Longstanding ulcerative colitis, particularly pancolitis, is associated with an increased risk of colorectal neoplasia. For this reason surveillance colonoscopy at regular intervals has been recommended to identify early cancers or high grade dysplasia. Three cases are described of patients with ulcerative colitis of greater than 10 years duration who presented with colorectal carcinoma within three years of colonoscopy.
Extraintestinal features of ulcerative colitis are well recognised. Pulmonary complications include pulmonary vasculitis, fibrosing alveolitis, asthma, and chronic bronchial suppuration. A case is described of a patient with longstanding quiescent ulcerative colitis who developed a life threatening pulmonary complication, which is extremely sensitive to corticosteroid treatment.
Morphometric measurements were performed on rectal biopsy specimens from 10 normal control subjects and 33 patients with a relapse of distal ulcerative colitis before and after treatment for four weeks in a double blind controlled trial with oral eudragit S coated 5 amino salicylic acid (n = 12) or rectal prednisolone enemas (n = 15). Measurements were assessed using a computer aided measuring system and a counting technique. When untreated patients were compared with the control group there were significant decreases in the area and height of the surface epithelium, in the area of crypt epithelium, and in the ratios of goblet cells to epithelial cells and of surface epithelium to lamina propria. The vascular and lamina propria areas and the number of intraepithelial polymorphs were increased. Treatment with 5 amino salicylic acid and corticosteroids resulted in similar morphological improvements: there was an increase in the area and height of the surface epithelium and the ratios of surface epithelium to lamina propria and of surface to crypt cell height. The ratio of goblet cells to epithelial cells also increased after treatment, while the numbers of polymorphs in the surface and crypt epithelium and lumen decreased. In conclusion...
In patients with ulcerative colitis a colon tissue bound IgG and serum antibodies against an Mr 40,000 colonic protein(s) has been identified. Using an anti-Mr 40,000 protein monoclonal antibody, 7E12H12, by an immunocytochemical method, the protein was localised in human tissue exclusively to colonic epithelial cells. In this study the presence of the Mr 40,000 protein was assessed in experimental animals by the direct and inhibition enzyme linked immunosorbent assays (ELISAs) using the anti-Mr 40,000 protein monoclonal antibody, 7E12H12 (IgM isotype). In addition, a total of 129 specimens including colon, small intestine, gall bladder, biliary tract, and kidney from nine strains of rats and mice, and from human tissue were studied by the immunocytochemical method using 7E12H12. All colon specimens from both humans and animals reacted with 7E12H12 in the immunocytochemical and ELISA assays. None of the non-colonic organs reacted with 7E12H12. While in human colon 7E12H12 recognised the absorptive epithelial cells, in all the animals it recognised mainly the colonic goblet cells. Extracts of animal colon but not of small intestine inhibited the binding of 7E12H12 to the human colon extract. This study shows the presence of an organ specific Mr 40...
The prognostic significance of excess small bowel gas on a plain abdominal radiograph has been assessed in 75 patients with severe attacks of ulcerative colitis requiring intravenous hydrocortisone. The radiographs were reviewed without knowledge of the subsequent outcome. Small bowel distension was defined as the presence of three or more loops of gas filled small bowel. Forty two patients responded to medical treatment and 33 underwent colectomy. The two groups were comparable for age, sex, and length of history. The surgical group had more extensive disease. Of those who did well on medical therapy, 18 (42.9%) had small bowel distension compared with 24 of 33 (72.7%) who failed medical therapy. The difference was significant (p less than 0.05, odds ratio = 3.55, 95% confidence interval of 2.27-5.87). Of the 24 patients with small bowel distension who came to surgery, five had more than four loops of gas filled small bowel. This degree of distension was not seen in any of the patients settling on medical therapy. Thus the presence of small bowel distension on a plain abdominal radiograph in a patient with severe ulcerative colitis may predict a poor response to medical therapy.
Fluticasone propionate is a new corticosteroid with low systemic bioavailability. This study reports the outcome of a double blind clinical trial comparing oral fluticasone propionate (5 mg four times daily) with placebo for the treatment of active distal ulcerative colitis. Sixty patients were treated for four weeks, with assessments at two and four weeks. One patient was withdrawn when she was found to have amoebiasis. Thus, results are presented for 29 patients who received placebo and 30 who received fluticasone propionate. The two groups were well matched for age, sex, length of history, and extent of disease. After four weeks of therapy the clinical, sigmoidoscopic, and histological responses were similar in the two groups. It is concluded that fluticasone propionate (5 mg four times daily) is not effective treatment for active distal ulcerative colitis.
