Peter Stubbe Teglbjærg

Budesonide treatment of collagenous colitis: a randomised, double blind, placebo controlled trial with morphometric analysis

Background: Collagenous colitis is characterised by diarrhoea, lymphocytic inflammation, and a thickened subepithelial collagen layer in the colorectal mucosa. No standard treatment of the disease is established. Aims: To investigate the clinical and histological effect of oral budesonide (Entocort, AstraZeneca) in the treatment of collagenous colitis. Patients: Twenty patients with collagenous colitis (collagen layer >10 μm) and diarrhoea (>4 stools/day and/or stool weight >200 g/day). Methods: A randomised, double blind, placebo controlled trial of budesonide treatment. Patients were randomised to placebo or budesonide for eight weeks. Stool frequency and stool weight were registered before and after treatment. Sigmoidoscopy was performed before and after treatment, and biopsies at fixed locations were obtained for morphometric analysis. Results: Ten patients were randomised to budesonide and 10 to placebo. All 10 patients receiving budesonide had a clinical response compared with two in the placebo group (p<0.001). In the budesonide group, stool weight was reduced from 574 g/day to 200 g/day and stool frequency was reduced from 6.2/day to 1.9/day (p<0.01). The histological inflammation grade in the sigmoid mucosa and the thickness of the collagen layer were significantly reduced. A correlation between the grade of inflammation as well as collagen layer thickness and stool weight was found. No side effects were reported. Eight of 10 patients had relapse of symptoms within eight weeks after stopping treatment. Conclusions: Budesonide is a highly effective and well tolerated treatment of collagenous colitis. There is a high risk of relapse after stopping eight weeks of treatment.

Microscopic Appearance of the Esophageal Mucosa in a Consecutive Series of Patients Submitted to Upper Endoscopy: Correlation with Gastroesophageal Reflux Symptoms and Macroscopic Findings

The histologic finding of basal-layer hyperplasia and papillosis as consequences of gastroesophageal reflux still constitute an area of controversy. Consequently, a prospective study of symptoms and endoscopy and biopsy interpretation was undertaken in 200 patients consecutively submitted to upper endoscopy, whereof 12 were excluded. Complete agreement among all three variables was found in half of the patients and harmony between two of the variables in one fourth. In the last fourth the outcome was positive in one variable only, equally distributed among the symptoms, endoscopy, and histology. It is concluded that histology is of considerable value in gastroesophageal reflux disease.

Long-term budesonide treatment of collagenous colitis: a randomised, double-blind, placebo-controlled trial

Objective: To evaluate the efficacy and safety of long-term budesonide therapy for the maintenance of clinical remission in patients with collagenous colitis. Design: Randomised, placebo-controlled study with a 24-week, blinded follow-up period without any treatment. Setting: Three gastroenterology clinics in Denmark. Patients: Forty-two patients with histologically confirmed collagenous colitis and diarrhoea (more than three stools/day). Interventions: Patients in clinical remission after 6 weeks’ open-label therapy with oral budesonide (Entocort CIR capsules, 9 mg/day) received 24 weeks’ double-blind maintenance therapy with budesonide 6 mg/day or placebo. Thereafter, patients entered the 24-week, blinded follow-up period. Main Outcome Measure: The proportion of patients in clinical remission (three or fewer stools/day) at the end of maintenance therapy. Findings: A total of 34 patients in remission at week 6 were randomly assigned to budesonide 6 mg/day (n  =  17) or placebo (n  =  17). After 24 weeks’ maintenance treatment, the proportions of patients in clinical remission were 76.5% (13 of 17) with budesonide and 12% (2 of 17) with placebo (p<0.001). At 48 weeks (the end of the follow-up period, without any treatment) these values were 23.5% (4 of 17) and 12% (2 of 17), respectively (p = 0.6). The median times to relapse after stopping active treatment (6 plus 24 weeks in the budesonide group; 6 weeks in the placebo group) were 39 and 38 days, respectively. Long-term treatment with budesonide was well tolerated. Conclusions: Long-term maintenance therapy with oral budesonide is efficacious and well tolerated for preventing relapse in patients with collagenous colitis. The risk of relapse after 24 weeks’ maintenance treatment is similar to that observed after 6 weeks’ induction therapy.

