Utilising the population based data resources of the Rochester Epidemiology Project, we estimated survival and risk of subsequent colon cancer in the 182 residents of Rochester, Minnesota, initially diagnosed with chronic ulcerative colitis (CUC) between 1985 and 1979. Twenty five (13.7%) had a proctocolectomy during the course of follow up. Three patients developed colorectal adenocarcinoma after the initial diagnosis of CUC (relative risk = 1.9, 95% CI 0.4-5.4). Excluding proctitis cases, the relative risk of cancer was 2.4 (95% CI 0.3-8.7). At last follow up, 37 (20.3%) were dead; only 10 patients had chronic ulcerative colitis mentioned on the death certificate. Overall survival was similar to that expected for the general population of like age and sex. Our results suggest that chronic ulcerative colitis in the community is typically a milder disease than would appear from hospital or referral centre series.
The incidence of ulcerative colitis in the Jewish population of Southern Israel has increased in the period 1961-85 and is presently 5.8/10(5)/year. The mean annual incidence was significantly higher in European and American born (10.8/10(5)/year) than in Asian and African or Israeli born Jews. The disease was significantly more prevalent in women, who developed the illness at a younger age and had a milder course. The age adjusted prevalence rate in each population group was greater than the rates detected by earlier studies in other areas of the country (p less than 0.05). The prevalence rate in the total population now approximates the moderate to high prevalence rates of ulcerative colitis found in many other localities. The particularly high rates of ulcerative colitis in the European and American born population in Israel, in Jews residing in Western countries, and in certain non-Jewish populations in Great Britain and Northern Europe may imply the presence of a common aetiological mechanism.
In seven patients with longstanding ulcerative colitis, multiple mucosal biopsies taken at colonoscopy were assessed for DNA content and histological dysplasia. DNA analyses were performed using flow cytometric analyses in biopsies and microspectrophotometry in imprint slides prepared from the biopsies. Abnormal aneuploid DNA content was detected in five of the patients in eight separate locations in the colon. There was good conformity between the two methods in the detection of aneuploidy. Both methods of DNA analysis are considered to be applicable in mucosal biopsies from patients with ulcerative colitis. In two patients with significant low grade dysplasia in association with macroscopical lesions (DALMs), there was a relationship with aneuploid DNA pattern found by flow cytometric or microspectrophotometric analyses. Indefinite changes, probably dysplastic were found in three other patients and two of those also displayed aneuploidy, although only once in the same biopsy location. In five locations aneuploidy was detected without concomitant dysplasia. DNA-aneuploidy seems therefore to appear earlier than dysplasia and may be an early marker of malignant transformation of the mucosa in ulcerative colitis. Prospective trials are needed before the clinical significance of early findings of aneuploidy can be determined.
The first significant experience with the straight endorectal pullthrough for the management of ulcerative colitis was presented before the American Surgical Association in 1977 by Lester Martin. Since then the operation with or without modification has been used extensively. High stool frequencies in some series led to disenchantment with the straight anastomosis and to the development of various reservoir procedures to increase rectal capacity and thereby reduce frequency. As a result, no large series of straight pullthroughs is available for comparison with the reservoir modifications. Between September 1977 and September 1986, 72 children and adults, 61 with ulcerative colitis and 11 with familial polyposis, underwent endorectal pullthrough (ERPT) and straight ileoanal anastomosis under the overall direction of a single surgeon (AGC). Sixty patients have undergone ileostomy closure and form the basis of this study. Mean age at operation was 22.7 years (range 4-48 yr), and duration of active disease averaged 6 years. One-half of the patients underwent total abdominal colectomy with ERPT as a primary procedure. There were 11 cases of adhesive bowel obstruction following ERPT, and in six patients in the series permanent revision to a Brooke ileostomy was required. One patient died of hepatic failure in the late postoperative period. Follow-up has ranged from 3 months to 9 years. Mean stool frequency for the group as a whole at 3...
