epithelium in UC was indicated by unchanged ENaC alpha-subunit expression, which points also against a mere immaturity or epithelial cell loss. Inhibition of electrogenic sodium transport as well as beta- and gamma-ENaC mRNA expression could be mimicked in control colon by in vitro preexposure for 8 hours to tumor necrosis factor alpha and interferon gamma. Promoter analysis revealed that down-regulation of beta- and gamma-ENaC gene expression was primarily induced by tumor necrosis factor alpha. CONCLUSIONS: We conclude that, in UC, elevated proinflammatory cytokines selectively impair beta- and gamma-ENaC expression, which contributes to diarrhea by reducing colonic sodium absorption.

Buhr HJ, Kroesen AJ. · Chirurgische Klinik I: Visceral- Gefäss- und Thoraxchirurgie; Universitätsklinikum Benjamin Franklin, FU Berlin. · Z Gastroenterol. · Pubmed #12467017 No free full text.

This publication has no abstract.

Kleessen B, Kroesen AJ, Buhr HJ, Blaut M. · German Institute of Human Nutrition (DIFE) Potsdam-Rehbrücke, Dept of Gastrointestinal Microbiology, Bergholz-Rehbrücke. · Scand J Gastroenterol. · Pubmed #12374228 No free full text.

Abstract: BACKGROUND: Endogenous intestinal bacteria and/or specific bacterial pathogens are suspected of being involved in the pathogenesis of inflammatory bowel diseases (IBD). The aim of this study was to investigate IBD tissues for different bacterial population groups harbouring the mucosal surface and/or invading the mucosa. METHODS: Tissue sections from surgical resections from the terminal ileum and/or the colon from 24 IBD patients (12 active ulcerative colitis (UC), 12 active Crohn disease (CD)) and 14 non-IBD controls were studied by fluorescent in situ hybridization on a quantifiable basis. RESULTS: More bacteria were detected on the mucosal surface of IBD patients than on those of non-IBD controls (P < 0.05). Bacterial invasion of the mucosa was evident in 83.3% of colonic specimens from the UC patients, in 55.6% of the ileal and in 25% of the colonic specimens from the CD patients, but no bacteria were detected in the tissues of the controls. Colonic UC specimens were colonized by a variety of organisms, such as bacteria belonging to the gamma subdivision of Proteobacteria, the Enterobacteriaceae, the Bacteroides/Prevotella cluster, the Clostridium histolyticum/Clostridium lituseburense group, the Clostridium coccoides/Eubacterium rectale group, high G + C Gram-positive bacteria, or sulphate-reducing bacteria, while CD samples harboured mainly bacteria belonging to the former three groups. CONCLUSION: Pathogenic events in CD and UC may be associated with different alterations in the mucosal flora of the ileum and colon.

Kroesen AJ, Stockmann M, Ransco C, Schulzke JD, Fromm M, Buhr HJ. · Department of Surgery, University Hospital Benjamin Franklin, Freie Universität Berlin, Germany. · Gut. · Pubmed #12010884 links to  free full text

Abstract: BACKGROUND AND AIMS: Little is known of the permeability of ileoanal pouches. Hence the aim of the present study was to determine changes in permeability and mucosal function after ileo-pouchanal anastomosis (IPAA) in patients with ulcerative colitis. MATERIALS AND METHODS: Biopsies were taken from 43 patients (male:female ratio 28:15; mean age 35.2 (12.5) years) prior to colectomy (ileum prior to pouch), prior to closure of ileostomy (deviation), and after closure of ileostomy (intact pouch) in the case of pouchitis, and from 14 healthy controls. Tissues were mounted in a miniaturised Ussing chamber. Epithelial and subepithelial resistance was determined by transmural impedance analysis. Active Na(+)-glucose cotransport was measured as change in short circuit current after stepwise addition of glucose, and active Cl(-) secretion was measured after stimulation with theophylline and prostaglandin E(2). RESULTS: Neither epithelial resistance nor mannitol fluxes were significantly altered compared with intact controls, indicating no barrier defect in pouchitis. Subepithelial resistances of intact pouches and pouchitis were increased compared with deviation (18.2 (1.6) and 24.3 (1.5) v. 13.6 (1.0) Omegaxcm(2)) consistent with an adaptive thickening of the subepithelial layer. In contrast, active Cl(-) secretion of pouchitis tissues was reduced versus intact pouch and controls (1.4 (0.3) v. 4.3 (0.7) and 4.6 (0.7) micromol/h/cm(2)), and Na(+)-glucose cotransport of pouchitis was reduced compared with intact pouch and controls (1.8 (0.5) v. 4.2 (0.8) and 8.8 (1.3) micromol/h/cm(2)). CONCLUSIONS: Ileal mucosa in pouchitis and terminal ileum prior to IPAA exhibit impaired secretory and absorptive transport functions whereas the epithelial barrier function remains unchanged. This differs from findings in ulcerative colitis. Thus the hypothesis that pouchitis represents a remanifestation of ulcerative colitis has to be questioned.

Kroesen AJ, Runkel N, Buhr HJ. · Benjamin Franklin Medical Center, Berlin, Germany. · Int J Colorectal Dis. · Pubmed #10367257 No free full text.

Abstract: A constant reduction in anal sphincter pressure follows an ileoanal pouch procedure for ulcerative colitis and familiar adenomatous polyposis. We analyzed whether this reduction is more likely due to neurogenic damage or to direct sphincter trauma. Three-dimensional vector volume manometry was performed in 75 patients prior to the ileoanal pouch procedure and 3 months thereafter. Resting pressure was significantly reduced from 83.5 +/- 24.4 to 58.1 +/- 18.0 mmHg and squeezing pressure from 204.7 +/- 63.3 to 173.4 +/- 50.6 mmHg. Moreover, significant vector volume reductions were recorded postoperatively, and the asymmetry index increased significantly (resting: 11.5 +/- 4.1% to 18.4 +/- 7.4%; squeezing: 9.6 +/- 3.1 to 13.0 +/- 6.7%). Functional anal sphincter length at the high-pressure zone remained unchanged. Thus, there was no local damage to proximal or distal anal sphincter segments, which suggests that the postoperative impairment of sphincter function is secondary to neurogenic rather than morphological damage.

Kroesen AJ, Runkel N, Becker K, Buhr HJ. · Chirurgische Klinik I, Universitätsklinikum Benjamin Franklin-FU, Berlin. · Z Gastroenterol. · Pubmed #10234795 No free full text.

Abstract: A 19-year-old woman suffered from recurrent peranal hemorrhage. Over a period of five years she was treated under the suspicion of ulcerative colitis. After a sigmoid resection with a colostomy, proctectomy with an end colostomy followed due to recurrent intractable peranal hemorrhage. Histology of the specimen showed surprisingly a hemangioma of the rectum. Thereafter reconstruction was performed by colopouchanal anastomosis. Afterwards the patient was free of disease and had a good stool-continence. Stool-frequency was twice daily. The second case consisted in a 27-year-old woman who underwent emergency sigmoidectomy due to massive peranal hemorrhage. Here as well diagnosis was a hemangioma of the sigmoid. One year after the first operation the patient had a recurrence of peranal bleeding again due to rectal hemangioma. Since endoscopy and endosonography confirmed a rectal hemangioma a rectal exstirpation with a colopouchanal reconstruction was performed successfully. The reviewed literature shows including the two presented cases a total of 81 cases with rectal hemangiomas. Because of the good results concerning function and morbidity the therapy of choice is rectal exstirpation with colopouchanal reconstruction.