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Biomedical subjects

A J Kroesen

Publications and source records attributed to A J Kroesen.

At least 19 recordsLinked to original sources

Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease.

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.

Adult↗

[Results of multivisceral resection of primary colorectal cancer].

BACKGROUND: In about 10 % of all patients with colorectal cancer, the primary invention already discloses adhesions or infiltration of adjacent organs. En bloc resection of the tumor-bearing bowel segment with adjacent organs is done to give patients a chance for curation, since intraoperative differentiation is not possible. The aim of this study is characterization of the patient population as well as evaluation of the morbidity and mortality associated with this type of extensive intervention. METHOD: Between 1/95 and 6/04, we analyzed all patients with progressive primary colorectal cancer, who underwent multivisceral surgery with en bloc resection of at least one other organ. The target parameters were tumor characteristics as well as postoperative morbidity and mortality. RESULTS: A total of 1 001 patients with colorectal cancer underwent surgery. 101 patients (10 %) required multivisceral resection. In 17 % the indication was exigent. About 70 % of the interventions involved the colon. Tumor perforation was seen in 17 % of patients with colon cancer and 16 % with rectal cancer. Resection of the inner genitals was most frequent in both colon and rectal cancer (26 and 84 %) followed by small bowel resection (21 %) and partial bladder resection (19 %). Other organs play a secondary role in rectal cancer while partial bladder resection (20 %) and abdominal wall resection (14 %) is observed more frequently in colon cancer. Resection of parenchymatous organs (kidney, suprarenal gland, spleen, pancreas, liver) and others like the stomach is quite rare in colon cancer. Actual tumor infiltration (T4 situation) was observed in 51 % of patients with colon cancer and in 64 % of those with rectal cancer. Local R0 resection (97 vs. 96 %) was successfully performed in nearly all colon and rectal cancer patients. The surgical major complication rate was 9 % in colon cancer and 19 % in rectal cancer. The mortality rate was 4 %. CONCLUSION: Multivisceral en-bloc resection enables local R0 resection in the majority of cases with primary colorectal cancer. Despite sometimes extensive surgery, this type of procedure is associated with an acceptable morbidity and mortality. Since long-term survival is comparable to that in the T category (T3 or T4), multivisceral en-bloc resection is not only justified but also absolutely required in interventions with curative intention.

Abdominal Wall↗

[The importance of diagnostics in faecal incontinence. Endosonography].

Endoanal sonography is a well established method for the morphological diagnosis of anal sphincter damage. The best images are obtained using a 7-10 MHz rotating rigid endoprobe. The internal anal sphincter and the external anal sphincter, as well as the other pelvic floor structures, can be clearly visualised with this technique. Endosonography has shown physiological differences in sphincter anatomy and brought new insights into the pathogenesis of anorectal disorders. Apart of anal fistulas, faecal incontinence represents the main indication for the use of this method. In addition, rectal evacuation disorders are an indication for which endosonography allows a first step towards a diagnosis. Anal ultrasound is a technique friendly to both the physician and the patient, and belongs in every coloproctological unit for the assessment of faecal incontinence. Accuracy, specificity and sensitivity for the detection of anal sphincter defects range between 83 and 100% in almost all studies. Additional methods are vaginal endosonography, three dimensional endosonography and perineal sonography.

Adult↗

[Biofeedback in faecal incontinence].

Biofeedback training is a well established method for the treatment of faecal incontinence. Prior to any biofeedback training program, a definitive diagnostic study is essential. Idiopathic faecal incontinence is the main indication for biofeedback training. Additional indications are a menacing faecal incontinence after deep anterior rectal excision with restoration of the rectal reservoir by an ileoanal pouch, anal sphincter reconstruction, rectopexy and rectocele repair. Only four studies provide evidence-based medical criteria. These, as well as numerous uncontrolled studies, show the effectiveness of biofeedback training for the treatment of faecal incontinence. Electrical stimulation of the anal sphincter is only shown to be effective in one controlled study in which it was combined with biofeedback training.

Anal Canal↗

Concepts in pathogenesis and treatment of chronic anal fissure--a review of the literature.

