Ulcerative colitis and colorectal cancer: a follow-up study in Fukuoka, Japan.

BACKGROUND: Our goal was to study the higher death rate and the causes of such deaths among ulcerative colitis (UC) patients in the Japanese population, and to compare our findings in such cases with those for Crohn's disease (CD). METHODS: In all, 174 UC (male/female: 54/120) and 66 CD (34/32) patients who were registered for the research promotion programme in Fukuoka prefecture (1971-1981) were traced up to the end of 1994. The standardized mortality ratios (SMR) were calculated based on the death rates of the Japanese population by age, sex and calendar year. RESULTS: The overall follow-up rate was 96.7%. Among the UC patients, the SMR for all causes were 0.84 (95% CI: 0.11-4.31) for men; 1.05 (95% CI: 0.08-4.69) for women; and 0.94 (95% CI :0.09-4.50) for both sexes combined. When excluding deaths due to colorectal cancer, the SMR for the same groups were 0.43, 0.94 and 0.67, respectively. The SMR for both sexes were 1.82 (95% CI: 0.17-5.96) for malignant neoplasms and 9.93 (95% CI: 4.67-17.3) for colorectal cancer. Patients who died from colorectal cancer showed onset at a younger age (mean: 25.5 years) as well as a longer disease course of UC (mean: 17.0 years). Regarding the CD patients, the SMR for all causes were 1.75 (95% CI: 0.15-5.75) for both sexes. Most deaths were caused by gastrointestinal complications. CONCLUSIONS: An excess mortality from colorectal cancers was indicated in the UC patients, especially in males. The overall SMR in male UC patients decreased by 50% when the deaths from colorectal cancer were excluded. The excess mortality in those with CD over UC patients was attributed to gastrointestinal complications rather than malignant diseases. Some carcinogenic factors therefore seem most likely to exist in the pathogenesis of UC.     

Uptake of influenza vaccine in ulcerative colitis

Background

The incidence of vaccine-preventable-disease is increasing. Current practice guidelines recommend annual influenza vaccination for all inflammatory bowel disease (IBD) patients.

Study

Using the Business Objects database of Clalit Health Services in the Tel Aviv district we identified all patients over 18 years-old with a diagnosis of ulcerative colitis (UC) on 31.12.05. This cohort was followed until 31.12.12. Subjects over age 50 without IBD who are also targeted for influenza vaccination served as controls. The uptake of annual influenza vaccination was recorded.

Results

470 UC patients were included (241 (51.3%) males, age 50.4 ± 18.4 years, disease duration 158.9 ± 86.5 months), and 2960 controls. During the years 2006, 2007, 2008, 2009, 2010, 2011 and 2012 the uptake of influenza vaccination was 101 (21.5%), 122 (26.0%), 147 (31.3%), 181 (38.5%), 177 (37.7%), 170 (36.2%) and 178 (37.9%) amongst UC patients, and 993 (33.5%), 1360 (45.9%), 1524 (51.5%), 1611 (54.4%), 1446 (48.9%), 1576 (53.2%) and 1557 (52.6%) amongst controls (p < 0.0001 for every year). Independent predictors of vaccination included age (OR, 1.05; 95% CI, 1.03–1.06; p < 0.001) and cardiovascular risk (OR, 1.81; 95% CI, 1.31–2.49; p < 0.01).

Conclusions

Although uptake influenza vaccination is consistently lower in UC compared to controls, an upward trend was observed over the study period. Public health initiatives should target this high-risk population to promote immunization.     

