Jayne Eaden

The risk of colorectal cancer in ulcerative colitis: a meta-analysis

BACKGROUND AND AIMS Controversy surrounds the risk of colorectal cancer (CRC) in ulcerative colitis (UC). Many studies have investigated this risk and reported widely varying rates. METHODS A literature search using Medline with the explosion of references identified 194 studies. Of these, 116 met our inclusion criteria from which the number of patients and cancers detected could be extracted. Overall pooled estimates, with 95% confidence intervals (CI), of cancer prevalence and incidence were obtained using a random effects model on either the log odds or log incidence scale, as appropriate. RESULTS The overall prevalence of CRC in any UC patient, based on 116 studies, was estimated to be 3.7% (95% CI 3.2–4.2%). Of the 116 studies, 41 reported colitis duration. From these the overall incidence rate was 3/1000 person years duration (pyd), (95% CI 2/1000 to 4/1000). The overall incidence rate for any child was 6/1000 pyd (95% CI 3/1000 to 13/1000). Of the 41 studies, 19 reported results stratified into 10 year intervals of disease duration. For the first 10 years the incidence rate was 2/1000 pyd (95% CI 1/1000 to 2/1000), for the second decade the incidence rate was estimated to be 7/1000 pyd (95% CI 4/1000 to 12/1000), and in the third decade the incidence rate was 12/1000 pyd (95% CI 7/1000 to 19/1000). These incidence rates corresponded to cumulative probabilities of 2% by 10 years, 8% by 20 years, and 18% by 30 years. The worldwide cancer incidence rates varied geographically, being 5/1000 pyd in the USA, 4/1000 pyd in the UK, and 2/1000 pyd in Scandinavia and other countries. Over time the cancer risk has increased since 1955 but this finding was not significant (p=0.8). CONCLUSIONS Using new meta-analysis techniques we determined the risk of CRC in UC by decade of disease and defined the risk in pancolitics and children. We found a non-significant increase in risk over time and estimated how risk varies with geography.

Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002)

The British Society of Gastroenterology (BSG) and the Association of Coloproctology for Great Britain and Ireland (ACPGBI) commissioned this update of the 2002 guidance. The aim, as before, is to provide guidance on the appropriateness, method and frequency of screening for people at moderate and high risk from colorectal cancer. This guidance provides some new recommendations for those with inflammatory bowel disease and for those at moderate risk resulting from a family history of colorectal cancer. In other areas guidance is relatively unchanged, but the recent literature was reviewed and is included where appropriate.

AGA medical position statement on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease.

The AGA Institute Medical Position Panel consisted of the authors of the technical review, a community-based gastroenterologist (Robert P. McCabe, MD, Minnesota Gastroenterology), academic-based gastroenterologists (Themistocles Dassopoulos, MD, James D. Lewis, MD, and Thomas A. Ullman, MD), an insurance provider representative (Tom James III, MD Physician Advisor, Strategic Advisory Group, Humana), a colon and rectal surgeon (Robin McLeod, MD, Mount Sinai Hospital-Canada), a pathologist (Lawrence J. Burgart, MD, Minnesota Gastroenterology), chair of the AGA Institute Clinical Practice and Quality Management Committee (John Allen, MD, Minnesota Gastroenterology), and chair of the Practice Management and Economics Committee (Joel V. Brill, MD, Predictive Health, LLC) .

AGA Technical Review on the Diagnosis and Management of Colorectal Neoplasia in Inflammatory Bowel Disease

