Background: Ten to 15% of patients with pouchitis experience refractory or recurrent disease. The aim of this study was to evaluate the effectiveness of a single daily high dose probiotic preparation (VSL#3) in maintaining antibiotic induced remission, and quality of life (QOL), for one year in such patients. Methods: Patients with pouchitis at least twice in the previous year or requiring continuous antibiotics, associated with a pouchitis disease activity index (PDAI) >7 (0 = perfect; 18 = worst), in whom remission was induced by four weeks of combined metronidazole and ciprofloxacin, were randomised to receive VSL#3 6 g or placebo once daily for one year or until relapse. Symptomatic, endoscopic, and histological evaluations were made before, and two and 12 months after randomisation or at the time of relapse. Remission was defined as a clinical PDAI (2 and endoscopic PDAI (1. Relapse was defined as an increased clinical PDAI score >2 and increased endoscopic PDAI score >3. QOL was assessed using the inflammatory bowel disease questionnaire (IBDQ). Results: Thirty six patients were randomised: 20 to VSL#3 and 16 to placebo. Remission was maintained at one year in 17 patients (85%) on VSL#3 and in one patient (6%) on placebo (p,0.0001). The IBDQ score remained high in the VSL#3 group (p = 0.3) but deteriorated in the placebo group (p = 0.0005). Conclusion: The once daily high dose probiotic VSL#3 is effective in maintaining antibiotic introduced remission for at least a year in patients with recurrent or refractory pouchitis. This is associated with a high level of quality of life.

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Background: Preliminary data suggest that short‐term antibiotic therapy with a single drug is effective for the treatment of patients with pouchitis. However, some patients are resistant to treatment. Aim: To evaluate the therapeutic efficacy of a prolonged course of a combination of two antibiotics in patients with refractory or recurrent pouchitis, as well as its impact on their quality of life. Methods: Patients with active refractory or recurrent pouchitis were recruited. This was defined as both: (i) a history of pouchitis at least twice in the last 12 months or persistent pouchitis requiring continual intake of antibiotics; and (ii) a Pouchitis Disease Activity Index score 3 7 (best to worst pouchitis=0–18) at the beginning of therapy. Treatment consisted of a combination of metronidazole, 400 or 500 mg twice daily, and ciprofloxacin, 500 mg twice daily, for 28 days. Symptomatic, endoscopic and histological evaluations were undertaken before and after antibiotic therapy using the Pouchitis Disease Activity Index score. Remission was defined as a combination of a Pouchitis Disease Activity Index clinical score of  2, endoscopic score of  1 and total score of  4. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire, which encompasses bowel, systemic and emotional symptoms as well as social function (worst to best=32–224). Results: Forty‐four patients (24 male, 20 female; median age, 37.5 years) entered the trial and completed treatment. Thirty‐six (82%) went into remission. The median Pouchitis Disease Activity Index scores before and after therapy were 12 (range, 8–17) and 3 (range, 1–10), respectively (P < 0.0001). The median Inflammatory Bowel Disease Questionnaire score also significantly improved from 96.5 (range, 74–183) to 175 (range, 76–215) with this therapy (P < 0.0001). The eight patients (five male, three female) who did not go into remission were significantly older (median 47.5 vs. 35 years; P=0.007), had a longer history of pouchitis (95.5 vs. 26 months; P=0.0008), had a greater proportion with chronic pouchitis (chronic/relapsing: 6/2 vs. 9/27; relative risk, 1.6; 95% confidence interval, 1.0–2.4) and tended to have a higher Pouchitis Disease Activity Index score before treatment (median 14.5 vs. 12; P=0.13) than those who went into remission. Even in these eight patients, the median Pouchitis Disease Activity Index score significantly improved from 14.5 (range, 8–16) to 9.5 (range, 7–10) (P=0.0078), as did the Inflammatory Bowel Disease Questionnaire score from 95.5 (range, 74–134) to 127 (range, 76–187) (P=0.039). The Inflammatory Bowel Disease Questionnaire score strongly correlated with the Pouchitis Disease Activity Index score (r=0.79, P < 0.0001), and was significantly related to the patients' overall assessment of satisfaction (P < 0.0001). No serious side‐effects were noted. Conclusions: Four‐week treatment with a combination of metronidazole and ciprofloxacin is highly effective in patients with active recurrent or refractory pouchitis, objectively impro...

SUMMARYThe clinical history and histological features of seven cases of granulomatous mastitis are presented. The lesion occurs in young parous women as a tender extra-areolar breast lump. Histologically, non-caseating discrete granulomas are present, confined to breast lobules with, in three cases, coalescence of the granulomas and microabscess formation. Pathogenesis of the changes is discussed. It is thought that granulomatous mastitis is an entity morphologically distinct from duct ectasia/plasma cell mastitis and the commoner forms of granulomatous breast diseases.

