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Restorative proctocolectomy with ileo-pouch-anal anastomosis is the standard procedure for ulcerative colitis. It provides complete removal of the diseased colorectum, avoids permanent ileostomy and allows the preservation of continence. Functional results and quality of life after restorative proctocolectomy are of great importance. Patients usually have 5-6 bowel movements per day, and continence is satisfactory in more than 90% of patients. A good pouch function strongly correlates with high quality of life. Postoperative septic complications are the main risk factor for bad pouch function and pouch failure; therefore nowadays most procedures are performed with a covering ileostomy. Quality of life is usually impaired by active ulcerative colitis, and restorative proctocolectomy improves the quality of life up to the level of a healthy reference population. Taken together, restorative proctocolectomy provides excellent results concerning function and quality of life.

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The intestinal epithelium constitutes a first line of defense of the innate immune system. Epithelial dysfunction is a hallmark of intestinal disorders such as inflammatory bowel diseases (IBDs). The actin cytoskeleton controls epithelial barrier integrity but the function of actin regulators such as cortactin is poorly understood. Given that cortactin controls endothelial permeability, we hypothesized that cortactin is also important for epithelial barrier regulation. We found increased permeability in the colon of cortactin-KO mice that was accompanied by reduced levels of ZO-1, claudin-1, and E-cadherin. By contrast, claudin-2 was upregulated. Cortactin deficiency increased RhoA/ROCK1-dependent actomyosin contractility, and inhibition of ROCK1 rescued the barrier defect. Interestingly, cortactin deficiency caused increased epithelial proliferation without affecting apoptosis. KO mice did not develop spontaneous colitis, but were more susceptible to dextran sulfate sodium colitis and showed severe colon tissue damage and edema formation. KO mice with colitis displayed strong mucus deposition and goblet cell depletion. In healthy human colon tissues, cortactin co-localized with ZO-1 at epithelial cell contacts. In IBDs patients, we observed decreased cortactin levels and loss of co-localization with ZO-1. Thus, cortactin is a master regulator of intestinal epithelial barrier integrity in vivo and could serve as a suitable target for pharmacological intervention in IBDs.

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BACKGROUND: To evaluate the efficacy of the over-the-scope clip (OTSC(®)) proctology set for the closure of refractory anal fistulas. METHODS: This retrospective single-center study included all consecutive patients undergoing an OTSC(®) proctology closure of anal fistulas between October 2012 and June 2014. The OTSC(®) was only used in refractory cases after previous fistula surgery, including patients with Crohn's disease, or multiple previous surgical approaches. RESULTS: There were ten patients (five males and five females) with a median age of 41 years (range 26-69 years). The etiology of the fistula was cryptoglandular in four patients, and perianal Crohn's disease in six patients (including one patient with an anovaginal fistula). The surgical procedure was technically successful in all patients. Permanent fistula closure was achieved in seven out of ten patients (70 %) within a median time of 72 days (range 31-109 days). Median total follow-up time was 230.5 days (range 156-523 days). There were three failures (30 %), including two cryptoglandular and one Crohn's disease-associated fistula. In all three cases, the OTSC(®) was lost spontaneously on days 22, 23, and 40, respectively. In three of the seven patients with successful closure, the OTSC(®) was removed after complete healing of the fistula. CONCLUSIONS: The novel OTSC(®) proctology system is a safe and effective method for the closure of even complex and recurrent fistulas.

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The demographic development leads to an increase of elderly patients (> 70 years) who require surgical interventions. Nowadays, even complex surgical interventions are performed with good results in very old patients. In view of an increasing life expectancy, radical oncological surgery makes sense even in high age. High age itself is not a risk factor for perioperative morbidity and mortality, and therefore there is no age limit for surgical interventions. However, comorbidities are more frequent in old patients, and these can massively increase the risk of surgery. Thus, for the individual patient, pros and cons of surgical interventions have to be weighed up. A specialised geriatric assessment and an optimal perioperative management of the old patient can improve the results of surgical therapy.

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BACKGROUND: Tight junction (TJ) proteins play a critical role in cellular adhesion, glandular differentiation, and cellular proliferation. The function of these proteins is compromised in a number of intestinal diseases, including ulcerative colitis that has an increased incidence for colorectal carcinoma (CAC). The aim of this study was to determine the expression of TJ proteins, claudin-1-4, occludin, ZO-1, and the adherens junction (AJ) protein beta-catenin in CAC. METHODS: Sixteen colectomy specimens with CAC, adjoining intraepithelial neoplasia, and normal mucosa were studied by immunofluorescence. A semiquantitative evaluation of all investigated proteins was performed by scoring the staining intensity, and the TJ and AJ protein expression in neoplastic cells was compared to normal and intraepithelial neoplastic colonic mucosa. RESULTS: Using an intensity scoring system, mucosa of crypts and surfaces of CAC exhibited significantly elevated expression levels of claudin-1, claudin-3, claudin-4, and beta-catenin compared to intraepithelial neoplasia and normal mucosa (p<0.05). These data were confirmed by a comparative score. The expression of claudin-2, occludin, and ZO-1 showed no differences between the groups. CONCLUSION: TJ proteins claudin-1, claudin-3, claudin-4, and the AJ protein beta-catenin are overexpressed in CAC. This suggests that these proteins may become potential markers and targets in CAC.

