Ulcerative Colitis: Jess T

Jess T, Gamborg M, Munkholm P, Sørensen TI. · Department of Medical Gastroenterology C, Herlev University Hospital, Copenhagen, Denmark. · Am J Gastroenterol. · Pubmed #17156150 No free full text.

Abstract: OBJECTIVES: It remains debated whether patients with ulcerative colitis (UC) are at greater risk of dying and whether a possible alteration in mortality can be attributed to specific causes of death. We aimed to clarify this issue by conducting a meta-analysis of population-based inception cohort studies on overall and cause-specific mortality in patients with UC. METHODS: The MEDLINE search engine and abstracts from international conferences were searched for relevant literature by use of explicit search criteria. STATA meta-analysis software was used to calculate pooled risk estimates (SMR, standardized mortality ratio, observed/expected deaths) of overall mortality and specific causes of death and to conduct metaregression analyses of the influence of specific variables on SMR. RESULTS: Ten papers fulfilled the inclusion criteria, reporting SMRs varying from 0.7 to 1.4. The overall pooled estimate was 1.1 (95% confidence interval [CI] 0.9-1.2, P= 0.42). However, greater risk of dying was observed during the first years of follow-up, in patients with extensive colitis, and in patients from Scandinavia. Metaregression analysis showed an increase in SMR by increasing cohort size. UC-related mortality accounted for 17% of all deaths. Mortality from gastrointestinal diseases, nonalcoholic liver diseases, pulmonary embolisms, and respiratory diseases was increased whereas mortality from pulmonary cancer was reduced. CONCLUSIONS: The overall risk of dying in patients with UC did not differ from that of the background population, although subgroups of patients were at greater risk of dying. The cause-of-death distribution seemed to differ from that of the background population.

Caspersen S, Elkjaer M, Riis L, Pedersen N, Mortensen C, Jess T, Sarto P, Hansen TS, Wewer V, Bendtsen F, Moesgaard F, Munkholm P, Anonymous00018. · Department of Medical Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. · Clin Gastroenterol Hepatol. · Pubmed #18848503 No free full text.

Abstract: BACKGROUND & AIMS: Data on safety and long-term follow-up evaluation of population-based cohorts of inflammatory bowel disease (IBD) patients treated with infliximab are sparse. The aim of this article is to describe the use of infliximab in a national Danish population-based IBD cohort during 1999-2005. METHODS: Medical records of all infliximab-treated IBD patients were scrutinized to abstract information on patient demographics, treatment efficacy, and adverse events. RESULTS: A total of 651 patients (619 with Crohn's disease, 15 with ulcerative colitis, and 17 with colonic IBD type unclassified) received infliximab during 1999-2005. A total of 3351 infusions were administered, with a median of 3 infusions per patient. A positive clinical response was observed in 82.7% (95% confidence interval, 79.9-85.5) of patients. Infusion reactions were observed after 146 of 3351 infusions (4.4%). Significantly fewer infusion reactions were seen in patients also receiving azathioprine or methotrexate (63 of 2079; 3.0%), compared with patients not receiving azathioprine or methotrexate (83 of 1272; 6.5%) (P < .0001). Severe adverse events were observed after 112 of 3351 infusions (3.3%) in a total of 95 patients (14.6%). Four patients developed cancer versus 5.9 expected (standardized incidence ratio, 0.7; 95 confidence interval, 0.2-1.7) and 13 patients died versus 6.9 expected (standardized mortality ratio, 1.9; 95% confidence interval, 1.0-3.2). Two deaths caused by infections were possibly related to infliximab. CONCLUSIONS: Infliximab seemed effective in IBD and generally was well tolerated. However, rare but severe adverse events occurred, and patients receiving infliximab therefore should be selected carefully and monitored closely. No lymphomas and no increased risk of cancer were observed.