Background—Increased production of reactive
metabolites of oxygen and nitrogen has been implicated in chronic
inflammation of the gut. The object of this study was to examine the
magnitude and location of nitric oxide synthase (NOS) activity and
peroxynitrite formation in the colonic mucosa of patients with
ulcerative colitis in relation to the degree of inflammation. Subjects—Thirty three patients with active
ulcerative colitis (17 with mild or moderate inflammation, 16 with
severe inflammation). Methods—Inducible NOS activity was determined in
the colonic mucosa by measuring the conversion of
L-arginine to citrulline in the absence of calcium. The
localisation of NOS and nitrotyrosine immunoreactivity was assessed
immunohistochemically using the labelled streptavidin biotin method. Results—Inducible NOS activity increased in
parallell with the degree of inflammation of the mucosa. Expression of
inducible NOS was found not only in the lamina propria, but also in the surface of the epithelium. Peroxynitrite formation as assessed by
nitrotyrosine staining was frequently observed in the lamina propria of
actively inflamed mucosa. Conclusions—Nitric oxide and peroxynitrite
formation may play an important role in causing irreversible cellular
injury to the colonic mucosa in patients with active ulcerative colitis.
Sera from 30 children, suffering from ulcerative colitis, were examined for the presence of antibodies capable of reacting with antigens of normal human tissue. It was possible to demonstrate that most of the sera contained a precipitating and hemagglutinating factor, reacting with a constituent of human colonic tissue. This constituent was obtained, within 1 hour after death, from colonic tissue of newborn babies who had died without feeding. It could also be prepared from fetal tissue. The antigen can be extracted with phenol-water at 65°C. and seems to be a polysaccharide. The precipitating factor in the sera of the patients behaves electrophoretically as a γ-globulin. Phenol-water extracts from liver and from kidney also reacted positively with the sera from certain patients. There are indications which suggest that the antigen obtained from these tissues is identical with that from colon. Sera from 38 healthy children did not give any reactions with the extracts used. In additional controls, the sera of 32 children with various diseases, all of suspected autoimmune origin, were also tested. A few of these reacted positively with the phenol-water extracts from the organs mentioned above. Most likely, the antigen reacting in these cases is different from that reacting with the antibodies in the sera from patients with ulcerative colitis. The possible role of the antibodies in the pathogenesis of ulcerative colitis and the mechanism of their formation are discussed.
Sera from patients with ulcerative colitis contain antibodies which hemagglutinate sheep red cells, sensitized with phenol-water extracts from. colon, cecum, or feces of germfree rats. Minor concentrations of such antibodies are also present in a certain fraction of normal human sera. Hemagglutination and hemagglutination inhibition experiments with human erythrocytes and with the rat extracts showed that the latter contained an antigen similar to human blood group A antigen. In contrast, a blood group B-like antigen could not be detected in these extracts. However, experiments with eel serum indicated that these extracts also contained an antigen similar to the H antigen of the human ABO system. Absorption of ulcerative colitis sera with human A1 erythrocytes but not that with B or O erythrocytes gave, in a few cases, a slight reduction of the hemagglutinating titers against rat cecum-sensitized sheep erythrocytes. In contrast, this treatment considerably reduced such titers when found in sera from healthy persons or from patients with unrelated diseases. It could be concluded that the rat extracts also contained a "colon" antigen, detected with antibodies, present at elevated titers, in the sera of ulcerative colitis patients, but not in those of the controls. This colon antigen is immunologically distinct from the blood group antigens studied. Hemagglutination inhibition experiments indicated that A...
This study compared the histologic characteristics of ulcerative colitis with findings on conventional colonoscopy and on magnification and dye application for 70 sites that underwent biopsy. The primary objective was to study the correspondence between histologic findings and endoscopic findings with respect to glandular restructuring and the resolution of inflammation from the active to the remission phase of ulcerative colitis. Widened grooves, as assessed by the endoscopic staining technique and magnified observation, most closely correlated with histologic evidence of resolution of inflammation, and vascular markings and color tone of the mucosa on general colonoscopy most closely correlated with histologic evidence of glandular restructuring, such as glandular maturity. Magnifying endoscopy after dye application, in addition to conventional endoscopy, is therefore considered essential in the evaluation of ulcerative colitis during the resolving phase.