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Recent clinical trials of the gum resin of Boswellia serrata have shown promising results in patients with ulcerative colitis. The objective of this study was to determine whether a semisynthetic form of acetyl-11-keto-beta-boswellic acid (sAKBA), the most potent anti-inflammatory component of the resin, also confers protection in experimental murine colitis induced by dextran sodium sulfate (DSS) to compare its effects with those standard medications of ulcerative colitis like steroids and to examine whether leukocyte-endothelial cell adhesion is a major target of action of sAKBA. Clinical measurements of disease activity and histology were used to assess disease progression, and intravital microscopy was employed to monitor the adhesion of leukocytes and platelets in postcapillary venules of the inflamed colon. sAKBA treatment significantly blunted disease activity as assessed both grossly and by histology. Similarly, the recruitment of adherent leukocytes and platelets into inflamed colonic venules was profoundly reduced in mice treated with sAKBA. Because previous studies in the DSS model have shown that P-selectin mediates these blood cell-endothelial cell interactions, the expression of P-selectin in the colonic microcirculation was monitored using the dual-radiolabeled antibody technique. The treatment of established colitis with sAKBA largely prevented the P-selectin upregulation normally associated with DSS colitis. All of the protective responses observed with sAKBA were comparable to that realized in mice treated with a corticosteroid. Our findings demonstrated an anti-inflammatory effect of sAKBA and indicated that P-selectin-mediated recruitment of inflammatory cells is a major site of action for this novel anti-inflammatory agent.

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BACKGROUND: Recruitment of circulating cells to the inflamed intestine is modulated by adhesion molecules expressed on the surface of both leucocytes and endothelial cells. AIMS: The objective of this study was to test whether 2'-O-methoxyethyl chimeric antisense oligonucleotides directed against endothelial intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) can downregulate leucocyte-endothelial interactions and thereby attenuate inflammation in rat experimental ileitis. METHODS: Indomethacin (7.5 mg/kg ) was injected subcutaneously into Sprague-Dawley rats 48 and 24 hours prior to intravital microscopy. Animals were treated with either ICAM-1 (ISIS 17470), VCAM-1 (ISIS 18155), or scrambled control antisense oligonucleotides administered subcutaneously or intravenously in parallel with indomethacin. Leucocyte trafficking was observed in ileal submucosal collecting venules. Macroscopic and histological grades of inflammation were measured 48 hours after the first indomethacin application. ICAM-1 and VCAM-1 expression in ileal submucosal venules was detected by immunohistochemistry. RESULTS: Intravenous administration of ICAM-1 oligonucleotides 2 mg/kg (rolling leucocytes 5.7 (2.4)/0.01 mm(2) endothelial surface, adherent leucocytes 0.8 (1.1)) and VCAM-1 oligonucleotides 8 mg/kg (9.2 (4.4), 0.6 (0.8)) significantly reduced leucocyte adhesion compared with diseased controls (27.8 (5.3), 14 (4.4)) in a dose dependent manner whereas subcutaneous treatment did not. Correspondingly, macroscopic and histological inflammation was significantly decreased. ICAM-1 oligonucleotides markedly reduced endothelial ICAM-1 expression while VCAM-1 oligonucleotides clearly diminished endothelial VCAM-1 expression. CONCLUSIONS: Both ICAM-1 and VCAM-1 2'-O-methoxyethyl chimeric antisense oligonucleotides attenuate rat ileitis by downregulation of leucocyte adherence and thus are potential candidates for anti-inflammatory treatment in inflammatory bowel disease.

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The feasibility of anal dynamic graciloplasty (transposition of the gracilis muscle and subsequent implantation of a stimulation device) to restore continence, was assessed in a 71 year old patient. Anal dynamic graciloplasty was capable to achieve continence by increasing the sphincter tone from 35 mm Hg without stimulation to 110 mm Hg with stimulation. The clinical results and anal manometry data are described and the pros and cons of the procedure are discussed.

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Ulcerative colitis and familial adenomatous polyposis may be treated by proctocolectomy with ileal pouch reconstruction, anastomosing the pouch to the anus. We studied 24 patients who underwent this procedure, of whom 12 had ulcerative colitis and 12 had familial adenomatous polyposis. Ileal absorption was investigated and pouch histology assessed more than one year after closure of the protective defunctioning loop ileostomy. The results showed a reduction in bile acid reabsorption and vitamin B12 absorption. These observations were associated with a morphologic transformation in the small bowel mucosa to large bowel mucosa. In 10 of the 12 colitis patients one or more of the histological features of the original disease (such as active inflammation, increased regeneration, atypia) were evident. Histological examination of the biopsies taken from the polyposis patients showed areas with an excess of sialomucins.

