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Antineoplastic-associated colitis in Chulalongkorn University Hospital.

Clostridium difficile is well known for causing pseudomembranous colitis. Most cases are associated with the use of antimicrobial agents. Non-antibiotic associated colitis has rarely been reported. The causes of colitis are related to dietary changes, anesthesia, uremia, and various non-antibiotics medications, especially antineoplastic agents. Most responsible antineoplastics in previous reports are methotrexate and 5FU. From July 1993 to August 1994, 34 cancer patients developed acute diarrhea after chemotherapy. Six cases hd chemotherapy-associated colitis. All patients presented with moderate to severe diarrhea and demonstrable C.difficile toxin in fecal specimens and did not receive any antibiotics before the onset of diarrhea. Premier enzyme immunoassay (EIA) was used for toxin A assay because it is easy to perform and needs no special tissue culture laboratory facility. Data from multicenters studies have shown good sensitivity and specificity of the test. We found documented antineoplastics associated colitis, 7 episodes from 35 episodes of diarrhea (20.0%) that had been tested with EIA for toxin A. Five of 6 episodes were 5FU related. One patient had 2 episodes of antineoplastic associated colitis with the same chemotherapy regimen. The underlying malignancies were GI malignancies in 3 of 6 patients. In conclusion, moderate to severe diarrhea in cancer patients after chemotherapy should alert the physician to be aware of a potential fatal complication caused by C.difficile infection. True incidence has been undoubtedly masked by concomitant antimicrobial treatment and physician unawareness. Early recognition, discontinuation of chemotherapy and prompt treatment should be done to reduce morbidity and mortality of this disease.

Aged↗

Colitis associated to chemotherapy with 5-fluorouracil.

Antitumoral agents, especially when administered in combination, can induce pseudomembranous colitis, due to their antimitotic and antibacterial properties. Although patients given 5-fluorouracil frequently show nonspecific colitis or diarrhea without colitis, very few cases of proven pseudomembranous colitis have been described during 5-fluorouracil monotherapy. We describe the second case reported in the English literature of a typical pseudomembranous colitis occurring in a patient given 5-fluorouracil as a single antimitotic agent for colonic cancer. Intestinal injury was not preceded by antibiotic therapy. Although both stool and pseudomembrane culture did not yield C. difficile, oral vancomycin was started. This treatment led to a prompt improvement of intestinal symptoms and colitis was resolved in one week.

Aged↗

Microscopic colitis in routine colonoscopies.

Lymphocytic colitis (LC) and collagenous colitis (CC), both known as microscopic colitis (MC), are uncommon entities with increasing incidence as more clinicians take biopsies from macroscopically normal colons and as pathologists use more rigorous diagnostic criteria to be confident of the diagnosis. Information on the incidence of this type of colitis is limited and based on reported cases. The purpose of this work is to estimate the incidence of LC and CC in reviewed routine colonoscopies. We reviewed 2815 colonoscopies performed at a tertiary referral center with an open-access service using restricted histological criteria in order to establish the frequency rate of LC and CC in routine colonoscopic biopsy material. Cases suspicious for MC were stained with Masson's trichrome or Congo red stain and immunohistochemically for lymphocytes, where appropriate. Review of routine colonoscopic biopsies showed that MC is underreported in our colonoscopic material. Incidence rates of LC and CC (0.9 and 0.4, respectively) were based on morphological assessment of colonoscopic biopsies using stringent criteria together with clinical data and after differentiation with other lesions which can mimic MC. The 10.2% rate of this type of colitis in patients with chronic watery diarrhea indicates the necessity to consider these lesions in older individuals with diarrhea and normal endoscopical colonic mucosa.

Adult↗

Indeterminate colitis: a pathologist's view.

Indeterminate colitis is only a partial diagnosis, which is provisional until sufficient information becomes available for a more precise diagnosis of either ulcerative colitis or Crohn's disease. As originally defined, i.e. based only on the pathological features in the colon resected for fulminant colitis, a few patients eventually developed Crohn's disease. If the term is used only after all available clinical and investigative evidence is considered, 'indeterminate colitis' behaves clinically like ulcerative colitis. This has important implications for pouch surgery.

Colitis↗

Campylobacter jejuni pancolitis mimicking idiopathic ulcerative colitis.

