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PubMed1993

[Risk of development of colorectal carcinoma in patients with ulcerative colitis].

In patients with ulcerative colitis of prolonged duration and major extent there is according to the majority of investigations an increased risk of development of colorectal carcinoma; the magnitude of the risk which is of major importance for clinical practice, however, differs according to different authors. The present study comprises 189 patients with ulcerative colitis, 103 men and 86 women, perspectively followed up for a period of 12.5 years (8.0-24.5). In 60 patients the distal form was present, in 68 left-sided colitis and in 61 pancolitis. The patients were monitored systematically--clinically colonoscopically and endoscopically. The intervals between these check-ups were gradually shorter when the disease persisted for 10 or 12 years, i.e. the patients were checked once to twice a year. The endoscopic findings were focused in particular on evidence of dysplasia. The follow-up system was modified with regard to individual conditions. In the course of the follow-up colorectal carcinoma was detected in 9 patients (4.8%) with a persistence of the disease for 9-25 years (in one patient after 9 years, in 5 after 10-20 years and in 3 after longer periods). In three instances the left-sided form was involved, in 6 pancolitis. Dysplastic changes were mostly medium grade and were found at least once in all patients. The preoperative diagnosis of carcinoma was established for certain in three patients, there was major suspicion in four patients. In two patients the carcinoma was detected only on operation (in active forms of the disease). All carcinomas were resectable, 4 times DUKES A, 4 times B, once C. As to the remaining 180 patients, 32 were operated on account of colitis; in 28 at least once dysplasia was proved, with a rising trend as the disease had a prolonged duration. These results confirm the increased risk of carcinoma in ulcerative colitis with a long duration and with a major extent and justify systematic colonoscopic and endobioptic follow-up of these patients.

Adolescent↗

PubMed1999

DNA aneuploidy as a marker of premalignancy in surveillance of patients with ulcerative colitis.

BACKGROUND: Patients with ulcerative colitis have an increased risk of developing colorectal cancer. Specific and sensitive markers for premalignancy are needed. The present study evaluates the status of DNA aneuploidy (abnormal stemlines) as such a marker. METHODS: A prospective surveillance programme was conducted for all patients with ulcerative colitis from a defined area. Regular colonoscopy with mucosal sampling for histological evaluation and flow cytometric DNA analysis was performed. Some 147 patients were studied from 1984 to 1997. RESULTS: DNA aneuploidy was found in 20 patients. All but one had total colitis. The time from onset of disease to aneuploidy ranged from 5 to 31 years. Fourteen of the patients developed morphological alterations. In the same interval 127 patients, of whom 75 had total colitis, did not develop aneuploidy. Among patients with morphological alterations and aneuploidy, aneuploidy preceded these alterations in four patients and was present at the same examination in three; in seven patients the morphological alterations preceded the aneuploidy. Aneuploidy was diagnosed before the appearance of a dysplasia- associated lesion or mass in four of five cases. CONCLUSION: Flow cytometric DNA analysis has definite value as a complement to histological examinations in cancer surveillance of patients with ulcerative colitis. Aneuploidy indicates a high risk for developing severe premalignant changes. However, there is no evidence to support the use of DNA aneuploidy as a sole indication for prophylactic surgery against cancer.

Aneuploidy↗

PubMed1972

Reaginic hypersensitivity in ulcerative colitis.

Reaginic hypersensitivity in ulcerative colitis has been investigated in respect of a hypersensitivity to the cow's milk proteins and the frequency of atopic asthma, hay fever, and eczema. Intradermal tests were frequently positive, especially to casein, but the results did not differ from those found in healthy individuals and in groups of patients with Crohn's disease, hypolactasia, and the irritable colon syndrome. No circulating IgE-specific antibodies to the milk proteins were found. An increased frequency of atopic diseases was found in patients suffering from ulcerative colitis (15.7%) and Crohn's disease (13.3%) compared with the findings in a control group (1.2%). It is concluded that, if an allergy to milk proteins is a factor in the pathogenesis of ulcerative colitis, it is not mediated by reaginic antibodies. It is possible, however, that the frequent occurrence of atopy indicates a susceptibility to develop reaginic responses even though this mechanism does not apply to the milk proteins.