Halfvarson J, Jess T, Bodin L, Järnerot G, Munkholm P, Binder V, Tysk C. · Department of Internal Medicine, Orebro University Hospital, Orebro, Sweden. · Inflamm Bowel Dis. · Pubmed #17828780 links to  free full text

Abstract: BACKGROUND: The genetic influence on disease course in inflammatory bowel disease (IBD) remains unknown. We therefore aimed to study longitudinal concordance for clinical characteristics and longitudinal stability using the Montreal Classification in an IBD twin population. METHODS: A total of 158 twins with ulcerative colitis (UC) (18 belonging to 9 concordant monozygotic pairs) and 141 twins with Crohn's disease (CD) (34 belonging to 17 concordant monozygotic pairs) were enrolled. Medical notes were scrutinized for clinical characteristics at diagnosis and after 10 years. Using the binominal distribution, we tested the hypothesis that clinical characteristics were independent within individuals in disease concordant monozygotic pairs. RESULTS: In CD, location was identical in 11/17 monozygotic concordant pairs at diagnosis (P = 0.008) and in 11/16 pairs after 10 years (P = 0.02). Behavior at diagnosis was identical in 13/17 pairs (P = 0.03) and in 11/16 pairs after 10 years (P = 0.01). Monozygotic UC twins were concordant (within 5 years) for age at diagnosis (6/9 pairs; P < 0.001) and symptomatic onset (4/9 pairs; P = 0.02) but not for extent of disease at diagnosis or after 10 years. The Montreal Classification did not demonstrate longitudinal stability, either regarding location or behavior of CD or extent of UC. CONCLUSIONS: The high phenotypic concordance, both at diagnosis and longitudinally, in monozygotic twins with CD supports a genetic influence not only on disease occurrence but also on disease course. This contrasts with UC, where the genetic impact appears less. Montreal Classification characteristics changed over time and should be used cautiously.

Jess T, Riis L, Vind I, Winther KV, Borg S, Binder V, Langholz E, Thomsen OØ, Munkholm P. · Department of Medical Gastroenterology, Herlev University Hospital, Copenhagen Denmark. · Inflamm Bowel Dis. · Pubmed #17206705 links to  free full text

Abstract: BACKGROUND: It remains uncertain whether the increasing incidence of inflammatory bowel disease (IBD) during the last decades has been accompanied by an alteration in the presentation, course, and prognosis of the disease. To answer this question, 3 consecutive population-based IBD cohorts from Copenhagen, Denmark (1962-2005), were assessed and evaluated. METHODS: Phenotype, initial disease course, use of medications, cumulative surgery rate, standardized incidence ratio of colorectal cancer (CRC), and standardized mortality ratio (SMR) were compared in the 3 cohorts, which had a total of 641 patients with Crohn's disease (CD) and 1575 patients with ulcerative colitis (UC). RESULTS: From 1962 to 2005, the proportion of IBD patients suffering from CD increased (P < 0.001), time from onset of symptoms to diagnosis of CD decreased (P = 0.001), and median age at diagnosis of UC increased (P < 0.01). The prevalence of upper gastrointestinal involvement and pure colonic CD varied significantly between cohorts. UC patients diagnosed in the 1990s had a higher prevalence of proctitis, received more medications, and had a milder initial disease course than did previous patients. The surgery rate decreased significantly in CD but not in UC. The risk of CRC in IBD was close to expected over the entire period, whereas the mortality of patients with CD increased (overall SMR, 1.31; 95% CI, 1.07-1.60). CONCLUSIONS: Despite variations in the presentation and initial course of IBD during the last 5 decades, its long-term prognosis remained fairly stable. Treatment of IBD changed recently, and future studies should address the effect of these changes on long-term prognosis.

Halfvarson J, Jess T, Magnuson A, Montgomery SM, Orholm M, Tysk C, Binder V, Järnerot G. · Division of Gastroenterology, Department of Internal Medicine, Orebro University Hospital, Orebro, Sweden. · Inflamm Bowel Dis. · Pubmed #17012962 links to  free full text

