Risk of acute pancreatitis in patients with chronic inflammatory bowel disease. A Danish 16-year nationwide follow-up study

BACKGROUND: There are few epidemiologic data about the risk of acute pancreatitis in chronic inflammatory bowel diseases; we therefore wanted to estimate the risk of a first episode of acute pancreatitis in patients with Crohn's disease and ulcerative colitis in the total Danish population. METHODS: The study included all patients discharged from Danish hospitals with a diagnosis of Crohn's disease or ulcerative colitis registered in the Danish National Registry of Patients in the period from 1977 to 1992. The first episode of acute pancreatitis was identified in the cohort. The observed number of patients with acute pancreatitis was compared with expected numbers on the basis of age, sex, and calendar-specific incidence rates in the general population. RESULTS: Overall, 15,526 patients were discharged and followed up for 112,824 person-years. The standardized incidence ratio (SIR) for acute pancreatitis was increased both in patients with Crohn's disease (SIR = 4.3; 95% confidence interval (CI), 2.9-6.1) and in those with ulcerative colitis (SIR= 2.1; 95% CI, 1.6-2.8). CONCLUSION: Patients with chronic inflammatory bowel disease seem to be at increased risk of acute pancreatitis. Further validation and refinement of this registration-based study are needed.     

Comparison of fecal granulocyte excretion in ulcerative colitis and Crohn's colitis

Impaired granulocyte migration has been suggested to be present in Crohn's disease on the basis ofin vitro granulocyte function tests andin vivo skin window studies. This idea is supported by the impression histologically that the acute inflammatory infiltrate in diseased bowel is less in Crohn's disease than ulcerative colitis. We have developed a method of quantitating the acute inflammatory infiltrate in inflamed bowel by measuring fecal indium-111 granulocyte excretion and have compared this assessment in patients with ulcerative colitis and Crohn's colitis matched for disease activity. For equivalent disease groups in ulcerative colitis and Crohn's colitis, there was no significant difference between fecal granulocyte excretion. These findings provide no support for the contention that there is a reduced granulocyte infiltration in Crohn's disease.     

Seasonal variations in onset of symptoms in Crohn''s disease

BACKGROUND: Seasonal variations in onset of symptoms have been reported in ulcerative colitis but not in Crohn's disease. AIM.: To investigate whether our inflammatory bowel diseases patients presented seasonal variations in onset of symptoms. PATIENTS AND METHODS: Patients with a diagnosis of inflammatory bowel diseases established between 1995 and May 2004, and consecutively observed from June 2003 to May 2004, were included in the study. Onset of symptoms (year, season and month) was recorded. Expected onsets with a uniform distribution during the year were calculated and compared to observed onsets. Statistical analysis: chi-square test, odds ratio (95% confidence interval). RESULTS: Overall 425 inflammatory bowel diseases patients were enrolled. Onset of symptoms (year and season) was established in 353/425 patients (83%; 150 Crohn's disease; 203 ulcerative colitis). Onset of symptoms in inflammatory bowel diseases patients as a whole occurred more frequently in spring-summer compared to autumn-winter (odds ratio 1.39; 95% confidence interval 1.03-1.87; p<0.03). This variation was observed in Crohn's disease (odds ratio 1.59; 95% confidence interval 1.00-2.51; p<0.05) and a similar trend, although not significant, was observed in ulcerative colitis (odds ratio 1.27; 95% confidence interval 0.86-1.88; p=0.27). CONCLUSIONS: These data indicate that onset of Crohn's disease symptoms occurred more frequently during spring-summer. A similar trend was observed in ulcerative colitis. Environmental factors, such as associated infections, smoking, use of drugs and seasonal changes in immune function may be responsible for triggering the clinical onset of inflammatory bowel diseases.     