Antibodies↗

PubMed1989

Malignancy in ulcerative colitis.

All patients with ulcerative colitis referred to Rigshospitalet, Copenhagen, from 1 April 1964 to 1 January 1983 (18 years and 9 months) were studied from time of referral until death, proctocolectomy, or end of the study (1983). There were 759 patients, 423 females (56%) and 336 males (44%). None was lost to follow-up study. Median time from onset of disease until death, proctocolectomy, or end of the study was 11 years (range, 0-54 years). Median age at onset was 28 years (range, 0-83) among the males and 28 years (range, 4-83) among the females. Pancolitis was present in 312 patients (41%), left-sided colitis in 212 (28%), and haemorrhagic proctitis in 235 (31%). Surgical treatment was performed in 299 patients (39%): proctocolectomy in 197 (26%), colectomy with occluded rectal stump in 72 (9%), and colectomy with ileorectal anastomosis in 30 (4%). Altogether, 49 patients developed cancer, 20 being intestinal and 29 extraintestinal cancer. Compared with the general population matched for age, sex, and calendar time, there was an excessive number with intestinal cancer in both sexes (p less than 0.05). In females the number with extraintestinal cancer was higher than in the general population (p less than 0.01), a finding that has not been reported elsewhere. We found a similar, significantly increased incidence of extraintestinal cancer in females with Crohn's disease in a previous report. We found no increased risk of colorectal cancer in patients with early onset of ulcerative colitis. For all age classes we found that the age of appearance of colorectal cancer followed the equation: age at colorectal cancer = 14 + age at onset of ulcerative colitis. We found no higher potential for development of colorectal cancer in patients with pancolitis. In our series the incidence of colorectal cancer in pancolitis and left-sided colitis was equal. The incidence in patients with haemorrhagic proctitis was zero.

Adolescent↗

PubMed1998

The DNA content of chromosome division figures and interphase nuclei classifies ulcerative colitis.

Long-standing ulcerative colitis is considered to be a precancerous condition. Therefore, a practical and reliable method is required for monitoring the progress of the disease. Liberation of the S-phase from karyokinesis occurs in DNA amplification and endoreplication, producing nuclei with more than 4 c DNA. The amount of Feulgen DNA was quantified with an image microphotometer in 8 microns sections for interphase nuclei and in 15 microns sections for chromosome division figures (CDFs). Development of ulcerative colitis was investigated in low grade dysplasia (n = 93 cases; score 3-7) and high grade dysplasia (n = 22; score 8-10). Bacterial colitis (n = 34) and invasive adenocarcinoma (n = 26) provided a basis for data interpretation in dysplasia. Lymphocyte nuclei served as an internal DNA standard. CDFs represent a novel type of aberrant 'mitoses'; they are different from and much more frequent than figures with multipolar spindles. Endoreplication began with low grade dysplasia in interphase nuclei as well as with CDFs; it was fully established in high grade dysplasia and carcinoma. Endoreplicated interphase nuclei and CDFs represent an early morphological mosaic of genomic instability. Both characteristics support a reproducible two-level classification of low and high grade dysplasia in ulcerative colitis.

Cell Nucleus↗

PubMed2006

[Predictive factors of failure of intravenous corticosteroid treatment in acute severe colitis of Crohn's disease and ulcerative colitis].