肠内营养在溃疡性结肠炎治疗中的应用

目的:研究EN支持在溃疡性结肠炎(UC)治疗中的适应证、耐受性、不良反应和疗效.方法:回顾分析220例活动期UC病人,有85例应用EN支持.结果:应用EN支持者,全结肠型占(70.6%)明显多于左半结肠型(18.8%)、直肠乙状结肠型(9.4%)和直肠型(1.2%);重度(56.5%)多于中度(32.9%)及轻度(10.6%).EN组病人BMI<18 kg/m2比例明显高于对照组(P<0.05);ALB水平(28.91±6.64)g/L低于对照组(36.03±6.59)g/L.不同类型EN制剂增加至3 347 kJ/d时间无显著性差异(P>0.05).在不良反应中,腹泻的发生率为14.1%,占所有不良反应的57.1%;EN组与对照组比较,激素减量时间、手术率和缓解率无显著性差异(P>0.05).总蛋白、ALB、PA水平在EN支持后有显著提高(P<0.05).结论:①对病变范围广,中、重度的UC病人,应给予充足的EN;②对存在中、重度营养不良UC病人,应补充EN;③UC病人对不同类型营养制剂耐受性无差异,腹泻是最常见的不良反应;④EN可作为UC活动期的一种辅助治疗.     

Predictive factors of failure of intravenous corticosteroid treatment in acute severe colitis of Crohn's disease and ulcerative colitis

We conducted a retrospective study on 78 cases of acute severe colitis (Crohn's disease in 51 cases, ulcerative colitis in 27 cases). Diagnosis of acute severe colitis was based on presence of Truelove's criteria and/or endoscopical gravity lesions. Failure of corticoid treatment was observed in 35 patients (45%). In overall patients, predictive factors of failure of intravenous corticoid treatment in univariate analysis are diagnosis of ulcerative colitis, number of bloody stool higher than 6/day. level of C-reactive protein lower than 25 mg/l. visibility of muscular mucosa at colonoscopy, absence of decrease in erythrocyte-sedimentation rate for more than 50% of initial value at day 3 of treatment, absence of decrease in C-reactive protein for more than 50% of initial value at day 3 of treatment, and a lower duration of corticoid treatment. In multivariate analysis, independent predictive factors of failure of corticoid treatment are a number of bloody stool higher than 6/day (p=0.01 adjusted OR [CI95%]: 10.2 [1.15 - 72.06]) and a value of initial C-reactive protein lower than 25 mg/l (p < 0.0001 adjusted OR [CI95%] : 3.25 [2.95 - 4.31]). In Crohn's disease, the only independent predictive factor of failure of corticoid treatment is an absence of decrease of C-reactive protein level for more than 50% of initial value at day 3 of treatment (p = 0.001 adjusted OR [CI95%] : 0.79 [0.45-0.95]). Existence of these predictive factors allows the early identification of patients who would be suitable for second-line therapy.     

血清IL-18与溃疡性结肠炎的关系

目的 探讨IL-18在溃疡性结肠炎(UC)发病、发展和治疗中的作用.方法 采用双抗体夹心ELISA法检测58例UC患者外周血中IL-18水平,并分别比较其与临床活动指数(CAI)和ESR、CRP等的相关性.结果 UC活动期患者血清IL-18水平较缓解期患者和健康对照者明显升高(P<0.05),而缓解期患者与健康对照者比较差异无统计学意义.重度UC患者血清IL-18水平[(392.78±50.17)pg/ml]明显高于中度UC患者[(138.92±23.41)pg/ml]和健康对照者[(73.76±20.27)pg/ml],但轻、中度UC之间差异无统计学意义.病变的范围越大,水平越高(P<0.05).并与临床指标ESR、CRP、WBC计数呈正相关.与CAI呈正相关(r=0.775,P<0.01).激素治疗后IL-18显著性下降.结论 IL-18可能参与UC的发病,血清IL-18可作为UC判断病情和活动性的参考指标.     