Abstract: BACKGROUND: Genetics and environmental factors are implicated in the etiology of inflammatory bowel disease (IBD). We studied environmental factors in a population-based Swedish-Danish twin cohort using the co-twin control method. SUBJECTS AND METHODS: A questionnaire was sent to 317 twin pairs regarding markers of exposures in the following areas: infections/colonization and diet as well as smoking, appendectomy, and oral contraceptives. Odds ratios (OR) were calculated by conditional logistic regression. When confounding appeared plausible, multivariate conditional logistic regression was added. The questions were also divided into topic groups, and adjustment was made for multiple testing within each of the groups. RESULTS: The response rate to the questionnaire was 83%. In consideration of the study design, only discordant pairs were included (Crohn's disease [CD], n = 102; ulcerative colitis [UC], n = 125). Recurrent gastrointestinal infections were associated with both UC (OR, 8.0; 95% confidence interval [CI], 1.0-64) and CD (OR, 5.5; 95% CI, 1.2-25). Hospitalization for gastrointestinal infections was associated with CD (OR, 12; 95% CI, 1.6-92). Smoking was inversely associated with UC (OR, 0.4; 95% CI, 0.2-0.9) and associated with CD (OR, 2.9; 95% CI, 1.2-7.1). CONCLUSIONS: The observed associations indicate that markers of possible infectious events may influence the risk of IBD. Some of these effects might be mediated by long-term changes in gut flora or alterations in reactivity to the flora. The influence of smoking in IBD was confirmed.

Jess T, Loftus EV, Velayos FS, Harmsen WS, Zinsmeister AR, Smyrk TC, Tremaine WJ, Melton LJ, Munkholm P, Sandborn WJ. · Department of Medical Gastroenterology, Herlev University Hospital, Herlev, Denmark. · Inflamm Bowel Dis. · Pubmed #16917220 No free full text.

Abstract: BACKGROUND AND AIMS: The risk, fate, and ideal management of colorectal dysplasia in inflammatory bowel disease (IBD) remain debated. We estimated the incidence, long-term outcome, and risk factors for progression of colorectal dysplasia (adenomas [adenoma-associated lesions or masses (ALMs)], flat dysplasia, and dysplasia-associated lesions or masses [DALMs]) in a population-based IBD cohort from Olmsted County, Minnesota. MATERIALS AND METHODS: The Rochester Epidemiology Project was used to identify cohort patients with colorectal dysplasia. Medical records were reviewed for demographic and clinical characteristics. Histology slides were reviewed by a pathologist blinded to previous pathology reports. The cumulative incidence of dysplasia was estimated, and the association between patient characteristics and recurrence/progression of dysplasia was assessed using proportional hazards regression. RESULTS: Twenty-nine (4%) IBD patients developed flat dysplasia (n = 8), DALMs (n = 1), ALMs in areas of IBD (n = 18), or ALMs outside areas of IBD (n = 2). Among 6 patients with flat low-grade dysplasia (fLGD) who did not undergo colectomy, none progressed during a median of 17.8 (range 6-21) years of observation with a median of 3 (range 0-12) surveillance colonoscopies. Four (22%) patients with ALMs in areas of IBD who did not undergo surgery developed LGD or DALMs. Primary sclerosing cholangitis and dysplasia located proximal to the splenic flexure were significantly associated with risk for recurrence/progression of dysplasia. CONCLUSIONS: This population-based cohort study from Olmsted County, Minnesota did not confirm an increased risk of cancer related to fLGD, whereas 22% of patients with ALMs in areas of IBD developed fLGD or DALMs.

Vind I, Riis L, Jess T, Knudsen E, Pedersen N, Elkjaer M, Bak Andersen I, Wewer V, Nørregaard P, Moesgaard F, Bendtsen F, Munkholm P, Anonymous00679. · Department of Gastroenterology, Hvidovre Hospital, University of Copenhagen, Denmark. · Am J Gastroenterol. · Pubmed #16771949 No free full text.

