Forty-seven patients with ulcerative colitis subjected to elective proctocolectomy were investigated with regard to the occurrence of precancerous changes in the rectal biopsy and the operation specimen. In the rectal biopsy from seven patients precancerous lesions were found and in the operation specimens from these patients precancer was also found in other parts of the colon. In five of these patients the precancer was associated with carcinoma and in four of the patients the tumour had not been detected before operation. It is concluded that rectal biopsy is of great value in patients with ulcerative colitis for detection of early cancer and patients at risk of developing a colitis carcinoma.
Culture for bacteria and assays for endotoxin were performed on specimens of mesenteric and peripheral venous blood from eight patients with ulcerative colitis who underwent surgery for severe uncontrolled disease. No significant bacteraemia occurred in either portal or systemic blood. Systemic endotoxaemia developed in three patients during surgery but occurred before bowel mobilisation only in the one patient whose colitis was complicated by hyposplenism. Mesenteric endotoxaemia occurred in only three patients before bowel mobilisation, but was detected during surgery in two of the three patients who developed systemic endotoxaemia. We conclude that, contrary to earlier reports, portal bacteraemia must be infrequent in ulcerative colitis. Systemic endotoxaemia does, however, occur in a significant proportion of cases during colectomy. Although in the patients studied this led to no clinical problems, it is likely to have been the precipitating factor for the syndrome of disseminated intravascular coagulation (DIC) that we have previously observed after colectomy in some of our patients with hyposplenism secondary to inflammatory bowel disease.
Epithelial cell proliferation in the rectal stump after ileorectal anastomosis for ulcerative colitis was studied in 19 patients. This was achieved through in vitro incorporation of tritiated thymidine in mucosal biopsies and radioautographic analysis of the number and position of labelled nuclei in the crypts. Rectal biopsies from nine unoperated patients with ulcerative colitis and from 10 controls, were processed simultaneously. Except for one, all patients were clinically in remission. The crypt length and number of labelled cells per crypt column were found to be similar in the rectal mucosa from the three groups of subjects. The mean labelling index, although low 8.9%, was higher (p less than 0.05) in operated patients compared with controls; but the dispersion of individual values was similar in both groups. There was an extension of the proliferative compartment towards the surface in 88% of unoperated patients and in 60% of operated patients. In addition, there was a shift of the major zone of proliferation from the lower to the middle third of the crypt in 17% of operated patients and from the lower to the upper third of the crypt in 14% of unoperated patients. No correlation was found between the labelling index and either the age of patient...
We present two cases of ulcerative colitis associated with a chronic pattern of hepatic vein thrombosis (Budd-Chiari syndrome). Progression of the hepatic disorder appeared to be unrelated to the activity of the colitis. Liver function tests were normal until a late stage in the disease except for a high serum alkaline phosphate and a low serum albumin. This combination of abnormalities together with ascites merit further investigation and should raise the suspicion of hepatic vein thrombosis complicating ulcerative colitis.
A diagnosis of idiopathic ulcerative colitis was made in a previously healthy 9-year-old boy. Symptoms persisted despite therapy with sulfasalazine, 50 mg/kg daily, but they eventually responded to treatment with parenteral nutrition and prednisone, 40 mg daily. Metronidazole was also given to eradicate persistent Dientamoeba fragilis from the stools. The symptoms resolved over 3 weeks, and the daily dose of prednisone was tapered. On two subsequent occasions a challenge with sulfasalazine caused an immediate recurrence of loose, blood-streaked stools and of nonspecific histologic features of ulcerative colitis, which resolved when the sulfasalazine was discontinued.
One hundred and twenty-two randomly selected patients with ulcerative colitis (28 of whom had undergone colectomy) were interviewed to obtain data on the quality of their family, emotional, social, and professional lives. They were compared with an age- and sex-matched group of patients with acute conditions from the same area. The two groups were similar in marital status, the frequency of severe family or sexual problems, leisure activities, physical and earning capacity, the incidence of mental disorders before the interview, and intake of alcohol and psychopharmacological drugs. A higher proportion of the patients with colitis had had a higher education and belonged to higher socioeconomic groups than the controls, and this difference had been present at the time of diagnosis. These results show that patients with ulcerative colitis seem to adapt themselves well to their condition and suffer few social or professional disabilities.
BACKGROUND AND AIMS—Controversy surrounds the risk of colorectal cancer (CRC) in ulcerative colitis (UC). Many studies have investigated this risk and reported widely varying rates. METHODS—A literature search using Medline with the explosion of references identified 194 studies. Of these, 116 met our inclusion criteria from which the number of patients and cancers detected could be extracted. Overall pooled estimates, with 95% confidence intervals (CI), of cancer prevalence and incidence were obtained using a random effects model on either the log odds or log incidence scale, as appropriate. RESULTS—The overall prevalence of CRC in any UC patient, based on 116 studies, was estimated to be 3.7% (95% CI 3.2-4.2%). Of the 116 studies, 41 reported colitis duration. From these the overall incidence rate was 3/1000 person years duration (pyd), (95% CI 2/1000 to 4/1000). The overall incidence rate for any child was 6/1000 pyd (95% CI 3/1000 to 13/1000). Of the 41 studies, 19 reported results stratified into 10 year intervals of disease duration. For the first 10 years the incidence rate was 2/1000 pyd (95% CI 1/1000 to 2/1000), for the second decade the incidence rate was estimated to be 7/1000 pyd (95% CI 4/1000 to 12/1000)...
