Archive for the ‘Ulcerative Colitis’ Category

REFERENCES

1. Kornbluth AA, Salomon P, Sacks HS, et al. Meta-analysis of the effectiveness of current drug therapy of ulcerative colitis. J Clin Gastroenterol 1993;16:215-8.

2. Meyers S, Janowitz HD. The “Natural History” of ulcerative colitis: An analysis of the placebo response. Am J Gastroenterol 1989;11:33-7.

3. Calkins BM. Inflammatory bowel diseases. In: Everhart JE, ed. Digestive Diseases in the United States. Epidemiology and Impact. National Institute of Health, 1994.

4. Waye JD. Endoscopy in inflammatory bowel disease. In: Kirsner JD, Shorter RG, ed. Inflammatory bowel disease. Philadelphia: Lea and Fabiger, 1988, pp 353-76.

5. Surawicz SM, Belic L. Rectal biopsy helps to distinguish acute self-limited colitis from idiopathic inflammatory bowel disease. Gastroenterology 1984;86:104-13.
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RECOMMENDATIONS FOR CANCER SURVEILLANCE

RECOMMENDATIONS FOR CANCER SURVEILLANCE

After 8-10 years of colitis, annual surveillance colonoscopy with multiple biopsies at regular intervals should be performed. The finding of definite dysplasia of any grade, confirmed by expert pathologists’ review, is an indication for colectomy.

Patients with UC are at increased risk for colorectal cancer; the degree of risk is related to duration of disease and anatomic extent of colitis [110] [111] . After 10 yr of universal disease, the cancer risk is in the range of 0.5-1%/yr [110] [111] [112] [113] . Even patients with left-sided colitis reach similar levels of cumulative cancer risk after 3-4 decades of disease [111] [114] [115] ; patients with proctosigmoiditis are not at increased cancer risk. Although some data suggest a later onset of cancer risk in left-sided than in more extensive colitis [110] , this evidence is not sufficiently strong to justify different guidelines for surveillance in the two groups. Compared with noncolitis-associated colorectal cancer, colitis-associated cancers are more often multiple, broadly infiltrating, anaplastic, and uniformly distributed throughout the colon, and seem to arise from flat mucosa instead of following the usual adenoma-cancer sequence [114] [116] . Furthermore, colitis-associated colorectal cancer often occurs in a much younger patient population than does colorectal cancer in the general population [111] [113] .

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RECOMMENDATION FOR SURGERY

SURGERYAbsolute indications for surgery are exsanguinating hemorrhage, perforation, and documented or strongly suspected carcinoma. Other indications for surgery are severe colitis with or without toxic megacolon unresponsive to conventional maximal medical therapy, and the patient with less severe, but medically intractable symptoms or intolerable steroid side effects.

There are no prospective randomized trials comparing medical treatment with surgery for any indication in ulcerative colitis, but three situations are absolute indications for surgery because continued medical therapy is doomed to failure and potentially fatal: exsanguinating hemorrhage, frank perforation, and documented or strongly suspected carcinoma, i.e., high grade dysplasia or low grade dysplasia in a mass lesion.

Massive hemorrhage in ulcerative colitis is due to diffuse mucosal ulceration. If the hemorrhage is exsanguinating or even persisting despite maximal medical therapy (see above), it is an indication for emergency surgery. If the patient’s condition permits, total proctocolectomy may be the most reliable procedure because a small group (approximately 12%) of patients may have continued hemorrhage from the retained rectal segment if only a subtotal colectomy is performed [96] [97] . On the other hand, subtotal colectomy with preservation of the rectum for a future restorative procedure is an acceptable choice, so long as the small risks of further hemorrhage are appreciated and appropriately monitored.

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MANAGEMENT OF SEVERE COLITIS

MANAGEMENT OF SEVERE COLITISThe patient with severe colitis refractory to maximal oral treatment with prednisone, oral aminosalicylate drugs, and topical medications, or the patient who presents with toxicity, should be treated for 7-10 days with intravenous steroids. Failure to demonstrate significant improvement within 7-10 days is an indication for either colectomy or treatment with intravenous cyclosporine in specialized centers.

The patient who continues to have severe symptoms despite optimal doses of oral steroids (40-60 mg daily of prednisone), oral aminosalicylates (4-6 g of sulfasalazine or 4.8 g of mesalamine), and topical medications, should be hospitalized for further treatment [78] [79] [80] [81] [82] . The mainstay of therapy at this point is intravenous steroids in a daily dose equivalent to 300 mg of hydrocortisone or 48 mg of methylprednisolone if the patient has received steroids in the prior month, or perhaps intravenous adrenocorticotropic hormone if the patient has not recently received steroids [82] [83] [84] . There is no benefit to treatment with a much higher daily dose of steroids [85] . The clinical impression that continuous infusion is preferable to bolus therapy has not been subjected to a controlled trial. Controlled trials of antibiotics, however, have demonstrated no therapeutic benefit from the use of either oral vancomycin [86] , or intravenous metronidazole [81] when added to intravenous steroids.

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MILD-MODERATE EXTENSIVE COLITIS: MAINTENANCE OF REMISSION

When the acute attack is controlled, a maintenance regimen is usually required, especially in patients with severe, extensive, or relapsing disease. Sulfasalazine, olsalazine, or mesalamine are all effective in reducing relapses. As a rule, patients should not be treated chronically with steroids. Azathioprine or 6-MP may be useful as steroid-sparing agents for steroid-dependent patients, and for maintenance of remission not adequately sustained by aminosalicylates, and occasionally for patients who are steroid-refractory but not acutely ill.

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MANAGEMENT OF MILD-MODERATE EXTENSIVE COLITIS: ACTIVE DISEASE

Patients with mild to moderate extensive colitis should begin therapy with oral sulfasalazine in daily doses titrated up to 4-6 g/day, or an alternate aminosalicylate in doses up to 4.8 g/day. Oral steroids are generally reserved for patients who are refractory to oral aminosalicylates with or without topical therapy, or for patients whose symptoms are so troubling as to demand a “quick fix.” 6-Mercaptopurine (6-MP) or azathioprine are effective for patients who do not respond to oral prednisone but are not so acutely ill as to require intravenous therapy.

When inflammation extends proximal to the reach of topical therapy (i.e., middescending colon-splenic flexure) oral therapy is required, either solely or in combination with topical therapy (though this latter option has not been studied in randomized controlled trials). For clinically mild to moderate, but anatomically extensive disease, the first-line therapy traditionally has been sulfasalazine. Responses are dose related with up to 80% of patients who receive daily doses of 4-6 g manifesting complete clinical remission or significant clinical improvement within 4 weeks [11] [12] and approximately half achieving sigmoidoscopic remission [11] . However, the benefits of greater efficacy with the higher dose are offset by the increase in side effects. The advantages of sulfasalazine compared with the newer aminosalicylates are its longer track record and considerably lower cost. If it happens or is anticipated that these higher doses of sulfasalazine will not be well tolerated, then a 5-aminosalicylate should be used at doses of at least 2 g/day, titrating up to 4.8 g/day [14] .

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MAINTENANCE OF REMISSION IN DISTAL DISEASE

mesalamineMesalamine suppositories in a dose of 500 mg twice daily are effective in the maintenance of remission, in patients with proctitis, whereas mesalamine enemas (2-4 grams) are effective in patients with distal colitis. Sulfasalazine (2-4 g/day) and mesalamine (1.5-4 g/day) are also effective in maintaining remission, whereas topical corticosteroids, on the other hand, have not proven effective for maintaining remission in distal colitis.

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