In this study, long term dextran sulphate sodium administration was studied to ascertain whether colorectal carcinoma could be produced in patients with long standing ulcerative colitis. Simultaneously, changes in the intestinal microflora were analysed. Low grade to high grade dysplasia was seen in three of the five hamsters treated with 1% dextran sulphate sodium solution for 100 days, while no dysplasia was detected in the eight animals concomitantly treated with metronidazole, an antianerobic microbial agent, which prevents colonic ulceration. In these two groups, none of the animals developed colorectal cancer over 100 day period. In a group treated for 180 days, seven of the eight animals had dysplasia, and one had two adenomas. Furthermore, four of the eight animals had adenocarcinoma in the transverse colon; they were protruding well differentiated adenocarcinoma in one and non-protruding lesions infiltrating into the musclaris propria in three. The three non-protruding infiltrating adenocarcinomas were classified to be well differentiated adenocarcinoma in one and mucinous adenocarcinoma in two, resembling the type of cancer which complicates ulcerative colitis in man.
BACKGROUND: Bacterial production of anionic sulphide is increased in the colon of ulcerative colitis and sulphides can cause metabolic damage to colonocytes. AIMS: To assess the reversal of the damaging effect of sulphide to isolated colonocytes by methionine and methionine derivatives. METHODS AND SUBJECTS: Isolated colonocytes were prepared from rat colons and 12 human colectomy specimens. In cell suspensions 14CO2/acetoacetate generation was measured from [1-14C]-butyrate (5.0 mmol/l) in the presence of 0-2.0 mmol/l sodium hydrogen sulphide. The effect of 5.0 mmol/l L-methionine, S-adenosylmethionine 1,4 butane disulphonate and DL-methionine-S-methylsulphonium chloride on sulphide inhibited oxidation was observed. RESULTS: In rat colonocytes sodium hydrogen sulphide dose dependently reduced oxidative metabolite formation from n-butyrate, an action reversed in order of efficacy by S-adenosylmethionine 1,4 butane disulphonate > DLmethionine-S-methyl-sulphonium chloride > L-methionine. In human colonocytes S-adenosylmethionine 1,4 butane disulphonate most significantly improved 14CO2 production (p = < 0.005) suppressed by sodium hydrogen sulphide. CONCLUSION: Sulphide toxicity in colonocytes is reversible by methyl donors. The efficiency of sulphide detoxification may be an important factor in the pathogenesis and treatment of ulcerative colitis for which S-adenosylmethionine 1...
Since ulcerative colitis is a mucosal disease, it would appear possible to remove the diseased rectal mucosa and preserve all anorectal musculature. When performed in conjunction with total colectomy, the terminal ileum could then be placed inside the retained muscular wall of the rectum and anastomosed to the anus. This would remove all of the disease and yet preserve anorectal continence. Seventeen patients with chronic ulcerative colitis have undergone this operation with satisfactory results in 15 and no deaths. Many details of preoperative, operative and postoperative management are presented which are imperative for a successful result. Sufficient experience has been gained that the operation can now be recommended.
A double-blind controlled trial of oral zinc sulphate as adjuvant treatment in idiopathic ulcerative colitis or proctitis in relapse is reported. Fifty-one patients were treated, and the clinical and sigmoidoscopic improvement in the zinc treated patients was similar to that in patients receiving placebo. No difference was found between plasma zinc levels in a further 46 patients with idiopathic ulcerative colitis or proctitis and those obtained in a group of healthy controls.
The isoenzyme pattern of lactic dehydrogenase was measured in rectal biopsies from six patients with ulcerative colitis in whom precancerous histological changes had been independently recognized. There was a highly significant increase in the ratio of isoenzymes IV + V to I + II. This suggests that lactic dehydrogenase isoenzyme measurement may prove a valuable addition to histology in the recognition of precancer in ulcerative colitis.
The number of argentaffin cells have been counted in the epithelium of rectal biopsies taken from a series of patients with ulcerative colitis and a control group. The number of argentaffin cells was decreased in ulcerative colitis, but this decrease was not related either to the severity of the inflammation or to the duration of illness.
In a review of 103 patients with carcinoma of the proximal bile ducts, eight patients were noted to have had ulcerative colitis also. This finding is strongly suggestive of a specific association between the two diseases. In three of the patients, carcinoma developed several years after proctocolectomy. Seven of the eight patients were significantly younger than the median age of the group as a whole, but no other apparent difference was noted between those with ulcerative colitis and the remainder of the group.