Cholelithiasis in inflammatory bowel disease

Cholelithiasis is considered an extraintestinal manifestation of Crohn's ileitis but has not been associated with ulcerative colitis. To evaluate if an increased risk of cholelithiasis exists in patients with ulcerative colitis, biliary ultrasonography was performed on 159 patients with inflammatory bowel disease, 114 patients with ulcerative colitis, and 45 patients with Crohn's disease. A control population of 2453 residents of the town near the authors' institute was also studied. An echographic survey of gallstones was performed on the control subjects, who participated in the Multicentrica Italiana Colelitiasi (MICOL). Seventeen patients with inflammatory bowel disease had gallstones (10.7 percent), 11 patients with ulcerative colitis had gallstones (9.6 percent), and 6 patients with Crohn's disease had gallstones (13.3 percent). In the control population, diagnosis of cholelithiasis was made in 239 subjects (9.7 percent). An estimate of the relative risk (odds ratio) of gallstones in ulcerative colitis and Crohn's disease and also in 4 subgroups formed on the basis of the extent of disease (total ulcerative colitis, partial ulcerative colitis, Crohn's disease with ileitis, Crohn's disease without ileitis) with respect to the general population was calculated using logistic regression with gallstones, sex, age, and body mass index as independent variables and inflammatory bowel disease as a dependent variable. The author's findings show an increased risk of gallstones in both patients with Crohn's disease (odds ratio = 3.6; 95 percent confidence limits = 1.2 - 10.4; P = 0.02) and patients with ulcerative colitis (odds ratio = 2.5; 95 percent confidence limits = 1.2 - 5.2; P = 0.01). The risk was highest in patients with Crohn's disease involving the distal ileum (odds ratio = 4.5; 95 percent confidence limits = 1.5 - 14.1; P = 0.009) and in patients with total ulcerative colitis extending to the cecum (odds ratio = 3.3; 95 percent confidence limits = 1.3 - 8.6; P = 0.01). These results confirm that there is an increased risk of gallstones in Crohn's ileitis but they show that there also exists an increased risk in patients with total ulcerative colitis.     

Development of acute myelocytic leukemia in patients with Crohn's disease

Summary In our hospital within one year two patients with Crohn's disease were seen who developed an acute myelocytic leukemia. A review of the literature reveals eight previously reported patients with both Crohn's disease and leukemia. Six of the reported 10 patients have had acute myelocytic leukemia and, interestingly, three of them, including our two patients, have shown monocytic differentiation (FAB type M4). It has been suggested that the relative risk of leukemia, especially acute myelocytic leukemia, is increased in patients suffering from ulcerative colitis. More data of patients with Crohn's disease and acute leukemia are needed to evaluate the possible association between these diseases.     

Evolving concepts on inflammatory bowel disease. Are we happy with the present nosology?

The term inflammatory bowel disease traditionally comprises ulcerative colitis, Crohn's disease and indeterminate colitis, an intermediate variant of the two major forms. The term is commonly used in the literature and in clinical practice even though it has never been revised in a Consensus Conference. The present nosology of inflammatory bowel disease seems not to be entirely satisfactory as it is limited to chronic diseases only and does not include several recently described idiopathic inflammatory bowel disorders. Although the aetiology of inflammatory bowel disease remains unknown, both ulcerative colitis and Crohn's disease are characterized by a similar pathogenesis which consists in a persistent intestinal inflammation resulting from disregulation of the gut mucosal immune system. The pathogenetic mechanisms could, therefore, provide a suitable criterion for the classification of idiopathic inflammatory bowel disease. A revised classification of inflammatory bowel disease is thus proposed. It seems reasonable to subclassify inflammatory bowel disease into acute and chronic forms. Acute forms should include the sudden attacks of ulcerative colitis and Crohn's disease with rapid and complete resolution and the so-called "acute self-limited colitis". The chronic forms should comprise, besides the classical forms of ulcerative colitis, Crohn's disease and indeterminate colitis, also other idiopathic inflammatory bowel conditions such as collagenous colitis, lymphocytic colitis and eosinophilic gastroenteritis.     

Mucosal changes in ileal pouches after restorative proctocolectomy for ulcerative and crohn's colitis