Abstract: OBJECTIVES: A continuous increase in the incidence of inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), and indeterminate colitis (IC) has been suggested. Since Denmark provides excellent conditions for epidemiological research, we aimed to describe contemporary IBD incidence rates and patient characteristics in Copenhagen County and City. METHODS: All patients diagnosed with IBD during 2003-2005 were followed prospectively. Demographic and clinical characteristics, such as disease extent, extraintestinal manifestations, smoking habits, medical treatment, surgical interventions, cancer, and death, were registered. RESULTS: Five-hundred sixty-two patients were diagnosed with IBD, resulting in mean annual incidences of 8.6/10(5) for CD, 13.4/10(5) for UC, and 1.1/10(5) for IC. Time from onset to diagnosis was 8.3 months in CD and 4.5 months in UC patients. A family history of IBD, smoking, and extraintestinal manifestations was significantly more common in CD than in UC patients. Only 0.6% of UC patients had primary sclerosing cholangitis. In CD, old age at diagnosis was related to pure colonic disease, whereas children significantly more often had proximal and extensive involvement. Twelve percent of CD patients and 6% of UC patients underwent surgery during the year of diagnosis, significantly less than earlier reported. CONCLUSIONS: The incidence of IBD in Copenhagen increased noticeably during the last decades. Time from onset of symptoms until diagnosis decreased markedly, extent of CD was related to age at diagnosis, and the risk of surgery was low in UC.

Velayos FS, Loftus EV, Jess T, Harmsen WS, Bida J, Zinsmeister AR, Tremaine WJ, Sandborn WJ. · Division of Gastroenterology and Hepatology, University of California San Francisco, San Francisco, California, USA. · Gastroenterology. · Pubmed #16762617 No free full text.

Abstract: BACKGROUND & AIMS: Predictive and protective factors associated with colorectal cancer in chronic ulcerative colitis are not well described. Surveillance colonoscopy and 5-aminosalicylic acid therapy may mitigate cancer risk, but there is debate because these variables have not been evaluated in the same study. The presence of postinflammatory pseudopolyps and use of other anti-inflammatory medications may be important variables that influence risk, but data are sparse. METHODS: Variables associated with colorectal cancer were registered in 188 patients with ulcerative colitis-related cancer and matched controls. Conditional logistic regression, adjusted for age at colitis diagnosis and colitis duration, identified a final set of variables independently associated with colorectal cancer. RESULTS: In the final multiple variable model, the most important factors associated with colorectal cancer were a history of pseudopolyps (OR, 2.5; 95% CI: 1.4-4.6), 1 or 2 surveillance colonoscopies (OR, 0.4; 95% CI: 0.2-0.7), smoking (OR, 0.5; 95% CI: 0.2-0.9) and use of corticosteroids (OR, 0.4; 95% CI: 0.2-0.8), aspirin (OR, 0.3; 95% CI: 0.1-0.8), nonsteroidal anti-inflammatory drugs (OR, 0.1; 95% CI: 0.03-0.5), and 5-aminosalicylic acid agents (OR, 0.4; 95% CI: 0.2-0.9), although the latter was not statistically significant after 5 years. Primary sclerosing cholangitis and immunosuppressive use were not statistically significant. CONCLUSIONS: These results suggest that, in a population matched for extent and duration of chronic ulcerative colitis, surveillance colonoscopy and use of anti-inflammatory medications may reduce the risk of colorectal cancer. A history of postinflammatory pseudopolyps appears to be a predictive factor for cancer.

Jess T, Loftus EV, Velayos FS, Harmsen WS, Zinsmeister AR, Smyrk TC, Schleck CD, Tremaine WJ, Melton LJ, Munkholm P, Sandborn WJ. · Department of Medical Gastroenterology, Herlev University Hospital, Herlev, Denmark. · Gastroenterology. · Pubmed #16618397 No free full text.

