Mucosal cytokine production in radiation-induced proctosigmoiditis compared with inflammatory bowel disease

OBJECTIVE: We measured the mucosal levels of interleukin 1beta (IL-1beta), IL-2, IL-6, and IL-8 in affected segments of radiation-induced proctosigmoiditis and compared these with the levels in normal controls and inflammatory bowel disease (IBD) patients. METHODS: Thirteen patients with histologically proven radiation proctosigmoiditis, 32 patients with active ulcerative colitis (UC), 35 patients with Crohn's disease, and 15 normal subjects undergoing routine colonoscopy were included in the study. All patients underwent colonoscopy and mucosal biopsies were obtained from both diseased and normal-appearing areas. Mucosal levels of IL-1beta, IL-2, IL-6, and IL-8 were determined by solid-phase enzyme-linked immunosorbent assay (ELISA) using the Quantikine method (R&D Systems, Minneapolis, MN). All the data were statistically analyzed using Student's t test. RESULTS: The mucosal levels of IL-2, IL-6, and IL-8 were significantly higher in both diseased segments (5.62 +/- 0.13, 1.60 +/- 0.31, and 21.45 +/- 4.03 pg/ml, respectively) and normal-appearing segments (3.83 +/- 0.78, 1.36 +/- 0.34, and 13.45 +/- 3.18 pg/mg) in the radiation proctitis group compared to those of normal control subjects (1.74 +/- 0.23, 0.67 +/- 0.09, and 4.99 +/- 1.39 pg/mg). These differences were statistically significant (p < 0.05). In the UC group, IL-1beta, IL-6, and IL-8 levels in diseased segments were 4.98 +/- 0.53, 2.22 +/- 0.28, and 88.85 +/- 8.05 pg/mg, respectively. In Crohn's disease patients, IL-1beta, IL-6, and IL-8 levels were 5.45 +/- 0.93, 2.88 +/- 0.58, and 61.68 +/- 10.02 pg/mg, respectively. All these levels were significantly higher (p < 0.05) compared with IL-1beta, IL-6, and IL-8 levels from normal segments of IBD patients. Compared with the radiation proctitis patients, the levels of IL-6 and IL-8 were significantly higher in the IBD group. CONCLUSIONS: The mucosal levels of IL-2, IL-6, and IL-8 were significantly higher in both diseased and normal segments of colon in patients with radiation proctitis, compared with normal controls. Only IL-1beta levels were significantly higher in diseased segments, compared with endoscopically normal-appearing segments in radiation proctitis. These results indicate that there is a similarity in the activation of mucosal cytokines between IBD and radiation proctosigmoiditis. This may partly explain the beneficial effects of similar topical and systemic agents such as steroids and mesalamine compounds when used in radiation-induced proctosigmoiditis.     

The intestinal mucus layer from patients with inflammatory bowel disease harbors high numbers of bacteria compared with controls.

BACKGROUND & AIMS: Whether the bacterial flora contributes to the pathogenesis of inflammatory bowel disease (IBD) by increased penetration in mucus, increased adherence to epithelial cells, or invasion of the epithelium is unknown. We therefore studied the spatial distribution of bacteria in the mucosa of rectal biopsy specimens from patients with IBD and from controls. METHODS: Rectal biopsy specimens from 19 patients with IBD and from 14 controls were studied by using nonradioactive ribosomal RNA in situ hybridization. Total mucosal surface length examined for each patient was measured, and the number of bacteria visualized was estimated semiquantitatively. RESULTS: No bacteria were observed in biopsy specimens from 10 controls (71%) and 6 IBD patients (32%) (P = 0.04; odds ratio, 5.42; 95% confidence interval, 1.23-23.9). IBD rectal specimens contained significantly more bacteria than control samples (P = 0.004). Bacteria were localized within the mucus layer but did not adhere to the epithelial cells and were not present within the lamina propria. There was no correlation between the numbers of bacteria present and either the degree of inflammation or the use of anti-inflammatory agents or sulfasalazine compounds. CONCLUSIONS: The intestinal mucus in IBD patients is less protective against the endogenous microflora than in controls, resulting in increased association of luminal bacteria with the mucus layer.     

Mucosal antibodies in inflammatory bowel disease are directed against intestinal bacteria.

