Mycobacteria and subgroups of patients in Crohn's disease.

Some recent studies have proposed a subclassification of Crohn's Disease (CD) on the basis of the pathological picture. In fact CD is a heterogeneous disease, and it is probable that the clinical and pathological disorders we now consider as CD may in the near future be divided into several conditions, probably with different causes as well, including environmental factors. Clinical and pathological similarities to mycobacterial disease, along with recent isolation of mycobacteria from tissues taken from patients with CD, and the recognition of atypical mycobacteria as causative agents of an enteritis pathologically similar to CD, all go to strengthen the hypothesis that these organisms are one of the above environmental factors. Researchers should therefore seek to identify and characterize this subgroup of CD patients who may have mycobacterial disease and to perform trials of antimycobacterial therapy. Analysis of the literature gives some suggestions for identifying this subgroup of patients: i) isolation of atypical mycobacteria from the tissues; ii) presence of high specific antibody levels and increase of same after antimycobacterial therapy; iii) presence of granulomas, and iv) strong suspicion of an environmental factor.     

Antibodies to Mycobacterium paratuberculosis-specific protein antigens in Crohn''s disease.

The possible role of infection with Mycobacterium paratuberculosis (MAP) for the etiopathogenesis of Crohn's disease (CD) has been a matter of long-term controversy. In addition to similarities with the pathology of ruminant paratuberculosis, DNA fingerprinting confirmed the organism isolated from gut tissue, but the specificity of the immune repertoire has not as yet been evaluated. We report here on a serological study of 29 patients with CD, 20 patients with ulcerative colitis and 18 healthy control subjects, using three antigens attributed with species-specificity and selective immunogenicity following MAP infection. Antibodies binding to the 38-kD band of MAP extract were demonstrable by the Western blot technique in 57% of CD patients. Antibody levels to the 24-kD (p24BCD) cathodic bands, determined by competition ELISA using a monospecific murine antiserum, and to the 18-kD protease-resistant purified bacterioferritin, detected by standard ELISA, were significantly elevated in 53% of CD patients. However, these three antibody specificities tested in individual CD patients did not show any correlation with each other. Thus, 18% of patients were positive for all three specificities, whilst 84% had antibodies to at least one of the specific antigens. Although the exact proportion of affected patients is yet to be defined, the serological results obtained support the view that MAP infection may play an etiological role in Crohn's disease.     

Analysis of clinical course of postoperative recurrence in Crohn's Disease of distal ileum

In the present study we have investigated whether in patients with Crohn's Disease the clinical course remains the same from the initial disease to postoperative recurrent disease. Fifty-eight resected patients who developed a postoperative recurrence were followed for 4.2±3 years (median 3 years). The yearly frequency of flare-up was 1.9±1.0 (median 1.5) in the initial disease and 1.7±1.0 (median 1.7) in recurrent disease. In patients who experienced complications during the initial disease, the frequency of complications during the course of recurrent disease was significantly higher than in the others (27/42 vs 3/16,P=0.002). The frequency of obstruction and extraintestinal manifestations in the recurrent disease was higher in patients who suffered these complications in the initial disease than in those who did not (19/29 vs 6/29,P=0.0006, and 4/5 vs 4/53,P=0.0008). The cumulative probability of complication during the course of recurrent disease was higher in patients with complications during the initial disease (P<0.001). The survival analysis showed that the cumulative probability of obstruction and extraintestinal complication in recurrent disease was higher in patients who suffered these complications in the initial disease (P<0.005). These data indicate that the clinical course of Crohn's disease of the distal ileum remains the same from the initial disease to postoperative recurrent disease. This study also suggests that the short-term course of recurrent disease can reasonably be predicted.This work was supported in part by a grant from the University of Rome La Sapienza (85/280/02.12.01.28).     

Does stapled functional end-to-end anastomosis affect recurrence of Crohn's disease after ileocolonic resection?

BACKGROUND/AIMS: Crohn's disease is characterized by a high incidence of perianastomotic recurrence after ileocolonic resection. The influence of anastomotic configuration on the incidence of reoperation was evaluated in patients undergoing resection for Crohn's disease. METHODOLOGY: 106 patients affected by ileocolonic Crohn's disease were divided in two groups: group I with a hand-sewn end-to-side or side-to-side isoperistaltic anastomosis (30 patients) and group II with functional end-to-end anastomosis made with linear staplers (76 patients). RESULTS: The morbidity was 4.7%: 3 complications and a postoperative death occurred in group I and two complications occurred in group II. There were 5 recurrences (16.7%) in the hand-sewn group and 2 recurrences (2.6%) in the stapled group, with a recurrence rate of 3.54 and 0.92, respectively. CONCLUSIONS: Our non-randomized study suggests a better trend toward the functional stapled technique, in terms of recurrence rate. These observations need further investigation with randomized controlled trials, to compare the two different anastomotic procedures.     