Between November 1976 and December 1985, 110 patients had restorative proctocolectomy for ulcerative colitis. The histological appearances in the reservoir mucosa were followed up in 60 of 109 survivors over 19-173 months (median 97). The median number of biopsy specimens taken per patient was six with a range of 3-13. These were examined by one pathologist (ICT) unaware of the clinical details using a scoring system previously described to assess the degree of chronic and acute inflammation. There was a significant correlation between the degree of severity of chronic and acute changes (r=0-6192, p<0000001). There was no correlation between the severity of inflammation and the following variables: preoperative duration ofdisease, presence of cancer or dysplasia in the original operative specimen, extra-alimentary manifestations or the type of reservoir. A significant correlation between severe inflammation and male sex was found (p<0.035). The 60 patients could be divided into three groups based on the severity and fluctuation of histological inflammation. In group A (n=27, 450/o) chronic changes were minor and acute inflammation was never seen. In group B (n=25, 42%) chronic changes were more severe and there were transient episodes of acute inflammation. In group C (n=8, 13%) severe chronic and severe acute inflammation were constantly present.

The histological appearances of the liver damage occurring after a paracetamol overdose are described in liver biopsies from 104 patients, of whom 38 developed fulminant hepatic failure. Confluent centrilobular necrosis of varying extent was followed by rapid disappearance of necrotic cells, leaving areas of reticulin collapse and a usually mild inflammatory reaction. The histological recovery in even the most severe cases was remarkable, and only one of the 17 survivors whose initial biopsy showed the pattern of interlobular bridging necrosis had appreciable residual fibrosis in a follow-up biopsy taken after 1 yr. A quantitative estimate was made of the amount of surviving liver parenchyma using a morphometric technique and the hepatocyte volume fraction (HVF) in biopsies performed within 10 days of the overdose correlated well with the clinical course and both the maximal prolongation of the prothrombin time and the peak plasma bilirubin concentration in the first 10 days. An HVF value (normal 85 +/- 5 per cent.) of less than 40 per cent. in a biopsy taken within 10 days of the overdose was found only in patients who died. However, HVF measurements on biopsies from three survivors taken later than 10 days after the overdose shows that survival is possible below this critical level.

The results of treatment and outcome in 52 consecutive patients presenting to Leicester from 1972 to 1984 are presented. The number of patients diagnosed increased from two per year before the introduction of duodenoscopy to nearly five per year afterwards. Endoscopic drainage (ED) was attempted in 21 patients with a success rate of 81 per cent. In eight cases ED was used pre-operatively and in the remainder as definitive treatment. Twenty-four patients had a Whipple's resection (12.5 per cent mortality), four patients had a local resection (no deaths), ten patients had surgical bypass (60 per cent mortality) and thirteen patients had ED alone (23 per cent mortality). The major risk factor score was significantly greater in patients undergoing surgical bypass compared with Whipple's resection. Age and risk factor scores were significantly greater in patients who had ED drainage alone than in surgical patients. The 5 year survival rate for resection was 56 per cent versus 13 per cent for drainage procedures (P less than 0.001). Survival in resection cases was directly related to the degree of tumour differentiation and a new staging system. It is proposed that all patients with ampullary tumours should have endoscopic biopsy followed by ED; Whipple's resection remains the surgical treatment of choice.

Aims-To investigate the association between immunohistochemical expression of Bcl-2 and p53 in colorectal cancer and tumour recurrence following surgery. Methods-Sixty six cases of Dukes' B colorectal carcinoma were studied. All tumours were moderately diVerentiated and were shown to be histologically clear of the resection margins. Immunohistochemistry was performed on formalin fixed paraYn wax embedded tissue using monoclonal antibodies for p53 and Bcl-2. The Bcl-2 staining was assessed separately for relative intensity of staining and percentage of positive tumour cells and given a final score which combined the two factors. The p53 staining was assessed on number of positive tumour cells only. The patterns of immunostaining of those cases in which there had been tumour recurrence were compared with those cases in which there was no tumour recurrence (controls). Results-A statistically significant inverse association was found between Bcl-2 score and tumour recurrence (median Bcl-2 score of 6 (interquartile range (IQR) 2-9) in patients with recurrent disease; median Bcl-2 score of 8 (IQR 6-10) in those without recurrence; p=0.03). When examined separately, both the intensity of expression and percentage of positive tumour cells were significantly associated with tumour recurrence (p=0.04 in each case). There was no association between p53 staining and tumour recurrence. Conclusion-Results suggest that, when controlled for diVerentiation, Bcl-2 expression is a prognostic marker and may be useful as an adjunctive test in clinical decision making. (Gut 1998;43:383-387)