溃疡性结肠炎病因的Meta分析

目的 分析溃疡性结肠炎(UC)发病的相关因素。方法 计算机检索英文数据库PubMed、Cochrane、Embase及中文数据库中国知网(CNKI)、万方数据知识服务平台(Wanfang)、中国生物医学文献服务系统(SinoMed)与维普期刊资源整合服务平台(VIP),纳入2000年1月至2014年10月有关UC病因的相关文献。根据纳入与排除标准筛选文献,提取资料和评价质量后采用Stata 12.0软件进行Meta分析。结果 共纳入24篇文献,合计病例组5 653例,对照组20 218例。Meta分析显示,炎症性肠病家族史、戒烟、胃肠道感染史、经常饮用牛奶、油脂饮食、阑尾切除术、吸烟和接受高等教育与UC发病相关,其OR值(95%CI)分别为4.68(3.59～6.11)、1.81(1.58～2.09)、5.10(2.38～10.92)、2.26(1.65～3.09)、2.21(1.49～3.27)、0.40(0.32～0.51)、0.44(0.32～0.60)和0.50(0.36～0.69)。结论 炎症性肠病家族史、戒烟、胃肠道感染史、经常饮用牛奶和油脂饮食是目前UC的危险因素,而吸烟、阑尾切除术以及接受高等教育为保护因素。     

Crohn's disease, ulcerative colitis, and measles vaccine in an English population, 1979-1998

STUDY OBJECTIVE:s: To study the hospitalised incidence of Crohn's disease (CD) and ulcerative colitis (UC) from 1979 to 1998; and to determine whether the introduction of the measles vaccination programme was associated with an increase in the young. DESIGN: Analysis of linked data on hospital admissions; a cohort analysis of the effect of the measles vaccination programme on the incidence of hospitalised CD and UC; and a comparison of these results with those from previous studies on the association between measles vaccine and CD or UC. SETTINGS: Southern England. SUBJECTS: People admitted to hospital with a main diagnosis of CD (1959 people) or UC (2018 people). MAIN RESULTS: Overall, the incidence of hospitalised CD showed no significant change over the 20 year period: the average change per year was 0.08% (95% confidence interval: -0.7% to 0.9%). The relative risk associated with the measles vaccination programme was not significant (0.91: 0.5 to 1.4). The estimate differed significantly from the relative risk of 3.0 obtained in the original study reporting an association, but agreed with the combined estimate from three subsequent studies (0.95: 0.6 to 1.5). The results for UC were similar. CONCLUSIONS: The incidence of hospitalised CD and UC remained stable over the 20 years, 1979 to 1998. Whatever caused the marked increases in CD and UC in the mid-20th century must itself have stabilised in this region. These results, together with those from other studies, provide strong evidence against measles vaccine causing CD or UC.     

Frequency of proximal colonic extension of distal ulcerative colitis

AIMS: To evaluate the frequency of colonic extension in patients with rectal or rectosigmoidal forms of ulcerative colitis and to look for factors associated with a higher risk of proximal colonic extension. METHODS: We conduct a retrospective study on cases of ulcerative colitis limited to the rectum and the rectosigmoid followed up at least for 6 months. Colonic extension was defined by apparition of endoscopic features of ulcerative colitis in initially normal segments of the colon. RESULTS: From 1984 to 2004, 70 patients with distal ulcerative colitis were studied. Initial location was the rectum in 25 cases and the rectosigmoid in 45 cases. After a mean follow-up of 49.4 months, proximal colonic extension was observed in 7 cases (10%), with an actuarial frequency of 12% at 5 years, 20% at 10 years and 20% at 20 years. Patients with colonic extension had a higher number of relapses compared to patients without extension (4.28 +/- 1.36 vs. 1,41 +/- 1.22, p = 0.001). Age, sex-ratio, initial location, maintenance therapy and diagnosis of refractory distal colitis were not associated with a higher risk of colonic extension. CONCLUSION: Colonic extension in our population occurs during the first years after the diagnosis of distal ulcerative colitis. Patients with more relapses are at increased risk of proximal colonic extension.     

