M. W. M. D. Lutgens

High frequency of early colorectal cancer in inflammatory bowel disease

Background and aim: To detect precancerous dysplasia or asymptomatic cancer, patients suffering from inflammatory bowel disease often undergo colonoscopic surveillance based on American or British guidelines. It is recommended that surveillance is initiated after 8–10 years of extensive colitis, or after 15–20 years for left-sided disease. These starting points, however, are not based on solid scientific evidence. Our aim was to assess the time interval between onset of inflammatory bowel disease (IBD) and colorectal carcinoma (CRC), and subsequently evaluate how many patients developed cancer before their surveillance was recommended to commence. Methods: A nationwide automated pathology database (PALGA) was consulted to identify patients with IBD-associated colorectal carcinoma in seven university medical centres in The Netherlands between January 1990 and June 2006. Data were collected retrospectively from patient charts. Time intervals between onset of disease and cancer diagnosis were calculated in months. Results: 149 patients were identified with confirmed diagnoses of IBD and CRC (ulcerative colitis n = 89/Crohn’s disease n = 59/indeterminate colitis n = 1). Taking date of diagnosis as the entry point, 22% of patients developed cancer before the 8 or 15 year starting points of surveillance, and 28% if surveillance was commenced 10 or 20 years after diagnosis for extensive or left-sided disease, respectively. Using onset of symptoms to calculate the time interval, 17–22% of patients would present with cancer prior to the surveillance starting points. Conclusions: These results show that the diagnosis of colorectal cancer is delayed or missed in a substantial number of patients (17–28%) when conducting surveillance strictly according to formal guidelines.

Colonoscopic surveillance improves survival after colorectal cancer diagnosis in inflammatory bowel disease

Background:Colonoscopic surveillance provides the best practical means for preventing colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients. Strong evidence for improved survival from surveillance programmes is sparse.Method:The aim of this study was to compare tumour stage and survival of IBD patients with CRC who were a part of a surveillance programme with those who were not. A nationwide pathology database (PALGA (pathologisch anatomisch landelijk geautomatiseerd archief)) was consulted to identify IBD patients with CRC treated in all eight university hospitals in The Netherlands over a period of 15 years. Patients were assigned to the surveillance group when they had undergone one or more surveillance colonoscopies before a diagnosis of CRC. Patients who had not undergone surveillance served as controls. Tumour stage and survival were compared between the two groups.Results:A total of 149 patients with IBD-associated CRC were identified. Twenty-three had had colonoscopic surveillance before CRC was discovered. The 5-year CRC-related survival rate of patients in the surveillance group was 100% compared with 74% in the non-surveillance group (P=0.042). In the surveillance group, only one patient died as a consequence of CRC compared with 29 patients in the control group (P=0.047). In addition, more early tumour stages were found in the surveillance group (P=0.004).Conclusions:These results provide evidence for improved survival from colonoscopic surveillance in IBD patients by detecting CRC at a more favourable tumour stage.

More Right-sided IBD-associated Colorectal Cancer in Patients with Primary Sclerosing Cholangitis

Background: Patients with inflammatory bowel disease (IBD) and concurrent primary sclerosing cholangitis (PSC) have a higher risk of developing colorectal cancer (CRC) than IBD patients without PSC. The aim of this study was to investigate potential clinical differences between patients with CRC in IBD and those with CRC in IBD and PSC, as this may lead to improved knowledge of underlying pathophysiological mechanisms of CRC development. Methods: The retrospective study from 1980–2006 involved 7 Dutch university medical centers. Clinical data were retrieved from cases identified using the national pathology database (PALGA). Results: In total, 27 IBD‐CRC patients with PSC (70% male) and 127 IBD‐CRC patients without PSC (59% male) were included. CRC‐related mortality was not different between groups (30% versus 19%, P = 0.32); however, survival for cases with PSC after diagnosing CRC was lower (5‐year survival: 40% versus 75% P = 0.001). Right‐sided tumors were more prevalent in the PSC group (67% versus 36%, P = 0.006); adjusted for age, sex, and extent of IBD, this difference remained significant (odds ratio: 4.8, 95% confidence interval [CI] 2.0–11.8). In addition, tumors in individuals with PSC were significantly more advanced. Conclusions: The right colon is the predilection site for development of colonic malignancies in patients with PSC and IBD. When such patients are diagnosed with cancer they tend to have more advanced tumors than patients with IBD without concurrent PSC, and the overall prognosis is worse. Furthermore, the higher frequency of right‐sided tumors in patients with PSC suggests a different pathogenesis between patients with PSC and IBD and those with IBD alone. (Inflamm Bowel Dis 2009)

