Ileal pouches: adaptation and inflammation.

Ileal pouch-anal anastomosis (IPAA) has become the operation of choice following proctocolectomy for ulcerative colitis (UC) and familial adenomatous polyposis. Functioning ileal pouch mucosa undergoes histological changes resembling the colon (colonic metaplasia). The possible role of stasis and luminal factors--bile acids, short-chain fatty acids and bacteria--are discussed. It seems likely that colonic metaplasia is an adaptive response to the new luminal environment in IPAA. Inflammation in the ileal reservoir ('pouchitis') is the most significant late complication in IPAA. It occurs in 20-30% of patients and is virtually confined to those with prior UC. The clinical picture in pouchitis is highly variable; however, it can be easily categorized into three groups. Nevertheless, in most cases it is likely to represent recurrent UC in the ileal pouch. Current treatments and possible preventative strategies for pouchitis have been outlined.

Ileal pouch dialysate is cytotoxic to epithelial cell lines, but not to CaCo-2 monolayers.

OBJECTIVE: All patients with ileal pouch-anal anastomosis (IPAA) have some degree of villous atrophy, mucin changes and chronic inflammation. The mechanism underlying these changes is unknown. This study investigates the hypothesis that luminal factor(s) may affect epithelial cells in in-vitro studies. DESIGN: IPAA dialysate from eight patients with prior ulcerative colitis was assessed. METHODS: The effect of the dialysate on epithelial cell (i-407, HT-29 and CaCo-2) proliferation (3H-thymidine incorporation) and cytotoxicity (51-chromium release) was determined. Bile acid(s) at concentrations measured in IPAA dialysate were assessed in isolation and in combination for cytotoxicity against CaCo-2 cells. The effect of dialysate and bile acids on immature and mature CaCo-2 monolayer cytotoxicity, transepithelial electrical resistance (TEER) and histology was investigated. RESULTS: IPAA dialysate is antiproliferative and cytotoxic to the cell lines. At concentrations present in dialysate chenodeoxycholic acid and deoxycholic acid were cytotoxic to CaCo-2 cells. IPAA dialysate was not cytotoxic to mature CaCo-2 cell monolayers. TEER was maintained across monolayers with dialysate but not with control Rheomacrodex (P = 0.02). Bile acids at concentrations present in dialysate were cytotoxic to monolayers. CONCLUSION: Ileal pouch dialysate is cytotoxic to epithelial cells due (in part) to bile acids. Bile acids in isolation are cytotoxic to both CaCo-2 cells and monolayers. Despite the presence of bile acid the dialysate is not cytotoxic to CaCo-2 monolayers and preserves epithelial resistance and histological structure.

Intestinal permeability in the ileal pouch.

BACKGROUND: Villous atrophy, mucin changes ('colonic metaplasia'), and chronic inflammation occur to varying degrees in all patients with ileal pouchanal anastomosis whereas acute inflammation (pouchitis) affects a subgroup of patients with prior ulcerative colitis. AIM: To measure epithelial barrier function looking for possible functional adaptation in ileal 'pouch' mucosa. PATIENTS: Patients with an ileal pouch prior to ileostomy closure (n = 12), functioning pouch (n = 14), pouchitis (n = 8), and ulcerative colitis (n = 12) were assessed. METHODS: 51Cr-EDTA was administered into the 'pouch' or rectum and urinary recovery over 24 hours was taken as an indication of permeability (barrier function). Histological analysis of 'pouch' biopsy specimens was undertaken. RESULTS: Mucosal permeability is decreased from median 9.4% (range 5.4% to 39.1%) to 1.4% (range 0.38% to 2.2%) after ileostomy closure (p < 0.002) with levels being negatively correlated with two histological parameters of colonic metaplasia-mucin changes (p = 0.03) and villous atrophy (p = 0.05). Pouchitis was associated with increased permeability 5.9% (1.9% to 19.5%) compared with healthy 'pouch' 1.4% (0.35 to 2.2%) (p < 0.006). CONCLUSION: Despite the presence of chronic inflammation in the mature 'pouch' functional adaptation with reduced permeability occurs in conjunction with colonic metaplasia.