PURPOSE: Inflammation and dysplasia may affect the ileal pouch after restorative proctocolectomy and ileal pouchanal anastomosis. The aim of this prospective study was to evaluate the morphologic changes and the risk of dysplasia within the pouch after ileal pouch-anal anastomosis. METHODS: Thirty-seven patients with ileal pouch-anal anastomosis underwent endoscopies and biopsies of the pouch: 21 patients were affected by ulcerative colitis and 16 by Crohn's colitis. The mucosal biopsy specimens were studied to investigate the degree of acute and chronic inflammation and the occurrence of dysplasia. A score system was calculated for each patient and correlated with the histologic diagnosis of ulcerative colitis or Crohn's colitis. RESULTS: After a median follow-up of 85 (range, 7–198) months, the inflammation histologic score evaluated was 3.8 (95 percent confidence interval, 2.4–5.1) and 3.5 (95 percent confidence interval, 2.6–4.3), respectively, in patients with Crohn's colitis and ulcerative colitis (mean and 95 percent confidence interval;P=0.74, not significant), and no patient developed mucosal dysplasia. Fifteen patients (40.5 percent) developed clinical pouchitis that occurred in Crohn's colitis (9/16 patients or 56 percent) and in ulcerative colitis (6/21 patients or 28 percent;P not significant). The score was 4.1 (95 percent confidence interval, 3.2–5) in patients with pouchitis and 3.2 (95 percent confidence interval, 2.1–4.3) in patients without clinical pouchitis (P=0.012) and was 4.1 (95 percent confidence interval, 2.6–5.5) and 4 (95 percent confidence interval, 2.9–5.3), respectively, in pouchitis patients with Crohn's colitis and ulcerative colitis. CONCLUSION: No difference in the inflammation histologic score was observed in ileal pouches after restorative proctocolectomy for ulcerative and Crohn's colitis. In our series, which includes those patients with longer follow-up (>5 years) or with chronic unremitting pouchitis, no case of dysplasia was found. The occurrence of pouchitis was higher in the case of ileal pouch-anal anastomosis for Crohn's disease than for ulcerative colitis, but no difference in the severity of the histologic score was noted.Presented at the XVIIth Biennial Congress of the International Society of University Colon and Rectal Surgeons, Malmö, Sweden, June 7 to 11, 1998.     

Incidence of inflammatory bowel disease in the French West Indies (1997-1999)

OBJECTIVES: To investigate the incidence of inflammatory bowel disease in the French West Indies. METHODS: From January 1st 1997 to December 31st 1999 all patients observed with clinical symptoms suggestive of inflammatory bowel disease attending gastroenterologists practicing in Guadeloupe and Martinique were included. Patients were interviewed with a standard questionnaire to record data used by an expert to establish the final diagnosis of definite, probable or possible Crohn's disease, ulcerative colitis, unclassifiable chronic colitis or acute colitis, according to the EPIMAD registry. RESULTS: Sixty-six cases of ulcerative colitis (47.48%) including 12 cases of ulcerative proctitis (18.18% of the ulcerative colitis cohort), 55 of Crohn's disease (39.57%), 11 of unclassifiable chronic colitis (7.91%), and 7 of acute colitis (5.04%) were recorded. The crude annual incidence (per 100,000 inhabitants) based on definite and probable cases only was 2.44 for ulcerative colitis and 1.94 for Crohn's disease. The female/male ratio and median age at time of diagnosis were 1.61 and 29 years for Crohn's disease and 1.46 and 34 years for ulcerative colitis respectively. The median time from symptom onset to diagnosis was 2 months for both diseases. CONCLUSIONS: The observed incidence of inflammatory bowel disease In the French West-Indies is lower than in metropolitan France. These data will serve as a basis to assess disease evolution.     

Histological diagnosis of chronic inflammatory bowel disease in childhood.

One hundred and four children were initially assessed by clinical, radiological, and endoscopic criteria as chronic inflammatory bowel disease. All were assessed independently using precise histological diagnostic criteria. Fifty eight patients were diagnosed as Crohn's disease, 25 as ulcerative colitis, 15 remained provisionally categorised as indeterminate colitis and six proved to be normal. Diagnostic granulomas were found in 36% of endoscopic biopsies from the 58 children with Crohn's disease. This appears to be an underestimate as only four of 14 children with granulomatous Crohn's disease operated on had granulomas on endoscopic biopsy. This study shows that there is a spectrum of histological appearances in endoscopic biopsies in chronic inflammatory bowel disease in childhood ranging from definite Crohn's disease to definite ulcerative colitis with indeterminate features in between. Accurate histological diagnosis of chronic inflammatory bowel disease is dependent upon either multiple endoscopic biopsies or assessment of a surgically resected specimen.     