Small-area variations and sociodemographic correlates for the incidence of Crohn's disease and ulcerative colitis

The objectives of this study were to describe variations in the incidence of inflammatory bowel disease (IBD) within the Canadian province of Manitoba and to analyze sociodemographic factors associated with these variations. The authors used the Manitoba Health insurance databases to measure incidence rates of Crohn's disease and ulcerative colitis for each of 52 postal areas in Manitoba, in 1987-1996. The sociodemographic characteristics of the postal areas were based on data from the 1996 Canadian census. The overall incidence rates of Crohn's disease and ulcerative colitis were identical-15.6 per 100,000. Both diseases showed substantial geographic variation, with incidence rates differing significantly from the provincial average in 15 postal areas for Crohn's disease and in 13 postal areas for ulcerative colitis. There was a significant geographic correlation in the incidence of Crohn's disease and ulcerative colitis (r = 0.49, p < 0.001). The incidence of IBD was higher in urban areas (incidence rate ratio (IRR) = 1.21, 95% confidence interval (CI): 1.00, 1.45). Aboriginal Canadians had significantly lower rates of both Crohn's disease (IRR = 0.11, 95% CI: 0.05, 0.22) and ulcerative colitis (IRR = 0.57, 95% CI: 0.42, 0.79). A higher incidence of IBD was ecologically associated with a higher average family income, a lower proportion of immigrant and Aboriginal Canadian populations, and a smaller average family size.     

Medical therapy of inflammatory bowel diseases: ulcerative colitis

There are fewer significant changes in the medical therapy of ulcerative colitis (UC) compared to Crohn's disease. The most important factors that determine therapy are disease extent and severity. 5-aminosalicylates (5-ASA) constitute the treatment of choice in mild-to-moderate UC. The efficacy of new compounds (e.g. mesalazine) is only mildly improved compared to sulphasalazine; however, their use has become more frequent due to a more favorable side effects profile. Topical medication is more effective in proctitis and distal colitis, and the combination of topical and orally-administered drugs is superior to oral therapy alone also in extensive disease. Thus, this latter regimen should be considered for cases where the escalation of treatment is required. Systemic steroids still represent the first line therapy in acute, severe UC, while in patients who do not respond to steroids, cyclosporine and infliximab should be considered as a second line therapy and as alternatives for colectomy. Maintenance treatment is indicated in all UC cases. 5-ASA compounds are suggested as first line maintenance therapy with the optimal dose still being under investigation. Topical compounds are effective also for maintenance in distal colitis or proctitis, if accepted by the patients. Immunosuppressives, especially azathioprine, should be considered in chronically active, steroid dependent or resistant patients. According to recent publications, azathioprine is almost equally effective in UC and CD. The question of chemoprevention is important during maintenance. There are increasing data supporting the notion that aminosalicylates may lower the risk for UC-associated colorectal cancer. The most important changes in the management of UC are the more frequent use of topical aminosalicylates and azathioprine, the availability of infliximab in severe UC, and increasing use of aminosalicylates for chemoprevention of colorectal carcinoma. Furthermore, adequate attention is needed to better organize the patient-doctor relationship and for greater adherence to medical therapy.     

粪便钙卫蛋白对溃疡性结肠炎的诊断及预测复发的价值

目的:探讨粪便钙卫蛋白在溃疡性结肠炎(UC)诊断和预测复发方面的价值.方法:选取UC病人49例、结肠息肉38例和对照组133例,均行结肠镜检查,于检查前1d内留取粪便,采用ELISA法测定粪便钙卫蛋白的含量.UC临床分级采用Mayo疾病活动指数(UCAI),评价粪便钙卫蛋白测定作为判断UC活动性的指标,随访UC病人2年...     

Possible treatment modalities of primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic progressive liver disease with the segmental inflammation, obliterative fibrosis and cholestasis of intra- and extrahepatic biliary ducts which leads to secondary biliary cirrhosis. Its aetiology is unknown. The disease is accompanied with ulcerative colitis in 70-80 percent. Its clinical progress is variable, the average duration of the disease is between the diagnosis and the final stage (liver transplantation) about 18 years. The prevalence of PSC is 1-5/100 000 inhabitants. Mainly it occurs in male patients (70 %), male-female rate is 2:1. The authors summarise the treatment modalities after reviewing the pathogenesis, clinical picture and the diagnostic procedures. The pathomechanism of the basis therapy with ursodeoxycholic acid (UDCA) is discussed in details, especially its effects on the clinical picture and the laboratory data. The authors review the results of the immunosuppressive therapy and the treatments of specific complications in PSC. They underline the importance and opportunities of the early diagnosis of cholangiocarcinoma, which is very frequent in this disease.     