Campylobacter jejuni is the most common cause of community-acquired acute bacterial diarrhea. Campylobacter diarrhea is usually accompanied by fever and abdominal pain. Campylobacter diarrhea is usually watery. Nausea, vomiting, headache, and myalgias may also be present. Tenesmus is a common feature. The majority of patients with Campylobacter diarrhea have some component of segmental colitis, usually beginning in the small bowel and progressing distally to the cecum and colon. C. jejuni is a rare cause of pancolitis. Community-acquired colitis may be caused by C. jejuni or other enteric pathogens, for example, Shigella, Entamoeba, Yersinia, Escherichia coli 0157:H7, Clostridium difficile colitis, ischemic colitis, or idiopathic ulcerative colitis. We present a case of C. jejuni pancolitis in an elderly woman. Differential diagnosis is included in the discussion. The patient's C. jejuni pancolitis was successfully treated with a 7-day course of oral moxifloxacin.

Aged↗

Influence of topical rectal application of drugs on dextran sulfate-induced colitis in rats.

A rat model of colitis [dextran sulfate (DSS)] was used to study the permeation of Evans blue (EB) from the lumen into the wall of proximal and distal colonic loops after exposure to the dye for 2 hr. Topical application of drugs used in human ulcerative colitis (lidocaine, mesalazine, prednisolone, or sucralfate) was given daily during induction of colitis to protect the mucosa. The mucosal changes were evaluated with special regard to peptidergic innervation [substance P (SP) and neuropeptide Y (NPY)], invasion of antigen-presenting polydendritic cells, and mucin-containing goblet cells. DSS-treatment caused a significantly increased permeation of EB. In the proximal loops a significant inhibition was obtained after treatment with lidocaine, prednisolone, or sucralfate. In the distal loops only treatment with lidocaine had a preventive effect. Immunocytochemically there was a clear hyperplasia of both mucosal SP- and NPY-immunoreactive nerve fibers in regions with crypt abnormalities. In these regions also most of the goblet cells were devoid of mucus. Like the changes in permeation, these morphological changes were most prominent in the distal loops. With induction of colitis, the mucosa and lamina propria were invaded by polydendritic cells; the visual score was markedly decreased in the proximal loops treated with lidocaine, prednisolone, or sucralfate. In the distal loops similar effects were obtained after treatment with lidocaine or prednisolone. Prevention of the influx of antigens in both loops after lidocaine treatment with reduced recruitment of polydendritic cells into the lamina propria is suggested. The nerve hyperplasia may thus be secondary to luminal challenge with antigens during induction of colitis. The discrepancy between increased permeation and absence of polydendritic cell response in the distal loops after prednisolone may reflect separate actions of steroids on the intestinal epithelium and the immune cells.

Administration, Rectal↗

Dextran sulfate sodium (DSS) colitis in rats: clinical, structural, and ultrastructural aspects.

Aim of this study was to assess the structural, ultrastructural, immunohistochemical, and clinical aspects in Sprague-Dawley rats with dextrane sulfate sodium (DSS)-induced colitis. Colitis was induced in Sprague-Dawley rats by seven days of DSS oral administration followed by seven days of tap water only (for one, two and three cycles). Controls were fed with water only. Segments of proximal, mid-, and distal colon of each animal were adequately prepared for light and scanning electron microscope observations. The severity of the lesions was scored histologically. For immunohistochemical study, a cocktail of S-100, NSE, and antineurofilament antibodies was used. Symptoms such as weight, feces consistency, diarrhea, hematochezia were recorded daily. From a clinical point of view symptoms appeared significantly later after the first cycle than after the second and third cycles and lasted significantly longer in the second and third cycles. Treated rats showed a slower weight gain rate by 20% compared to controls, and the whole colon length appeared to be significantly shorter after colitis induction compared to controls. Structural observations by light microscopy showed prominent involvement of the distal colon. Immunohistochemical study of both submucosal and myoenteric nerve plexuses was similar to controls. Scanning electron microscope observations of the colonic mucosal surface in colitis rats showed a complete subversion of its architecture, characterized by dilatations of gland crypt openings, dropout of goblet cells, and inhomogeneous distribution or lack of microvilli. These were most evident after the third cycle. In conclusion, experimental DSS colitis in SD rats appeared to be highly reproducible and shared most features with human UC, not only from a structural and clinical but also from an ultrastructural point of view.

Animals↗

Diagnosing colitis: a prospective study on essential parameters for reaching a diagnosis.