Non-invasive evaluation of activity in inflammatory bowel disease by power Doppler sonography

BACKGROUND: To study the vascularization in the diseased bowel wall by power Doppler sonography in patients with inflammatory bowel disease. PATIENTS AND METHODS: The diseased bowel wall was investigated in 99 patients with inflammatory bowel disease (60 patients with Crohn's disease and 39 patients with ulcerative colitis) either with active disease or in remission by B-mode and power Doppler sonography. Disease activity was determined by clinical indices. Twenty healthy age and sex matched individuals served as controls. RESULTS: Bowel wall was thickened in active Crohn's disease (mean 7 mm, range 4-14) and ulcerative colitis (mean 5 mm, range 2-15) as compared to healthy controls (mean 2 mm, range 1-3), p < 0.001. In contrast to healthy controls blood vessels were detected in the bowel wall in 100 % of patients with active Crohn's disease and 91 % with active ulcerative colitis. Vascularization was significant decreased in patients with quiescent versus active disease in ulcerative colitis (p < 0.05), while in Crohn's disease there was no significance between active and remission phase. CONCLUSIONS: Thickened and hypervascularized bowel wall are characteristic findings in inflammatory bowel disease. A combination of B-mode and power Doppler sonography offers an additional noninvasive procedure for the determination of activity in patients with inflammatory bowel disease.     

Total abdominal colectomy and ileorectal anastomosis for inflammatory bowel disease

PURPOSE: This retrospective study assesses the results of total colectomy and ileorectostomy for inflammatory bowel disease. METHODS: Between January 1974 and December 1990, 90 patients underwent total colectomy and ileorectal anastomosis for chronic ulcerative colitis (n=48) or Crohn's colitis (n=42) at the Mayo Clinic. Patients' records were reviewed retrospectively. Long-term results were assessed by chart reviews and postal questionnaires. Conversion to a permanent ileostomy, with or without proctectomy, was considered a failure of the procedure. The Kaplan-Meier method was used to estimate survivorship free of failure. The log-rank test was used to compare survivorship curves. Ninety-five percent confidence intervals were calculated at selected time points.P values<0.05 were considered to be statistically significant. RESULTS: The main indication for surgery was refractory chronic disease. There were no immediate postoperative deaths. The anastomotic leakage rate was 4.4 percent, and small-bowel obstruction occurred in 15.6 percent. At the time of follow-up (mean, 6.5±4.8 years), 46 patients (58.9 percent) had recurrence or exacerbation of the disease. This was the most common indication for subsequent proctectomy/permanent ileostomy in the follow-up period. There were 8 failures in 48 patients with ulcerative colitis (16.7 percent) and 11 failures in 42 patients with Crohn's disease (26.2 percent), although this difference was not statistically significant. Cumulative probability of having a functioning ileorectal anastomosis at five years was 84.2 percent (95 percent confidence interval, 71–95.9 percent) for ulcerative colitis and 73.8 percent (95 percent confidence interval, 58.6–88.6 percent) for Crohn's disease. In the latter group, females showed a significantly lower cumulative probability of having a functioning ileorectal anastomosis (females, 634 percent; males, 92.3 percent;P =0.04). Crohn's patients 36 years of age or younger also showed a lower probability of success (patients 36 years, 57 percent; patients >36 years, 93.8 percent;P =0.03). In the group with chronic ulcerative colitis, younger patients also seemed to require additional surgery more frequently; however, this difference was not statistically significant. Previous duration of symptoms, with mild or moderate disease in a distensible rectum, had no effect on results in either disease group. Functional results were acceptable in 63.6 and 87.5 percent of patients with Crohn's and ulcerative colitis, respectively. Eighty-four percent of ulcerative colitis patients and 91 percent of Crohn's disease patients reported an improvement in their quality of life, and overall, more than 90 percent considered their health status to be better than before surgery. One patient with ulcerative colitis developed carcinoma of the rectal stump 11.5 years after the colectomy and ileorectal anastomosis (cumulative probability of remaining free of cancer, 85.7 percent at 12 years; 95 percent confidence interval, 57.7–100 percent). CONCLUSIONS: These results demonstrate that, in selected patients with a relatively spared rectum and without severe perineal disease, total colectomy and ileorectal anastomosis still remains a viable option to total proctocolectomy with extensive Crohn's colitis. In addition, ileorectal anastomosis, as a sphincter-saving procedure, continues to have a place in the surgical treatment of chronic ulcerative colitis for high-risk or older patients who are not good candidates for ileal pouch-anal anastomosis, when the latter procedure cannot be done because of technical reasons and in the presence of advanced carcinoma concomitant with colitis, when life expectancy is limited.     