Immunogenetics of chronic ulcerative colitis

Genetic factors have a definitive role in the etiology of ulcerative colitis (UC). The mode of inheritance suggests a polygenic disease with the penetrance of the genetic factors being strongly influenced by environmental factors. Several studies have been reported associations between UC and the polymorphism of genes that are located in the major histocompatibility complex (MHC) on the short arm of chromosome 6. The human leukocyte antigen (HLA) class II genes are candidates for a role in the pathogenesis of UC, because their products play a central role in the immune response. The MHC region contains numerous immune related genes, and it has now become clear that different alleles of the MHC genes are strongly linked. Association studies have suggested a role for HLA-DR alleles in disease susceptibility to UC. Thus, HLA-DRB1*0103, DRB1*1502 and DRB1*12 were found to be positively associated with UC. On the other hand, the tumor necrosis factor alpha (TNF-alpha) gene encodes a proinflammatory cytokine that is found in increased concentrations in the mucosa of patients with inflammatory bowel disease. The regulation of TNF expression is in part genetically determined because the polymorphisms -238, -308, -863, -857, and -1031 found in the promoter region are associated with increased TNF production. Recent data suggests that TNF polymorphism may be more important in determining susceptibility to UC and these TNF markers could predict response to infusion with chimeric anti-TNF antibody.     

The course of illness in ulcerative colitis

The data of 301 ulcerative proctitis/colitis patients, with a mean follow-up of 10 (1/2-26) years were analysed retrospectively. In 84 patients (28%) the diagnosis was made in this hospital (non-selected group), the other 217 patients were referred from other hospitals with an established diagnosis of ulcerative colitis. At any time after the fifth year of illness approximately 55% of the non-selected patients were free of symptoms, for the referred patients this proportion was 30%. In one half of the cases the inflammation started as a proctitis, almost 60% of these progressed to colitis later. Fourteen patients (5%) had a toxic megacolon, and a colon carcinoma developed in 9 patients (3%) on average 13 years after the first symptoms of colitis. We recorded 9 colitis-related deaths. Fifty patients (17%) underwent a colectomy, mostly because of failure of conservative therapy.     

溃疡性结肠炎发病机制研究进展

溃疡性结肠炎(UC)是一种慢性特发性炎症性疾病,包括从直肠开始的结肠的任何部分,其典型症状包括血性腹泻、黏液脓血便、腹痛和里急后重。该病的临床表现通常决定了治疗药物的选择,治疗目标是首先诱导缓解临床症状,然后维持无皮质类固醇缓解临床症状。目前UC发病机制并未完全阐明,大多数研究认为UC是一种遗传因素为背景,后天社会、心理、生理因素为诱发因素的复杂疾病。同时也有证据显示UC是一种自身免疫性疾病。在一些UC患者中观察到结肠硫酸盐还原菌数量增加,导致有毒气体硫化氢浓度升高。硫化氢通过阻断β-氧化途径中的短链乙酰辅酶a脱氢酶,在破坏β-氧化途径中起作用。吸烟对UC的保护作用是由于香烟烟雾中的氰化氢与硫化氢反应生成无毒的异硫氰酸盐,抑制了硫化物干扰这一途径。本文对近年来关于UC发病机制的研究作一综述,以期为临床UC的诊治提供一定的参考。     

Anti-TNF-alpha therapy in ulcerative colitis

The most important factors that determine treatment strategy in ulcerative colitis (UC) are disease extent and severity. Orally-topically administered 5-aminosalicylates (5-ASA) remain the treatment of choice in mild-to-moderate UC. In contrast, the treatment of refractory (to steroids, azathioprine or 5-ASA) and fulminant cases is still demanding. New evidence supports a role for infliximab induction and/or maintenance therapy in these subgroup of patients leading to increased remission and decreased colectomy rates. The aim of this paper is to review the rationale for the use of TNF-alpha inhibitors in the treatment of UC.     