This article has an accompanying continuing medical education activity on page e12. Upon completetion of reading this article, successful learners will be able to: 1. Understand the predisposing and protective factors for the development of colorectal neoplasia in patients with IBD 2. Understand the natural history of flat and raised dyspla-sia 3. Review the indications for colectomy in patients with flat and raised dysplasia 4. Review surveillance guidelines in patients with IBD 5. Understand the role of chromoendoscopy in detecting colorectal neoplasia in patients with IBD 6. Review the data on the use of chemopreventive agents to lower the risk of colorectal neoplasia in patients with IBD C olorectal carcinoma (CRC) complicating ulcerative co-litis (UC) was first recognized in 1925 by Crohn and Rosenberg, 1 but it was not until 1948 that Warren and Sommers reported CRC in a patient with Crohns disease (CD). 2 There has been much dispute regarding the magnitude of risk in both of these conditions. For many years it was believed that the risk in CD was insignificant. However, it is now recognized that the risk of developing CRC is equivalent, in both conditions given a similar extent and duration of disease. Inflammatory bowel disease (IBD) is relatively rare in the general population. Consequently Ͻ1% of all cases of CRC are attributable to IBD. However, it remains 1 of the 3 high-risk conditions predisposing to CRC, along with fa-milial adenomatous polyposis and Lynch Syndrome. Patients have up to a 1 in 5 chance of developing CRC after 30 years of disease. 3 Thus, it is an important issue for both the patient and the physician. The risk is not equivalent for all patients and depends on a number of factors. This necessitates an individualized and sensible approach to surveillance in patients with IBD. Patients with long-term UC have an increased risk of CRC, but the magnitude has been difficult to estimate. A number of factors have rendered the magnitude difficult to assess. First, a direct comparison between studies is difficult because of inconsistent methods used to calculate risk. Some studies reported the cumulative risk of developing CRC in a given population of patients with IBD, but unfortunately, many assume that all subjects have the same risk. Other studies have calculated the risk of CRC in IBD cohorts as a standardized incidence ratio (SIR) compared with a control population. These estimates can be adjusted for age …

Colorectal carcinoma and inflammatory bowel disease

The risk of colorectal cancer for any patient with ulcerative colitis is estimated to be 2% after 10 years, 8% after 20 years and 18% after 30 years of disease. The relative risk of colorectal cancer in Crohns colitis is approximately 5.6 and should raise the same concerns as in ulcerative colitis. Risk factors for colorectal cancer include disease duration, early onset, extensive disease, primary sclerosing cholangitis and a family history of sporadic colorectal cancer. All patients should have a review colonoscopy 8–10 years after diagnosis to establish the extent of the disease. Surveillance should begin 8–10 years after disease onset for pancolitis and 15–20 years after disease onset for left‐sided disease. Regular surveillance is recommended, with a screening interval every 3 years in the second decade of disease and annually by the fourth decade. Random biopsies should be taken at regular intervals with attention paid to dysplasia‐associated lesions or masses, irregular plaques, villiform elevations, ulcers and strictures. Dysplasia is recognized as a premalignant condition, but the likelihood of progression to cancer is difficult to predict. High‐grade dysplasia, confirmed by two expert gastrointestinal pathologists, is a strong indication for colectomy, as is low‐grade dysplasia, although the diagnosis of low‐grade dysplasia is unreliable. Surveillance programmes indicate that the overall 5‐year survival rate is higher in surveyed patients, although patients still present with Dukes C cancers or disseminated malignancy. Surveillance has huge socioeconomic implications. As surveillance is not 100% effective, alternative ways of reducing the cancer risk with chemopreventive agents, such as aminosalicylates, are being considered.

Review article: the data supporting a role for aminosalicylates in the chemoprevention of colorectal cancer in patients with inflammatory bowel disease.

The chemoprevention of colorectal cancer (CRC) with long‐term sulfasalazine and 5‐aminosalicyclic acid (5‐ASA) treatment has been demonstrated through epidemiological and experimental studies, in patients with ulcerative colitis. In a large case‐controlled study, there was a trend for long‐term nonsteroidal anti‐inflammatory consumption to be protective against CRC in patients with inflammatory bowel disease (IBD) (OR, 0.84). Sulfasalazine treatment over a 3‐month period was shown to be protective (OR, 0.38), independently of disease activity. A longer‐term study of sulfasalazine also revealed a relationship with treatment compliance, where 3% of compliant patients developed CRC compared with 31% of the noncompliers. Treatment with 5‐ASA was associated with an increase in apoptosis, a decrease in proliferation of colorectal mucosa and has been shown to lower the rate of spontaneous mutation.

Modifiable factors associated with nonadherence to maintenance medication for inflammatory bowel disease.

