Histopathology of liver biopsies from a thiopurine-naïve inflammatory bowel disease cohort: prevalence of nodular regenerative hyperplasia.

OBJECTIVE: Nodular regenerative hyperplasia (NRH) and sinusoidal dilatation have been described in relation to thiopurine use in patients with inflammatory bowel disease (IBD). However, there is a dearth of data on the prevalence of these histological abnormalities in general. The aim of our study was to describe the prevalence of these histological liver changes in a thiopurine-naïve IBD cohort. MATERIAL AND METHODS: Liver biopsy specimens were obtained from patients who were treated in a referral center and who underwent gastrointestinal surgery for IBD. Patients were excluded if thiopurines were ever used. The liver specimens were pathohistologically assessed with special attention to NRH. RESULTS: A total of 83, properly stained, liver specimens (Crohn's disease 61%) were evaluated. NRH was observed in 6% compared to sinusoidal dilatation of varying degree in 34% of specimens. An older age at biopsy was correlated with NRH (p=0.015). Fibrosis and steatosis of varying degrees were detected in 31% and 36% of liver biopsies, respectively. No cases of liver cirrhosis were observed. CONCLUSIONS: Pathohistological hepatic abnormalities are common in non-thiopurine using IBD patients. The association between thiopurine use, NRH and sinusoidal dilatation may be weaker than as reported in recent literature, as there is relatively high background prevalence in selected series.

Detection of Helicobacter species DNA by quantitative PCR in the gastrointestinal tract of healthy individuals and of patients with inflammatory bowel disease.

In many animal species different intestinal Helicobacter species have been described and a few species are associated with intestinal infection. In humans, the only member of the Helicobacter family which is well described in literature is Helicobacter pylori. No other Helicobacter-associated diseases have definitely been shown in humans. We developed a sensitive quantitative PCR to investigate whether Helicobacter species DNA can be detected in the human gastrointestinal tract. We tested gastric biopsies (including biopsies from H. pylori positive persons), intestinal mucosal biopsies and fecal samples from healthy persons, and intestinal mucosal biopsies from patients with inflammatory bowel disease (IBD) for the presence of Helicobacter species. All gastric biopsies, positive for H. pylori by culture, were also positive in our newly developed PCR. No Helicobacter species were found in the mucosal biopsies from patients with IBD (n = 50) nor from healthy controls (n = 25). All fecal samples were negative. Our study suggests that Helicobacter species, other than H. pylori, are not present in the normal human gastrointestinal flora and our results do not support a role of Helicobacter species in IBD.

Influence of gender, parity, and caloric load on gastrorectal response in healthy subjects: a barostat study.

The gastrocolonic response consists of a prompt increase in colonic tone after a meal. With a barostat and a high compliant air-filled bag, it is possible to measure rectal tone by recording changes in volume at a constant intrabag pressure. The aim of this study was to evaluate the gastrorectal response in males and females as well as the effect of different caloric loads on the gastrorectal response. In 33 volunteers a barostat procedure during basal conditions and after a 600-kcal meal was performed. In 26 volunteers the procedure was repeated with a 1000-kcal meal. A meal response was defined as a decrease in volume of more than 10%. Phasic volume events (PVE) were defined as a 10% decrease in volume of 15-60 sec duration. After a 600-kcal meal, the decrease in volume after 1 hr was 28 +/- 7% (mean +/- SEM, P < 0.001). A meal response was found in 64% of the subjects. Parous females had a diminished meal response compared with nulliparous females (2 +/- 5% and 48 +/- 11%, P < 0.001). After the 600-kcal meal, PVEs increased from 3 to 10/hr (P = 0.001). In the 26 subjects, volume decrease was 40 +/- 9% after the 1000-kcal meal and 20 +/- 7% after the 600-kcal meal (P = 0.28). In the high-calorie meal, 18 subjects (69%) had a response versus 14 (54%) in the low-calorie meal (NS). Enhancing the caloric load of the meal did not increase the amounts of PVEs. In conclusion, a gastrorectal response occurs in 64% of the healthy subjects after a 600-kcal meal. The gastrorectal response can be measured to a similar extent in men and nulliparous women; however, the response is significantly impaired in parous women. This is possibly due to neurogenic damage during childbirth. Increasing the caloric load did not increase the gastrorectal response. Therefore, to study gastrorectal meal response with the barostat, a meal of 600-kcal is sufficient and a correction for parity should be made when results are compared.

Alternative approach to massive gastrointestinal bleeding in ulcerative colitis: highly selective transcatheter embolization.

Massive haemorrhage in ulcerative colitis mainly occurs as a result of exacerbated disease, usually acute or even fulminant colitis. Emergency proctocolectomy is currently advocated as the only reliable treatment of this patient group. However, this type of surgical intervention has a high rate of morbidity and mortality. Recently, several promising studies have been published that describe transcatheter embolization for the treatment of massive lower gastrointestinal bleeding in cases of bleeding colonic diverticular disease and angiodysplasia. Success rates of 48-88% have been reported. To avoid the high risk associated with emergency colectomy, this modern procedure was performed in an ulcerative colitis patient with intractable lower gastrointestinal bleeding. To our knowledge, this is the first patient with ulcerative colitis presenting with massive lower gastrointestinal blood loss to be successfully treated by highly selective transcatheter embolization. This interventional procedure is suggested as an alternative therapeutic approach to haematochezia in selected ulcerative colitis patients.