治疗溃疡性结肠炎的现状与进展

溃疡性结肠炎（ulcerative colitis,UC）是消化内科常见疾病,对本病的治疗要点是阻断炎症过程,达到消除炎症的目的.近几年有很多新疗法的研究,尤以免疫治疗和生物治疗较为突出.本文主要对近几年该病的治疗现状与进展作一综述.     

Malnutrition and impaired muscle strength in patients with Crohn's disease and ulcerative colitis in remission

OBJECTIVE: This prospective, controlled, and multicentric study evaluated nutritional status, body composition, muscle strength, and quality of life in patients with inflammatory bowel disease in clinical remission. In addition, possible effects of gender, malnutrition, inflammation, and previous prednisolone therapy were investigated. METHODS: Nutritional status (subjective global assessment [SGA], body mass index, albumin, trace elements), body composition (bioelectrical impedance analysis, anthropometry), handgrip strength, and quality of life were assessed in 94 patients with Crohn's disease (CD; 61 female and 33 male, Crohn's Disease Activity Index 71 +/- 47), 50 patients with ulcerative colitis (UC; 33 female and 17 male, Ulcerative Colitis Activity Index 3.1 +/- 1.5), and 61 healthy control subjects (41 female and 20 male) from centers in Berlin, Vienna, and Bari. For further analysis of body composition, 47 well-nourished patients with inflammatory bowel disease were pair-matched by body mass index, sex, and age to healthy controls. Data are presented as median (25th-75th percentile). RESULTS: Most patients with inflammatory bowel disease (74%) were well nourished according to the SGA, body mass index, and serum albumin. However, body composition analysis demonstrated a decrease in body cell mass (BCM) in patients with CD (23.1 kg, 20.8-28.7, P = 0.021) and UC (22.6 kg, 21.0-28.0, P = 0.041) compared with controls (25.0 kg, 22.0-32.5). Handgrip strength correlated with BCM (r = 0.703, P = 0.001) and was decreased in patients with CD (32.8 kg, 26.0-41.1, P = 0.005) and UC (31.0 kg, 27.3-37.8, P = 0.001) compared with controls (36.0 kg, 31.0-52.0). The alterations were seen even in patients classified as well nourished. BCM was lower in patients with moderately increased serum C-reactive protein levels compared with patients with normal levels. CONCLUSION: In CD and UC, selected micronutrient deficits and loss of BCM and muscle strength are frequent in remission and cannot be detected by standard malnutrition screening.     

Mortality among patients with ulcerative colitis: Rome 1970--1989

The aim of this study was to analyze the pattern of mortality among patients with ulcerative colitis (UC) and compare it with mortality in the general population of the same age and sex. All patients with UC admitted to one of the Inflammatory Bowel Disease Clinics in Rome, from January 1970 to December 31, 1989 were enrolled. Vital status was ascertained through the Registry Office of the last municipality of residence as of July 1, 1990. Cause of death was ascertained through record linkage with the national or regional mortality file and coded using the ninth revision of the International Classification of Diseases. Standardized Mortality Ratios (SMRs) were computed to compare mortality among UC patients with mortality in the general population of the same age and sex. Out of a total of 508 UC patients admitted during the study period, 27 deaths were observed, compared with 27.6 expected (SMR = 98). After excluding prevalent cases, an excess risk of death was observed among newly diagnosed cases in the first year after diagnosis (SMR = 644; p < 0.001); ulcerative colitis was the main reason for this excess mortality. Mortality for other diseases was close to that expected. In conclusion, ulcerative colitis impairs life expectancy in the first year after diagnosis, while no excess mortality seems to be present afterwards.