We conducted a retrospective study on 78 cases of acute severe colitis (Crohn's disease in 51 cases, ulcerative colitis in 27 cases). Diagnosis of acute severe colitis was based on presence of Truelove's criteria and/or endoscopical gravity lesions. Failure of corticoid treatment was observed in 35 patients (45%). In overall patients, predictive factors of failure of intravenous corticoid treatment in univariate analysis are diagnosis of ulcerative colitis, number of bloody stool higher than 6/day. level of C-reactive protein lower than 25 mg/l. visibility of muscular mucosa at colonoscopy, absence of decrease in erythrocyte-sedimentation rate for more than 50% of initial value at day 3 of treatment, absence of decrease in C-reactive protein for more than 50% of initial value at day 3 of treatment, and a lower duration of corticoid treatment. In multivariate analysis, independent predictive factors of failure of corticoid treatment are a number of bloody stool higher than 6/day (p=0.01 adjusted OR [CI95%]: 10.2 [1.15 - 72.06]) and a value of initial C-reactive protein lower than 25 mg/l (p < 0.0001 adjusted OR [CI95%] : 3.25 [2.95 - 4.31]). In Crohn's disease, the only independent predictive factor of failure of corticoid treatment is an absence of decrease of C-reactive protein level for more than 50% of initial value at day 3 of treatment (p = 0.001 adjusted OR [CI95%] : 0.79 [0.45-0.95]). Existence of these predictive factors allows the early identification of patients who would be suitable for second-line therapy.

Adolescent↗

PubMedDate not supplied

Biological therapies for ulcerative colitis.

Biological therapies are being increasingly investigated for the treatment of inflammatory bowel disease. However, a great deal more study has been devoted to studies of Crohn's disease rather than ulcerative colitis. Ulcerative colitis, like Crohn's disease, represents an area of high clinical need, particularly for those patients who have disease inadequately responsive to corticosteroids and 5-aminosalicylates. The distinct anatomic distribution of inflammation in ulcerative colitis represents an important model for study, with the entire involved mucosa entirely accessible to endoscopy. In addition, there is an opportunity for local delivery of biologic agents in left-sided disease. Distinct pathogenetic factors in ulcerative colitis raise the possibility of therapies quite different from those used in Crohn's disease. This work describes the current state of knowledge regarding biological therapy in ulcerative colitis. The role of probiotic therapy, and studies of cytokine-directed therapies, therapies targeting adhesion and recruitment, and restitution and repair are described.

Animals↗

PubMed2000

Defective hMSH2/hMLH1 protein expression is seen infrequently in ulcerative colitis associated colorectal cancers.

BACKGROUND: Ulcerative colitis is associated with an increased risk of colorectal cancer above that of the normal population. The relative risk correlates with the extent and duration of the disease but the genetic basis of ulcerative colitis associated cancer risk is not known. AIMS: To assess the prevalence of microsatellite instability and mismatch repair gene abnormalities in ulcerative colitis associated colorectal cancer. PATIENTS: Forty six patients with colorectal cancer, with a previous histological diagnosis of ulcerative colitis. METHODS: The frequency of microsatellite instability and/or immunohistochemical expression of hMSH2 and hMLH1 was assessed. Thirty three cases were investigated using both approaches. RESULTS: Although 6/41 (14.6%) cases showed microsatellite instability at one or more markers, only one case (2. 4%) exhibited high level instability (at least two markers affected). Of 38 cases which were assessed using antibodies against hMSH2 and hMLH1, only one case (2.6%) showed loss of expression. This case, which showed loss of hMSH2 expression, was the same case which exhibited high level microsatellite instability. The 33 cases which were investigated using both approaches showed that loss of expression of either hMSH2 or hMLH1 was not seen in any case which exhibited microsatellite instability in no more than one marker. CONCLUSIONS: This study suggests that both high level microsatellite instability and loss of expression of hMSH2/hMLH1 are infrequent events in ulcerative colitis associated colorectal cancers. Low level microsatellite instability was not associated with loss of expression of either hMSH2 or hMLH1.

Biomarkers↗

PubMed1995

Paradoxical response to heparin in 10 patients with ulcerative colitis.

