Clinical symptom tool that raises the index of suspicion for eosinophilic oesophagitis in adults and drives earlier biopsy for definitive diagnosis.

BACKGROUND: Eosinophilic oesophagitis (EoE) and gastro-oesophageal reflux disease (GERD) present with overlapping symptomatology and it is challenging to distinguish EoE from GERD clinically before endoscopy. AIM: To investigate the prognostic value of a set of clinical symptoms and laboratory values in patients with EoE and GERD. METHODS: In this prospective, single-centre, observational study, we compared clinical and laboratory data from 202 patients with EoE or GERD (10 relevant characteristics). Those characteristics showing potential significance in a univariate analysis were then included in a multivariate analysis. RESULTS: The set of 10 characteristics (10-marker set) was able to distinguish between EoE and GERD with good reliability (correct assignment, i.e. agreement with subsequent EGD, of 94.4%). Reduction of the set to the six statistically and clinically most relevant markers continued to give good reliability (88.9%), and further stepwise reduction led to four-marker sets comprising history of atopy, history of food impaction, proton pump inhibitor refractory symptoms and either immunoglobulin E or peripheral eosinophilia, with correct assignment rates of 91.3% and 85.1% respectively. CONCLUSIONS: We have developed a simple and easily applicable clinical/laboratory marker set that helps to distinguish EoE from GERD earlier in the treatment course, thus guiding the endoscopist to perform biopsies from the oesophagus to ensure the diagnosis. The application of the scoring system is expected to diagnose EoE earlier and avoiding delay of adequate treatment.

Vedolizumab provides clinical benefit over 1 year in patients with active inflammatory bowel disease - a prospective multicenter observational study.

BACKGROUND: Vedolizumab, a monoclonal antibody targeting the α4ß7-integrin, is effective in inducing and maintaining clinical remission in Crohn's disease and ulcerative colitis according to randomised clinical trials. AIM: To determine the long-term effectiveness of vedolizumab in a real-world clinical setting. METHODS: This observational registry assessed the clinical outcome in patients treated with vedolizumab for clinically active Crohn's disease (n = 67) or ulcerative colitis (n = 60). Primary endpoint was clinical remission (HBI ≤ 4/pMayo ≤ 1) at week 54. Secondary endpoints included clinical response rates (HBI/pMayo score drop ≥3) and steroid-free clinical remission at weeks 30 and 54. RESULTS: Vedolizumab was stopped in 69/127 (56%) patients after a median time of 18 weeks (range 2-49) predominantly owing to lack or loss of response. Using nonresponder imputation analysis, clinical remission and steroid-free remission rates were 21% and 15% in Crohn's disease and 25% and 22% in ulcerative colitis, respectively. Lack of clinical remission was associated with prior treatment with anti-TNF or with steroids for more than 3 months in the last 6 months in ulcerative colitis. At week 14, the absence of remission in Crohn's disease or nonresponse in ulcerative colitis indicated a low likelihood of clinical remission at week 54 [2/31 (7%) in Crohn's disease, 4/41 (10%) in ulcerative colitis]. Accordingly, declining C-reactive protein in inflammatory bowel disease and/or lower faecal calprotectin in ulcerative colitis at week 14 predicted remission at week 54. CONCLUSION: Among patients who started vedolizumab for active inflammatory bowel disease, clinical remission rates are 21-25% after 54 weeks.

Helicobacter pylori infection is associated with a reduced risk of developing eosinophilic oesophagitis.

BACKGROUND: Eosinophilic oesophagitis (EoE) represents a chronic immune-antigen-mediated allergic disease of the oesophagus of still unknown aetiology. Environmental exposure has been postulated to play a pathogenetic role. Helicobacter pylori (H. pylori) infection has been inversely associated with allergic diseases including atopic dermatitis, asthma and allergic rhinitis and H. pylori may play a protective role in these conditions. Little is known about the relationship between EoE and H. pylori. AIM: To investigate in a case-control study whether H. pylori infection is associated with a reduced risk of developing EoE. METHODS: H. pylori infection was evaluated by serology in 58 [11(19%) female, 47 (81%) male, median age: 36.5 years, range 20-72 years] patients with a clinical and histologically proven diagnosis of EoE and 116 age and sex-matched controls (1 case: 2 controls). Antibodies against H. pylori were identified by enzyme-linked immunosorbent assay. Patients with H. pylori-specific IgG ≥ 30 enzyme immunounits were classified as H. pylori-positive. RESULTS: 3/58 (5.2%) patients with EoE had serological evidence of H. pylori infection (EoE - H. pylori current infection) and 5/58 (8.6%) reported prior eradication therapy for H. pylori infection (EoE - H. pylori former infection). The control group demonstrated significantly higher seroprevalence of H. pylori (37.9%, P < 0.0001) when compared to patients with EoE. EoE was inversely associated with H. pylori infection [odds ratio (OR) 0.24, 95% confidence interval (CI) 0.11-0.50]. CONCLUSION: Helicobacter pylori infection is inversely associated with EoE. Our results may contribute to further understanding the pathogenesis and evolving aetiology of EoE.