Anti-tumour necrosis factor alpha (Infliximab) in the treatment of severe ulcerative colitis: result of an open study on 13 patients

BACKGROUND: Conventional treatment options for patients with severe steroid-refractory ulcerative colitis include intravenous cyclosporine, which is frequently burdened by toxicity, or colectomy. Preliminary data suggest a benefit from anti-tumour necrosis factor alpha (Infliximab) therapy in patients with steroid refractory ulcerative colitis. AIM: To evaluate the efficacy of Infliximab in the treatment of severe ulcerative colitis refractory to conventional therapy PATIENTS AND METHODS: A series of 13 patients with severe ulcerative colitis, refractory to therapy with methyl-prednisolone, 60 mg daily for seven or more days, were treated with a single intravenous infusion of Infliximab 5 mg/kg. RESULTS AND CONCLUSIONS: Of these 13 patients, 10 (77%) had a clinical response to therapy defined by a clinical activity index 10 on two consecutive days. In 2 patients (15%) total colectomy was necessary on account of clinical worsening whilst one patient refused surgery and was lost to follow-up. All patients who responded showed very rapid clinical improvement, within 2 to 3 days of infusion. Infusion with Infliximab produced no significant adverse events. The mean time of follow-up was 10.1 months (range 5-12; during this time, 9 out of 10 patients (90%) maintained clinical remission and were able to discontinue corticosteroid therapy. Infliximab appears to be an effective agent for inducing long-standing remission in refractory patients with severe ulcerative colitis.     

Reversible sustained increase of gastrin and gastric acid secretion in a subgroup of duodenal ulcer patients on long-term treatment with H2 antagonists.

We assessed the effect of long-lasting inhibition of gastric acid secretion on basal and meal-stimulated serum gastrin and gastric acid secretion in 37 patients on long-term maintenance treatment with H2 antagonists for severe relapsing and/or complicated duodenal ulcer disease. After a mean of 142 weeks (range, 28-324 weeks) of continuous treatment, gastric acid secretion, basal plasma gastrin, and gastrin response to a test meal were evaluated. All tests were performed a week after drug discontinuation to exclude rapidly reversible hypergastrinemia. Gastrin levels were above the normal range in seven patients (18.9%). After H2 antagonist were stopped for 6 weeks, basal gastrin returned to normal levels in all cases [from a median of 180 (range, 130-350) pg/ml to 58 (25-90) pg/ml] and peak meal-stimulated gastrin significantly decreased from a median of 500 pg/ml to 245 pg/ml (p = 0.02). In patients with hypergastrinemia, the discontinuation of H2 antagonists for 6 weeks led to a significant decrease of gastric acid secretion. Patients who developed hypergastrinemia spent more weeks on full-dose treatment and had more recurrences during therapy. The results of the present investigation demonstrate that a long-lasting inhibition of gastric acid secretion can induce, in a small percentage of patients, a reversible sustained hypergastrinemia and a consequent increase of acid secretion, which conceivably could lead to more frequent relapses of duodenal ulcer disease.     

The plain abdominal film accurately estimates extent of active ulcerative colitis

The aim of our study was to establish whether plain abdominal film can accurately assess the extent of active ulcerative colitis. Ninety-seven ulcerative colitis patients were studied, in whom the extent of the macroscopic lesion was established either by colonoscopy (n = 75) or by resection (n = 22). Of these, 42 had proctosigmoiditis, 12 left-sided colitis, 12 subtotal colitis, and 31 total colitis. Nine well-tested features were used for the radiological classification of lesion extent. The radiologists were not given any clinical information. Seventy-eight patients (80.4%) were correctly classified by plain abdominal film (r = 0.86); the best concordance was achieved for proctosigmoiditis and total colitis (80.9 and 90.3%, respectively). In total colitis the most reliable radiological features were "irregularity of the mucosal edge" and "increased thickness of the colon wall, " which were present in 74.2 and 67.7%, respectively, of the correctly classified patients. The fourfold combination of these two features with "loss of haustral clefts" and "empty right colon" was present only in patients with total colitis, and at least one of these features was present in all but one of them. Conversely, all nine abnormalities were absent in 73.8% of patients with proctosigmoiditis. In conclusion, plain abdominal film is a reliable tool for judging the extent of lesion in active ulcerative colitis. It seems particularly accurate in total colitis, where, in the acute phases, it is most important to avoid invasive examinations.     

Current treatment for prevention of relapse and recurrence in Crohn's disease

Maintenance of remission induced by medical therapy and prevention of recurrence after intestinal resection are two of the major goals in Crohn's disease treatment. Two main groups of drugs are employed in prevention of relapse and recurrence: sulfasalazine and 5-aminosalicylic derivatives and the group of azathioprine/6-mercaptopurine. Although most clinical trials on the efficacy of sulfasalazine as maintenance therapy of Crohn's disease have given negative results, it could probably be favourably used in remission maintenance of Crohn's colitis. Controlled studies and two reviews have shown that 5-aminosalicylic derivatives are effective in reducing the risk of relapse. Ileitis and ileocolitis respond better than colitis. These drugs are also able to reduce the severity of lesions and of symptoms after surgery. 6-mercaptopurine and azathioprine can be used in more aggressive forms of the disease. The efficacy of this immuno-suppressive therapy is reported in over 70% of patients and the incidence of associated side effects is acceptable, but 6-mercaptopurine and azathioprine act slowly and the long latency period limits the usefulness of these drugs in some patients.