1161 pts over 25 years. Langholz 3. 1586 Swedish study showed 10% year 1 colectomy, 4% year 2, and 1%/year over following 20-y. likely ¼-1/3 get tac. 5-year tac 32, 12, 14% for pan, left, proctitis
Cumulative probabilities for various disease courses after diagnosis of ulcerative colitis. At 25 years after the diagnosis, 90% of patients had an intermittent course with remission and relapses. The cumulative probability of a completely relapse-free course decreased rapidly with time to approximately 10% after 25 years. Similarly, the cumulative probability of a continuously active course was low—1% after 5 years and 0.1% after 25 years. (Adapted from Langholz E, Munkholm P, Davidsen M, et al: Course of ulcerative colitis: Analysis of changes in disease activity over years. Gastroenterology 107:3, 1994.)
Figure 109-4 Percentage of pa-tients with ulcerative colitis who had active disease, were in remission, or who have had colectomy each year after diagnosis. After a few years, the proportion of patients in remission remains relatively constant, with approximately 50% of all patients being in remission at any time point during follow-up. The proportion of patients with active disease gradually decreases to about 30%, and approximately 30% of patients undergo colectomy within 25 years after diagnosis. (Adapted from Langholz E, Munkholm P, Davidsen M, et al: Course of ulcerative colitis: Analysis of changes in disease activity over years. Gastroenterology 107:3, 1994.)
Slide 6 The prognosis of UC including survival, colectomy rate, activity of disease, and working capacity was estimated from a follow-up study of 783 patients with UC comprising all patients from the county of Copenhagen. The period of observation ranged from 1 to 18 years with a mean of 6.7 years. The following observations were made: The survival rate of woman did not differ from that of the general population. At diagnosis, men over age 40 had a slight excess mortality rate in the first 2 years after diagnosis. Colon cancer was seen in only 7 of 783 patients. Annual risk was 0.07%. The colectomy rate was 9.6% in first year of diagnosis. After 10 years, the colectomy rate was 23%. After 18 years, the colectomy rate was 31%. At 3 years after diagnosis, the capacity to work including those with colectomy was not different from that of the general population. The study also indicated that, at any given time, 50% of those with UC were without symptoms, 30% had low disease activity, and 20% had moderate to high disease activity. Within 10 years of diagnosis, 97% of patients experienced at least one relapse. References Hendriksen C, Kreiner S, Binder V. Long term prognosis in ulcerative colitis – based on results from a regional patient group from the county of Copenhagen. Gut 1985; 26:158-163.
220. INDICATIONS FOR SURGERY IN ULCERATIVE COLITIS Approximately 30% of patients with ulcerative colitis undergo surgery within the first ten years of their illness, of which a substantial number have surgery for refractory disease during the initial presentation. Indications for surgery may be divided into those that are absolute and those that are relative. In the former group, exsanguinating hemorrhage, though rare, accounts for about 10% of emergency colectomies performed for ulcerative colitis. Perforation may occur in as many as 10% of all ulcerative colitis patients hospitalized with severe disease, whether or not the colon is manifesting toxic dilation. Patients with established carcinoma and high-grade dysplasia clearly should undergo colectomy. Although some clinicians do not feel that low-grade dysplasia is an absolute indication for surgery unless it is multifocal or recurrent, most experts now believe that finding the lesion in flat mucosa should lead to colectomy. Finally unresponsive severe acute disease with or without megacolon should lead to colectomy. Intractable chronic disease, usually steroid-dependent or resistant, is the most common relative indication for elective surgery. Growth retardation in the pediatric age group is an uncommon but justifiable reason for surgery. On rare occasions, severe pyoderma gangrenosum has prompted colectomy, but extra-colonic manifestations of ulcerative colitis are generally managed without surgery. • Becker JM. Indications for colectomy and choice of procedures. In: Bayless TM, Hanauer SB eds. Advanced Therapy of Inflammatory Bowel Disease. London, BC Decker, Inc. 2001;175-78 • Bernstein CN, Weinstein WM, Levine DS et al. Physician’s perceptions of dysplasia and approaches to surveillance colonoscopies in ulcerative colitis. Am J Gastroenterol 1995;90:2106-14. • Lindberg B, Persson B, Veress B et al. Twenty years’ colonoscopy surveillance of patients with ulcerative colitis: detection of dysplastic and malignant transformation. Scand J Gastroenterol 1996;31:1195-1204.