Peripheral blood eosinophils and other non-invasive biomarkers can monitor treatment response in eosinophilic oesophagitis.

BACKGROUND: Monitoring of the treatment response in eosinophilic oesophagitis (EoE) requires structured endoscopical and histological examination of the oesophagus. Less invasive methods would be highly desirable. AIM: To evaluate the utility of several EoE-associated blood and serum markers in order to non-invasively monitor the response to treatment with swallowed topical corticosteroids in adult EoE patients. METHODS: In a randomised, controlled double-blind trial blood samples of EoE patients (n = 69) were collected at baseline and after 14 days of treatment with budesonide (n = 51) or placebo (n = 18) respectively. Absolute blood eosinophil count (AEC) as well as serum levels of CCL-17, CCL-18, CCL-26, eosinophil-cationic-protein (ECP) and mast cell tryptase (MCT) were determined and correlated with oesophageal eosinophil density and with symptom and endoscopy scores. RESULTS: Histological remission, defined as mean number of <16 eos/mm(2) hpf at end-of-treatment, was achieved in 98% of the budesonide and 0% of the placebo recipients. AEC [380.2 vs. 214.7/mm(3) (P = 0.0001)], serum-CCL-17 [294.3 vs. 257.9 pg/mL (P = 0.0019)], -CCL-26 [26.7 vs. 16.2 pg/mL (P = 0.0058)], -ECP [45.5 ± 44.7 vs. 27.5 ± 25.0 µg/L (P = 0.0016)] and -MCT [5.3 ± 2.9 vs. 4.5 ± 2.6 µg/L (P = 0.0019)] significantly decreased under budesonide but not under placebo. AEC significantly correlated with oesophageal eosinophil density before (r = 0.28, P = 0.0236) and after (r = 0.42, P = 0.0004) budesonide treatment. In ROC-AUC analyses post-treatment values of AEC were significantly associated with histological remission (ROC-AUC 0.754; 95% CI: 0.617-0.891; P = 0.0003). CONCLUSIONS: The budesonide-induced treatment response in EoE is mirrored by several blood and serum markers, and the absolute blood eosinophil count is the most valuable as it shows correlation with the oesophageal eosinophil density.

[Gastroparesis. Definition, diagnostics, and therapy]. / Gastroparese : Definition, Diagnostik und Therapie.

Gastroparesis is characterized by a constellation of upper gastrointestinal symptoms in association with delayed gastric emptying in the absence of mechanical outlet obstruction from the stomach. Major symptoms are nausea, vomiting, early satiety or postprandial fullness, bloating, and abdominal or epigastric pain. Idiopathic, diabetic, and postsurgical causes represent the most common etiologies. Diagnostic procedures for the evaluation of gastroparesis comprise gastric emptying scintigraphy (gold standard), (13)C-octanoate breath testing, and a wireless motility capsule. Management of gastroparesis includes normalization of nutritional state, relief of symptoms, glycemic control, and improvement of gastric emptying. Medical treatment entails use of prokinetic drugs, which are currently the first-line therapy. Nausea and vomiting might be positively influenced by antiemetic drugs. Gastric electronic stimulation and surgical interventions should be used in well-defined patients and represent a therapeutic option in tertiary centers.

[Eosinophilic esophagitis - update - pathogenesis, diagnosis and therapy]. / Eosinophile Ösophagitis - Neues zur Pathogenese, Diagnostik und Therapie.