Review article: the relevance of surveillance endoscopy in long-lasting inflammatory bowel disease

Background Development of colitis‐associated colorectal cancer is an important clinical problem in patients with colonic inflammatory bowel disease (IBD). British and American guidelines recommend to start surveillance after a disease duration of 8–10 or 15–20 years for patients with extensive or left‐sided colitis, respectively.

Easily obtainable clinical features increase the diagnostic accuracy for latent autoimmune diabetes in adults: An evidence-based report

BACKGROUND Latent autoimmune diabetes in adults (LADA) represents a subgroup of diabetes mellitus. LADA is characterised by adult-onset diabetes and circulating autoimmune antibodies. LADA patients may need a different therapeutic approach than the usual type 2 diabetes mellitus. When LADA is inadequately diagnosed as type 2 diabetes mellitus, LADA patients will mistakenly be exposed to a high dose of oral glucose lowering drugs and their possible side effects. AIM To assess which clinical features predict the presence or absence of LADA in patients older than 25 years presenting with hyperglycemia. METHODS A structured Medline and Embase search was conducted. Titles and abstracts were screened using predetermined selection criteria. Critical appraisal was based on standardized validity criteria for diagnostic research. RESULTS One-hundred and eighty-four papers were retrieved of which after assessment of relevance and validity 2 studies remained for further analysis. One study reported a probability of LADA of 0.99 with one or two out of the following five clinical features: age at onset <50 years; acute symptoms; BMI<25 kg/m(2); a history of autoimmune disease; a family history positive for diabetes mellitus. The other study reported a probability of LADA of zero with none of the following clinical features and of 0.32 with one out of three: fasting blood glucose> or =15 mmol/l and/or HbA(1c)> or =10%; 10% reduction in body weight in the previous 3 months; BMI<25 kg/m(2). CONCLUSION Further testing for LADA by measurement of autoimmune antibodies appears to be unnecessary in the absence of a specific set of clinical features. Before initiating therapy applying the above criteria may help to separate LADA from usual type 2 diabetes.

Disease severity does not affect the interval between IBD diagnosis and the development of CRC: Results from two large, Dutch case series

BACKGROUND The increased risk of colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) is well established. The incidence of IBD-related CRC however, differs markedly between cohorts from referral centers and population-based studies. In the present study we aimed to identify characteristics potentially explaining these differences in two cohorts of patients with IBD-related CRC. METHODS PALGA, a nationwide pathology network and registry in The Netherlands, was used to search for patients with IBD-associated CRC between 1990 and 2006. Patients from 7 referral hospitals and 78 general hospitals were included. Demographic and disease specific parameters were collected retrospectively using patient charts. RESULTS A total of 281 patients with IBD-associated CRC were identified. Patients from referral hospitals had a lower median age at IBD diagnosis (26 years vs. 28 years (p=0.02)), while having more IBD-relapses before CRC diagnosis than patients from general hospitals (3.8 vs. 1.5 (p<0.01)). In patients from referral hospitals, CRC was diagnosed at a younger age (47 years vs. 51 years (p=0.01)). However, the median interval between IBD diagnosis and diagnosis of CRC was similar in both cohorts (19 years in referral hospitals vs. 17 years in general hospitals (p=0.13)). CONCLUSIONS IBD patients diagnosed with CRC treated in referral hospitals in The Netherlands are younger at both the diagnosis of IBD and CRC than IBD patients with CRC treated in general hospitals. Although patients from referral centers appeared to have a more severe course of IBD, the interval between IBD and CRC diagnosis was similar.