In contrast with normal subjects where IgA is the main immunoglobulin in the intestine, patients with active inflammatory bowel disease (IBD) produce high concentrations of IgG from intestinal lymphocytes, but the antigens at which these antibodies are directed are unknown. To investigate the specificities of these antibodies mucosal immunoglobulins were isolated from washings taken at endoscopy from 21 control patients with irritable bowel syndrome, 10 control patients with intestinal inflammation due to infection or ischaemia, and 51 patients with IBD: 24 Crohn's disease (CD, 15 active, nine quiescent), 27 ulcerative colitis (UC, 20 active, seven inactive). Total mucosal IgG was much higher (p < 0.001) in active UC (median 512 micrograms/ml) and active CD (256 micrograms/ml) than in irritable bowel syndrome controls (1.43 micrograms/ml), but not significantly different from controls with non-IBD intestinal inflammation (224 micrograms/ml). Mucosal IgG bound to proteins of a range of non-pathogenic commensal faecal bacteria in active CD; this was higher than in UC (p < 0.01); and both were significantly greater than controls with non-IBD intestinal inflammation (CD p < 0.001, UC p < 0.01) or IBS (p < 0.001 CD and UC). This mucosal IgG binding was shown on western blots and by enzyme linked immunosorbent assay (ELISA) to be principally directed against the bacterial cytoplasmic rather than the membrane proteins. Total mucosal IgA concentrations did not differ between IBD and controls, but the IgA titres against faecal bacteria were lower in UC than controls (p < 0.01). These experiments show that there is an exaggerated mucosal immune response particularly in active CD but also in UC directed against cytoplasmic proteins of bacteria within the intestinal lumen; this implies that in relapse of IBD there is a breakdown of tolerance to the normal commensal flora of the gut.     

Mucosal flora in inflammatory bowel disease.

BACKGROUND & AIMS: Microorganisms that directly interact with the intestinal mucosa are obscured by fecal flora and poorly characterized. METHODS: We investigated the mucosal flora of washed colonoscopic biopsies of 305 patients with bowel inflammation and 40 controls. The microbial cultures were validated by quantitative polymerase chain reaction with subsequent cloning and sequencing, fluorescence in-situ hybridization, and electron microscopy. RESULTS: We found high concentrations of mucosal bacteria in patients with bowel inflammation, but not in controls. The concentrations of mucosal bacteria increased progressively with the severity of disease, both in inflamed and non-inflamed colon. In patients with >10,000 cfu/microL, a thick bacterial band was attached to the intact mucosa without signs of translocation. Patients with inflammatory bowel disease (IBD) and concentrations of mucosal bacteria >50,000 cfu/microL had characteristic inclusions of multiple polymorphic bacteria within solitary enterocytes located next to the lamina propria, without or having no contact with the fecal stream. The identified bacteria were of fecal origin. CONCLUSIONS: Our findings suggest that the changes in the mucosal flora in IBD are not secondary to inflammation, but a result of a specific host response. We hypothesize that the healthy mucosa is capable of holding back fecal bacteria and that this function is profoundly disturbed in patients with IBD.     

Mucosal glucosamine synthetase activity in inflammatory bowel disease

Abnormalities in colonic glycoprotein synthesis have been implicated in the pathogenesis of ulcerative colitis and Crohn's disease. Glucosamine synthetase is the rate-limiting step in the biosynthesis of gastrointestinal glycoprotein and has been measured in control subjects (N=23) and patients with ulcerative colitis (N=26) or Crohn's disease of the colon (N=20) classified according to the macroscopic status of the rectum. Glucosamine synthetase activity was relatively constant around the normal colon but lower levels were found in the terminal ileum. In ulcerative colitis, glucosamine synthetase activity was similar to controls (24.0±1.9) mmol/g wet (wt/hr) irrespective of disease activity (quiescent:N=13, =27.3±1.9; activeN=16, =26.2±2.3). Rectal glucosamine synthetase activity was normal in the presence of active Crohn's proctocolitis (29.4±3.1) but raised in patients with Crohn's colitis and rectal sparing (37.2±4.9P<0.02). Glucosamine synthetase activity was strongly influence by the degree of epithelial preservation.     

Psychological wellbeing and physical activity in children and adolescents with inflammatory bowel disease compared to healthy controls

Background

Children and adolescents with inflammatory bowel disease (IBD) report impairments in daily activities, social interactions and coping. Findings regarding psychological functioning are inconsistent, while limited information is available on objectively assessed physical activity (PA). The aims of the present study were therefore to compare anthropometric dimensions, blood values, psychological functioning and PA of children and adolescents with IBD with healthy controls.