Abstract: BACKGROUND & AIMS: The risk for colorectal cancer in Crohn's disease and ulcerative colitis patients from the United States currently is unknown. We estimated the risk for small-bowel and colorectal cancer in a population-based cohort of 692 inflammatory bowel disease patients from Olmsted County, Minnesota, from 1940 to 2001. METHODS: The Rochester Epidemiology Project was used to identify cohort patients with colorectal and small-bowel cancer. The cumulative probability of cancer and standardized incidence ratios (SIR) were estimated using expected rates from Surveillance, Epidemiology, and End Results, white patients from Iowa, from 1973 to 2000, and Olmsted County, from 1980 to 1999. RESULTS: Colorectal cancer was observed in 6 ulcerative colitis patients vs 5.38 expected (SIR, 1.1; 95% confidence interval [CI], 0.4-2.4), but 4 of these occurred among those with extensive colitis or pancolitis (SIR, 2.4; 95% CI, 0.6-6.0). Six Crohn's disease patients (vs 3.2 expected) developed colorectal cancer (SIR, 1.9; 95% CI, 0.7-4.1). Three Crohn's disease patients developed small-bowel cancer vs 0.07 expected (SIR, 40.6; 95% CI, 8.4-118). CONCLUSIONS: The risk for colorectal cancer was not increased among ulcerative colitis patients overall, but appeared to be increased among those with extensive colitis. The colorectal cancer risk was increased slightly among Crohn's disease patients, who also had a 40-fold excess risk for small-bowel cancer.

Jess T, Loftus EV, Harmsen WS, Zinsmeister AR, Tremaine WJ, Melton LJ, Munkholm P, Sandborn WJ. · Department of Medical Gastroenterology C, Herlev University Hospital, Denmark. · Gut. · Pubmed #16423890 No free full text.

Abstract: BACKGROUND AND AIMS: We followed a population based cohort of patients with inflammatory bowel disease (IBD) from Olmsted County, Minnesota, in order to analyse long term survival and cause specific mortality. Material and METHODS: A total of 692 patients were followed for a median of 14 years. Standardised mortality ratios (SMRs, observed/expected deaths) were calculated for specific causes of death. Cox proportional hazards regression was used to determine if clinical variables were independently associated with mortality. RESULTS: Fifty six of 314 Crohn's disease patients died compared with 46.0 expected (SMR 1.2 (95% confidence interval (CI) 0.9-1.6)), and 62 of 378 ulcerative colitis (UC) patients died compared with 79.2 expected (SMR 0.8 (95% CI 0.6-1.0)). Eighteen patients with Crohn's disease (32%) died from disease related complications, and 12 patients (19%) died from causes related to UC. In Crohn's disease, an increased risk of dying from non-malignant gastrointestinal causes (SMR 6.4 (95% CI 3.2-11.5)), gastrointestinal malignancies (SMR 4.7 (95% CI 1.7-10.2)), and chronic obstructive pulmonary disease (COPD) (SMR 3.5 (95% CI 1.3-7.5)) was observed. In UC, cardiovascular death was reduced (SMR 0.6 (95% CI 0.4-0.9)). Increased age at diagnosis and male sex were associated with mortality in both subtypes. In UC but not Crohn's disease, a diagnosis after 1980 was associated with decreased mortality. CONCLUSIONS: In this population based study of IBD patients from North America, overall survival was similar to that expected in the US White population. Crohn's disease patients were at increased risk of dying from gastrointestinal disease and COPD whereas UC patients had a decreased risk of cardiovascular death.

Jess T, Riis L, Jespersgaard C, Hougs L, Andersen PS, Orholm MK, Binder V, Munkholm P. · Department of Medical Gastroenterology C, Herlev Hospital, University of Copenhagen, Denmark. · Am J Gastroenterol. · Pubmed #16279904 No free full text.

Abstract: OBJECTIVES: A Danish cohort of twins with inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), has previously been collected. The aim of the present study was to reassess this cohort in order to compare clinical characteristics in concordant versus discordant twin pairs, test twin zygosity genetically, follow-up on disease concordance, and examine NOD2/CARD15 genetic status. METHODS: The Danish cohort is one of two population-based cohorts worldwide and consists of 103 twin pairs. After median 13 yr of follow-up, all twins were contacted and hospital files were scrutinized to reassess disease concordance and obtain phenotype data. DNA was obtained from 123 twins for analysis of zygosity and prevalence of the three common NOD2/CARD15 mutations. RESULTS: Zygosity tested genetically was consistent with the former assessment based on questionnaires. The proband concordance for CD remained fairly stable: 63.6% among monozygotic (MZ) twins and 3.6% among dizygotic (DZ) twins. Clinical characteristics were similar in twins from concordant versus discordant pairs. Forty-four percent of patients with CD were positive for >or=1 mutant allele of NOD2/CARD15 compared to 2% of UC patients (p < 0.001) and 19% of healthy twins (p= 0.02). The allele mutation frequency was 43% among the healthy twins to patients with CD versus 9% among twins to UC patients (p= 0.01). CONCLUSIONS: Previous questionnaire assessment of twin zygosity was confirmed by genetic test. Concordance for CD remained quite stable and was significantly higher among MZ than DZ twins. A high NOD2/CARD15 mutation frequency was observed both among CD twins and their healthy siblings.

