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Notes: Ten cases of malignant lymphoma of the colon and rectum complicating chronic inflammatory bowel disease are presented. Seven patients had chronic ulcerative colitis with a history varying from 6 to 20 years. There was extensive colitis in six of these patients and left-sided colitis in one. All seven lymphomas showed the pathological and immunohistological features of primary B-cell tumours of the gastrointestinal tract with a predominance of high-grade tumours. Three patients had Crohn's disease of the large intestine complicated by malignant lymphoma of the sigmoid colon or rectum. The history of Crohn's disease varied from 30 months to 20 years and in each case there was fissuring and fistulae. There was extensive anal involvement in two cases. Histologically the three lymphomas were heterogeneous: one was of ‘granulomatous’ T-cell type and the other two were markedly polymorphic and of equivocal phenotype. They were also characterized by numerous multinucleate tumour giant cells. Primary colorectal malignant lymphoma should be regarded as a rare, but significant, complication of ulcerative colitis. Immunosup-pression may be an additional factor in the genesis of intestinal lymphoma in Crohn's disease. The prognosis appears to be dependent on factors already known to be of prognostic significance in primary gut lymphomas: a predominance of high-grade tumours suggests that the outlook is generally worse than that for idiopathic primary large intestinal lymphoma.

Notes: Six histopathologists allocated 100 sections from patients with long-standing ulcerative colitis into four diagnostic categories, regular hyperplasia, reactive atypia, low-grade and high-grade dysplasia. Their allocations were analysed using kappa statistics, including Fleiss's multiple kappa for groups of observers, and agreement on specific diagnoses was explored by constructing a conditional probability matrix. The nature of their disagreements was investigated using coefficients for systematic and haphazard errors. Over the four diagnostic categories there was a wide range of pairwise agreement from a low of 49% up to 72% and kappa values were only ‘fair’ or ‘moderate’. As expected, agreement over the two categories ‘dysplasia’vs‘no dysplasia’ was better, ranging from 68% to 84%, and for ‘atypia present’ (reactive atypia, low- and high-grade dysplasia) vs‘no atypia’ two pairings achieved over 90% and 11 pairings over 80% agreement. In view of its clinical importance, conditional agreement on high-grade dysplasia was examined. Given that a first observer allocates a case as high-grade dysplasia, pairwise agreement on this diagnosis ranged from 100% down to as low as 33%. However, most of these disagreements fell into the low-grade dysplasia category so that closer follow-up and further biopsies would still have been indicated. It is a truism that the basis for safe management is careful co-operation between clinicians and pathologists who have all the relevant facts and who know and trust one another's judgement. Thus, several aspects of the ideal diagnostic process cannot be evaluated in inter-observer studies and the element of artificiality should be borne in mind when applying the findings to diagnostic practice. Nevertheless, the low level of agreement on the diagnosis of high-grade dysplasia achieved by certain pairings of specialist pathologists is a disturbing outcome of this study. Inaccuracies should be minimized by a concensus approach and we therefore recommend referral of putative cases of dysplasia to interested pathologists for further opinions. We would also advocate that pathologists faced with appearances which are indefinite between reactive atypia and dysplasia, would do better to describe them in terms of ‘atypia, significance uncertain’, so that closer surveillance is undertaken, rather than force them into more precise diagnostic categories which may be incorrect.

Notes: Histological appearances indistinguishable from Crohn's disease have been described in patients undergoing sigmoid colectomy for complicated diverticular disease. To investigate whether this finding represents coincidental dual pathology or merely a granulomatous colitis confined to the diverticular segment, we undertook clinical follow-up of affected patients.〈section xml:id="abs1-2"〉〈title type="main"〉Methods and resultsEight patients (median age 64 years, four males) whose sigmoid colectomy specimens showed acute diverticulitis and granulomatous inflammation were identified. All had a pre-operative diagnosis of diverticular disease and no previous evidence of Crohn's disease. Non-caseating epithelioid granulomas, unrelated to foreign material and usually unrelated to inflamed diverticula were present in the bowel wall of seven cases and in the regional lymph nodes of five. Three had granulomatous vasculitis and two had granulomas in ‘background’ mucosa. Mural lymphoid aggregates were identified in all cases. However, fissuring ulcers distinct from inflamed diverticula were not identified. On median follow-up of 51 months (range 18–112 months) none of the patients developed evidence of chronic inflammatory bowel disease. Three had died from unrelated causes.〈section xml:id="abs1-3"〉〈title type="main"〉ConclusionsGranulomatous inflammation appears to be part of a spectrum of sigmoid diverticulitis. In this setting, caution should be exercised to avoid an inappropriate diagnosis of Crohn's disease.