Methods

Forty-seven children and adolescents took part in the study. Of these, 23 were diagnosed with IBD (mean age: 13.88 years, 44% females). The IBD group was divided into a medically well adjusted “remission-group” (n?=?14; IBD-RE) and a group with an “active state” of disease (n?=?8; IBD-AD). Healthy controls (n?=?24; HC) were age- and gender-matched. Participants’ anthropometric data, blood values and objective PA were assessed. Further, participants completed questionnaires covering socio-demographic data and psychological functioning.

Results

Participants with IBD-AD showed higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) values, haemoglobin, and leukocyte values. IBD-AD had poorer psychological functioning and lower PA (average steps per day) compared to IBD-RE and HC. No mean differences were found between IBD-RE and HC.

Conclusions

The pattern of results suggests that effective medical treatment of IBD in children and adolescents is associated with favorable physiological parameters, psychological dimensions and PA. Psychological counselling of children and adolescents in an active state of IBD seem to be advised in addition to standard treatment schedules.

Trial registration

NCT NCT02264275; Registered 8 October 2014.

     

Higher platelet P-selectin in male patients with inflammatory bowel disease compared to healthy males

AIM: To observe if the total amount of platelet P-selectin (tP-selectin) in patients with inflammatory bowel disease (IBD) was related to disease entity or activity, 5-aminosalicylic acid (5-ASA) medication or gender. METHODS: tP-selectin was measured by immunoassay in seventeen IBD patients and twelve healthy controls. RESULTS: Compared to controls, there was no difference of tP-selectin in patients related to disease entity or activity and 5-ASA medication. When the groups were split according to gender the male patient group showed higher levels of tP-selectin compared to male controls (153 ng/mL vs 94 ng/mL, P<0.05). CONCLUSION: Increased tP-selectin levels may alter the inflammatory response and susceptibility to thromboembolic disease. As previously shown with soluble P-selectin, tP-selectin shows gender dependent differences important to consider in future studies.     

Mucosal bacterial microflora and mucus layer thickness in adolescents with inflammatory bowel disease

AIM: To assess the mucosa-associated bacterial microflora and mucus layer in adolescents with inflammatory bowel disease (IBD).METHODS: Sixty-one adolescents (mean age 15 years, SD ± 4.13) were included in the study. Intestinal biopsies from inflamed and non-inflamed mucosa of IBD patients and from controls with functional abdominal pain were cultured under aerobic and anaerobic conditions. The number of microbes belonging to the same group was calculated per weight of collected tissue. The mucus thickness in frozen samples was measured under a fluorescent microscope.RESULTS: The ratios of different bacterial groups in inflamed and non-inflamed mucosa of IBD patients and controls were specific for particular diseases. Streptococcus spp. were predominant in the inflamed mucosa of Crohn’s disease (CD) patients (80% of all bacteria), and Lactobacillus spp. were predominant in ulcerative colitis patients (90%). The differences were statistically significant (P = 0.01-0.001). Lower number of bifidobacteria was observed in the whole IBD group. A relation was also found between clinical and endoscopic severity and decreased numbers of Lactobacillus and, to a lesser extent, of Streptococcus in biopsies from CD patients. The mucus layer in the inflamed sites was significantly thinner as compared to controls (P = 0.0033) and to non-inflamed areas in IBD patients (P = 0.031).CONCLUSION: The significantly thinner mucosa of IBD patients showed a predominance of some aerobes specific for particular diseases, their numbers decreased in relation to higher clinical and endoscopic activity of the disease.     