Helicobacter pylori –negative duodenal ulcers: prevalence, clinical characteristics, and prognosis—results from a randomized trial with 2-year follow-up

ObjectiveThe proportion of Helicobacter pylori–negative duodenal ulcer disease appears to be increasing. Data on clinical outcome and prognosis in this subgroup are lacking.METHODS:Two hundred seventy-six duodenal ulcer patients randomized, irrespective of H. pylori status, to either eradication therapy or maintenance omeprazole (double-blind, double-dummy design) for 1 yr were studied. Patients were followed up for a total of 2 yr, with visits performed every 2 months the first year and every 6 months the following year. Endoscopies for assessment of ulcer relapse were done at 6 and 12 months or in the event of symptomatic relapse. H. pylori status was assessed by culture, immunohistochemistry, and urea breath test at entry, at 6, 12, and 24 months or at failure. The primary endpoint was discontinuation, irrespective of reason. Patients were considered H. pylori negative if all three tests were negative. Patients were considered H. pylori–positive if any of the three diagnostic tests were positive. Study staff were blinded to H. pylori results.RESULTS:Thirty-two (12%) patients were H. pylori negative at entry. There were no differences according to H. pylori status for a number of clinical and demographic characteristics. However, H. pylori–negative patients had a shorter history of ulcer symptoms and were more likely to be NSAID users (19% vs 1%, p < 0.001). Only 28% of the H. pylori–negative patients completed the study, as compared with 40% of H. pylori–positive patients (p = 0.0005). The main reasons for the poorer prognosis in H. pylori–negative patients were relapse of ulcer/ulcer not healed (35% vs 26%) and relapse of severe dyspepsia symptoms without ulcer relapse (16% vs 7%). H. pylori–negative patients randomized to eradication therapy left the study early compared with H. pylori–negative patients randomized to long-term omeprazole therapy. Outcome in omeprazole-treated patients did not differ according to H. pylori status (p = 0.3).CONCLUSIONS:Clinical characteristics in H. pylori–negative and positive duodenal ulcer patients differ little. Clinical outcome over 2 yr is significantly poorer in H. pylori–negative patients, especially if treated empirically with eradication therapy. These results suggest that H. pylori infection should be assessed in all duodenal ulcer patients before treatment is decided.

Diagnostic examination of human intestinal spirochetosis by fluorescent in situ hybridization for Brachyspira aalborgi, Brachyspira pilosicoli, and other species of the genus Brachyspira (Serpulina).

ABSTRACT Human intestinal spirochetosis, characterized by end-on attachment of densely packed spirochetes to the epithelial surface of the large intestines as a fringe has been associated with the weakly beta-hemolytic spirochetes Brachyspira aalborgi andBrachyspira (Serpulina)pilosicoli. In this study, fluorescent in situ hybridization with oligonucleotide probes targeting 16S or 23S rRNA ofB. aalborgi, B. pilosicoli, and the genusBrachyspira was applied to 40 sections of formalin-fixed, paraffin-embedded intestinal biopsy specimens from 23 Danish and 15 Norwegian patients with histologic evidence of intestinal spirochetosis. Five biopsy specimens from patients without intestinal spirochetosis and three samples from pigs with experimental B. pilosicoli colitis were examined as well. In addition, the 16S ribosomal DNAs of two clinical isolates of B. aalborgi were sequenced, and a PCR procedure was developed for the identification ofB. aalborgi in cultures. The genotypic characteristics of the two clinical isolates showed very high (99.5%) similarity with two existing isolates, the type strain of B. aalborgi and a Swedish isolate. Hybridization with the Brachyspiragenus-specific probe revealed a brightly fluorescing fringe of spirochetes on the epithelia of 39 biopsy specimens, whereas 1 biopsy specimen was hybridization negative. The spirochetes in biopsy specimens from 13 Danish and 8 Norwegian patients (55.3%) were identified as B. aalborgi. The spirochetes in the biopsy specimens from the other 17 patients hybridized only with theBrachyspira probe, possibly demonstrating the involvement of as-yet-uncharacterized Brachyspira spirochetes in human intestinal spirochetosis.

Is there an association between alcohol intake or smoking and small bowel adenocarcinoma? Results from a European multi-center case–control study

AbstractObjective:To discover whether tobacco smoking and intake of different types of alcoholic drinks are associated with small bowel adenocarcinoma (SBA). Methods:A population-based European multi-center case–control study was conducted from 1995 to 1997. Results:After a histological review using uniform diagnostic criteria, 47 (33%) of the 142 identified cases of SBA were excluded due to reclassification as either tumors of the papilla of Vater (n = 22), stromal tumors, or metastases; 95 cases were accepted for study. In all, 70 cases of SBA together with 2070 controls matched by age, sex, and region were interviewed. A high intake (more than 24 g alcohol per day) of beer or spirits was associated with SBA, an odds ratio (OR) of 3.5 and 95% confidence intervals (CI) of 1.5–8.0 and 3.4 (95% CI 1.3–9.2), respectively). There was no association with wine intake or total alcohol intake. Tobacco smoking was probably unrelated to SBA. Conclusions:A high intake of beer or spirits seems to be a risk factor for SBA. Since this association was not seen for wine drinkers, protective components of wine may counterbalance a carcinogenic effect of alcohol on the small bowel. Alternatively, the result may be confounded by other factors, e.g. dietary factors.