OBJECTIVES: A patient with ulcerative colitis refractory to standard therapy was treated with heparin for a deep vein thrombosis. Paradoxically, rectal bleeding did not increase; instead, his colitis rapidly went into remission. The same effect occurred when this patient was later treated for a pulmonary embolism. On the basis of these observations and reports of a hypercoagulable state in ulcerative colitis, heparin was tested as a therapeutic agent in nine additional patients. METHODS: Nine of the 10 patients had ulcerative colitis poorly controlled on sulfasalazine and prednisolone. Two had associated thromboembolic disease, and one was on no medication. Patients were started on heparin in hospital, taught to self-inject subcutaneously, and discharged to continue on 10,000 U of unfractionated heparin twice daily. Current doses of sulfasalazine were maintained; prednisolone was tapered and stopped. Patients were carefully monitored for adverse side-effects. Sections of colonic mucosa from nine patients were examined for intravascular thrombosis of the mucosal blood vessels. RESULTS: Nine patients became asymptomatic (normal stool frequency, no rectal bleeding) on combined heparin and sulfasalazine therapy; one patient had a partial improvement in symptoms. Highly significant statistical differences between pre- and posttreatment mean scores were found for all disease parameters. Intravascular fibrin thrombi were identified in sections from six of nine patients. No serious complications were associated with this use of heparin. CONCLUSIONS: The heparin-linked remission of ulcerative colitis, observed by chance in our first patient, was followed by similar responses in eight of nine further patients. This suggests that, used as described, heparin may have a role in treating refractory ulcerative colitis.

Adult↗

PubMed1998

Direct determination of colonic nitric oxide level--a sensitive marker of disease activity in ulcerative colitis.

OBJECTIVE: In active ulcerative colitis, colonic nitric oxide (NO) generation is enhanced and probably has an important role in its pathogenesis. We tested the reliability of an NO electrode in monitoring colonic NO levels in ulcerative colitis patients and control subjects and its possible usage as a marker of disease activity. METHODS: Colonic NO level was determined by the NO detection system model NO-501 (InterMedical, Nagoya, Japan). The working electrode was inserted into a 7-mm diameter polyvinyl tube and introduced at a distance 6 cm from the anus. In each subject sigmoidoscopy was performed and mucosal biopsies were obtained. NO synthase (NOS) activity was determined by monitoring the conversion of 3H-arginine to citrulline. RESULTS: Colonic NO level is significantly increased in patients with active ulcerative or Crohn's colitis--more than 2-fold higher than in control subjects. There was good correlation between colonic NO level and NOS activity and the clinical and endoscopic indices of disease activity. CONCLUSION: Direct determination of colonic NO level is convenient, and reliable, and may help to monitor disease activity in ulcerative colitis.

Adult↗

PubMed1982

Surgical management of ulcerative colitis.

Most patients with universal ulcerative colitis ultimately require a colectomy either to treat the inflammatory process or to prevent the subsequent development of a malignant tumour. Since the introduction of total proctocolectomy and ileostomy for the definitive surgical management of ulcerative colitis, this procedure has become the standard operative therapy for this disease. The description of the eversion technique of ileostomy in 1952 improved the life-style of patients with an ileostomy and made the total proctocolectomy a more attractive procedure. Nevertheless, many patients are emotionally disturbed by having an incontinent ileostomy and often will delay their surgery because of the associated psychologic trauma. Because of this, the Kock pouch or continent ileostomy has been introduced and advocated during the past decade. This procedure has met with notable success but has found less application in the younger patient. However, even the continent ileostomy is associated with a certain amount of psychologic trauma because of the abdominal stoma. Therefore, the endorectal pull-through has recently been used for the management of ulcerative colitis. First introduced in 1948, this procedure allows total removal of the diseased bowel, maintains continence and eliminates the need for an ileostomy. During the last 3 1/2 years, the author has used the endorectal pull-through to treat 24 patients with ulcerative colitis and 1 with familial polyposis. The results are encouraging in that all patients are continent and the average daily stool frequency is 6 to 10. These results and those of others support the continued use of this new surgical approach to the management of ulcerative colitis.