Anxiety in close relationships is higher and self-esteem lower in patients with irritable bowel syndrome compared to patients with inflammatory bowel disease

BackgroundPrevious research has suggested an interaction between personality factors and inflammatory bowel disease (IBD) as well as irritable bowel syndrome (IBS). We therefore aimed to elucidate differences in psychological and coping functioning between patients with IBD and IBS, and to assess the relationship of disease activity with these functions.MethodsSeventy-four patients with IBD (mean age 43 ± 17 years, range 18–82 years) and 81 patients with IBS (mean age 37 ± 12 years, range 21–66 years) completed the questionnaires; Rosenberg Self-Esteem Scale, Toronto Alexithymia, Experiences in Close Relationships, and Sense of Coherence. Disease activity was evaluated either by the Harvey-Bradshaw index, the Simple Clinical Colitis Activity Index, or the Visual Analogue Scale for Irritable Bowel Syndrome.ResultsThe study revealed that patients with IBS had higher degree of anxiety in close relationships than patients with IBD (p = 0.003), and lower self-esteem (p = 0.001). No other statistical differences between the whole groups IBS and IBD or between subgroups were seen.ConclusionsThe fact that patients with IBS seem to have higher levels of anxiety in relationships and lower self-esteem could influence the way the patient deal with the disease and how the communication with health care professionals works out. A higher awareness of the importance of past negative life events should be taken into consideration. Whether the disease or the personal traits are the primary event should be addressed in future research.     

Vaccinations in patients with inflammatory bowel disease

Treatment of inflammatory bowel disease (IBD) frequently requires administration of immunosuppressive therapies, which increases susceptibility to a number of infectious pathogens. However, many infections can be prevented by correct and appropriate utilization of vaccinations. While several guidelines have been published on vaccination schedules in patients with IBD, vaccination rates remain suboptimal and even lower than those in the general population. This is due to many factors including poor awareness of the importance of vaccines by gastroenterologists and general practitioners as well as potential prejudices of patients regarding the safety and benefits of vaccines. With the aim of increasing awareness about the key role of immunization in the management of patients with IBD, the present review examines the existing literature relating to the main vaccinations and their application in these patients. We also summarize current evidence in order to provide clinicians with an easy source of reference for the principal recommendations for prevention of infectious diseases in patients with IBD. In addition, the recommendations about traveling for IBD patients are briefly explored. Lastly, since it is important for gastroenterologists to be aware of recommendations on vaccination, we recommend implementing educational programs to ensure compliance with current guidelines.     

Mucosal T-cell immunoregulation varies in early and late inflammatory bowel disease

Background and aims

Crohn''s disease is a life‐long form of inflammatory bowel disease (IBD) mediated by mucosal immune abnormalities. Understanding of the pathogenesis is limited because it is based on data from adults with chronic Crohn''s disease. We investigated mucosal T‐cell immunoregulatory events in children with early Crohn''s disease.

Methods

Mucosal biopsies and T‐cell clones were derived from children experiencing the first attack of Crohn''s disease, children with long‐standing Crohn''s disease, infectious colitis, and children without gut inflammation.

Results

As in acute infectious colitis, interleukin (IL) 12 induced T cells from early Crohn''s disease to acquire a strongly polarised T helper (Th) type 1 response characterised by high IFN‐γ production and IL12Rβ2 chain expression. Th1 polarisation was not induced in clones from late Crohn''s disease. Mucosal levels of IL12p40 and IL12Rβ2 messenger RNA were significantly higher in children with early than late Crohn''s disease. These results demonstrate that susceptibility to IL12‐mediated modulation is strongly dependent on the stage of Crohn''s disease.