BACKGROUND AND STUDY AIMS: It is generally believed that making a correct histological diagnosis of colitis at colonoscopy requires segmental mucosal biopsies, information on the endoscopic features, and clinical data. This prospective study was carried out to determine the essential parameters required for an accurate diagnosis of colitis. PATIENTS AND METHODS: Two hundred consecutive patients with suspected or established colitis who underwent colonoscopy were prospectively examined. A double biopsy was taken at a macroscopic site of typical inflammation, or, if no abnormalities could be found, from normal mucosa. In addition, segmental biopsies were obtained. Endoscopic features and the patient's clinical history and symptoms were recorded. Histology was analyzed by providing the pathologist with the double-biopsy sample, segmental biopsies, and endoscopic and clinical information in a segmental fashion. Changes in the diagnoses were noted after each step of the analysis. RESULTS: Colitis was diagnosed in 152 patients (76 %). Double-biopsy examination provided the correct final diagnosis in 66 % of cases. After assessment of the segmental biopsies, the diagnosis had to be changed in 26 % of cases. Information on the endoscopic features altered the diagnosis in 2.5 %. Finally, the diagnosis was changed in an additional 5.5 % of cases after clinical data (the patient's history and symptoms) had been provided. CONCLUSIONS: Segmental biopsy specimens are essential for the differential diagnosis of intestinal inflammation. Information on the endoscopic features and clinical data are useful in differentiating some forms of colitis.

Adolescent↗

Oral microemulsion cyclosporine in the treatment of steroid-refractory attacks of ulcerative and indeterminate colitis.

BACKGROUND: To assess the efficacy of oral microemulsion cyclosporine (CyA Neoral) in the treatment of steroid-refractory attacks of ulcerative an indeterminate colitis. METHODS: In this non-randomized study on the use of oral microemulsion cyclosporine in steroid refractory ulcerative colitis, we used CyA Neoral in 10 patients suffering from ulcerative colitis and in 1 patient suffering from indeterminate colitis with a steroid-refractory attack. The initial dose was 7-7.5 mg kg-1 day-1 adjusted to maintain whole blood cyclosporine levels between 250 and 350 ng/mL, as measured by RIA using monoclonal antibodies. RESULTS: Nine patients presented a favourable response in a mean time of 3.6 days, that is, 81.8% of cases. One initial responder developed megacolon on the 11th day and another did not respond; surgical treatment was performed in both cases. The remaining nine patients, followed for a mean period of 14.6 months (2-36 months). Nine patients presented side effects, the most frequent being slight hand tremor with hypomagnesaemia, followed by hypertension, slight increase in creatinine and hirsutism. No one needed to withdraw from treatment, but the dose was lowered in three cases. CONCLUSIONS: Oral microemulsion cyclosporine is an effective drug in the initial management of patients suffering from a steroid-refractory attack of ulcerative and indeterminate colitis. Additional controlled studies with the new oral formulation are required to confirm these results.

Administration, Oral↗

Clinical and laboratory indicators of extent of ulcerative colitis. Serum C-reactive protein helps the most.

We estimated the extent of the inflammatory mucosal lesion by colonoscopy and biopsy in 60 patients with their first attack of ulcerative colitis. Proctitis was found in 12, proctosigmoiditis in 19, left-sided colitis in 10, and extensive colitis in 19. Fourteen clinical variables and laboratory measurements (bowel frequency, stool consistency, rectal bleeding, fecal mucus/pus, temperature, pulse rate, white blood cell count, hematocrit, sedimentation rate, serum iron, serum albumin, serum alpha 2-globulin, serum C-reactive protein, and seromucoids) were determined. All the variables except rectal bleeding and hematocrit were correlated (p less than 0.001) with the extent of colitis. On stepwise discriminant analysis, only C-reactive protein distinguished proctosigmoiditis from more improved the discrimination. Cross-validation by the "jack-knife method" showed that 86.7% of patients were correctly classified, the errors consisting in underestimation of disease in 8/29 patients with extensive colitis.

Adolescent↗

Controlled trial of bowel rest in the treatment of severe acute colitis.

In a prospective, randomised clinical trial, 47 patients with severe, acute, non-infective colitis treated with 60 mg intravenous prednisolone daily, received either bowel rest with parenteral nutrition or oral diet. Although those who received 'bowel rest' experienced a reduction in daily stool weight, there were no differences in the operation or mortality rates between the groups. Fourteen of the 27 patients with ulcerative colitis, but none of the 16 patients with Crohn's disease required urgent surgery. Bowel rest did not affect the outcome in severe ulcerative colitis treated with intravenous prednisolone. Ulcerative colitis and Crohn's colitis behaved differently in the acute attack.

Acute Disease↗

Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis.