Risk Factors for Rectal Stump Cancer in Inflammatory Bowel Disease

BACKGROUND: Patients with long-standing colitis carry an increased risk of colorectal cancer and are therefore enrolled in colonoscopic surveillance programs. It is presently not known if endoscopic surveillance of patients with colitis with a closed rectal stump after a subtotal colectomy is justified. Neither is it clear which of these patients might be at increased risk for rectal stump cancer. OBJECTIVE: The aim of this study is to identify the risk factors for rectal stump cancer. DESIGN: This investigation is a retrospective descriptive case-control study. SETTINGS: This study was conducted at tertiary referral centers in the Netherlands. PATIENTS: Colorectal cancer cases associated with inflammatory bowel disease diagnosed between 1990 and 2006 were selected in a nationwide pathology archive. Patients with rectal stump cancer were selected from this group. The pathology archive was also used to identify inflammatory bowel disease controls matched for referral center with a closed rectal stump after subtotal colectomy, but without neoplasia. Follow-up started at the date of subtotal colectomy with the formation of a rectal stump. Demographic and disease characteristics were collected at baseline. MAIN OUTCOME MEASUREMENTS: Hazard ratios with 95% confidence intervals were calculated for factors associated with the development of rectal stump cancer with the use of univariate Cox regression analysis. End points were rectal stump cancer, end of follow-up, or death. RESULTS: A total of 12 patients with rectal stump cancer and 18 matching controls without neoplasia were identified. Univariate analysis showed an association between rectal stump cancer and primary sclerosing cholangitis, and disease duration until subtotal colectomy. LIMITATIONS: This study is limited by its retrospective design, and, despite being the largest series to date, it still has a limited number of cases. CONCLUSIONS: Risk factors for rectal stump cancer in a closed rectal stump after subtotal colectomy were primary sclerosing cholangitis and disease duration until subtotal colectomy.

Oral Presentations5 COLONOSCOPIC SURVEILLANCE IN INFLAMMATORY BOWEL DISEASE IMPROVES SURVIVAL AFTER COLORECTAL CANCER DIAGNOSIS

Background & Aims: Colonoscopic surveillance provides the best practical means for preventing colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients. Strong evidence for improved survival from surveillance programs is sparse however. The aim of this study was to compare tumor stage and survival of IBD patients with CRC between those who were part of a surveillance program and those who were not. Methods: A nationwide pathology database was used to identify all IBD patients with CRC in all 8 university hospitals in The Netherlands over a period of 15 years. Patients were assigned to the surveillance group when they had undergone one or more surveillance colonoscopies prior to the diagnosis of CRC. Patients who had not undergone surveillance served as controls. Tumor stage and survival were compared between the two groups. The chi-square, Fishers exact and students t tests were used where appropriate to compare patient characteristics. KaplanMeier and Cox-regression analyses were employed for survival calculations. Results: A total of 149 IBD-associated CRCs were found. Twenty-three had undergone colonoscopic surveillance before CRC was discovered and 126 had not. Patient characteristics showed no significant differences between the two groups. Surveillance was started after a median of 14.5 [range: 0-33] years after histological diagnosis of IBD. CRC developed after a median of 6.4 years [1-21] after initiation of surveillance. Median age at time of CRC diagnosis was 48 [38-71] and 49 [21-85] years in the surveillance and non-surveillance groups respectively. Mean follow-up time after CRC diagnosis was 57 months [0-188] in the surveillance group and 51 months [0-235] in the non-surveillance group. The 5-year survival rate of the surveillance group was 100% versus 74% in the control group (p=0.041). This association was also visible after a Cox-regression analysis with co-morbidity, primary sclerosing cholangitis and age at CRC diagnosis as co-variables (p=0.08). In the surveillance group, only 1 patient died as a consequence of colorectal cancer compared to 29 patients in the control group (p=0.047). More early stage tumors (AJCC stage 0 and 1) were found in the surveillance group (p=0.004). Likewise, in the surveillance group significantly fewer patients had Stages 3B-C and 4 tumors (p=0.049). Conclusions: These results provide evidence for improved survival from colonoscopic surveillance in IBD patients as a result of detecting CRC at a more favorable tumor stage.