Background: Poor adherence frequently impaired the efficacy of therapy to maintain remission from inflammatory bowel diseases (IBD). There is a lack of practical and effective interventions to improve adherence. This study aimed to identify modifiable risk factors, which may yield targets for new interventions. Methods: Participants with IBD were recruited from hospital outpatient clinics and office-based gastroenterologists. Demographic and disease-related data were recorded by means of self-administered questionnaires. Modifiable risk factors were assessed with the validated Belief about Medicine Questionnaire, Hospital Anxiety and Depression Score, and short inflammatory bowel disease questionnaire. Adherence was assessed separately for 5-aminosalicylates, thiopurines, and biological agents using the validated Medicine Adherence Report Scale (good adherence defined as >16). Results: Nonadherence occurred in 102 of 356 participants (28.7%). Adherence increased significantly with more aggressive therapies (median Medicine Adherence Report Scale: 5-aminosalicylates 18, thiopurines 19, biological 20; P < 0.0001). Nonadherence was not associated with anxiety and depression or disease-related patient knowledge. Adherent patients had significantly higher belief of necessity for medication (P < 0.0001) and a trend toward lower concerns about medication (P = 0.08). Membership of an IBD patient organization was associated with better adherence (P < 0.0001). Concerns about medication rose significantly with more aggressive therapies (P = 0.009), but belief of necessity was similar for all medications. Conclusions: Nonadherence occurs most frequently with 5-aminosalicylates. Belief of necessity may prove the key target for future interventions, although general IBD education is unlikely to yield an adherence benefit. Patient organization membership should be encouraged.

Cancer Prevention in Inflammatory Bowel Disease and the Chemoprophylactic Potential of 5-Aminosalicylic Acid

The risk of colorectal cancer is increased in ulcerative colitis and Crohns colitis. Regular dysplasia surveillance colonoscopy in chronic colitis generally has been adopted as a strategy to prevent colorectal cancer or at least to diagnose it in an earlier stage. This has not been proven to reduce mortality, but it does provide the clinician and the patient with some confidence that they are participating in an active strategy to deal with the problem of colorectal cancer in chronic colitis. Disease extent and duration have long been held to be risk factors for colorectal cancer in chronic colitis, and recently some special risk groups have been identified which may require either more intensive surveillance or alternative approaches to cancer prevention. These include patients with primary sclerosing cholangitis, patients with first-degree relatives with sporadic colon cancer, and possibly, patients with backwash ileitis. There is an emerging interest in potential chemopreventative strategies in both sporadic and colitis-associated colorectal cancer. There also have been suggestive data that chronic maintenance 5-aminosalicylate use might reduce the risk of developing colorectal cancer. Recent data have suggested some potential preventative benefit of using ursodeoxycholic acid in patients with ulcerative colitis and primary sclerosing cholangitis. The scientific rationale for using these agents is sound but clinical data are lacking to fully support these approaches as chemoprevention in chronic colitis at present.

Patients' knowledge of pregnancy‐related issues in inflammatory bowel disease and validation of a novel assessment tool (‘CCPKnow’)

Inflammatory bowel diseases (IBD) require complex therapeutic decisions and life choices concerning pregnancy, but little is known about patients knowledge of IBD and its treatment before and during pregnancy.

Better disease specific patient knowledge is associated with greater anxiety in Inflammatory Bowel Disease

BACKGROUND Inflammatory bowel disease (IBD)-related knowledge not only empowers patients, but may also engender anxiety. The study aimed to identify predictors of anxiety in IBD and examine the interplay between anxiety and disease-related patient knowledge. The effect of anxiety on quality of life was also explored. METHODS Ambulatory IBD patients provided data on demographics, their IBD and Crohns Colitis Association (CCA) membership status. Disease-related knowledge was assessed using the validated Crohns and Colitis Knowledge score (CCKnow) and disease related QOL using the short IBD questionnaire (SIBDQ). Anxiety and depression were assessed with the Hospital Anxiety and Depression Scores. RESULTS Of the 258 patients 19.4% had a potential anxiety and a further 22.4% had a probable anxiety disorder. Females (P=0.003), tertiary care patients (P=0.014) and non-Caucasian patients (P=0.037) had significantly higher anxiety levels. CCA members had marginally higher levels of anxiety (P=0.07). Anxiety was associated with significantly better patient knowledge (P=0.016) and increased depression (P<0.001). Disease related quality of life was significantly lower in patients with anxiety (P<0.001). CONCLUSIONS This is the first study to demonstrate that better patient knowledge is associated with higher anxiety levels. The reason for this is unclear: educating patients about their disease might trigger anxiety, but, equally, anxious patients might seek out information and hence have better knowledge. It is thus noteworthy that an educational intervention may not necessarily reduce anxiety. Further work is needed to evaluate the association between anxiety and knowledge and to develop targeted interventions that will improve knowledge and simultaneously reduce anxiety.