It has been suggested that ulcerative colitis might be associated with excessive production of histamine released locally from mast cells. These cells also contain a proteolytic enzyme, leucine aminopeptidase, which might also be released at the same time if this hypothesis were correct. The studies reported do not invalidate this concept of aetiology in ulcerative colitis but provide no positive evidence in support of it.
The authors have produced a unique study of 624 patients with ulcerative colitis for they have achieved a 100% follow-up of all these patients admitted to the Radcliffe Infirmary or to the Churchill Hospital, Oxford, from 1938 to March 1962 inclusive or who attended as out-patients during the same period. They are therefore able to present a most important analysis of the natural history of ulcerative colitis as it occurs in the general population. Part I concerns the short-term prognosis in the initial attack, Part II the long-term prognosis; Part III discusses the complications of the disease, and Part IV the risk of carcinoma.
Serial measurements of 11 serum proteins have been made throughout 39 admissions of 36 patients to hospital for the treatment of acute attacks of ulcerative colitis. There was a striking correlation between rapid changes in C-reactive protein and pre-albumin concentrations and the clinical response to medical treatment. Measurements of the alpha1-acid glycoprotein, albumin, and total serum protein concentrations at the time of admission were found to correlate with the outcome of the attack. Measurement of these proteins provides a useful guide to the management of patients with attacks of ulcerative colitis.
Olsalazine (azodisalicylate) is a new drug in which two molecules of 5-aminosalicylic acid are linked by an azo bond. Its role in the treatment of mildly active, distal ulcerative colitis was investigated. Sixty patients were randomly allocated to receive olsalazine 1 g or a placebo as a retention enema nightly for two weeks. Clinical improvement was seen in 19 (66%) and sigmoidoscopic improvement in 17 (59%) of the 29 patients receiving olsalazine compared with 12 (43%) and 11 (39%), respectively, of the 28 in the control group. These differences were not significant. In a second trial 40 patients were randomised to receive oral olsalazine 2 g daily or a placebo capsule for two weeks. Significant clinical and sigmoidoscopic improvement was seen in the patients receiving oral olsalazine compared with the patients receiving placebo capsules. Oral olsalazine may be valuable in the treatment of mildly active ulcerative colitis. Its role in maintaining remission is yet to be determined.
We report two cases of pan-proctocolectomy for ulcerative colitis who some time postoperatively developed an obstructive uropathy with the clinical and radiological features of retroperitoneal fibrosis. The incidence of this complication appears to be around 10% and the possibility of such a diagnosis should be borne in mind in any patient who has non-specific symptoms after surgery for ulcerative colitis.
Immunofluorescence staining for carcinoembryonic antigen, secretory component, and epithelial IgA was evaluated semiquantitatively in routine formalin-fixed mucosal biopsy samples from five patients with ulcerative colitis who had undergone colectomy because of carcinomas. Selected areas were given fluorescence intensity scores without knowledge of whether dysplasia or reactive hyperplasia was present as judged by another observer from conventional histopathological features in adjacent sections. The two types of lesion did not differ significantly with regard to the expression of the three marker antigens. In a prospective study based on cold ethanol-fixed mucosal biopsy samples, lesions from 11 ulcerative colitis patients with dysplasia were compared blindly with lesions from six patients with reactive hyperplasia and with samples obtained endoscopically from eight normal controls. The range of disease-associated fluorescence intensity scores was wide, but staining for all markers tended to be brighter in reactive hyperplasia than in dysplasia (P less than 0.01). In the controls, the fluorescence intensity score tended to be lower for carcinoembryonic antigen but was significantly (P less than 0.01) higher for secretory component and epithelial IgA than in both types of lesion. Moreover...
A series of experiments has been performed in healthy male volunteers to investigate the disposition of orally administered disodium azodisalicylate, a potentially useful drug for the treatment of ulcerative colitis. The drug was given by mouth in doses of up to 2 g a day for six weeks and there were no adverse effects. Serum concentrations of the intact compound were low and the serum half-time was 4-12.8 days, probably because of a combination of a low clearance rate and a high apparent volume of distribution. Less than 5% of the ingested dose was excreted unchanged in the urine. Circulating concentrations of 5-ASA and N-acetyl-5-ASA were low and 30% of the equivalent daily dose was excreted in the urine, predominantly as N-acetyl-5-ASA. In most subjects more than 30% of the equivalent daily dose of 5-ASA was recovered from the faeces, either as 5-ASA itself or as the acetylated derivative. As 5-ASA has been shown to be the active therapeutic moiety of sulphasalazine, disodium azodisalicylate appears to be suitable for therapeutic trial in ulcerative colitis.