Quantification of bacteria adherent to gastrointestinal mucosa by real-time PCR.

The use of real-time quantitative PCR (5' nuclease PCR assay) as a tool to study the gastrointestinal microflora that adheres to the colonic mucosa was evaluated. We developed primers and probes based on the 16S ribosomal DNA gene sequences for the detection of Escherichia coli and Bacteroides vulgatus. DNA was isolated from pure cultures and from gut biopsy specimens and quantified by the 5' nuclease PCR assay. The assay showed a very high sensitivity: as little as 1 CFU of E. coli and 9 CFU of B. vulgatus could be detected. The specificities of the primer-probe combinations were evaluated with samples that were spiked with the species most closely related to E. coli and B. vulgatus and with eight other gut microflora species. Mucosal samples spiked with known amounts of E. coli or B. vulgatus DNA showed no PCR inhibition. We conclude that the 5' nuclease PCR assay may be a useful alternative to conventional culture techniques to study the actual in vivo composition of a complex microbial community like the gut microflora.

Evaluation of serological markers to differentiate between ulcerative colitis and Crohn's disease: pANCA, ASCA and agglutinating antibodies to anaerobic coccoid rods.

BACKGROUND: Accurate diagnosis of inflammatory bowel disease, in particular the differentiation between ulcerative colitis and Crohn's disease, is important for treatment and prognosis. Several serological markers have been used as non-invasive diagnostic tools in inflammatory bowel disease patients both to differentiate ulcerative colitis from Crohn's disease and to define patient subgroups. AIM: To evaluate the diagnostic accuracy of three serological tests in differentiating ulcerative colitis from Crohn's disease by single or combined use. METHODS: Sera from 51 patients with clinically well-defined ulcerative colitis and 50 patients with clinically well-defined Crohn's disease were analysed. Detection assays for the presence of perinuclear anti-neutrophil cytoplasmatic antibodies (pANCA), antibodies against (ASCA) and serum agglutinating antibodies to anaerobic coccoid rods were studied. Sensitivity, specificity, predictive values and likelihood ratios of each of these serological tests were determined. RESULTS: In supporting the diagnosis of ulcerative colitis, the sensitivity and specificity of the pANCA test were 63% and 86%, respectively. The ASCA test (immunoglobulin A or immunoglobulin G positive) for diagnosing Crohn's disease had a sensitivity of 72% and a specificity of 82%. The sensitivity of antibodies to anaerobic coccoid rods in diagnosing Crohn's disease was 52%, whereas specificity was 90%. A combination of pANCA-positive and ASCA-negative results in the case of ulcerative colitis showed a sensitivity and specificity of 51% and 94%, respectively. However, for ASCA-positive and pANCA-negative results in the case of Crohn's disease, sensitivity was 64% and specificity was 94%. The combination of all three tests increased positive predictive value and specificity to 100% for both ulcerative colitis and Crohn's disease. In Crohn's disease patients, positive pANCA was correlated with colonic involvement. No correlation was found between the presence of any of these antibodies and disease activity, duration and behaviour or medical treatment. CONCLUSIONS: The value of these serological tests in differentiating ulcerative colitis from Crohn's disease is limited when used separately but, by combining two or more tests, the positive predictive value and specificity can be improved substantially. These tests might be of help in studying disease heterogeneity, and may contribute to defining various subgroups of patients with different pathogeneses.

Endosonographic evidence of persistence of Crohn's disease-associated fistulas after infliximab treatment, irrespective of clinical response.

PURPOSE: Infliximab has been reported to improve fistulizing Crohn's disease. Moreover, prompt healing of mucosal ulcers has been described. Whether fistulas disappear or remainders of fistulas persist is unknown. This study documents fistulous tracts before and after infliximab therapy by means of hydrogen peroxide-enhanced endosonography METHODS: Eight patients with perianal, vaginal, or perineal fistulas were treated with a triplet of infliximab 5 mg/kg infusions. At baseline, and at Week 4 after the last infusion, fistulas were documented by local inspection, digital examination, and hydrogen peroxide-enhanced anal or vaginal endosonography. RESULTS: Patients with vaginal or perineal fistulas did not respond clinically to therapy, whereas patients with perianal fistulas improved considerably. However, in all patents remainders of fistulous tracts were demonstrated by endosonographic techniques. CONCLUSIONS: Short-term treatment of Crohn's disease-associated fistulas with infliximab does not induce disappearance of fistulous tracts, irrespective of therapeutic response.

Extraintestinal Complications of Inflammatory Bowel Disease.

Extraintestinal complications of inflammatory bowel disease (IBD) are often secondary to the underlying disease. Therefore, the first priority is to get active IBD into remission with medications, since surgery for IBD is not indicated for the treatment of extraintestinal complications. Symptoms of extraintestinal complications usually can be treated with simple agents; the treatment of patients with refractory symptoms and the use of more complex drug regimens should be done in cooperation with specialists on affected organ systems. Careful consideration of prescribed drugs is necessary because they may negatively influence the course of IBD.