BACKGROUND: Reactive oxygen species may mediate tissue injury in inflammatory bowel disease. Aminosalicylates have antioxidant activity and the antioxidants, superoxide dismutase and allopurinol, are of reported benefit in inflammatory bowel disease. AIM: To develop a convenient technique for testing the antioxidant potential of standard and novel therapeutic agents for use in inflammatory bowel disease. METHODS: Amplified chemiluminescence was used to measure reactive oxygen species production by colonic biopsy specimens from rats with acetic acid induced colitis and to assess the in vitro effect of conventional antioxidants, standard therapies and proposed novel therapies for inflammatory bowel disease. RESULTS: The model was validated by demonstrating that the profile of effects on chemiluminescence of acetic acid induced colitis biopsy specimens given by conventional antioxidants (sodium azide, catalase, copper-zinc superoxide dismutase, dimethyl sulphoxide, N-acetylcysteine and ascorbate) and standard therapies (5-aminosalicylate and hydrocortisone) resembled that previously reported using biopsy specimens from ulcerative colitis. Human recombinant manganese superoxide dismutase did not alter chemiluminescence. Two novel compounds, LY231617 (10 mM) and amflutizole (20 mM), reduced chemiluminescence by 98% (n = 5, p = 0.009) and 88% (n = 5, p = 0.03), respectively. CONCLUSIONS: The similarity of the chemiluminescence responses of colonic biopsy specimens from acetic acid induced colitis and ulcerative colitis to a range of conventional antioxidants and standard treatments suggests that this model is a useful method for testing the antioxidant potential of new therapies for inflammatory bowel disease. The antioxidant actions of dimethyl sulphoxide, ascorbate, and the novel compounds, amflutizole and LY231617 in this model suggest that these agents merit further assessment in the treatment of inflammatory bowel disease.

Acetic Acid↗

A quantitative study of immunoglobulin containing cells in the differential diagnosis of acute colitis.

In colonic biopsies of 33 patients with acute colitis caused by campylobacter, salmonella, or shigella immunoglobulin containing cells were determined quantitatively using an indirect immunoperoxidase technique and morphometry with a graphic tablet. The findings were compared with those of 10 patients without histological abnormalities, 10 patients with Crohn's disease of the colon, and 10 patients with ulcerative colitis. Biopsies of patients with acute infectious colitis had increased numbers of IgA containing cells and to a lesser extent IgM containing cells but not IgG containing cells compared with controls. Compared with the patients with active chronic idiopathic inflammatory bowel disease the patients with acute colitis showed significantly lower relative and absolute numbers of IgG containing cells. We therefore conclude that quantitative assessment of immunoglobulin containing cells in colonic biopsies may be useful in the differential diagnosis of acute infectious colitis and chronic idiopathic inflammatory bowel disease.

Campylobacter Infections↗

Roles of mucosal bacteria and succinic acid in colitis caused by dextran sulfate sodium in mice.

Intestines of mice with colitis caused by dextran sulfate sodium (DSS) contain more Bacteroidaceae cells than untreated controls. We investigated the roles of intestinal bacteria and succinic acid, a by-product of Bacteroidaceae metabolism, in this model of colitis. CBA/J mice were given 3% DSS in water for 14 days. After mice were anesthetized and killed, concentrations of organic acids in stools from the cecum and colon were measured. The resected rectum and colon were washed with sterile saline; some specimens were incubated with imipenem in saline for 1 h to kill bacteria on the surfaces and others were not. Their homogenates were cultured anaerobically and aerobically. Separately, 1 mL of 20 mM succinic acid was infused into the rectum of mice, whose anal verge was glued. Animals were anesthetized and killed the next day. The rectum and colon were examined histologically. Concentrations of succinate were higher everywhere in the colon of mice with colitis than in controls. Mice with colitis had more Bacteroidaceae cells, especially B. caccae, than controls. Mice given succinate enemas had focal erosions of the mucosa and edema of the submucosa. Succinic acid, produced abundantly by members of the family Bacteroidaceae, especially B. caccae, may be the ulcerogenic agent in DSS colitis.

Acetates↗

Behçet syndrome with "aphthous colitis".

A 46-year-old man with Behçet syndrome and a long history of recurrent bouts of colitis was studied by sigmoidoscopy, barium enema x-ray film, and colon biopsy. A nonspecific colitis characterized by shallow mucosal ulcerations and submucosal mononuclear infiltration in the absence of meaningful roentgenolographic changes was seen. A histopathological comparison was made between the oral and colonic lesions. The aphthous colitis appears, therefore, to be a colonic manifestation of Behçet syndrome, differing from typical chronic nonspecific ulcerative colitis in terms of clinical course, severity, and histologic appearance. The simultaneous occurrence of Behçet syndrome and inflammatory disease of the colon was discussed in terms of the differential diagnosis of colitis.

Adult↗

Rectal biopsy helps to distinguish acute self-limited colitis from idiopathic inflammatory bowel disease.