Smoking may prevent pouchitis in patients with restorative proctocolectomy for ulcerative colitis.

Epidemiological studies have shown an increased risk of ulcerative colitis (UC) in non-smokers and particularly recent ex-smokers. Patients with UC have an increased risk of pouchitis following ileal pouch-anal anastomosis, which may be a manifestation of the original disease susceptibility. The aim of this study was to test the hypothesis that smoking habit may influence the incidence of pouchitis. All patients with a functioning pouch > or = 12 months at one centre were assessed. Patients were excluded if (a) the original indication was not UC (n = 5), (b) the excised pouch showed histology diagnostic of Crohn's disease (n = 2), and (c) data were inadequate (n = 4). Smoking data were collected by questionnaire, or direct interview, or both. Ex-smokers were those who had stopped smoking < 7 years before colectomy. Non-smokers included ex-smokers who had stopped > 7 years before colectomy. Pouchitis was defined as an increase in stool frequency > 8/day with acute inflammation on biopsy specimen histology. Each presentation requiring treatment was regarded as an episode. For comparison smoking habit was assessed with regard to three other adverse outcomes - haemorrhage, sepsis, and pouch excision. Of 72 non-smokers (mean follow up 3.5 years) 18 had 46 episodes of pouchitis. Of 12 ex-smokers (mean follow up 3.3 years) four patients have had 14 episodes of pouchitis. Only one smoker from 17 has had a single episode of pouchitis. This shows that smokers have significantly less episodes of pouchitis compared with non-smokers (p = 0.0005) and ex-smokers (p = 0.05). There was no association of smoking habit with other adverse outcomes.

5-Aminosalicylic acid inhibits the impaired epithelial barrier function induced by gamma interferon.

Gamma interferon (IFN gamma) impairs epithelial barrier function and induces HLA-DR expression on colonic cancer cell lines. Salicylates have been shown to reduce IFN gamma induced HLA-DR expression. The effect of 5-aminosalicylic acid (5-ASA) on IFN gamma induced changes in transepithelial resistance and permeability was investigated in HT29 clone 19A and Caco 2 monolayers. Monolayers were incubated with different concentrations of IFN gamma (100, 500, 1000, and 3000 U/ml) and 5-ASA. IFN gamma induced class II expression in a time and dose dependent manner in HT29:19A but not Caco 2 cells. HT29:19A monolayers incubated with both IFN gamma and 5-ASA showed lower HLA-DR expression compared with monolayers incubated with IFN gamma alone. Electrical resistance and 14C-mannitol flux across HT29:19A monolayers were significantly changed by IFN gamma. Addition of both IFN gamma and 5-ASA to the basolateral surface of the monolayers significantly reduced paracellular permeability compared with addition of IFN gamma alone. These data show that IFN gamma is able to induce HLA-DR expression and to impair the barrier function of HT29:19A monolayers, and that 5-ASA reduces IFN gamma induced HLA-DR expression and inhibits the effects of IFN gamma on epithelial barrier function.

Expression of colonic antigens by goblet and columnar epithelial cells in ileal pouch mucosa: their association with inflammatory change and faecal stasis.

AIMS: To investigate colonic metaplasia of goblet and columnar epithelial cells in ileal pouch mucosa; to correlate this with the degree of morphological and inflammatory change; and to assess whether such changes are related to the presence of faecal stasis. METHODS: Biopsy specimens of ileal pouch mucosa were taken from 31 patients (30 with ulcerative colitis, one with familial adenomatous polyposis) either before (eight patients) or after (23 patients) ileostomy closure. A simple morphological technique was used to assess changes in villous height. Inflammatory change was estimated using an established scoring system for pouchitis, and acquisition of colonic antigens was determined by immunohistochemistry using three monoclonal antibodies which recognise components of the two major epithelial cell types in the colorectum. The degree of staining with the monoclonal antibodies was graded and the grades correlated with an index of villous atrophy and with the inflammatory scores. RESULTS: Five of eight (63%) pre-closure and 15 of 23 (65%) post-closure biopsy specimens showed increased staining with an antibody against components of columnar epithelial cells. One of eight (12%) pre-closure and 15 of 23 (65%) post-closure biopsy specimens stained with an antibody for colonic mucin. Although both types of staining showed a positive correlation with the pouchitis score, they also occurred in the absence of inflammation. CONCLUSIONS: Both goblet and columnar cells acquire colonic characteristics which are incomplete, but may represent a true adaptive response as they can develop in the absence of inflammation. As the change in goblet cells occurs after ileostomy closure, faecal stasis is likely to be a major contributory factor. Changes in columnar cells may occur before ileostomy closure in the absence of faecal stasis.