OBJECTIVE: Chronic anal fissures are associated with a persistent hypertonia and spasm of the internal anal sphincter. Classic treatment is surgical sphincterotomy to reduce the anal tone and eliminate sphincteric spasm. However, concerns have been raised about the incidence of fecal incontinence after surgery. Therefore, pharmacological means to treat chronic anal fissures have been explored. METHODS: We conducted a literature review on MEDLINE database. RESULTS: All treatments address the anomaly of a high anal pressure. Several studies have investigated the effect of topical glyceryl trinitrate ointment. Healing rates range from 30% to 86%. Therapy is limited because of a high incidence of moderate to severe headaches in up to 84% of patients. Comparable results are observed after injection of botulinum toxin into the anal sphincter (43-96%). Minor incontinence for flatus and soiling has been reported in up to 12% of patients. Further pharmacological approaches including treatment via calcium channel blockade and treatment with alpha-adrenoceptor antagonists are still at a developmental stage. CONCLUSIONS: Topical glyceryl trinitrate ointment and injection of botulinum toxin into the anal sphincter are advocated as the first-line treatment for chronic anal fissure. Lateral sphincterotomy should be offered to patients with relapse and therapeutic failure of prior pharmacological treatment.

Administration, Topical↗

[Pouchitis--pathophysiology and therapy].

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.

Chronic Disease↗

Mucosal and invading bacteria in patients with inflammatory bowel disease compared with controls.

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.

Adolescent↗

Impairment of epithelial transport but not of barrier function in idiopathic pouchitis after ulcerative colitis.

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.

Adult↗

[Colon pouch as neorectum. Technique, indications and results].

Colon pouch as neorectum. Technique, indications and results.The possibilities to preserve the intestinal continuity after surgery for rectal cancer have remarkably improved. After straight coloanal anastomosis the problem of a high stool frequency together with urgency was frequently to observe. The introduction of the colonic J-Pouch improved the functional outcome of rectal cancer-surgery very much. In a review of the literature the stool-frequency after one year was 0.5-4 bowel movements per day compared to 0.5-10 per day after straight coloanal anastomosis. Urgency was as well reduced. The parameter of urgency can be best expressed by measuring the urgency volume in balloon-volumetry. Here the volume for J-Pouch was 75 ml compared to 50 ml in straight coloanal anastomosis. At the beginning of colonic J-pouch-surgery evacuation disorders were more frequent observable. Clinical and experimental studies could demonstrate that a big pouch-size caused this problem. Since a pouch-length of 6 cm is used evacuation disorders are very rare. The improved perfusion of the side-to-end anastomosis in pouch-anastomosis reduces the rate of anastomotic leakage's (pouch 1.9 % vs. coloanal anastomosis 15.2 %). In published retrospective studies the oncological outcome is completely comparable to straight coloanal anastomosis. In the case of technical impossibility of J-pouch formation the ileocecal interponant is a possible alternative. This procedure has the same functional outcome.

Anal Canal↗

New aspects of surgical therapy of recurrent Crohn's disease.

Crohn's disease can neither be cured by surgery nor by medical therapy. Surgical therapy of recurrent Crohn's disease requires special precautions. The recurrence rate is 60% after 15 years. There are no certain data of the risk factors influencing the recurrence rate. The only clear facts are that wide resection out of the resection margins and smoking negatively influence recurrence. Hence, the major principles of therapy is a minimally-resected surgery. This mainly concerns strictures and stenosis. Strictures should be treated by stricturoplasty and stenosis by limited resection with Crohn-free resection margins. Just in case of interenteric and enterocutanous with a concomitant short bowel syndrome, in blind-ending fistulas with an abscess or in enterovesical fistulas, we recommend immediate operation. The therapy of recurrent anorectal Crohn's disease underlies the same rules as primary therapy. If necessary, proctectomy remains the last option. Also, emergency surgery in recurrent Crohn's disease follows the same rules as in elective surgery.

Crohn Disease↗

Manometric analysis of anal sphincter damage after ileal pouch-anal anastomosis.

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.

Adenomatous Polyposis Coli↗