Winther KV, Jess T, Langholz E, Munkholm P, Binder V. · Herlev Hospital, University of Copenhagen, Department of Medical Gastroenterology C, Herlev 2730, Denmark. · Clin Gastroenterol Hepatol. · Pubmed #15625654 No free full text.

Abstract: BACKGROUND & AIMS: Ulcerative colitis (UC) is associated with an increased risk for colorectal cancer (CRC) and possibly also increased risk for cancers outside the intestinal tract. We followed-up a population-based cohort of 1160 patients with UC diagnosed in Copenhagen County between 1962 and 1987 for up to 36 years to analyze the overall and site-specific cancer risk. METHODS: Observed vs. expected cancers were presented as standardized morbidity ratio (SMR) with 95% exact confidence intervals (CI) calculated by using individual person-years at risk and sex- and age-specific incidence rates for the Danish background population in 1995. RESULTS: The cohort was followed-up for a median of 19 years, or 22,290 person-years. A total of 124 malignancies were observed compared with 139.85 expected (SMR, .89; 95% CI, .74-1.07). The observed number of CRCs was almost exactly equal to expected: 13 cases vs. 12.42 (SMR, 1.05; 95% CI, .56-1.79). The cumulative probability of CRC was .4% by 10 years, 1.1% by 20 years, and 2.1% by 30 years of disease. Among men, melanoma was increased (SMR, 3.45; 95% CI, 1.38-7.10); otherwise, no increased risk for cancer could be detected. No hepatobiliary cancers and no increased risk for lymphoma or leukemia were found. CONCLUSIONS: Neither the overall cancer risk, nor the CRC risk, were increased in this population-based cohort after a median of 19 years of follow-up evaluation. An active surgical approach in medical treatment failures and long-term use of 5-aminosalicylic acid (5-ASA) as relapse prevention may explain this remarkable result.

Winther KV, Jess T, Langholz E, Munkholm P, Binder V. · Department of Medical Gastroenterolgy C, Herlev Hospital, University of Copenhagen, Denmark. · Gastroenterology. · Pubmed #14724807 No free full text.

Abstract: BACKGROUND & AIMS: A population-based cohort from Copenhagen County comprising 1160 patients diagnosed with ulcerative colitis between 1962 and 1987 was followed-up until 1997 to describe survival and cause-specific mortality. METHODS: Observed vs. expected deaths were presented as standardized mortality ratio (SMR) with exact 95% confidence intervals (CI) calculated by using individually registered person-years at risk and Danish 1995 mortality rates. Cumulative survival curves were calculated. RESULTS: A total of 261 deaths occurred, not significantly different from the expected number of 249 (SMR, 1.05; 95% CI, 0.92-1.19). The median age at death among men was 70 years (range, 6-96 years) and among women 74 years (range, 25-96 years). Twenty-five deaths (9.6%) were caused by complications to ulcerative colitis, mostly infectious and cardiovascular postoperative complications. Patients older than 50 years of age at diagnosis and with extensive colitis showed an increased mortality within the first 2 years because of ulcerative colitis-associated causes. The mortality from colorectal cancer was not increased and that of cancer in general was significantly lower than expected: 50 vs. 71 (SMR, 0.70; 95% CI, 0.52-0.93). A significantly increased mortality from pulmonary embolism and pneumonia was found. Among women only, death from genitourinary tract diseases and suicide was significantly increased. CONCLUSIONS: Despite an overall normal life expectancy for patients with ulcerative colitis, patients >50 years of age and with extensive colitis at diagnosis had increased mortality within the first 2 years after diagnosis, owing to colitis-associated postoperative complications and comorbidity.