Another model of acetic acid-induced colitis in the rat.
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Biomedical subjects
Publications and source records attributed to B F Warren.
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The mucosa of the pelvic ileal reservoir undergoes adaptive changes--inflammatory, architectural, and metaplastic--on exposure to the faecal stream. Twenty three quadruple loop ileal pouches constructed for ulcerative colitis (20 patients) and familial adenomatous polyposis (FAP) (three patients) were studied. No patient fulfilled clinical, endoscopic, or histopathological criteria for pouchitis. Standard duplicate biopsy specimens were taken from the proximal limb, the anterior wall, the posterior wall, and the body of the reservoir. An established scoring system was used and showed a highly significant increase in inflammatory scores in posterior wall biopsy specimens compared with those from the anterior wall. These results suggest that the adaptive changes are the direct result of contact with static faecal contents. One patient only showed significant inflammation in the proximal limb. There was no evidence of mucosal prolapse in any anterior wall biopsy specimen. Patients with colitis showed substantially more inflammatory and architectural changes than those with FAP. Ninety six per cent of pouches showed some colonic phenotypic expression as defined by mucin histochemical and PR 3A5 immunohistochemical studies. Our results suggest, however, that there may not be complete colonic metaplasia and that the mucin changes and other phenotypic alterations may represent a non-specific response to pouch inflammation and not a prerequisite for the development of pouchitis. The focal nature of the inflammatory and architectural changes, which may be the result of direct contact with static faecal residue, are clearly shown. A single random biopsy specimen of pouch mucosa is of limited value in assessing pathological changes and screening for potential neoplastic change within the reservoir.
To measure the effects of defunction in the anorectum, 12 patients (seven men and five women aged 59 (44-81) years) were studied after the Hartmann operation. The operation was for septic complications of diverticular disease in nine and sigmoid carcinoma in three patients. Physiology studies were undertaken 1 and 3 months after surgery, and diversion colitis was assessed endoscopically and by mucosal biopsy at 3 months. There was no change in anal sphincter function by three months. Proctometrogram studies, however, showed an appreciable decrease in rectal volume in all cases, by a mean of 35% of the 1 month volume. The maximum tolerable volume at 1 month was 157 (111-210) ml and at 3 months 87 (71-145) ml; p < 0.01. There was no change in rectal sensation or compliance. Erythema and granularity without gross erosions or ulceration were found at endoscopy. Histology showed abnormalities in all cases by 3 months. The characteristic features were of a chronic inflammatory cell infiltrate with surface exudate, microscopic erosions, and lymphoid follicular hyperplasia. Crypt abscesses were not a feature at this stage and there was no distortion of crypt architecture. After defunction the previously normal rectum is affected by diversion colitis which, at 3 months, is mild but has characteristics that distinguish the changes from those of inflammatory bowel disease. It is associated with progressive rectal stump involution.
Faecal stream diversion may induce inflammatory changes in the defunctioned segment of the large intestine. These changes are predominantly mucosal, although confusing histological features including granulomas may be present. The pathology of 15 defunctioned rectal stumps has been studied. All patients had previously undergone urgent total colectomy for ulcerative colitis and rectal stumps had been left in situ while they awaited pelvic ileal reservoir construction. All rectal stumps showed predominantly mucosal disease but there were additional features such as florid lymphoid follicular hyperplasia (12 cases), transmural inflammation (nine cases), granulomas (four cases), fissures (eight cases), and changes akin to ischaemia or to pseudomembraneous colitis (four cases). These changes may result from a combination of defunctioning and of active ulcerative proctitis. Some induce a histological appearance that may mimic Crohn's disease. Nevertheless review of all 15 colectomy specimens showed unequivocal ulcerative colitis and none of the patients has subsequently shown any clinical, radiological, or pathological evidence to support a diagnosis of Crohn's disease. Histology of the rectal stump in ulcerative colitis may lead to an erroneous diagnosis of Crohn's disease and the patient may subsequently be denied the advantage of a pelvic ileal reservoir.
