Annika Lapidus

Risk Factors for Surgery and Postoperative Recurrence in Crohn’s Disease

OBJECTIVE To assess the impact of possible risk factors on intestinal resection and postoperative recurrence in Crohns disease (CD) and to evaluate the disease course. SUMMARY BACKGROUND DATA The results of previous studies on possible risk factors for surgery and recurrence in Crohns disease have been inconsistent. Varying findings may be explained by referral biases and small numbers of patients in some studies. METHODS Data on initial intestinal resection and postoperative recurrence were evaluated retrospectively in a population-based cohort of 1,936 patients. The influence of concomitant risk factors was assessed using uni- and multivariate analyses. RESULTS The cumulative rate of intestinal resection was 44%, 61%, and 71% at 1, 5, and 10 years after diagnosis. Postoperative recurrences occurred in 33% and 44% at 5 and 10 years after resection. The relative risk of surgery was increased in patients with CD involving any part of the small bowel, in those having perianal fistulas, and in those who were 45 to 59 years of age at diagnosis. Female gender and perianal fistulas, as well as small bowel and continuous ileocolonic disease, increase the relative risk of recurrence. CONCLUSIONS Three of four patients with CD will undergo an intestinal resection; half of them will ultimately relapse. The extent of disease at diagnosis and the presence of perianal fistulas have an impact on the risk of surgery and the risk of postoperative recurrence. Women run a higher risk of postoperative recurrence than men. The frequency of surgery has decreased over time, but the postoperative relapse rate remains unchanged.

Risk of haematopoietic cancer in patients with inflammatory bowel disease

Background and aims: Several chronic inflammatory conditions are associated with an increased risk of lymphoma. Whether this applies to inflammatory bowel disease (IBD) is still unclear but of paramount interest, particularly in the safety evaluation of newer immunosuppressive drugs. Reports also indicate a possible increase in the risk of leukaemia in IBD. We therefore assessed the risk of haematopoietic cancers in a large cohort of patients with IBD. Subjects and methods: We performed a population based cohort study using prospectively recorded data, including 47 679 Swedish patients with Crohn’s disease (CD) or ulcerative colitis (UC) assembled from regional cohorts of IBD from 1955 to 1990 (n = 8028) and from the Inpatient Register of 1964–2000 (n = 45 060), with follow up until 2001. Relative risks were expressed as standardised incidence ratios (SIR). Results: Overall, we observed 264 haematopoietic cancers during follow up, which corresponded to a borderline significant 20% increased risk in both UC and CD. In UC, lymphomas occurred as expected (SIR 1.0, n = 87) but myeloid leukaemia occurred significantly more often than expected (SIR 1.8, n = 32). In CD, there was a borderline significant increased lymphoma risk (SIR 1.3, n = 65), essentially confined to the first years of follow up. Proxy markers of disease activity had little impact on lymphoma risk. Conclusion: On average, patients with IBD have a marginally increased risk of haematopoietic cancer. In UC, this is accounted for by an excess of myeloid leukaemia. In CD, a modest short term increase in the risk of lymphoma of unknown significance cannot be excluded but any long term risk increase seems unlikely.

Incidence of Crohn's disease in Stockholm County 1955-1989

Aim—To evaluate the incidence of Crohn’s disease in Stockholm County between 1955 and 1989. Methods—A cohort of 1936 patients with Crohn’s disease was retrospectively assembled. Incidence rates and changes in disease distribution were assessed. Results—The mean increase in incidence was 15% (95% confidence intervals 12% to 18%) per five year period with a mean annual incidence rate at 4.6/105during the last two decades. The mean incidence for the entire study period was similar for men and women. The mean age at diagnosis increased from 25 years in 1960–64 to 32 years in 1985–89, partly because of an increasing proportion of patients aged at least 60 years at diagnosis. The proportion of patients with colonic Crohn’s disease at the time of diagnosis increased from 15% to 32% (17% difference; 95% confidence intervals 12% to 23%) whereas the proportion of patients with ileocaecal disease decreased from 58% to 41% (17% difference; 95% confidence intervals 10% to 24%) during the study period. Elderly patients had a higher proportion of small bowel disease and a lower proportion of ileocolonic disease compared with the younger patients. Conclusion—The incidence rate of Crohn’s disease in Stockholm has stabilised at 4.6/105 and the proportion of elderly patients has increased during a 35 year period. Colonic Crohn’s disease has increased in frequency with a reciprocal decrease in ileocaecal disease.