Conclusions

At the onset of Crohn''s disease mucosal T cells appear to mount a typical Th1 response that resembles an acute infectious process, and is lost with progression to late Crohn''s disease. This suggests that mucosal T‐cell immunoregulation varies with the course of human IBD. Patients with the initial manifestations of IBD may represent an ideal population in which immunomodulation may have optimal therapeutic efficacy.Both forms of inflammatory bowel disease (IBD), Crohn''s disease and ulcerative colitis are life‐long conditions whose initial clinical manifestations appear in the first decades of life. The incidence of IBD is increasing worldwide, and recent epidemiological data show that the diagnosis of IBD is increasingly more frequent in children as the age of onset is decreasing,^1,2 with an equal incidence among all ethnic groups.³ Investigation of IBD has largely relied on studies of adult patients with established disease or animal models of acute IBD,⁴ making it difficult to reconcile data from humans with chronic disease with data from animals with acute disease. Pathogenic events may vary during the course of chronic gut inflammation,⁵ but claims that new‐onset and long‐standing IBD may be different, or that IBD in children is distinct from IBD in adults are so far unsubstantiated.⁶ The investigation of human IBD at the earliest possible time, as in children with the first clinical manifestations of Crohn''s disease, could obviate the many confounding variables associated with chronicity. In this population early mechanisms of gut inflammation could be examined before masking or modification by disease evolution or therapy. In addition, unique immunological reactivities associated with specific types of inflammation may be uncovered, as demonstrated in children with Crohn''s disease.⁷In addition to the type of triggering agents and the intrinsic properties of the affected tissue, the long‐term outcome of an inflammatory response is strongly influenced by the local cytokine milieu. This milieu changes with time, and different mediators are involved in the inductive versus the effector phase of an immune response, which eventually acquires distinctive T helper (Th) type 1, Th2, Th17 or alternative profiles.^8,9 On the basis of this paradigm, evidence indicates that Crohn''s disease is a Th1/Th17‐like condition,^10,11 whereas ulcerative colitis appears to represent an atypical Th2 condition.¹² These conclusions are largely based on T‐cell cytokine profiles from adults with long‐standing disease and numerous animal models of IBD.¹³ There is some evidence that cytokine levels may vary with the evolution of human IBD,⁵ but whether T cells produce quantitatively or qualitatively different cytokine profiles in the early compared with the late stages of IBD is unclear. More importantly, no information is available on cytokines produced by mucosal T cells at the time of disease onset. In addition to the type and quantity of antigen, and how antigen‐presenting cells handle the antigen(s), the outcome of an inflammatory process also depends on the cytokine make‐up at the beginning of such a process. Therefore, it seems essential to define as early as possible in the course of Crohn''s disease the response of mucosal T cells to the immunoregulatory cytokines that condition T helper cell differentiation.¹⁴ This could reveal whether the cytokine profiles found in late Crohn''s disease reflect a fixed response set in motion at the initiation of disease, or represent an evolutionary response to the progression of IBD. This fundamental question cannot be answered using T cells from resected tissues because children with early Crohn''s disease seldom undergo an operation. Therefore, with the caveat that the chosen approach may not be entirely representative of the intestinal immune response because other compartments such as the mesenteric lymph nodes are not sampled, we studied T cells derived from colonoscopic mucosal biopsies from a unique population of children with the very first attack of Crohn''s disease. The production of interleukin (IL) 2, IFN‐γ, IL4, and IL10, as well as IL12 receptor (IL12R) β1 and β2 chain expression were measured in T‐cell clones exposed to the immunomodulatory effects of IL12 and IL4. In addition, total levels of IL12 and IL12Rβ2 chain messenger RNA were measured in the biopsies. The results show that differences in cytokine production and susceptibility to immune modulation occur exclusively in early Crohn''s disease. IL12 conditioning of mucosal T cells from children with early Crohn''s disease induces high levels of IFN‐γ similar to those produced by IL12‐stimulated T cells from children with acute infectious colitis. In contrast, mucosal T cells of children with late Crohn''s disease fail to upregulate IFN‐γ production in response to IL12. In addition, the expression level of the IL12Rβ2 chain is significantly higher in T cells from children with early Crohn''s disease and infectious colitis than children with late IBD, and tissue IL12 and IL12Rβ2 chain mRNA were also higher in early than late Crohn''s disease. Therefore, at the beginning of IBD, mucosal T cells mount a Th1 response that resembles an acute infectious process, and is lost with progression to late disease.     

Communicating with patients with inflammatory bowel disease

Ulcerative colitis and Crohn's disease, the two main forms of inflammatory bowel disease (IBD), are chronic illnesses that affect hundreds of thousands of Americans. Patients with IBD suffer chronically from diarrhea, abdominal pain, gastrointestinal bleeding, malabsorption, and weight loss requiring continuous medical and surgical attention. Despite recent advances in therapy, IBD follows a course of exacerbations and remissions with approximately 25-50% of patients relapsing annually. Hence, these diseases are readily encountered in primary care and gastroenterology clinics. Though medical and surgical treatment options have improved significantly, little has been written about the psychosocial aspects of IBD. Currently, there is a paucity of data concerning effective communication methods enabling physicians to develop stronger rapport with patients suffering from IBD, the care of whom requires a multidisciplinary approach involving primary care physicians, gastroenterologists, and colorectal surgeons. Because IBD has a high morbidity, it is worthwhile to further investigate those social factors that will improve patients' quality of life. In this paper, we summarize some of the common problems that emerge when taking care of patients with IBD and provide initial guidelines based on the world literature regarding the management and education of patients with IBD. Both primary care physicians and specialists (gastroenterologists, colorectal surgeons) need to be aware of the questions and concerns of IBD patients and to be capable of dispensing the information in a clear and concise manner. Using the case scenario format, we review the most common aspects of communication for health care professionals taking care of IBD patients and suggest ways to establish and maintain long-term doctor-patient relationships. The two most significant interventions that dramatically improve quality of life and patient-physician relationships are proper patient education and appropriate treatment of concurrent depression and anxiety. We hope that our review will form a framework by which different members of the medical team learn their roles in the complex management decisions affecting IBD patients.     