First-line therapies in the treatment of patients with mild-to-moderate ulcerative colitis are sulfasalazine or one of the mesalamine derivatives. Mesalamine is popular given its safety profile and reasonable efficacy in many patients. However, compliance is poor with regimens demanding large number of pills dosed multiple times a day and non-compliance has been correlated with disease relapse. Mesalamine requires direct contact with the inflamed colonic mucosa. To avoid proximal absorption, a variety of delivery systems has been utilized to time the release of active mesalamine to the areas affected by colitis. The most common mesalamine release mechanisms include azo-bond prodrug carriers, pH-dependent dissolution, and moisture-sensitive product dispersion. Novel technology has resulted in the development and FDA-approval of a multi-matrix release (MMX) mesalamine. Pharmacodynamic studies suggest a reliable drug delivery system with homogenous release throughout the entire colon. By incorporating the largest amount of mesalamine (1.2 g) per pill, this new product dramatically decreases the number of pills needed to attain a therapeutic daily dosage, and is the first agent approved at once-daily dosing. These factors are expected to increase patient compliance with prescribed mesalamine dosing...
Thrombophlebitis migrans complicating ulcerative colitis has been reported only once previously when it occurred in a patient with chronic and extensive bowel disease. This report describes the occurrence of thrombophlebitis before any bowel upset in a patient who proved to have only a mild colitis, and no laboratory evidence of hypercoagulability. It seems that thrombophlebitis migrans is a further systemic complication of ulcerative colitis, and that its occurrence may precede overt bowel disease.
Monozygous twin sisters developed ulcerative colitis within 7 years of each other. Both had distal colitis confirmed by histology and radiology. Their maternal grandmother subsequently developed the disease. The long interval between the onset of the disease in the twins suggests a role for environmental factors in addition to genetic influences. Although about five hundred sets of twins with ulcerative colitis may be expected in Britain, this is the first set to be reported.
Forty-four Asian immigrants in Birmingham and 44 age- and sex-matched white Caucasians with ulcerative colitis were compared to investigate the existence of any ethnic differences in the pattern of disease. Asian immigrants demonstrated a male preponderance of 2:1, and compared to the matched Caucasians there was a higher incidence of presenting eosinophilia and a milder course of disease, with more patients experiencing only a single initial attack. In spite of this clinical difference, total or subtotal colitis was the commonest pathological type in both white Caucasians and Indians, whereas in Pakistanis localized distal disease predominated. All ethnic groups suffered the same overall complication rate (55%) which is at variance with the experience of low complication rates in India. The age of onset of ulcerative colitis was related to age at immigration with a mean interval of 11 years. Although in some respects Asian immigrants share the disease pattern of the indigenous population, the observed significant differences could be of importance with regard to pathogenesis.
A man presented with unilateral visual blurring associated with bilateral retinal periphlebitis which was felt to be a complication of his biopsy-proven active ulcerative colitis. Retinal periphlebitis has been associated rarely with some forms of colitis but we can find no report of its occurrence in association with ulcerative colitis although other ocular inflammatory disorders are well recognized.
The role of biological agents in moderate to severe ulcerative colitis has been shown to be effective in the induction of clinical remission. However, the role of infliximab therapy for induction of remission in patients with fulminant colitis is debatable. A case of a hospitalized patient with a new diagnosis of severe ulcerative colitis refractory to intravenous steroids is presented. The patient was treated with infliximab and discharged with clinical remission, but subsequently presented back to hospital with a lower gastrointestinal hemorrhage.
Restorative proctocolectomy with ileal pouch-anal anastomosis is the procedure of choice for patients with ulcerative colitis requiring surgery. A J-pouch with a stapled anastomosis has been the preferred technique because it is quicker, safer, and associated with good functional outcomes. A diverting loop ileostomy is usually created at the time of ileal pouch-anal anastomosis. In patients with severe fulminant colitis or toxic megacolon, restorative proctocolectomy with ileal pouch-anal anastomosis is performed in multistages. The technical aspects of ileal pouch-anal anastomosis in patients with ulcerative colitis are reviewed in this article.