221. SURGICAL OPTIONS IN ULCERATIVE COLITIS Until the last one or two decades, the conventional operation for ulcerative colitis was a standard Brooke ileostomy. The operation is curative and requires no anastomosis to heal, but it does result in permanent fecal incontinence and requires the wearing of an external appliance. A continent ileostomy can be fashioned from an ileal-reservoir with a nipple valve (Kock pouch). No external appliance is needed, but emptying requires regular catheterization through the nipple valve. Complications include pouchitis and nipple malfunction leading to incontinence. The ileal pouch-anal anastomosis (IPAA) is a sphincter-saving operation that allows anal continence with an overall 95% chance of success. Complications of this procedure include anastomotic leaks, stricture formation, pouchitis, and partial incontinence. In a limited group of patients with relatively mild distal disease, a straight ileo-rectal anastomosis can be considered. Such patients require ongoing cancer surveillance of the remaining rectal segment. • Becker JM. Indications for colectomy and choice of procedures. In: BaylessTM, Hanauer SB. eds. Advanced Therapy of Inflammatory Bowel Disease. London, BC Decker Inc., 2001;175-178. • Pastore RL, Wolff BG, Hodge D. Total abdominal colectomy and ileo- rectal anastomosis for inflammatory bowel disease. Dis Colon Rectum 1997;40:1455-64. • Kock NG. Continent ileostomy. Prog Surg 1973;12:180.
Literally, &quot;fecundity&quot; means the ability to produce live offspring, and &quot;fertility&quot; means the actual production of live offspring. So fecundity refers to the potential production, and fertility to actual production, of live offspring. Fecundity cannot be measured, but it can be assessed clinically. Fertility and its impairments and aberrations are recorded for individuals in their medical charts and are measured in the population by routinely collected vital statistics about reproductive outcomes such as births, stillbirths, miscarriages, and so on. Fecundity and fertility are often confused. The confusion is further confounded by the fact that in French the meanings of the two similar-sounding words are reversed: fécondité means &quot;fertility,&quot; and fertilité means &quot;fecundity.&quot; Communication among demographers and others about these demographic details therefore requires care and awareness of this fact.
BACKGROUND & AIMS: The aim of this study was to determine the 1-year outcome after the first course of corticosteroids in an inception cohort of patients with inflammatory bowel disease. METHODS: All patients in Olmsted County, Minnesota, diagnosed with Crohn's disease (n = 173) or ulcerative colitis (n = 185) from 1970 to 1993 who were treated with systemic corticosteroids were identified (4 denied research authorization). Immediate outcome (30 days) and 1-year outcome after the first course of corticosteroids were determined. RESULTS: Seventy-four (43%) patients with Crohn's disease and 63 (34%) with ulcerative colitis were treated with corticosteroids. Immediate outcomes for Crohn's disease were complete remission in 43 (58%), partial remission in 19 (26%), and no response in 12 (16%). Immediate outcomes for ulcerative colitis were complete remission in 34 (54%), partial remission in 19 (30%), and no response in 10 (16%). One-year outcomes for Crohn's disease were prolonged response in 24 (32%), corticosteroid dependence in 21 (28%), operation in 28 (38%), and lost to follow-up in 1 (1%). One-year outcomes for ulcerative colitis were prolonged response in 31 (49%), corticosteroid dependence in 14 (22%), and operation in 18 (29%). CONCLUSIONS: Most patients with Crohn's disease and ulcerative colitis initially respond to corticosteroids. At 1 year, 32% of patients with Crohn's disease and 48% with ulcerative colitis are corticosteroid free without operation.
20 pts with iv steroid-refractory severe uc (7day 300hc equiv.) dbrct 4 mg/kg cya vs. placebo. 0/9 placebo response vs. 9/11 (82%) response (drop in Lichtiger index to <10 on 2 consecutive days) at 7days p<0.001. Study was initially for 50, but DSMB stopped after interim analysis. 5/9 (55%) placebo nonresponders responded to open label cya after x-over. No nephrotoxitiy. 1 GM seizure. All five of the placebo group who did not go on to colectomy had a subsequent response to cyclosporine in an open phase of the study. Patients who improved on IV cyclosporine were discharged on an oral form of this medication
30pts cyA vs. steroids. 8days, 64% vs. 53% remission. Cya responders continued CyA and Imuran orally. At 1 year, 78% vs. 37% remission. (D’Haens 2001)
Belgian SCDBRCT 73 pts, No diff between doses in day 8 response rates between 2mg/kg/day and 4mg/kg/day ( ≈ 84%); Similar short-term colectomy rates (9 and 13%); not all patients were failing steroids (55-60%). Higher drug levels and more htn in 4mg-24 v 9%, p<0.08 (Van Assche 2003)
HTN (new DBP>90 day1 through 8)
42 pts treated w/CyA. 36 responded. 25/36 subsequently treated with 6-mercaptopurine or azathioprine; remaining 11 not. Mean 5.5 years, 20 of the 25 (80%) 6-MP avoided colectomy vs. 6 of 11 (55%) w/o 6-MP. All colectomies within 18 months of receiving cyclosporine. Although 16 of 42 patients (36%) initially treated with intravenous cyclosporine had undergone colectomy by the time a 5.5 year mean follow-up, the data suggest that the chance of retaining the colon is measurably improved when 6-MP or azathioprine therapy is added early after induction of remission by IV cyclosporine. In all, 62% of all patients, 72% of initial CSA responders, and 80% of initial CSA responders receiving 6MP/aza have avoided colectomy, with a life table analysis of &quot;noncolectomy survival&quot; of 58%, 70%, and 71%, respectively, at 5.5 yr.
