Christian Felley

Effect of Whey-Based Culture Supernatant of Lactobacillus acidophilus (johnsonii) La1 on Helicobacter pylori Infection in Humans

Background: Specific strains of Lactobacillus acidophilus are known to inhibit intestinal cell adhesion and invasion by enterovirulent bacteria. As L. acidophilus can survive transiently in the human stomach, it may downregulate Helicobacter pylori infection. Methods: The ability of L. acidophilus (johnsonii) La1 supernatant to interfere with H. pylori bacterial growth, urease activity, and adhesion to epithelial cells was tested in vitro. Its effect on H. pylori infection in volunteers was monitored in a randomized, double-blind, controlled clinical trial, using a drinkable, whey-based, La1 culture supernatant. H. pylori infected volunteers were treated 14 days with 50 ml of La1 supernatant four times a day combined with either omeprazole 20 mg four times a day or with placebo. Infection was assessed by breath test, endoscopy, and biopsy sampling, performed at inclusion, immediately at the end of the treatment (breath test only), and 4 weeks after the end of the treatment. Results: La1 supernatant inhibited H. pylori growth in vitro, regardless of previous binding of H. pylori to epithelial cells. In 20 subjects (8 females, 12 males, mean age 33.1 years) a marked decrease in breath test values was observed immediately after treatment with La1 supernatant, both in the omeprazole and in the placebo group (median 12.3 vs. 28.8 and 9.4 vs. 20.4, respectively; p < 0.03). In both treatment groups, breath test values remained low 6 weeks after treatment (omeprazole treated 19.2, placebo treated 8.3; p < 0.03 vs. pretreatment), but the persistence of H. pylori infection was confirmed in gastric biopsies. Conclusion: La1 culture supernatant shown to be effective in vitro has a partial, acid-independent long-term suppressive effect on H. pylori in humans.

Favourable effect of an acidified milk (LC-1) on Helicobacter pylori gastritis in man

Objective The supernatant of Lactobacillus johnsonii La1 culture was shown to be bactericidal and to have a partial, acid-independent suppressive effect on Helicobacter pylori in humans. The aim of the present study was to investigate the effect of L. johnsonii La1-acidified milk (LC-1) on H. pylori infection. Design and methods Fifty-three volunteers infected with H. pylori as determined by positive 13C-urea breath test and positive serology were randomized to receive either LC-1 or a placebo 180 ml twice a day for 3 weeks. All subjects also received clarithromycin 500 mg bid during the last two weeks of acidified milk therapy. Oesophagogastroduodenoscopy and biopsies were performed at inclusion and repeated 4–8 weeks after the end of the treatment. H. pylori infection was confirmed by urease test and histology. H. pylori density and inflammation were scored using a modified Sydney classification. Results LC-1 ingestion induced a decrease in H. pylori density in the antrum (P = 0.02) and the corpus (P = 0.04). LC-1 also reduced inflammation and gastritis activity in the antrum (P = 0.02 and P = 0.01, respectively) and of activity in the corpus (P = 0.02). Clarithromycin eradicated H. pylori in 26% of the subjects; LC-1 did not improve the antibiotic effect. Conclusion These results suggest that H. pylori infection and gastritis can be down-regulated by LC-1.

Systematic evaluation of risk factors for diagnostic delay in inflammatory bowel disease

Background: The diagnosis of inflammatory bowel disease (IBD), comprising Crohns disease (CD) and ulcerative colitis (UC), continues to present difficulties due to unspecific symptoms and limited test accuracies. We aimed to determine the diagnostic delay (time from first symptoms to IBD diagnosis) and to identify associated risk factors. Methods: A total of 1591 IBD patients (932 CD, 625 UC, 34 indeterminate colitis) from the Swiss IBD cohort study (SIBDCS) were evaluated. The SIBDCS collects data on a large sample of IBD patients from hospitals and private practice across Switzerland through physician and patient questionnaires. The primary outcome measure was diagnostic delay. Results: Diagnostic delay in CD patients was significantly longer compared to UC patients (median 9 versus 4 months, P < 0.001). Seventy‐five percent of CD patients were diagnosed within 24 months compared to 12 months for UC and 6 months for IC patients. Multivariate logistic regression identified age <40 years at diagnosis (odds ratio [OR] 2.15, P = 0.010) and ileal disease (OR 1.69, P = 0.025) as independent risk factors for long diagnostic delay in CD (>24 months). In UC patients, nonsteroidal antiinflammatory drug (NSAID intake (OR 1.75, P = 0.093) and male gender (OR 0.59, P = 0.079) were associated with long diagnostic delay (>12 months). Conclusions: Whereas the median delay for diagnosing CD, UC, and IC seems to be acceptable, there exists a long delay in a considerable proportion of CD patients. More public awareness work needs to be done in order to reduce patient and doctor delays in this target population. (Inflamm Bowel Dis 2012;)