Notes: Forty-five patients taking long-term indomethacin and with endoscopic erosions or superficial ulcers in the oesophagus, stomach or duodenal bulb were randomized in a double-blind study to continue with standard indomethacin or receive a ‘delayed-release’ formulation. This consisted of microgranules of indomethacin coated with an acrylic resin, Eudragit L, which releases drug in the small intestine. Endoscopy was repeated after 8 weeks and biopsies taken on both occasions. Changes in endoscopic lesions and histological appearances were similar in both groups, although mucosal erythema was less in those given Eudragit L indomethacin. Systemic, rather than topical, effects of indomethacin may therefore be responsible for persistence of gastro-duodenal mucosal lesions in these patients. There is reason to question the clinical practice of using expensive, delayed-release preparations.

Notes: Ulcerative colitis is a condition of nonsmokers in which nicotine is of therapeutic benefit.〈section xml:id="abs1-2"〉〈title type="main"〉Aims:To examine the in vitro effect of nicotine on colonic smooth muscle activity and the role of nitric oxide (NO) as a mediator.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Nicotine, 1–10 μM, was administered to strips of circular muscle from the distal sigmoid colon of 9 patients with active ulcerative colitis and 18 with colorectal cancer. The effect of electrical field stimulation (EFS) was examined before nicotine was added. Finally L-NAME, a NO synthetase inhibitor, was added before nicotine was administered again.〈section xml:id="abs1-4"〉〈title type="main"〉Results:Muscle strips developed similar spontaneous resting tone. In response to EFS, ulcerative colitis tissue developed lower tensions than the controls. Nicotine significantly reduced the resting tone and peak tension after EFS, with a greater effect in controls. With L-NAME, peak tensions were increased more in ulcerative colitis than controls, and nicotine produced a much smaller reduction.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:Nicotine reduces circular muscle activity, predominantly through the release of nitric oxide—this appears to be ‘up-regulated’ in active ulcerative colitis. These findings may explain some of the therapeutic benefit from nicotine (and smoking) in ulcerative colitis and may account for the colonic motor dysfunction in active disease.

Notes: Eleven patients with active proctitis or proctosigmoiditis completed one month's treatment with tripotassium dicitrato bismuthate enemas administered at night. Symptoms, sigmoidoscopic appearances, and the histological grade of acute inflammation were assessed at the commencement of therapy and after one month. An overall score of these features showed improvement in 9 of 11 patients, which encourages further investigation of bismuth in controlled trials for patients with inflammatory bowel disease.

Notes: Since transdermal nicotine is of value in the treatment of active ulcerative colitis but is often associated with side-effects, an alternative in the form of topical therapy with nicotine enemas has been developed.〈section xml:id="abs1-2"〉〈title type="main"〉MethodsIn an open study, 22 patients with active colitis, all non-smokers, were asked to take a 100 mL enema containing 6 mg of nicotine every night for 4 weeks. Pre-trial treatment using mesalazine (n=16), oral prednisolone (8), cyclosporin (1) and azathioprine (1) was kept constant for the month prior to assessment and during the study period. Symptoms, with stool frequency, were recorded on a diary card and an endoscopy was performed with rectal biopsy at the beginning of the study and after 4 weeks.〈section xml:id="abs1-3"〉〈title type="main"〉ResultsSeventeen of the 22 patients completed 1 month of treatment. Mean duration of relapse was 29 weeks, range 3–94. Sixteen of 17 improved their St Mark's score. Urgency and stool frequency improved in 12 patients, sigmoidoscopic and histological scores in 10. Three patients had a full remission of symptoms with normal sigmoidoscopy. Six of 10 with a partial response continued with the enemas for a second month and five showed further improvement with full remission in two. The enema appeared effective when added to conventional treatment and produced few side-effects.〈section xml:id="abs1-4"〉〈title type="main"〉ConclusionTopical nicotine therapy for ulcerative colitis may have a place in future management, but controlled studies are needed.