Blood eosinophilia is an alleged manifestation of ulcerative colitis. To investigate this association and to determine the effect of race, the occurrence of eosinophilia in all 44 Asians presenting between 1968-84 was compared to that in an age- and sex-matched group of indigenous white Caucasian patients presenting over the same period. Nineteen (43%) of the Asians presented with an eosinophilia compared to only 3 Caucasians (P less than 0.0001); similar numbers (14 and 13) in both groups demonstrating transient eosinophilia on occasions during maintenance treatment although not related to clinical relapse. A control group of Asians with other disorders not known to be associated with eosinophilia did not manifest this abnormality on presentation although 3 patients did so transiently during out-patient observation. Eosinophilia is a feature of ulcerative colitis in many Asians possibly due either to an unusual racial response to ulcerative colitis or as a reflection of the underlying pathogenesis of their disease. We have not confirmed earlier suggestions of such a feature in white Caucasians. Eosinophilia occurring during maintenance treatment in both groups may be drug-related.
Ulcerative colitis is a chronic inflammatory disease of the colon that presents as diarrhea and gastrointestinal bleeding. We performed a genome-wide association study using DNA samples from 1,052 individuals with ulcerative colitis and pre-existing data from 2,571 controls, all of European ancestry. In an analysis that controlled for gender and population structure, ulcerative colitis loci attaining genome-wide significance and subsequent replication in two independent populations were identified on chromosomes 1p36 (rs6426833, combined P = 5.1×10−13, combined OR = 0.73) and 12q15 (rs1558744, combined P = 2.5×10−12, combined OR = 1.35). In addition, combined genome-wide significant evidence for association was found in a region spanning BTNL2 to HLA-DQB1 on chromosome 6p21 (rs2395185, combined P = 1.0×10−16, combined OR = 0.66) and at the IL23R locus on chromosome 1p31 (rs11209026, combined P = 1.3×10−8, combined OR = 0.56; rs10889677, combined P = 1.3×10−8, combined OR = 1.29).
A critical step in the mechanism of action of inflammatory cytokines is the stimulation of sphingolipid metabolism, including activation of sphingosine kinase (SK) which produces the mitogenic and pro-inflammatory lipid sphingosine 1-phosphate (S1P). We have developed orally-bioavailable compounds that effectively inhibit SK activity in vitro, in intact cells and in cancer models in vivo. In the present study, we have assessed the effects of these SK inhibitors on cellular responses to TNFα, and evaluated their efficacies in the dextran sulfate sodium (DSS) model of ulcerative colitis in mice. Using several cell systems, it was shown that the SK inhibitors block the ability of TNFα to: activate NFκB; induce the expression of adhesion proteins; and promote the production of PGE2. In an acute model of DSS-induced ulcerative colitis, the SK inhibitors were equivalent to or more effective than Dipentum in reducing disease progression, colon shortening, and neutrophil infiltration into the colon. The effects of the SK inhibitors were associated with decreased colonic levels of the inflammatory cytokines TNFα, IL-1β, IFN-γ and IL-6, and reduction of S1P levels in the colon. A similar reduction in disease progression was provided by the SK inhibitors in a chronic model of ulcerative colitis in which the mice received three week-long cycles of DSS interspaced with week-long recovery periods. In the chronic model...