Non-calculus suppurative cholangitis in Danish patients with inflammatory bowel disease

BACKGROUND/AIMS: We examined the risk of non-calculus suppurative cholangitis in patients with inflammatory bowel disease in the entire Danish population. METHODOLOGY: The study included all patients discharged from Danish hospitals with a diagnosis of Crohn's disease or ulcerative colitis as registered in the Danish National Registry of Patients from January 1, 1977 to December 31, 1992. We compared the observed number of patients hospitalized with suppurative cholangitis with expected numbers on the basis of age, gender, and calendar-specific incidence rates in the general population. RESULTS: Overall, 15,317 eligible patients with inflammatory bowel disease were discharged during the study period. Among these were 52 cases of non-calculus suppurative cholangitis. The incidence rate of non-calculus suppurative cholangitis in the cohort with inflammatory bowel disease was 46.1 per 100,000 person-years. The standardized incidence ratio (SIR) for suppurative cholangitis was increased similarly for patients with Crohn's disease [SIR=6.7, 95% confidence interval (CI): 3.1-12.7] and for patients with ulcerative colitis (SIR=6.6, 95% CI: 4.7-9.1). The highest relative risk was found in male patients younger than 40 years of age, for both Crohn's disease and ulcerative colitis (SIR=70.5 and 78.7, respectively). CONCLUSIONS: Patients with inflammatory bowel disease have an increased risk of non-calculus suppurative cholangitis.     

Utility of a Rapid Fecal Latex Agglutination Test Detecting the Neutrophil Protein, Lactoferrin, for Diagnosing Inflammatory Causes of Chronic Diarrhea

Objective: The utility of tests for fecal neutrophils in the setting of chronic diarrhea has not been established. The purpose of this study was to determine the causes of chronic diarrhea associated with fecal neutrophils.
Methods: One fecal specimen from each of 10 normal subjects, 26 patients with known microscopic colitis, 13 with celiac sprue, eight with Crohn's disease, four with ulcerative colitis, and 103 with chronic diarrhea of unknown origin, as well as 10 fecal specimens from a patient with chronic nongranulomatous enterocolitis were analyzed blindly for the presence of a neutrophil granule protein called lactoferrin using a commercial latex agglutination kit. Diagnostic evaluation of the 103 patients with chronic diarrhea was carried out to determine the diagnostic accuracy of this test for chronic inflammatory bowel disease.
Results: None of the normal control subjects, three of 39 patients with microscopic colitis or celiac sprue, all 10 specimens from the patient with enterocolitis, and all 12 control patients with ulcerative colitis or Crohn's disease had a positive fecal lactoferrin test. Eleven of 103 patients with chronic diarrhea presenting without a diagnosis had a positive test, and all were diagnosed with an inflammatory condition of the colon (five-, ulcerative colitis; four-, Crohn's disease; one-, ischemic colitis; and one-, microscopic colitis). Only one patient with inflammatory bowel disease had a negative lactoferrin test. The sensitivity, specificity, and positive and negative predictive values of the fecal lactoferrin test for ulcerative or Crohn's colitis were 90%, 98%, 82%, and 99%, respectively.
Conclusion: The major cause of fecal neutrophils in patients with chronic diarrhea is chronic inflammatory bowel disease of the colon. The latex agglutination test for fecal lactoferrin offers a highly sensitive, specific, and simple means for detection of fecal neutrophils in these patients.     

Increased production of vascular endothelial growth factor by intestinal mucosa of patients with inflammatory bowel disease.

BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) is a heparin-binding glycoprotein with potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells. Recent studies have shown significantly increased VEGF serum levels in patients with active Crohn's disease and ulcerative colitis. The origin of the circulating VEGF is not yet completely described. The present investigation examines the VEGF production of colonic mucosa in consideration of mucosal disease activity in patients with inflammatory bowel disease. METHODOLOGY: Fifteen patients with inflammatory bowel disease were studied, 9 patients with Crohn's disease and 6 patients with ulcerative colitis. Biopsies were taken from endoscopically inflamed and non-inflamed colonic mucosa. Therefore, an analysis of the spontaneous VEGF production of cultured biopsies without stimulus and of the histological grade of inflammation scored on a scale of 0-3 (normal mucosa--severe chronic colitis) were performed. Eight patients with irritable bowel syndrome served as controls. VEGF levels in the supernatant of cultured mucosal biopsies were measured using an enzyme linked immunosorbent assay. RESULTS: VEGF production is expressed as pg/mg wet weight of the biopsies. Inflamed mucosa of patients with active ulcerative colitis (16.27 +/- 10.39, p = 0.003, n = 6) and active Crohn's disease (9.88 +/- 5.98, p < 0.012, n = 9) showed a significantly higher spontaneous production of VEGF by colonic mucosa than normal mucosa of controls (3.16 +/- 1.63, n = 8). In addition, there was an increased unstimulated VEGF production by cultured inflamed mucosa of patients with Crohn's disease compared with non-inflamed mucosa (3.88 +/- 3.66, p < 0.015, n = 9). In both Crohn's disease and ulcerative colitis, there was no significant difference between VEGF production by non-inflamed mucosa and normal mucosa of controls. CONCLUSIONS: The present study identifies the intestinal mucosa as one of the origins of the elevated VEGF serum levels in patients with active inflammatory bowel disease and verifies the findings of recent studies about the importance of VEGF in Crohn's disease and ulcerative colitis.     