Gastrointestinal symptoms in the irritable bowel compared with peptic ulcer and inflammatory bowel disease.

Symptoms of 50 patients with the irritable bowel syndrome were compared with those of 49 with endoscopically proven peptic ulcer disease and 49 with radiologically or endoscopically proven inflammatory bowel disease using a questionnaire which was administered after the diagnosis was made. Symptoms of bowel dysfunction including pain related to bowel movements were more likely to occur in the irritable bowel syndrome than peptic ulcer disease. Only abdominal distension, straining at stool and scybala, however, were significantly more likely in the irritable bowel syndrome than inflammatory bowel disease. Four symptoms previously shown to be more common in irritable bowel syndrome than in organic abdominal disease were combined. The more of these symptoms that were present, the more likely were the patients to have the irritable bowel syndrome than peptic ulcer disease. Symptoms of gut dysfunction are highly discriminating between irritable bowel syndrome and peptic ulcer disease but less so between irritable bowel syndrome and inflammatory bowel disease.     

Psychiatric comorbidities in patients with inflammatory bowel disease

Background

Psychiatric comorbidities are associated with inflammatory bowel disease (IBD). We conducted an observational study to evaluate the prevalence of depression and anxiety in patients with IBD.

Methods

Seventy consecutive consenting patients with IBD (62 ulcerative colitis [UC], 8 Crohn’s disease [CD]; 40 males, mean age [SD] 36.2 [11.3] years) and 100 healthy volunteers (44 males, age 31.22 [SD] [10.5] years) as controls were enrolled. All participants were directed to take self-assessment tests, Patient Health Questionnaire -9 (PHQ-9) and Symptom Checklist Anxiety Scale (SCL-A20). Participants having a score ≥ 10 on PHQ-9, or ≥ 29 on SCL-A20 were administered the Hamilton Depression Rating Scale (HAM-D) or Hamilton Anxiety (HAM-A) scales, respectively. The severity of depression and anxiety was graded with HAM-D and HAM-A scales, respectively. The protocol was approved by the Institutional Ethics Committee.

Results

The prevalence of depression (34.3% vs. 5%, p?<?0.0001, OR 9.7) and anxiety (18.6% vs. 2%, p?=?0.0002, OR 11.17) was higher in patients with IBD as compared to controls. The severity of depression was higher in patients compared to controls (mean rank 17 vs. 7, p?=?0.04). The prevalence of depression was not different between UC and CD; all IBD patients with anxiety had UC. The mean duration of disease and history of corticosteroid treatment or surgery for IBD were not associated with the presence of depression or anxiety. Patients with severe CD (Crohn’s disease activity index, CDAI?>?450) had more severe depression. The severity of UC did not correlate with severity of anxiety or depression in UC.

Conclusions

Anxiety and depression are more prevalent in IBD patients as compared to healthy individuals.

     

Smoking habits in patients with inflammatory bowel disease

The proportion of smokers in this study was significantly lower among patients with ulcerative colitis (13%) than among patients with Crohn's disease (47%), the difference being significant for both sexes and for the age groups both below and above 40 years. The proportion of male ex-smokers among patients with ulcerative colitis (28%) was higher than among patients with Crohn's disease (8%), whereas the proportions of non-smokers differed less. Many of the patients with ulcerative colitis who had a late onset were male ex-smokers. The smoking patients with ulcerative colitis were mainly women. They smoked less than the smoking patients with Crohn's disease and less than the ex-smokers in each group. No smoking patient with ulcerative colitis smoked greater than 20 cigarettes/day. In the group of male ex-smokers with ulcerative colitis, there was an accumulation of onsets during the 4 years after the definitive smoking stop. The number of colectomies performed on patients with ulcerative colitis did not vary with smoking habits. In the group of ex-smokers the colectomy was performed after the smoking stop in 19 out of 20 patients.