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The connective tissue changes that accompany intestinal Crohn's disease have received little attention from pathologists. This is particularly so with fat hypertrophy, and yet surgeons have long recognized the phenomenon of fat-wrapping in the intestines and used it to delineate the extent of active disease. A consecutive, unselected series of 27 intestinal resections performed on 25 patients for histologically confirmed Crohn's disease was studied to correlate fat-wrapping with other clinicopathological features. Fat-wrapping was identified in 12 of 16 ileal resections and in seven of 11 large bowel resections. It correlated closely with transmural inflammation and there was a relationship between fat-wrapping and other connective tissue changes including fibrosis, muscularization and stricture formation. Morphometry demonstrated that there was true hypertrophy and that fat-wrapping does not relate solely to bowel wall shrinkage. There was correlation with ulceration but in 11 cases macroscopic ulceration extended beyond the fat-wrapping and in six to surgical resection margins. The pathological features of 225 small intestinal resections were reviewed and fat-wrapping was seen only in Crohn's disease. Fat-wrapping correlates best with transmural inflammation and represents part of the connective tissue changes that accompany intestinal Crohn's disease. Findings also suggest that fat-wrapping alone should not be used as an accurate marker of disease extent at the time of surgery.
The pattern of mucin synthesis and secretion in mucosal biopsies from the proximal ileum, distal ileum, rectum and pouch before and after ileostomy closure was monitored in patients undergoing restorative proctocolectomy by metabolic labelling with [3H]glucosamine and [35S]sulphate and compared with the mucin histochemistry in each patient. Metabolic labelling clearly demonstrated a reduction in sulphation associated with the rectal mucosa in colitis. Significant differences in the turnover of isolated secreted mucin between proximal and distal ileum and rectum were also found, as was a metaplastic change towards a colonic-type mucosa in the pouch before and after ileostomy closure relative to the proximal and distal ileum, and rectum. This technique can be used to monitor colonic metaplasia in the pouch mucosa and is suitable for comparative studies where mucin changes are implicated.
The increasing use and success of pelvic ileal reservoir surgery places an ever more demanding role onto the surgical pathologist. Close surgical and pathological cooperation is critical for preoperative patient selection, for intraoperative diagnostic confirmation and for postoperative follow up. The long term consequences of pouch construction are, as yet, unknown, but there is much evidence to substantiate the need for life-long surveillance by clinical, endoscopic and pathological means to maximise the benefits of the pelvic ileal reservoir to the patient. This paper reviews the pathological input into these aspects of pelvic ileal reservoir surgery together with a critical appraisal of the likely long term consequences of pelvic ileal reservoir construction.
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The value of many histological stains depends on the ability of the observer to differentiate colour. This ability was assessed in 30 histopathologists and cytopathologists of varying experience using the Farnsworth-Munsell 100-hue test. As a group, the pathologists performed better than a reference population. Twenty eight subjects showed a wide ranging ability to differentiate colour: none was colour blind. Three of the 30 pathologists, however, fell below the twentieth centile for normal subjects and only one was aware of this deficiency! They may unknowingly misinterpret subtle stains. Two of these three had specific and major defects which could affect their ability to interpret a wide range of less subtle stains. Those with the poorest colour discrimination were not those with the least experience of microscopy. Pathologists should be apprised of the importance of their ability to discriminate colour, and that formal colour vision testing of prospective histopathologists may be appropriate.
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The biopsy diagnosis of prolapsing rectal mucosa syndrome can be difficult. We present two newly described features--'diamond-shaped' crypts and mucosal elastin--which appear to be helpful in histological diagnosis. Of 32 biopsies of prolapsing rectal mucosa syndrome, all showed diamond-shaped crypts or mucosal elastin, and 28 contained both. Control biopsies comprised cases of normal or irritable bowel syndrome (46), irradiation colitis and ischaemic colitis (16), inflammatory bowel disease (26), and adenomas (30). Mucosal elastin and 'diamond-shaped' crypts with distinctive scalloped edges, which were never seen in prolapse, were observed in half the cases of irradiation and ischaemic colitis. Diamond-shaped crypts were seen in one case of inflammatory bowel disease. Diamond-shaped crypts and elastin were seen in the base of adenomas large enough to cause localized prolapse, and in four biopsies from patients with irritable bowel syndrome, all of whom had given a history of straining at stool.