Göran Hellers

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.

Crohn's disease and cancer: A population-based cohort study

BACKGROUND/AIMS To study the association between Crohns disease and cancer, we performed a population-based study of 1251 subjects with Crohns disease diagnosed in Stockholm from 1955 to 1984 and followed in both the National Cancer Register and the National Cause-of-Death Register until 1989. METHODS For comparisons, regional cancer incidence rates in Stockholm County were used together with individually computed person-years at risk in the Crohns disease cohort. RESULTS Overall, 69 malignancies occurred among 67 individuals as compared with 59.80 expected malignancies (standardized morbidity ratio [SMR] = 1.15; 95% confidence interval, 0.90-1.46). An excess number of cancers of the upper gastrointestinal tract (SMR, 3.05; 95% confidence interval, 1.67-5.11) was observed, mainly because of an increased number of cancers of the small intestine (SMR, 15.64; 95% confidence interval, 4.26-40.06). An increased occurrence of urinary bladder cancer was also observed (SMR, 2.68; 95% confidence interval, 1.08-5.53). CONCLUSIONS The occurrence of colorectal cancer was not increased.

Oral budesonide for prevention of postsurgical recurrence in Crohn's disease

BACKGROUND & AIMS Prevention of postoperative recurrence after resection for Crohns disease (CD) would be of great clinical benefit. The efficacy of oral budesonide for prevention of endoscopic recurrence was evaluated in patients undergoing resection for ileal or ileocecal CD. METHODS Sixty-three patients received budesonide and 66 received placebo in a double-blind, randomized trial with parallel groups. Ileocolonoscopy, including biopsy, was performed after 3 and 12 months. Indications for surgery were fibrostenosis (78 patients), disease activity (41), and other reasons (10). RESULTS The frequency of endoscopic recurrence did not differ between the groups at 3 and 12 months. In patients with disease activity as indication for surgery, the endoscopic recurrence rate at the anastomosis was lower in the budesonide group at 3 months, although not significantly (21% vs. 47%; P = 0.11), and at 12 months (32% vs. 65%; P = 0.047). There was no such difference with respect to fibrostenosis as indication for surgery. No differences in adverse event patterns were found between the two groups. CONCLUSIONS Oral budesonide, 6 mg daily, offered no benefit in prevention of endoscopic recurrence after surgery for ileal/ileocecal fibrostenotic CD but decreased the recurrence rate in patients who had undergone surgery for disease activity.

Clinical course of colorectal Crohn's disease: A 35-year follow-up study of 507 patients

BACKGROUND & AIMS Crohns disease (CD) confined to the colon and rectum is an increasing clinical entity. The aim of this study was to assess the features and clinical course of colorectal CD. METHODS This was a retrospective cohort study of 507 patients in whom colonic or rectal CD had been diagnosed between 1955 and 1989. RESULTS Colonic distribution was segmental in 40%, total in 31%, and left-sided in 26%. Perianal/rectal fistulas occurred in 37%. In patients who attained clinical remission, the 5-year cumulative relapse rate after diagnosis was 67% (95% confidence interval [CI], 62-72). At the initial presentation of CD, the frequency of major surgery decreased from 24% to 14% (P < 0.005) over time. Still, the overall long-term probability of major surgery after 10 years was unaltered (49% vs. 47%). The presence of fistulas increased the probability of surgical resection (relative risk [RR], 1.7 [95% CI, 1.3-2.2]), whereas left-sided disease was associated with a decrease (RR, 0.6 [95% CI, 0.4-0.8]). Twenty-four percent of the patients developed inflammation in the small bowel. The cumulative risk for a permanent ileostomy was 25% (95% CI, 21-29) 10 years after diagnosis. CONCLUSIONS Colorectal CD is an increasing entity carrying substantial morbidity. Half of the patients will undergo surgical resection within the first 10 years, and half of those will ultimately undergo ileostomy. Changed management at diagnosis has not affected the long-term probability of resection.

Increased risk of cancer in ulcerative colitis: a population-based cohort study

OBJECTIVE:There is an increased risk of colorectal cancer among patients with ulcerative colitis (UC). However, the overall and site specific cancer risks in these patients have been investigated to a limited extent. To study the association between UC and cancer, a population-based study of 1547 patients with UC in Stockholm diagnosed between 1955 and 1984 was carried out.METHODS:The patients were followed in both the National Cancer Register and the National Cause of Death Register until 1989. For comparisons, regional cancer incidence rates in Stockholm County were used together with individually computed person-years at risk in the UC disease cohort.RESULTS:A total of 121 malignancies occurred among 97 individuals as compared with 89.8 expected (standardized morbidity ratio [SMR] = 1.4; 95% confidence interval (CI), 1.1–1.6). Overall, an excess number of colorectal cancers (SMR, 4.1; 95% CI, 2.7–5.8), and hepatobiliary cancers in men (SMR = 6.0; 95% CI, 2.8–11.1) associated with primary sclerosing cholangitis, was observed. The risk of pulmonary cancer was decreased (SMR = 0.3; 95% CI, 0.1–0.9). In all, 91 extracolonic malignancies were observed, compared with the 82.3 expected (SMR = 1.11; 95% CI, 0.9–1.3).CONCLUSIONS:In UC patients, the overall cancer incidence is increased mainly because of an increased incidence of colorectal and hepatobiliary cancer. This increase is partly counterbalanced by a decreased risk of pulmonary cancer compared with that in the general population.