Despite the growing use of medical salvage therapy, colectomy has remained a cornerstone in managing acute severe ulcerative colitis (ASC) both in children and in adults. Colectomy should be regarded as a life saving procedure in ASC, and must be seriously considered in any steroid-refractory patient. However, colectomy is not a cure for the disease but rather the substitution of a large problem with smaller problems, including fecal incontinence, pouchitis, irritable pouch syndrome, cuffitis, anastomotic ulcer and stenosis, missed or de-novo Crohn’s disease and, in young females, reduced fecundity. This notion has led to the widespread practice of offering medical salvage therapy before colectomy in most patients without surgical abdomen or toxic megacolon. Medical salvage therapies which have proved effective in the clinical trial setting include cyclosporine, tacrolimus and infliximab, which seem equally effective in the short term. Validated predictive rules can identify a subset of patients who will eventually fail corticosteroid therapy after only 3-5 d of steroid therapy with an accuracy of 85%-95%. This accuracy is sufficiently high for initiating medical therapy, but usually not colectomy, early in the admission without delaying colectomy if required. This approach has reduced the colectomy rate in ASC from 30%-70% in the past to 10%-20% nowadays...
A 21-year-old lady was admitted to a hospital with an 8-week history of bloody diarrhoea. She had been diagnosed with ulcerative colitis 2 years previously and had remained in remission until the gradual onset of bloody diarrhoea. Her bowel frequency was 20 times per day and associated with significant abdominal pain and weight loss. She was started on intravenous steroids, topical therapy and anti-tumour necrosis factor therapy; however, this failed to achieve symptom control. Histology of tissue obtained from flexible sigmoidoscopy eventually demonstrated cytomegalovirus (CMV)-associated colitis. Intravenous anti-viral valganciclovir was initiated and the patient made a rapid recovery. This case discusses the differentials for steroid-refractory ulcerative colitis, including the common pitfall of inflammatory bowel disease management and CMV infection. This case also discusses CMV pathophysiology including histological features, appropriate investigations and current management guidelines.
In this study, the syntheses of 4-aminophenylbenzoxazol-2-yl-5-acetic acid, (an analogue of a known nonsteroidal anti-inflammatory drug [NSAID]) and 5-[4-(benzoxazol-2-yl-5-acetic acid)phenylazo]-2-hydroxybenzoic acid (a novel mutual azo prodrug of 5-aminosalicylic acid [5-ASA]) are reported. The structures of the synthesized compounds were confirmed using infrared (IR), hydrogen-1 nuclear magnetic resonance (1H NMR), and mass spectrometry (MS) spectroscopy. Incubation of the azo compound with rat cecal contents demonstrated the susceptibility of the prepared azo prodrug to bacterial azoreductase enzyme. The azo compound and the 4-aminophenylbenzoxazol-2-yl-5-acetic acid were evaluated for inflammatory bowel diseases, in trinitrobenzenesulfonic acid (TNB)-induced colitis in rats. The synthesized diazo compound and the 4-aminophenylbenzoxazol-2-yl-5-acetic acid were found to be as effective as 5-aminosalicylic acid for ulcerative colitis. The results of this work suggest that the 4-aminophenylbenzoxazol-2-yl-5-acetic acid may represent a new lead for treatment of ulcerative colitis.
Reactive oxygen species has been implicated to contribute significantly to tissue injury associated with ulcerative colitis. Thus compounds with antioxidant properties could be potential therapeutic agents in this disease. Flavonoid compounds are known to possess antioxidative and antiinflammatory properties. Two derivatives of the flavonoid quercetin (Q), chloronaphthoquinone quercetin (CNC) and monochloropivaloyl quercetin (MCP), showed improved antioxidant properties and moreover, they efficiently inhibited aldose reductase activity in vitro. The aim of the work was to test the potential efficacy of quercetin and these synthetic derivatives in vivo in prevention of intestinal inflammation during ulcerative colitis in rats. Colitis was induced by intracolonic administration of acetic acid (4% solution). The control group received the same volume of saline. The vehicle dimethyl sulfoxide (DMSO) and the drugs Q, CNC or MCP were administered orally two hours and then one hour before the acetic acid or saline instillation. After 48 hours, the animals were sacrificed and the colon was weighed, measured and scored for visible damage. Acetic acid triggered an intense inflammatory response of the colon, characterised by haemorrhage, ulceration and bowel wall thickening. From the drugs tested...
The early hypersensitivity reaction and late bone marrow depression are well-known side-effects of azathioprine, whereas interstitial pneumonia is a rare complication. A 40-year old male patient had been treated with azathioprine in consequence of extensive ulcerative colitis for 10 years. He then complained of 7 d of fever, cough and catarrhal signs, without symptoms of active colitis. Opportunistic infections were ruled out. The chest X-ray, CT and lung biopsy demonstrated the presence of interstitial inflammation. Azathioprine therapy was discontinued as a potential source of the pulmonary infiltrate. In response to steroid therapy, and intensive care, the pulmonary infiltrate gradually decreased within 4 wk. Three months later, his ulcerative colitis relapsed, and ileo-anal pouch surgery was performed. In cases of atypical pneumonia, without a proven infection, azathioprine-associated interstitial pneumonitis may be present, which heals after withdrawal of the drug.