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After the first successful laparoscopic closure of a perforated peptic ulcer in 1990, 13 consecutive patients with laparoscopic closure were compared to 8 previous patients with conventional surgery. The endpoints adverse advents (complications), pain intensity, fever, leucocytosis and hospital stay showed no clinically relevant differences. Consumption of analgesics was lower in the laparoscopy group. Laparoscopic closure of perforated peptic ulcer is technically feasible. The safety of the method and the benefit for the patient need proof by a randomized controlled trial.

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After low colo-rectal or colo-anal anastomosis there is in 25% a degree of urgency and increased bowel movements. In order to improve the reservoir continence the construction of a J-shaped colonic pouch seems reasonable. We have operated 5 patients with the new technique and worked up our preliminary results in connection with a literature overview. Increased bowel movements and urgency are reduced postoperatively but some patients report pouch evacuation problems, using enemas or suppositories to empty their reservoirs. To estimate the value of this new technique innovative endpoints as overall well-being and quality of life might be more important than conventional endpoints measuring only functional results.

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Two techniques for preparation of the colon for colonoscopy were compared in a controlled trial. Fifty patients given a low residue diet and the laxative Prepacol were compared with 50 patients given whole gut irrigation. Significantly more patients suffered from vomiting (P = 0.0005), shivering (P = 0.0062) and nausea (P = 0.031) following irrigation; in two cases the procedure had to be abandoned because of profuse vomiting. Irrigation was less well tolerated by the patients (P = 0.00002) than preparation with Prepacol. On the other hand, the quality of bowel preparation was found to be better (P = 0.0005) after irrigation. On two occasions colonoscopy was not possible following Prepacol preparation because of faecal residue. Patients with a previous colorectal resection showed a similar quality of cleansing to those patients prepared with irrigation. We conclude that Prepacol is as efficient as irrigation for patients who have had a previous colorectal resection because the quality of bowel preparation is as good and the associated patient discomfort is small.

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The term colitis suggests mucosal inflammation as the key event. However, it may be that the disease starts with mucosal hyperproliferation, and inflammation of the impaired mucosa is a succeeding event. Therefore we studied the activity of the intestinal diamine oxidase (DAO) in ulcerative colitis (UC). This enzyme was shown to have a mucosal antiproliferative function. Biopsy specimens of 30 patients having a normal rectosigmoidal mucosa showed a DAO activity of 22.8 nmol/min g. In 12 UC patients the DAO activity was 2.7 nmol/min g (p = 0.01). In 3 patients where UC was in remission the DAO activity was 103, 107 and 208 nmol/min g, indicating an antiproliferative rebound effect. Together with the strongly reduced monoamine oxidase (MAO) activity, the decrease in DAO activity indicates that the large bowel in UC is unable to produce a proliferation terminating substance (probably gamma-aminobutyrate) derived from polyamine metabolism by oxidative deamination (DAO) or by the interconversion pathway (MAO).

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After low colo-rectal anastomosis there is in 25% a degree of urgency and increased bowel movements. In order to improve the reservoir continence the construction of a J-shaped colonic pouch seems reasonable. We have operated 5 patients with the new technique and worked up our preliminary results in connection with a literature overview. Increased bowel movements and urgency are reduced postoperatively but some patients report pouch evacuation problems, using enemas or suppositories to empty their reservoirs. To estimate the value of this new technique innovative endpoints as overall well-being and quality of life might be more important than conventional endpoints measuring only functional results.

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Some mutagenic hydrazino compounds are also diamine oxidase inhibitors. Therefore, this interrelationship was studied for the intestinal carcinogen azoxymethane. In vitro, azoxymethane was a very weak inhibitor of rat intestinal diamine oxidase activity. In vivo, after subcutaneous injection of a single dose of azoxymethane, diamine oxidase activity was increased in the duodenum but was mainly inhibited in the colon. Intestinal diamine oxidase activity may then be influenced by regulatory processes induced by azoxymethane rather than by a direct effect.

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We have suggested previously that the histamine-diamine oxidase system is involved in cell proliferation. Therefore, the diamine oxidase activity and the histamine content were studied during mucosal proliferation induced by 70% resection of the small intestine of the rat with and without aminoguanidine (AG), a specific inhibitor of diamine oxidase (DAO). The DAO activity underwent a marked alteration during the period of mucosal proliferation, probably as an expression of an antiproliferative regulation mechanism. The histamine content decreased in the proliferating mucosa. No influence of AG on mucosal proliferation could be found, which might be due to a compensatory activity of the interconversion pathway.

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