Colorectal cancer rates among first-degree relatives of patients with inflammatory bowel disease: a population-based cohort study

BACKGROUND Inflammatory bowel disease (IBD) and colorectal cancer might share a common cause and, therefore, relatives of patients with IBD could be at increased risk of this malignant disease. We aimed to assess cancer rates among first-degree relatives of patients with IBD to try to determine whether an association between the two diseases exists. METHODS In a population-based study, we identified 114,102 first-degree relatives by registry linkage and followed them up for cancer occurrence. We used standardised incidence ratio (SIR) of cancer as relative risk. FINDINGS 560 colorectal cancers were identified among relatives. First-degree relatives of patients with Crohns disease or ulcerative colitis were not at increased risk of cancer (SIR 0.90, 95% CI 0.82-0.97). The relative risk was 0.96 (0.87-1.06, n=379) for colon cancer and 0.78 (0.68-0.91, 181) for rectal cancer. The SIRs were not affected by age, relation to patient, or type or extent of IBD in the patient. Relatives of patients with both IBD and colorectal cancer had an 80% increased risk of colorectal cancer. INTERPRETATION Our results do not endorse a common cause of IBD and colorectal cancer. The slightly decreased relative risk for colorectal cancer among relatives could indicate the proportion of all colorectal cancer cases attributable to IBD.

Recurrence after colectomy in Crohn's colitis.

PURPOSE: Previous studies on recurrence and reoperation after colectomy in Crohns colitis have been based on heterogeneous groups of patients, and divergent findings may be explained by referral biases and small numbers of patients. The aim of this study was to account for recurrence rates, present risk factors for recurrence after primary colectomy, and account for the ultimate risk of having a stoma after colectomy with ileorectal anastomosis in patients with Crohns colitis. METHODS: Data on the primary resection, postoperative recurrence, influence of concomitant risk factors, frequency of stoma operations and proctectomy were evaluated retrospectively using multivariate analysis in a population-based cohort of 833 patients with Crohns colitis. RESULTS: The cumulative 10-year risk of a symptomatic recurrence was 58 percent (95 percent confidence interval, 53–63 percent) and 47 percent (95 percent confidence interval, 42–52 percent), respectively, after colectomy with ileorectal anastomosis and segmental colonic resection. In colectomy with ileostomy, lower rates were found with respectively 24 percent (95 percent confidence interval, 18–30 percent) and 37 percent (95 percent confidence interval, 32–43 percent) after subtotal colectomy and proctocolectomy with ileostomy. The multivariate analysis showed that perianal disease, ileorectal anastomosis, and segmental resection were independent risk factors for postoperative recurrence. In 76 percent of patients with ileorectal anastomosis, a stoma-free function could be retained during a median follow-up of 12.5 years. CONCLUSION: Colectomy with ileorectal anastomosis or segmental resection is a feasible option in the surgical treatment of Crohns colitis, although anastomoses, in addition to perianal disease, carry an increased risk of recurrent disease.

Increased risk of colorectal cancer and dysplasia in patients with Crohn's colitis and primary sclerosing cholangitis.

BACKGROUND: Almost 10% of all patients with primary sclerosing cholangitis receive a diagnosis of Crohns disease. Clinical characteristics and the risk of colon cancer or dysplasia in Crohns disease and primary sclerosing cholangitis are less well examined than in ulcerative colitis. OBJECTIVE: This study aimed to describe the clinical characteristics and risk of colorectal dysplasia and cancer in Crohns disease in patients with primary sclerosing cholangitis. DESIGN: This is a cohort study of all patients diagnosed with primary sclerosing cholangitis and colorectal Crohns disease at Karolinska University Hospital, Huddinge, 1978 to 2006. Each patient was matched for age and the onset of Crohns disease to 2 controls with colorectal Crohns disease without liver disease. SETTING: This study was conducted at a tertiary referral center. PATIENTS: Twenty-eight patients (61% male) with primary sclerosing cholangitis and Crohns disease and 46 patients (50% male) with Crohns disease alone were studied. Clinical and endoscopic data were retrieved from medical records. Colonic biopsies from patients with primary sclerosing cholangitis were re-reviewed. MAIN OUTCOME MEASURES: The primary outcome measured was the proportion of patients developing colorectal cancer. RESULTS: Colorectal cancer or dysplasia developed in 9 patients with primary sclerosing cholangitis and in 3 controls. Patients with primary sclerosing cholangitis were more likely to develop colorectal dysplasia or cancer than controls (OR 6.78; 95% CI (1.65-27.9); P = .016). In patients with primary sclerosing cholangitis compared with controls, perianal fistulas occurred in 3% vs 33% (P = .003), bowel strictures occurred in 7% vs 30% (P = .03), and bowel surgery was performed in 18% vs 46% (P = .01). Histological granulomas were seen in 29% of the patients with primary sclerosing cholangitis compared with 43% in controls (P = not significant). LIMITATIONS: This study was limited by its retrospective nature and the limited cohort. CONCLUSIONS: Primary sclerosing cholangitis is a risk factor for the development of colorectal cancer and dysplasia in Crohns disease. Obstructing disease and perianal fistulas are rare in primary sclerosing cholangitis and less common than in colonic Crohns disease without liver disease.