Identification of a prodromal period in Crohn's disease but not ulcerative colitis

OBJECTIVES: Irritable bowel syndrome, a common gastrointestinal diagnosis, has not been clearly studied in inflammatory bowel disease. Some of the residual symptoms in subjects treated with Crohn's disease and ulcerative colitis are thought to be related to irritable bowel syndrome. The aims of this study were 1) to describe the duration and nature of complaints before the diagnosis of Crohn's disease and ulcerative colitis (prodromal period), and 2) to determine the role of IBS in this prodromal period. METHODS: A total of 66 patients with confirmed inflammatory bowel disease were enrolled in the study. The subjects received a questionnaire to ascertain the nature and duration of symptoms preceding the diagnosis of Crohn's disease or ulcerative colitis, including features described under the Rome criteria for irritable bowel syndrome. RESULTS: Of the 66 subjects analyzed, 45 had Crohn's disease and 21 had ulcerative colitis. The prodromal period was 7.7 +/- 10.7 yr for Crohn's disease and 1.2 +/- 1.8 yr for ulcerative colitis (p < 0.05). Once patients meeting the Rome criteria for irritable bowel syndrome during the prodrome were excluded, the duration of the prodromal period (non-IBS) for ulcerative colitis dropped to 0.8 +/- 1.3 yr compared to 6.9 +/- 9.8 yr in the Crohn's disease group (p < 0.05). The symptoms of the non-IBS prodrome in subjects with Crohn's disease were bloating, diarrhea, stomach pain, heartburn, fever, weight loss, and fatigue. Further analysis demonstrated that subjects whose Crohn's disease initially began as colonic disease had a longer prodrome than with small bowel. In the non-IBS Crohn's group, there was also a correlation between the age at the time of diagnosis and the duration of prodrome (r = 0.67, p < 0.0001). CONCLUSIONS: There is a significant prodromal period before the time of diagnosis of Crohn's disease that is not found in ulcerative colitis even after exclusion of subjects with IBS.     

Appendectomy, tonsillectomy, and risk of inflammatory bowel disease

PURPOSE: Appendectomy has been suggested as a possible protective factor in ulcerative colitis and as a risk factor in Crohn's disease. Tonsillectomy has also been associated with Crohn's disease. We performed a case-controlled study to investigate these associations in a homogeneous Greek population. METHODS: One hundred thirty-four consecutive cases of ulcerative colitis and 76 cases of Crohn's disease were included in the study. For each inflammatory bowel disease patient and a corresponding healthy control subject, matched for gender, age, and educational level, a standard record on various risk factors was completed by interview. The association between disease status and risk factors was assessed by Pearson's chi-squared test and the independent contribution of each risk factor was analyzed by means of logistic regression analysis. RESULTS: Appendectomy had been performed in 11 (8.2 percent) patients with ulcerative colitis, in 18 (13.4 percent) of their matched healthy control cases, in 19 (25.0 percent) patients with Crohn's disease, and in 10 (13.2 percent) of their matched healthy control cases. Odds ratio for development of ulcerative colitis after appendectomy was 0.6 (95 percent confidence interval, 0.26–1.27). Odds ratio for Crohn's disease was 2.2 (95 percent confidence interval, 0.94–5.12). Odds ratio for development of ulcerative colitis or Crohn's disease after tonsillectomy was 0.95 (95 percent confidence interval, 0.49–1.82) and 3.29 (95 percent confidence interval, 1.29–8.37), respectively. The logistic regression analysis showed that appendectomy and tonsillectomy have no independent association with the risk of developing ulcerative colitis, whereas in Crohn's disease both appendectomy and tonsillectomy have positive associations. Wellestablished risk factors, such as family history and smoking status, were also verified in this study. CONCLUSIONS: This case-control study, using multivariate logistic regression analysis, showed a less pronounced association between ulcerative colitis and appendectomy than previous reports. Our data also support the conclusion that tonsillectomy is a risk factor for developing Crohn's disease.Poster presentation at the World Congress of Gastroenterology, Vienna, Austria, September 6 to 11, 1998.     