A retrospective blind evaluation of rectal biopsy specimens from 44 patients with acute self-limited colitis and 104 patients with idiopathic inflammatory bowel disease was done. Seven histologic features proved highly discriminant because they occurred often in idiopathic inflammatory bowel disease but rarely, if at all, in acute self-limited colitis. The features with a high predictive probability (87%-100%) of diagnosing idiopathic inflammatory bowel disease were distorted crypt architecture, increased numbers of both round cells and neutrophils in the lamina propria, a villous surface, epithelioid granuloma, crypt atrophy, basal lymphoid aggregates, and basally located isolated giant cells. One or more of these features was present in 79% of all idiopathic inflammatory bowel disease cases. They were seen in both acute and chronic idiopathic inflammatory bowel disease. The biopsy features favoring acute self-limited colitis were less useful. Biopsy diagnosis of acute self-limited colitis is thus primarily based on the absence of histologic criteria favoring idiopathic inflammatory bowel disease. This study provides objective validation of histologic criteria in rectal biopsy that help differentiate acute self-limited colitis from idiopathic inflammatory bowel disease.

Acute Disease↗

Tumour necrosis factor alpha blocking agents for induction of remission in ulcerative colitis.

BACKGROUND: Anti-TNF-alpha agents have been shown to be effective for the induction of remission in Crohn's disease. The role of TNF-alpha blocking agents in ulcerative colitis is, however, unclear and recent studies have yielded conflicting results. OBJECTIVES: To evaluate the efficacy of TNF-alpha antibody for induction of remission in ulcerative colitis, and to determine adverse events associated with TNF-alpha antibody treatment. SEARCH STRATEGY: We searched MEDLINE (1966 to 2005), EMBASE (1984 to 2005), the Cochrane Central Register of Controlled Trials (Issue 3, 2004) and the IBD/FBD Review Group Specialized Trials Register. We hand-searched the articles cited in each publication. SELECTION CRITERIA: Only randomised controlled trials in which patients with active ulcerative colitis (defined by a combination of clinical, radiographic, endoscopic and histologic criteria) were randomly allocated to receive a TNF-alpha blocking agent in the treatment arm, and to receive placebo or another treatment in the comparison arm were included. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of methodological quality of each study were independently performed by two reviewers. Any disagreement among reviewers was resolved by consensus. The main outcome measure was the occurrence of remission as defined by the primary studies. Other endpoints were clinical, histological or endoscopic improvement as defined by the primary studies; improvement in quality of life as measured by a validated quality of life tool and the occurrence of adverse events. MAIN RESULTS: Seven randomised controlled trials were identified that satisfied the inclusion criteria. In patients with moderate to severe ulcerative colitis whose disease was refractory to conventional treatment using corticosteroids and/or immunosuppressive agents, infliximab (three intravenous infusions at 0, 2, and 6 weeks) was more effective than placebo in inducing clinical remission (Relative Risk (RR) 3.22, 95% CI 2.18 to 4.76); inducing endoscopic remission (RR 1.88, 95% CI 1.54 to 2.28); and in inducing clinical response (RR 1.99, 95% CI 1.65 to 2.41) at 8 weeks. A single infusion of infliximab was also more effective than placebo in reducing the need for colectomy within 90 days after infusion (RR 0.44, 95% CI 0.22 to 0.87). AUTHORS' CONCLUSIONS: In patients with moderate to severe ulcerative colitis whose disease is refractory to conventional treatment using corticosteroids and/or immunosuppressive agents, infliximab is effective in inducing clinical remission, inducing clinical response, promoting mucosal healing, and reducing the need for colectomy at least in the short term. Serious adverse events attributable to infliximab were not common in the included studies but physicians should be aware of and be prepared to deal with potential adverse events such as anaphylactic reactions and infections.

Anti-Inflammatory Agents↗

Colitis and diarrhoea: a problem with antibiotic therapy.

During a 19-month study the incidence of diarrhoea and colitis was estimated in 1158 orthopaedic inpatients admitted to the Guy's group of hospitals. The highest incidence of diarrhoea followed the use of lincomycin (22.2 per cent), ampicillin with cloxacillin (17.2 per cent), clindamycin (15.3 per cent) and combined therapy with cloxacillin and tetracycline (12.5 per cent). There were 3 documented cases of colitis; 2 followed lincomycin and 1 clindamycin. The incidence and relationship of antibiotic-related diarrhoea and colitis to possible aetiological factors are discussed. In orthopaedic inpatients, in whom lincomycin and clindamycin are often the antibiotics of choice, their continued use appears to be fully justified by the low incidence of colitis. However, if a patient receiving treatment with either of these antibiotics does develop diarrhoea, the antibiotic should be discontinued immediately, to reduce the risk of subsequent colitis.

Adolescent↗