Pouchitis following pelvic pouch operation for ulcerative colitis

AIM: This study was undertaken to assess the risk for pouchitis in patients with ulcerative colitis who underwent surgery with colectomy, restorative pelvic pouch, and ileoanal anastomosis and to evaluate possible factors predictive for pouchitis development. PATIENTS AND METHODS: All patients receiving a pelvic pouch because of ulcerative colitis at Huddinge University Hospital between 1980 and 1993 (n=149; 89 men) were prospectively evaluated for symptoms suggestive of pouchitis. Diagnosis of pouchitis was based on occurrence of certain symptoms in combination with endoscopic findings. Pouchitis was divided into mild and severe, and the time span until the first attack of mild or severe pouchitis was calculated for each patient. RESULTS: Median follow-up time was 54 (5–152) months. The absolute cumulative risk of developing mild pouchitis was 21, 26, and 39 percent at 6, 12, and 48 months, respectively. The corresponding cumulative risk of developing severe pouchitis was 9, 11, and 14 percent, respectively. Risk for both groups together was 51 percent at 48 months. The occurrence of pouchitis, calculated at six-month intervals after closure of the loop ileostomy, was highest (23.1 percent) during the first six months. Incidence during the next six-month period was 11.4 percent and then only 3.1 percent thereafter. Thirty-two patients (21.5 percent) had chronic continuous symptoms requiring long-term metronidazole treatment, and 14 (9.4 percent) of those had chronic severe pouchitis. In two patients, removal of the pouch and permanent ileostomy became necessary. Extracolonic manifestations and early onset of ulcerative colitis were predictive factors for developing pouchitis. Former smoking seemed to be a protective factor. CONCLUSION: The risk for pouchitis was highest during the initial six-month period. Cumulative risk leveled off after two years but was substantial (51 percent) at four years. Less than 10 percent of patients had severe, chronic pouchitis, and only two patients (1.3 percent) had their pouches removed.

Factors affecting colectomy rate in ulcerative colitis: an epidemiologic study.

Factors affecting colectomy rate were studied in a retrospective population based series of 1586 patients with ulcerative colitis, in Stockholm County during 1955-84. Five hundred and sixty eight patients (36%) had total colitis at diagnosis, 603 patients (38%) left sided colitis, and 397 patients (25%) proctitis. During a median period of observation of 13 years 514 patients were treated by colectomy. The five, 10, and 25 year cumulative colectomy rate were 20% (CI 18-22%), 28% (CI 26-30%), and 45% (CI 41-49%) respectively. The main factor affecting the colectomy rate was the extent of disease at diagnosis. Patients with total colitis showed a five, 10, and 25 year cumulative colectomy rate of 32% (CI 28-36%), 42% (CI 38-46%), and 65% (CI 58-72%) respectively. Ten per cent of the 1586 patients had a colectomy during the first year after diagnosis, 4% during the second year and 1% during subsequent years. The age at diagnosis and sex did not affect the cumulative colectomy rate. Elective colectomy was performed in 322 cases (63%) and acute colectomy in 192. The duration of disease before colectomy fell during the study period due to a more standardised criteria for colectomy in severe attacks. One hundred and twenty nine (66%) of the acute colectomies were performed within two years from diagnosis.

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.

Inflammatory bowel disease and tobacco smoke--a case-control study.

A case-control study was carried out in Stockholm, Sweden between 1984 and 1987 to evaluate the association of cigarette smoking and exposure to environmental tobacco smoke during childhood and the subsequent development of inflammatory bowel disease. Information on smoking was obtained by a postal questionnaire. The relative risk of Crohns disease in current smokers compared with those who had never smoked was 1.33 (95% confidence limits 0.7; 2.6) in men and 4.99 (2.7; 9.2) in women; the corresponding results for ulcerative colitis were 0.96 (0.5; 1.8) and 0.72 (0.4; 1.4). The relative risk of ulcerative colitis in recent exsmokers compared with those who had never smoked was 2.18 (0.9; 5.0). Furthermore, an increase in the risk of Crohns disease was found in those who were exposed to environmental tobacco smoke during childhood, the relative risk being 1.50 (1.0; 2.3). The corresponding relative risk of ulcerative colitis was 0.98 (0.6; 1.5).

Long-term results of ileorectal anastomosis in ulcerative colitis in Stockholm County

The long-term results of ileorectal anastomosis in patients with ulcerative colitis in Stockholm County over a 30-year period, 1955 to 1984, were investigated. During this time, 486 patients underwent colectomy and ileorectal anastomosis was performed in 60 of those patients (12 percent). A retrospective histologic examination of the slides of the operative specimens in the latter group revealed that nine patients had Crohns disease. Of the 51 remaining patients with ulcerative colitis, the colectomy and ileorectal anastomosis was performed as an elective procedure in 44 cases (86 percent) and as a one-stage procedure in 48 patients (94 percent). Complications occurred in 7 of 43 patients (16 percent) undergoing an elective, one-stage procedure. There were two postoperative deaths (4 percent). There were 22 patients (43 percent) who had their ileorectal anastomosis in function at the time of follow-up, with a mean time of observation of 13 years. The cumulative probability of having the ileorectal anastomosis in function at 10 years was 51 percent. The causes of rectal excision were recurrent inflammation in the retained rectum (N=23), dysplasia (N=3), and postoperative complications (N=3). No rectal carcinoma occurred. Patients with preoperative mild rectal disease had a better outcome (ileorectal anastomosis in function at time of follow-up) compared with patients with moderate rectal disease (P<0.001). The functional outcome of ileorectal anastomosis was, if anything, better than what is stated in the literature following pelvic pouch procedure.