A 47-year-old man with a history of ulcerative colitis on prednisone and azathioprine was admitted to the hospital with a four-day history of fever, skin rash, arthralgias and leukocytosis. A skin biopsy demonstrated neutrophilic infiltration of the dermis that was consistent with Sweet’s syndrome. He improved after several days with an increase in his prednisone and azathioprine. Sweet’s syndrome is a rare cutaneous manifestation of inflammatory bowel disease, with approximately 40 cases reported in the literature. In a previously reported case of a patient with ulcerative colitis-associated Sweet’s syndrome who was on azathioprine at the time of the skin eruption, the azathioprine was stopped, raising the possibility of drug-induced Sweet’s syndrome. In the present case, the azathioprine was actually increased with complete resolution of the skin manifestations. This would support the theory that immunosuppressive therapy is the mainstay of therapy for this condition. In conclusion, Sweet’s syndrome is a neutrophilic dermatosis that is rarely associated with ulcerative colitis. It may occur while on immunosuppressive therapy and responds to an intensification of immunosuppression.
A 48-year-old female with severe ulcerative colitis refractory to conventional therapy was referred to our facility for management. The patient showed extensive ulcerative colitis since the age of 20 years and had failed therapy with 5-aminosalicylic acid agents and azathioprine. The disease remained active despite treatment with steroids and cyclosporine. The clinical and endoscopic parameters were consistent with severe disease. Infectious precipitants were ruled out. Given the severity of the disease and in order to avoid a colectomy, we started the patient on infliximab therapy. A dramatic clinical and endoscopic response was observed and she remained in remission at the end of a 1-year follow-up period. We discuss findings in the literature regarding the use of infliximab therapy in patients with ulcerative colitis who have failed steroids and cyclosporine.
A small subset of patients with active ulcerative colitis is non-responsive to major known non-biological therapies. We reported 5 patients with positive serum proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA) and tried to (1) identify the common clinical features of these patients; (2) investigate the efficacy of a novel therapy using a Chinese medicine compound; and (3) attract more gastroenterologists to be engaged in further study of this subset of patients. The common manifestations of disease in these 5 patients included recurrent bloody diarrhea and inflammatory lesions involving the entire colorectal mucosa. Initial treatment with intravenous methylprednisolone successfully induced remission. Four of these 5 patients were steroid-dependence, and immunosuppressants, such as azathioprine and cyclophosphamide, were ineffective. In 3 patients, only the particular Chinese medicine compound could induce and maintain remission. One patient underwent colectomy. No vascular inflammatory lesions were found by histopathological examination. Although more cases are needed for confirmation, our study indicates that ulcerative colitis with positive PR3-ANCA may belong to a subtype of refractory ulcerative colitis. The particular Chinese medicine compound used in our study is by far the most effective in the management of these patients...
Various extraintestinal manifestations including pulmonary abnormalities have been reported in patients with ulcerative colitis. Acute respiratory distress syndrome (ARDS) is a serious and fatal pulmonary manifestation. We have experienced a 67-year-old male patient with ARDS associated with a severe type of ulcerative colitis (UC). Severe dyspnea symptoms occurred during the treatment of UC in a previous hospital and the patient was transferred to our hospital on June 27, 2007. Both blood and sputa cultures for bacteria and fungi were negative. Cytomegalovirus antigenemia was also not detected. From the clinical and radiological [Chest X-ray, computed tomography (CT)] findings, the patient was diagnosed with ARDS on the basis of the definition of ARDS developed by the European-American Consensus Conference on ARDS. Both colonic inflammations and ARDS symptoms of the patient were resistant to any medical treatment including corticosteroids and antibiotics. However, ARDS symptoms were dramatically improved after surgical colectomy. We believe that severe colonic inflammation from UC was closely associated with the onset of ARDS of the patient. Our case report suggests that a severe type of ulcerative colitis might be taken into consideration as one of the predisposing factors of ARDS.