208. TOXICITY OF CYCLOSPORINE One hundred eleven patients with severe ulcerative colitis or fistulizing Crohn’s disease were treated initially with intravenous cyclosporine (4 mg/kg/d), and then with oral cyclosporin (6-8 mg/kg/d) depending on renal function. Twenty-eight patients (26%) developed renal insufficiency which usually improved when the cyclosporin dose was lowered. Five of the 28 patients, however, required discontinuation of the drug and one had a sustained rise in creatinine. Twenty percent (20%) developed an infection which included one pneumocystis, three bacterial pneumonia, and three catheter-related sepsis. Seizures occurred in patients with low cholesterol levels and/or higher than desired cyclosporine blood levels. The only two deaths were related to septic shock in one patient with irreversible renal failure and to massive duodenal bleeding in the second patient. • Sternthal M, George J, Kornbluth A et al. Toxicity associated with the use of cyclosporine in patients with inflammatory bowel disease. Gastroenterology 1996;110:A1019.
Usually get 5mg/kg/d po cya for 3 months as tapering steroids and imuran doses achieved
ACT I-II data: RCT 364 pts, 5mg/kg, 10mg/kg, placebo. Response (3pt abd 30% decrease mayo score) at 8 and 30 weeks.23 8wk: 69% vs 37%; 30wk: 52% vs 30% p=0.002. No diff in 5/10mg doses at either point. No effect of 5-asa or IM on remission/response in subgroup There was a significant difference in clinical response for the REMICADE-treated patients compared to the placebo-treated patients at both Week 8 and Week 30. 69% of the patients receiving 5 mg/kg and 62% receiving 10 mg/kg achieved clinical response at Week 8 vs. 37% of the placebo patients. 52% of the patients receiving 5 mg/kg and 51% receiving 10 mg/kg achieved clinical response at Week 30 vs. 30% of the placebo patients. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2.
There was a significant difference in the proportion of patients achieving clinical remission in the REMICADE-treated patients compared to the placebo-treated patients at both Week 8 and Week 30. 39% of the patients receiving 5 mg/kg and 32% receiving 10 mg/kg achieved clinical remission at Week 8 vs. 15% of the placebo patients. 34% of the patients receiving 5 mg/kg and 37% receiving 10 mg/kg achieved clinical remission at Week 30 vs. 16% of the placebo patients. HRqol improvement sig better through 1 year in infliximab vs placebo (Feagan 2007) Post-hoc analysis: 43% reduced risk of colectomy at 54 weeks vs. placebo. (Sandborn 2007) Cochrane review of 7 RCT: infliximab more effective in inducing response, clinical and endoscopic remission. A single infusion more effective in reducing need for colectomy within 90 days (Lawson 2006)
Methods: dbrct infliximab v placebo in severe-mod severe uc not responding to IIVT. infliximab/placebo either on day 4 if they fulfilled criteria for fulminant ulcerative colitis on day 3, or on day 6–8 if they fulfilled index criteria on day 5–7 for a severe or moderately severe acute attack of ulcerative colitis. ITT. PEP colectomy or death @ 3months. Secondary end points were clinical and endoscopic remission at that time in patients who did not undergo operation. Results: Forty-five patients were included (24 infliximab and 21 placebo). No patient died. Seven patients in the infliximab group and 14 in the placebo group had a colectomy ( P = .017; odds ratio, 4.9; 95% confidence interval, 1.4–17) within 3 months after randomization. No serious side effects occurred. Three patients in the placebo group required operation for septic complications. RCT. 45 pts w/mod-severe uc (seo) hosp on iv steroids. If fulminant (FCI>8) day 3 or mod-severe (seo>150) day 5-7 pts randomoized to 4-5mg/kg vs placebo once. Responders got 40 and tapering pred. Endpoint was 3 month colectomy. 14/21 (67%) placebo had colectomy vs. 7/24 (29%) in IFX had p=0.017. If severe/fulminant, it was 9/13 (69%) vs. 7/15 (47%) p=0.276 In the 2 year f/u of Jarnerot: 11/24 (46%) ufx and 16/21 (76%) placebo had colectomy at 2 years p=0.008. (Gustavsson 2007)
The Seo index formula 60 x blood in feces + 13 X bowel movements ⁄ day + 0.5ESR - 0.4Hb(g ⁄ l) - 1.5albumin(g ⁄ l) + 200 for blood in feces, 0=none and 1=present for bowel movements, 0=0–3; 1=4; 2=5–7; 3=8 150 = remission or mild UC 150–220 = moderately severe UC 220 corresponds = severe UC. The fulminant colitis index number of bowel movements ⁄ day(0.14CRP > 8mg ⁄ L)