Adolescent↗

PubMed2003

Incidence and prevalence of ulcerative colitis in Punjab, North India.

INTRODUCTION: Ulcerative colitis occurs worldwide. It is considered common in most of Europe and North America and uncommon in most of the developing Asian countries. The incidence/prevalence of ulcerative colitis varies not only according to geographical region but also with race and ethnicity. There are no reported data from India on the incidence of the disease and its prevalence. MATERIAL AND METHODS: A house to house survey was conducted by questionnaire, formulated to enquire about symptoms that are suggestive of ulcerative colitis. Those with prolonged diarrhoea with or without rectal bleeding were considered as suspected cases. These suspected cases were subjected to video sigmoidoscopy/colonoscopy and rectal biopsy. In addition, patients already diagnosed and receiving treatment for ulcerative colitis, encountered during the survey, were reviewed. Resurvey of the same areas was conducted after a one year interval to detect new cases. Using direct methods, standardised rates were calculated using world standard population weights 22, 18, 16, 12, 12, 9, 7, 3, and 1 for each 10 year age group. Standardised rates were also obtained separately for males, females, and combined populations, using the Punjab state 1991 population census data. Rates were also estimated according to UK 2000 population data. Ninety five per cent confidence intervals (95% CI) of prevalence and incidence rates of ulcerative colitis were estimated under the assumption that the distribution of cases followed a Poisson probability model. RESULTS: A total population of 51 910 were screened from January to March 1999. We identified 147 suspected cases and of these 23 were finally established as ulcerative colitis cases, giving a crude prevalence rate of 44.3 per 100 000 inhabitants (95% CI 29.4-66.6). A second visit to the same areas after one year identified 10 suspected cases in a population of 49 834. Of these, three were confirmed as "definite" ulcerative colitis giving a crude incidence rate of 6.02 cases per 100 000 inhabitants (95% CI 1.2-17.6). CONCLUSIONS: This is the first population based study from India reporting on the incidence and prevalence of ulcerative colitis. The disease frequency is not much less than that reported from Europe and North America.

Adolescent↗

PubMed1984

Psychological factors in ulcerative colitis.

Almost 50 years ago ulcerative colitis was included among the seven classical psychosomatic diseases. The psychodynamics and personality structures specific to ulcerative colitis sufferers were sought and the main-stay of treatment was psychotherapy. However, for the past decade the psychogenic approach to this disorder has been replaced by physiological and immunological explanations and treatments. The history of medical and psychogenic explanations and treatments of ulcerative colitis has been traced to the present. Ulcerative colitis remains a "riddle," as it was described almost 50 years ago, a complex disorder whose pattern is to flare up and subside, its cause and cure still unknown despite almost 100 years of study.

Colitis, Ulcerative↗

PubMed1996

The role of cigarettes and nicotine in the onset and treatment of ulcerative colitis.

Epidemiological evidence suggests that ulcerative colitis is a disease of nonsmokers, while Crohn's disease is a disease of smokers. The relative risk of developing ulcerative colitis is not only greater in nonsmokers, in addition there appears to be a rebound effect in smokers who quit, with the heaviest (ex-)smokers increasing their relative risk of the disease the most. This factor poses an ethical dilemma for health professionals giving advice on stopping smoking, which may thus have a serious detrimental effect on the health of some patients. Nicotine is believed to be the pharmacological ingredient of tobacco that is responsible for this beneficial effect and several clinical trials using nicotine have demonstrated it to be an effective therapeutic agent in the treatment of ulcerative colitis. Although the aetiology of ulcerative colitis is unclear, current research using nicotine-based products has produced some interesting clues, together with the possibility of some form of therapeutic treatment based on nicotine administration.