The importance of smoking and medical history for development of small bowel carcinoid tumor: a European population-based case-control study

Objective: Little is known about the etiology of small bowel carcinoid tumor (SBC), but a few studies have pointed to certain medical and lifestyle factors as potential risk factors. This study aims to evaluate these findings and to identify new associations. Methods: A population-based European multicenter case–control study was conducted from 1995 through 1997. Incident histologically verified 35–69 year-old SBC cases (n = 99) and 3335 controls were recruited; 84 cases and 2070 controls were interviewed. Results: Ever being a smoker was associated with SBC (odds ratio = 1.9; 95% confidence interval 1.1–3.2) and increased risk estimates were seen for all smoking categories. SBC was associated with previous gallstone disease and ovariectomy, but only when these conditions occurred within two years prior to the SBC diagnosis. No association was seen for a history of cholecystitis, liver cirrhosis, ulcerative disease, or Crohns disease. Intake of alcoholic beverages – as well as medical treatments with radioactive substances, hormones, or corticosteroid tablets – were not associated with SBC. Conclusions: This study indicates that tobacco smoking is a risk factor for SBC. The associations with gallstone and ovarian diseases may be due to enhanced medical surveillance during the early phase of the cancer disease.

Neuronal features of oligodendrogliomas—an ultrastructural and immunohistochemical study

Aims:  To assess neuronal differentiation in oligodendrogliomas (ODGs).

Occupational risk factors for small bowel carcinoid tumor: A European population-based case-control study

Learning Objectives (1) Characterize small bowel carcinoid tumor (SBC) as to its clinical features and relationship to occupational exposures. (2) Identify specific industries and occupations that, in this case-control study, seem to confer an increased risk of SBC. (3) Give examples of common denominators that may connect identified types of work with an increased risk of SBC. Small bowel carcinoid tumor (SBC) is a rare disease of unknown etiology but with an age-, sex-, and place-specific occurrence that may indicate an occupational origin. A European multicenter population-based case-control study was conducted from 1995 through 1997. Incident SBC cases between 35 and 69 years of age (n = 101) were identified, together with 3335 controls sampled from the catchment area of the cases. Histological review performed by a reference pathologist left 99 cases for study; 84 cases and 2070 population controls were interviewed. The industries most closely associated (a twofold or more odds ratio [OR]) with SBC, taking into account a 10-year time lag after exposure were, among women, employment in wholesale industry of food and beverages (OR, 8.2; 95% confidence interval [CI], 1.9 to 34.9]) and among men, manufacture of motor vehicle bodies (OR, 5.2; 95% CI, 1.2 to 22.4), footwear (OR, 3.9; 95% CI, 0.9 to 16.1), and metal structures (OR, 3.3; 95% CI, 1.0 to 10.4). The identified high-risk occupations with an OR above 2 were shoemakers, structural metal preparers, construction painters and other construction workers, bookkeepers, machine fitters, and welders (men). The OR for regular occupational use of organic solvents for at least half a year was 2.0 (95% CI, 1.0 to 4.2). Exposure to rust-preventive paint containing lead was suggested as another potential occupational exposure (OR, 9.1; 95% CI, 0.8 to 107). This explorative study suggests an association between certain occupational exposures and SBC, but some of these associations could be attributable to chance. All findings should be regarded as tentative.

Risk Factors for Symptom Relapse in Collagenous Colitis After Withdrawal of Short-term Budesonide Therapy

Background:Oral budesonide has been proven effective in short- and long-term treatment of collagenous colitis; however, symptom relapse frequently occurs after drug withdrawal. The aim of this study was to identify the risk factors for symptom relapse in patients with collagenous colitis after withdrawal of short-term budesonide therapy. Methods:One hundred twenty-three patients from 4 randomized controlled studies who achieved clinical remission after short-term treatment with budesonide (9 mg/d) were analyzed, including 40 patients receiving subsequent budesonide maintenance therapy (6 mg/d) for 6 months and 83 patients without active maintenance treatment. Variables available for analysis were age, sex, baseline stool frequency, duration of diarrhea, collagenous band thickness, and lamina propria inflammation. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were calculated by Cox proportional hazard model. Results:The overall symptom relapse rate was 61%. By multivariate analysis, a baseline stool frequency >5 per day (HR, 3.95; 95% CI, 1.08–14.39), history of diarrhea >12 months (HR, 1.77; 95% CI, 1.04–3.03), and the absence of budesonide maintenance therapy (HR, 2.71; 95% CI, 1.37–5.38) were associated with symptom relapse. The time to relapse was shorter in patients with a baseline stool frequency >5 per day (56 versus 199 d, P = 0.024), as in those with history of diarrhea >12 months (56 versus 220 d, P = 0.009). Budesonide maintenance therapy delayed the time to relapse (56 versus 207 d, P = 0.005). Conclusions:Our data demonstrate that a high stool frequency at baseline and a long duration of diarrhea are risk factors for symptom relapse in collagenous colitis, whereas budesonide maintenance therapy is a protective factor against symptom relapse.