Cytokine production in patients with inflammatory bowel disease.

The production of cytokines in peripheral blood mononuclear leukocytes of patients with inflammatory bowel disease was investigated. T cell subset analysis and differential white blood cell counts were also performed. Thirty five patients with ulcerative colitis, 14 with Crohn's disease, and 15 age matched healthy volunteers were studied. No differences were observed in T cell subsets and OKT4/OKT8 ratios in patients with ulcerative colitis or Crohn's disease compared with controls. Interleukin 1 beta production was significantly increased in active ulcerative colitis and Crohn's disease, compared with values in controls, but returned to control levels in the inactive stages. In addition, in active ulcerative colitis and Crohn's disease, there were significant correlations between the interleukin 1 beta production and the ulcerative colitis activity index or Crohn's disease activity index. Interleukin 2 production was also significantly increased in the active ulcerative colitis and significantly correlated to the activity index, but there was no change in Crohn's disease patients compared with controls. Gamma interferon production in patients was the same as that in controls. This study suggests that the interleukin 1 beta and 2 values in peripheral mononuclear leukocytes of active untreated inflammatory bowel disease are indicators of the disease states of ulcerative colitis or Crohn's disease, or both.     

Anergy to dinitrochlorobenzene and depression of T-lymphocytes in Crohn's disease and ulcerative colitis.

Skin reactivity to dinitrochlorobenzene (DNCB) and levels of circulating T-lymphocytes were measured in 15 patients with ulcerative colitis, 15 patients with Crohn's disease, and 12 normal control subjects. Diminished reactivity to DNCB was demonstrated in 87% of patients with Crohn's disease (P less than 0-001) and in 53% with ulcerative colitis (P less than 0-02), as compared with only 8-5% of controls; anergy was more frequent in Crohn's disease than in ulcerative colitis (P less than 0-05). Levels of circulating T-lymphoctes were also depressed in both Crohn's disease and ulcerative colitis (P less than 0-001) as compared with controls, with the values lower in Crohn's disease than in ulcerative colitis (P less than 0-02). There were no correlations of DNCB response with extent, duration, or severity of disease nor with T-cell levels within any patient group. These data provide further support for the concept that there is impairment of cell-mediated immunity among many patients with chronic inflammatory bowel disease, including both Crohn's disease and ulcerative colitis.     

Indium-111-labeled autologous leukocyte imaging and fecal excretion

This study was designed to evaluate the role of¹¹¹In-labeled leukocyte imaging and fecal excretion in the assessment of inflammatory bowel disease. We compared these tests to various indices of disease activity in Crohn's disease, to Truelove's grading in ulcerative colitis, and to endoscopy, x-ray, and pathology in both diseases. Eleven controls, 16 patients with Crohn's disease, 13 with ulcerative colitis, and 3 with other types of acute bowel inflammation were studied (positive controls). Indium scanning was performed at 1,4, and 24 hr. Fourteen of 16 patients with active Crohn's disease had positive scans but in only five was localization accurate. One patient had inactive ulcerative colitis, and the scan was negative. Of 12 patients with active ulcerative colitis, 10 had positive scans but disease localization was accurate in only four. Disease extent was correctly defined in 1 of the 3 Positive Controls. There was no significant difference in the accuracy of scanning at 1,4 or 24 hr.¹¹¹In fecal excretion was significantly higher in patients with inflammatory bowel disease than in controls, and there was correlation between¹¹¹In fecal excretion and most of the indices of disease activity in Crohn's disease. In ulcerative colitis,¹¹¹In fecal excretion did not correlate with Truelove's grading but reflected colonoscopic assessment of severity. In conclusion,¹¹¹In-labeled leukocyte scanning lacks sensitivity with respect to disease extent, but fecal excretion of¹¹¹In correlates well with disease severity as determined by other methods.Supported by the Physicians' Services Incorporated and the Medical Research Council of Canada grant MT. 4257