Infliximab as rescue therapy in hospitalised patients with steroid‐refractory acute ulcerative colitis: a long‐term follow‐up of 211 Swedish patients

Rescue therapy with infliximab (IFX) has been proven effective in a steroid‐refractory attack of ulcerative colitis (UC). The long‐term efficacy is not well described.

Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial

Objective This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis. Design A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase. Results Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), p<0.001). Health-related quality of life was maintained during the 12-month double-blind phase in budesonide-treated patients. During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious. Conclusions Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation. Trial registration numbers http://www.clinicaltrials.gov (NCT01278082) and http://www.clinicaltrialsregister.eu (EudraCT: 2007-001315-31).

Inflammatory bowel disease-related lesions in the duodenal and gastric mucosa

Objective. In 10–15% of patients with colorectal inflammatory bowel disease it is not possible to determine whether they have Crohns disease or ulcerative colitis and they are therefore classified as having inflammatory bowel disease unclassified (IBDU) (formerly referred to as “indeterminate colitis”). The aim of this study was to determine whether upper endoscopy with biopsies could be a useful tool for diagnosing patients with colorectal inflammatory disease. Material and methods. Fifty-two patients (14 colorectal Crohns disease, 19 ulcerative colitis, 6 IBDU, 8 microscopic colitis and 5 without IBD) were examined by upper endoscopy. Biopsies from gastric and duodenal mucosa were examined histologically and the frequency of focal cryptitides was estimated. Helicobacter pylori-positive patients were excluded. Results. Focal cryptitides (sometimes called focally enhanced gastritis) were found in 8/14 of patients with Crohns disease, 4/19 patients with ulcerative colitis, 2/6 patients with IBDU, 2/8 of patients with microscopic colitis and in 2/5 patients without IBD. Conclusions. Focal cryptitides are more commonly found in gastric and/or duodenal mucosa in patients with colorectal Crohns disease than in other patients. Upper endoscopy with mucosal biopsies contributes towards a diagnosis in patients with colitis.

Microscopic colitis in patients with ulcerative colitis or Crohn’s disease: a retrospective observational study and review of the literature

Abstract Objectives: Onset of microscopic colitis (MC) in patients with ulcerative colitis (UC) or Crohn’s disease (CD), or vice versa, has been reported occasionally but the subject is not well described. We therefore report a retrospective observational study of such patients and review the literature. Methods: Forty-six Swedish gastroenterology clinics were contacted about patients with diagnoses of both inflammatory bowel disease (IBD) and MC. Publications were searched on PubMed. Results: We identified 31 patients with onset of MC after a median (range) of 20 (2–52) years after diagnosis of IBD, or vice versa; 21 UC patients developed collagenous colitis (CC) (n = 16) or lymphocytic colitis (LC) (n = 5); nine CD patients developed CC (n = 5) or LC (n = 4); one CC patient developed CD. Of the 21 UC patients, 18 had extensive disease, whereas no consistent phenotype occurred in CD. Literature review revealed 27 comprehensive case reports of patients with diagnoses of both IBD and MC. Thirteen MC patients developed IBD, of which four required colectomy. Fourteen IBD patients later developed MC. There were incomplete clinical data in 115 additional reported patients. Conclusions: Altogether 173 patients with occurrence of both IBD and MC were found. The most common finding in our patients was onset of CC in a patient with UC. Although these are likely random associations of two different disorders, MC should be considered in the patient with UC or CD if there is onset of chronic watery diarrhoea without endoscopic relapse of IBD.