Cohort Profile: The Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS)

Background Crohn’s disease, ulcerative colitis and indeterminate colitis are the three subtypes of disease collectively known as inflammatory bowel diseases: relapsing and remitting conditions characterized by chronic inflammation which is limited to the colon in ulcerative colitis, whereas it can involve various sites in the gastrointestinal tract in Crohn’s disease. The pathogenesis of inflammatory bowel disease is currently still unclear, although humoral and cell-mediated immune system, as well as environmental [hygiene, smoking, nonsteroidal anti-inflammatory drugs (NSAIDs) use, geographic location] and genetic factors are known to be involved in the occurrence of these diseases. Patients often require continuous medication as well as one or more intestinal resections. The care of these patients is evolving rapidly with the introduction of novel therapies and treatment plans. Some of these new treatments are expensive and their efficacy is usually limited to 30–50% of patients. In the absence of markers able to predict response to specific therapies, all eligible patients currently receive several of these drugs. They are thus exposed to side-effects which contribute to the high overall cost of these therapies—half the average medical costs associated with the disease,—while only a fraction of those treated will benefit at each stage. Impact on patient quality of life is often considerable, especially because disease onset can occur already in the first or second decade of life, while patients are either in full-time education or just entering the workforce. The negative impact on social life or ability to achieve, either scholastically or professionally, can severely affect professional as well as family life. Indeed, 450% of patients with Crohn’s disease indicate that their disease has an influence on their professional and personal life. The course of the disease is often characterized by progressive worsening of the patient’s condition, with increasing frequency of hospitalization and considerable indirect costs through absenteeism and disability allowances. Disease activity is known to be influenced by psychological factors.

Extraintestinal Manifestations of Crohn’s Disease

In each case of extraintestinal manifestations of Crohn’s disease, active disease, if present, should be treated to induce remission, which may positively influence the course of most concomitant extraintestinal manifestations. For some extraintestinal manifestations, however, a specific treatment should be introduced. This latter part of disease management will be discussed in this chapter, in particular for pyoderma gangrenosum, uveitis, spondylarthropathy – axial arthropathy – and primary sclerosing cholangitis, which have also been described in quiescent Crohn’s disease. Few new drugs for the treatment of extraintestinal manifestations of Crohn’s disease have been developed in the past and only the role of infliximab has increased in Crohn’s disease-related extraintestinal manifestations. Drugs specifically aimed at this treatment, stemming from a few randomized controlled studies or case series, are sulfasalazine, 5-ASA, corticosteroids, azathioprine or 6-mercaptopurine, methotrexate, infliximab, adalimumab, etanercept and cyclosporine or tacrolimus. Unfortunately, because of the paucity of data in this field, the best evidence presented and discussed in this article for the treatment of these extraintestinal manifestations is extrapolated from patients that for the most part did not suffer from Crohn’s disease.

Inflammatory Gene Profiles in Gastric Mucosa during Helicobacter pylori Infection in Humans

Helicobacter pylori infection is associated with an inflammatory response in the gastric mucosa, ultimately leading to cellular hyperproliferation and malignant transformation. Hitherto, only expression of a single gene, or a limited number of genes, has been investigated in infected patients. cDNA arrays were therefore used to establish the global pattern of gene expression in gastric tissue of healthy subjects and of H. pylori-infected patients. Two main gene expression profiles were identified based on cluster analysis. The data obtained suggest a strong involvement of selected Toll-like receptors, adhesion molecules, chemokines, and ILs in the mucosal response. This pattern is clearly different from that observed using gastric epithelial cell lines infected in vitro with H. pylori. The presence of a “Helicobacter-infection signature,” i.e., a set of genes that are up-regulated in biopsies from H. pylori-infected patients, could be derived from this analysis. The genotype of the bacteria (presence of genes encoding cytotoxin-associated Ag, vacuolating cytotoxin, and blood group Ag-binding adhesin) was analyzed by PCR and shown to be associated with differential expression of a subset of genes, but not the general gene expression pattern. The expression data of the array hybridization was confirmed by quantitative real-time PCR assays. Future studies may help identify gene expression patterns predictive of complications of the infection.