Circular RNAs reminiscent of viroids and the human hepatitis delta virus have been proposed as possible nonconventional pathogens responsible for Crohn’s disease and ulcerative colitis, two inflammatory bowel diseases. Consequently, RNA was extracted from various areas of intestinal tissues from individuals with either Crohn’s disease or ulcerative colitis as well as several appropriate control diseases, and analyzed by two-dimensional gel electrophoresis. No circular viroid-like RNAs (<1500 nucleotides) were detected, confirming a previous report that was limited to the investigation of small RNAs (<300 nucleotides). However, three small, unusually stable, linear RNAs were shown to be associated to both Crohn’s disease and ulcerative colitis tissues: a specific 28S ribosomal RNA cleavage product characterized previously; a 5.8S ribosomal RNA conformer; and a fragment homologous to transcripts from DNA CpG islands. The two last RNAs were detected prior to visible morphological tissue alterations, suggesting that they are produced early during the inflammation and that they have value as molecular diagnostic tools for the inflammatory bowel diseases. The potential cellular mechanisms producing these RNAs and their involvement in inflammatory bowel disease are discussed.
Eosinophil migration into the gut and the release of granular mediators plays a critical role in the pathogenesis of inflammatory bowel diseases, including ulcerative colitis. We recently demonstrated that eosinophil migration into the lung requires cell surface expression of the sialomucin CD34 on mast cells and eosinophils in an asthma model. Based on these findings, we investigated a similar role for CD34 in the migration of eosinophils and other inflammatory cells into the colon as well as explored the effects of CD34 ablation on disease development in a dextran sulfate sodium-induced model of ulcerative colitis. Our findings demonstrate decreased disease severity in dextran sulfate sodium-treated Cd34−/− mice, as assessed by weight loss, diarrhea, bleeding, colon shortening and tissue pathology, compared with wild-type controls. CD34 was predominantly expressed on eosinophils within inflamed colon tissues, and Cd34−/− animals exhibited drastically reduced colon eosinophil infiltration. Using chimeric animals, we demonstrated that decreased disease pathology resulted from loss of CD34 from bone marrow-derived cells and that eosinophilia in Cd34−/−IL5Tg animals was sufficient to overcome protection from disease. In addition...
Left ventricular thrombi usually occur in the setting of an acute myocardial infarction, left ventricular aneurysm, or dilated cardiomyopathy. In the absence of ventricular wall motion abnormalities, they are rare. This report describes a patient with ulcerative colitis in whom two-dimensional echocardiography revealed a left intraventricular mass. Thrombosis in ulcerative colitis is a serious condition and can occur in a very young population. This case also shows that left ventricular thrombi can occur in the active setting of ulcerative colitis.
Until the development of the ileal pouch-anal anastomosis in the early 1980s, proctocolectomy with end ileostomy was the only definitive surgery for ulcerative colitis and colectomy with ileorectal anastomosis was the procedure of choice for affected patients who were reluctant to have a permanent ileostomy. Currently, ileal pouch-anal anastomosis is the most common procedure for patients with ulcerative colitis requiring surgical treatment. However, there is still a role for ileorectal anastomosis and proctocolectomy with end ileostomy for a selected group of patients. In this review, the authors summarize the current indications for ileorectal anastomosis and proctocolectomy with end ileostomy in patients with ulcerative colitis.
Ulcerative colitis (UC) is a chronic disease featuring recurrent inflammation of the colonic mucosa. The goal of medical treatment is to rapidly induce a steroid-free remission while at the same time preventing complications of the disease itself and its treatment. The choice of treatment depends on severity, localization and the course of the disease. For proctitis, topical therapy with 5-aminosalicylic acid (5-ASA) compounds is used. More extensive or severe disease should be treated with oral and local 5-ASA compounds and corticosteroids to induce remission. Patients who do not respond to this treatment require hospitalization. Intravenous steroids or, when refractory, calcineurin inhibitors (cyclosporine, tacrolimus), tumor necrosis factor-α antibodies (infliximab) or immunomodulators (azathioprine, 6-mercaptopurine) are then called for. Indications for emergency surgery include refractory toxic megacolon, perforation, and continuous severe colorectal bleeding. Close collaboration between gastroenterologist and surgeon is mandatory in order not to delay surgical therapy when needed. This article is intended to give a general, practice-orientated overview of the key issues in ulcerative colitis treatment. Recommendations are based on published consensus guidelines derived from national and international guidelines on the treatment of ulcerative colitis.