Colitis, Ulcerative↗

PubMed2002

Alteration in expression of beta 2 integrins on lamina propria lymphocytes in ulcerative colitis and Crohn's disease.

We have previously demonstrated by immunohistochemistry that mucosal expression of beta 2 integrins was enhanced in Crohn's disease and ulcerative colitis as compared to normal controls. We aimed, therefore, to determine whether there was a corresponding alteration in the expression of CD11a/CD18 (LFA-1), the primary lymphocyte beta 2 integrin, among the principal subsets of lamina propria lymphocytes (LPLs). Accordingly, LPLs were extracted from surgical resection specimens derived from patients with Crohn's colitis, ulcerative colitis, and from noninflamed controls. Following immunofluorescent staining, three-color flow-cytometry analysis identified LPLs on the basis of CD45 side scatter gating, which in turn, were further subdivided into CD4(+), CD8(+), and CD19(+) cells to account for the predominant T and B cells in the lamina propria. Expression patterns of CD11a, the alpha-subunit of LFA-1; CD18, the beta-subunit of LFA-1; and alpha d, a novel alpha-subunit of the beta 2 integrin family were assessed for each of these lymphocyte subsets. In Crohn's disease and ulcerative colitis there was an increased mean percentage expression of CD4(+) cells and CD11a(+) cells compared with noninflamed controls. CD11a was more likely to be expressed on CD4(+) cells in both Crohn's disease and ulcerative colitis and compared with controls and less expressed on CD19(+) cells. It is likely that an influx of CD4(+)11a(+) cells into the lamina propria accounted for these changes. These results suggest that although currently there is great interest in harnessing alpha 4 beta 7 in treatment of inflammatory bowel disease, further consideration should be given to the role of CD11a in these disease states.

Antigens, CD19↗

PubMed1999

[Ocular complications in ulcerative colitis].

Ocular complications in ulcerative colitis has been reviewed. Ocular complications usually occur in 1% of patients with ulcerative colitis(UC) and include anterior uveitis, episcleritis and conjunctivitis in the order of increasing frequency. Anterior uveitis represents most common ocular complications encountered in UC and most belongs to a nongranulomatous variety, accompanied by a hypopyon in 50% of UC. Although occasionally compromised first by an intensive hypopyon, outcomes in visual acuity, in the majority of cases, are favorable. The anterior uveitis usually is able to be treated with topical or sub-Tenon injections of corticosteroids combined with short-acting mydriatics. Uveitis occurs after UC in 82% of cases and in 18%, contemporary with. Preceded by arthritis, uveitis arise in 44% of UC patients in Japan.

Anti-Inflammatory Agents↗

PubMed2005

Case report: Fatal acute exacerbation of usual interstitial pneumonia in ulcerative colitis.

Pulmonary involvement in ulcerative colitis may manifest as a variety of disorders. Ulcerative colitis-related interstitial lung disease is exceedingly rare and has been reported to be steroid-responsive. We describe the first case of a patient with acute exacerbation of ulcerative colitis-induced usual interstitial pneumonia, who did not respond to corticosteroid therapy and died 12 weeks after the onset of pulmonary symptoms. Early recognition of pulmonary disease in patients with ulcerative colitis is necessary to initiate further diagnostic work-up and may aid treatment decisions.

Acute Disease↗

PubMed2004

Current therapy of ulcerative colitis in children.

Ulcerative colitis presents in childhood in 10% of those affected, usually with pancolitis. Important features in management include growth, development and avoidance of treatment toxicity. This review addresses the current treatment options including both the paediatric evidence-based experience and areas where paediatric practice is informed by adult studies. Standard treatments include sulfasalazine or 5-aminosalicylates, corticosteroids, purine derivatives (azathioprine or 6-mercaptopurine) and surgery. Other immunosuppressant therapies and the emerging roles for biological therapies and probiotics are discussed.

Adrenal Cortex Hormones↗