Cyclosporin A retention enemas in refractory distal ulcerative colitis and 'pouchitis'.

The aim of this study was to evaluate the use of cyclosporin enemas in patients with distal ulcerative colitis and 'pouchitis' resistant to all conventional medical therapy. In an trial 12 patients with distal ulcerative colitis unresponsive to treatment with topical and oral corticosteroids, 5-aminosalicylic acid, and oral immunosuppressive therapy together with 1 patient with 'pouchitis' unresponsive to repeated courses of antibiotics, topical corticosteroids, and oral mesalazine received 250 mg cyclosporin administered daily as a retention enema. Changes in symptoms and the sigmoidoscopic/histologic appearances of the rectal mucosa were assessed at monthly intervals. Seven of 12 patients with ulcerative colitis improved. There was a strong correlation between clinical and histologic improvement (p < 0.005). Four of 12 patients showed no response. Three of these required colectomy, two of whom had more extensive disease than had previously been documented. The patient with pouchitis showed improvement in symptoms and 'pouchoscopy' appearance but not in histologic score. Cyclosporin blood concentrations were very low and side effects negligible. Cyclosporin A retention enemas are safe and may be useful in the treatment of severe refractory distal ulcerative colitis. A controlled trial would now seem warranted.

Watermelon stomach: an unusual cause of chronic gastrointestinal blood loss.

Watermelon stomach, or gastric antral vascular ectasia, is an uncommon cause of gastrointestinal blood loss, which can easily be overlooked and which is eminently curable. A 76 year old woman who was repeatedly misdiagnosed as having incidental antral gastritis with occult iron deficiency is described.

Extracorporeal shock wave lithotripsy for bile duct stones: an Australian experience.

Choledocholithiasis requires prompt therapy, particularly if complicated by ascending cholangitis. Endoscopic sphincterotomy with balloon and basket extraction clears the bile duct in 90% of patients. Failure is usually associated with large stones, that is, greater than 2 cm. Until recently such patients would have required surgical intervention. In 1986 St Vincent's Hospital installed a Dornier HM3 Lithotriptor to be used for both urinary tract and bile duct calculi. A retrospective analysis of patients referred for extracorporeal shock wave lithotripsy (ESWL) to bile duct stones was performed. There were 47 patients (28 female, 19 male) with an average age of 76 years. Twenty-two patients had a single stone with a mean diameter of 2.4 cm and 25 had multiple stones. In two patients the stone was not able to be visualized, so ESWL could not be performed. Complete stone clearance was achieved without further intervention in 13 patients, and in a further 23 after endoscopic extraction of fragments. In five patients only partial duct clearance was achieved. However, this provided palliation and enabled the patient to be discharged. Surgical intervention was required in the remaining four cases. Overall success rate was 80% with a further 11% being palliated with improved biliary drainage. There were no serious adverse effects from ESWL. All patients were discharged from hospital. Mortality at 30 days was 4.7% and at 6 months was 19.4%. One patient succumbed to ascending cholangitis 22 weeks post-ESWL (2.7%). All other deaths were unrelated to ESWL or biliary disease. We conclude that ESWL is a safe and effective treatment for bile duct stones not amenable to endoscopic extraction.

Orange/black discolouration of the bowel (at laparotomy) due to clofazimine.

Clofazimine, a commonly used anti-lepromatous drug, is now being prescribed for the treatment of pyoderma gangrenosum, a complication of inflammatory bowel disease. This drug can cause an obstructive exacerbation of Crohn's disease. Surgeons should be aware of the orange/black discolouration of the bowel, which may mimic ischaemia macroscopically. A case, the first reported in Australia, is described and the literature discussed.