Fistulizing Crohn’s Disease

Fistulas are common in Crohn’s disease. A population-based study has shown a cumulative risk of 33% after 10 years and 50% after 20 years. Perianal fistulas were the most common (54%). Medical therapy is the main option for perianal fistula once abscesses, if present, have been drained, and should include antibiotics (both ciprofloxacin and metronidazole) and immunomodulators. Infliximab should be reserved for refractory patients. Surgery is often necessary for internal fistulas.

CT enteroclysis: technique and clinical applications

CT enteroclysis (CTE) has been gradually evolving with technical developments of spiral and multidetector row CT technology. It has nowadays become a well-defined imaging modality for the evaluation of various small bowel disorders. Volume challenge of 2L of enteral contrast agent administrated to the small bowel via a nasojejunal catheter ensures luminal distension, the prerequisite for the detection of mural abnormalities, also facilitating the accurate visualization of intraluminal lesions. CT acquisition is centered on small bowel loops, reconstructed in thin axial slices and completed by multiplanar views. Image analysis is essentially done in cine-mode on work-stations. CTE is of particular diagnostic value in intermediate or advanced stages of Cohns disease, including the depiction of extraintestinal complications. It has become the imaging modality of choice for the localization and characterization of small bowel tumors. The cause and degree of low-grade small bowel obstruction is more readily analyzed with the technique of CTE than conventional CT. Limitations of CTE concern the assessment of pure intestinal motility disorders, superficial mucosal lesions and arteriovenous malformations of the small bowel, which are not consistently visualized. CTE should be selectively used to answer specific questions of the small bowel. It essentially contributes to the diagnostic quality of modern small bowel imaging, and therefore deserves an established, well-defined place among the other available techniques.

Combined written and oral information prior to gastrointestinal endoscopy compared with oral information alone: a randomized trial

BackgroundLittle is known about how to most effectively deliver relevant information to patients scheduled for endoscopy.MethodsTo assess the effects of combined written and oral information, compared with oral information alone on the quality of information before endoscopy and the level of anxiety. We designed a prospective study in two Swiss teaching hospitals which enrolled consecutive patients scheduled for endoscopy over a three-month period. Patients were randomized either to receiving, along with the appointment notice, an explanatory leaflet about the upcoming examination, or to oral information delivered by each patients doctor. Evaluation of quality of information was rated on scales between 0 (none received) and 5 (excellent). The analysis of outcome variables was performed on the basis of intention to treat-analysis. Multivariate analysis of predictors of information scores was performed by linear regression analysis.ResultsOf 718 eligible patients 577 (80%) returned their questionnaire. Patients who received written leaflets (N = 278) rated the quality of information they received higher than those informed verbally (N = 299), for all 8 quality-of-information items. Differences were significant regarding information about the risks of the procedure (3.24 versus 2.26, p < 0.001), how to prepare for the procedure (3.56 versus 3.23, p = 0.036), what to expect after the procedure (2.99 versus 2.59, p < 0.001), and the 8 quality-of-information items (3.35 versus 3.02, p = 0.002). The two groups reported similar levels of anxiety before procedure (p = 0.66), pain during procedure (p = 0.20), tolerability throughout the procedure (p = 0.76), problems after the procedure (p = 0.22), and overall rating of the procedure between poor and excellent (p = 0.82).ConclusionWritten information led to more favourable assessments of the quality of information and had no impact on patient anxiety nor on the overall assessment of the endoscopy. Because structured and comprehensive written information is perceived as beneficial by patients, gastroenterologists should clearly explain to their patients the risks, benefits and alternatives of endoscopic procedures. Trial registration: Current Controlled trial number: ISRCTN34382782.

Pregnancy and Breastfeeding in Patients with Crohn’s Disease

Crohn’s disease commonly affects women of childbearing age. Available data on Crohn’s disease and pregnancy show that women with Crohn’s disease can expect to conceive successfully, carry to term and deliver a healthy baby. Control of disease activity before conception and during pregnancy is critical, to optimize both maternal and fetal health. Generally speaking, pharmacological therapy for Crohn’s disease during pregnancy is similar to pharmacological therapy for nonpregnant patients. Patients maintained in remission by way of pharmacological therapy should continue it throughout their pregnancy. Sulfasalazine, mesalazine and corticosteroids are safe, azathioprine and 6-mercaptopurine are reasonably safe with few discordant data, infliximab seems safe as well, whereas methotrexate is contraindicated during pregnancy. During breastfeeding, mesalazine and prednisone are considered safe, azathioprine/6-mercaptopurine, budesonide and infliximab probably safe and methotrexate is contraindicated.