Eosinophilic esophagitis (EoE) is a clinicopathological condition of the esophagus that has become increasingly recognised over the last decade. EoE represents a chronic immune-mediated inflammatory disease of the esophagus. In adults dysphagia is the predominant symptom. Upper gastrointestinal endoscopy is required in order to take biopsies from the esophagus. The diagnose is confirmed histologically by typical eosinophilic infiltration of the esophagus mucosa. Until now there is no approved therapy world-wide although we know that topic and systemic steroids are highly effective in EoE. Elimination diet is another option and in well selected patients endoscopic balloon dilation represents a therapeutic possibility.

[Splenic granulomas - rare extraintestinal manifestation of Crohn's disease]. / Milzbefall - seltene extraintestinale Manifestation bei Morbus Crohn.

Extraintestinal manifestations of inflammatory bowel disease occur frequently in parallel to the inflammation in the bowel. The activity of extraintestinal manifestations is often divergent to the activity of intestinal inflammation. We here present the case of a rare extraintestinal manifestation of Crohn's disease and report on a 52-year-old patient with known Crohn's disease and primary sclerosing cholangitis (PSC) in clinical remission. Multiple lesions of the spleen were observed in routine MR tomography. The histological examination of a specimen obtained by MR-guided fine needle biopsy showed non-caseating epitheloid cell granulomas. The splenic granulomas regressed completely and spontaneously without specific immunmodulatory therapy.

[Eosinophilic esophagitis--pathogenesis, clinical presentation and therapeutic management]. / Eosinophile Osophagitis--Pathogenese, klinische Präsentation und therapeutisches Management.

Eosinophilic esophagitis (EE) is a relatively new, chronic, TH 2-type allergic inflammation of the esophagus. EE occurs more frequently in men. Allergic diseases such as asthma or atopic dermatitis are present in 50-70 % of patients or their relatives. In adults, the most common presenting symptom of EE is dysphagia, with or without food bolus impaction. Endoscopic findings of EE include mucosal furrows, corrugated or concentric rings or ridges in the esophagus ("feline esophagus"), with or without tiny whitish exudates. The diagnosis is confirmed by the observation of high counts of eosinophils in the esophageal epithelium (at least 24 /HPF). The cornerstones of medical therapy are either topical or systemic corticosteroids. Additional therapies included leukotriene receptor antagonists (montelukast) and IL-5 blockers (Mepolizumab). Complications of EE such as esophageal strictures should be carefully dilated using either bougies or a balloon. Currently it is still not known whether the late complications of EE can be prevented by the use of anti-inflammatory agents and this can only be demonstrated through further long-term follow-up studies.

[Sonographic diagnosis of a liver abscess caused by an enterohepatic fistula in a patient with Crohn's disease]. / Sonographische Diagnose eines Leberabszesses infolge einer enterohepatischen Fistel bei einem Patienten mit Morbus Crohn.

Liver abscesses in patients with Crohn's disease are rare. We report on a patient with Crohn's disease and a liver abscess of the left lobe caused by an enterohepatic fistula. With treatment of antibiotics and Infliximab the abscess showed complete regression. Percutaneous drainage of the liver abscess was not performed because the abscess was shown not to be completely liquefied at echo-enhanced ultrasound. This case report demonstrates the usefulness of percutaneous conventional and echo-enhanced ultrasound for the diagnosis of liver abscesses. Furthermore, this case also shows that enterohepatic fistulas can be diagnosed precisely with percutaneous ultrasound.

High rate of post-therapeutic resistance after failure of macrolide-nitroimidazole triple therapy to cure Helicobacter pylori infection: impact of two second-line therapies in a randomized study.

BACKGROUND: The optimal second-line treatment after failed Helicobacter pylori therapy has not been established. AIMS: To ascertain whether quadruple therapy or triple therapy with omeprazole, clarithromycin and amoxicillin is the superior re-treatment after triple therapy containing a macrolide and a nitroimidazole, and to determine the impact of microbial in vitro resistance. METHODS: Patients after failed triple therapy were randomly allocated to one of two 1-week second-line treatments: omeprazole, 40 mg, clarithromycin, 500 mg, and amoxicillin, 1 g, all b.d.; or omeprazole, 20 mg b.d., bismuth subsalicylate, 600 mg q.d.s., metronidazole, 400 mg t.d.s., and tetracycline, 500 mg q.d.s. Post-therapeutic Helicobacter pylori status was assessed by 13C-urea breath test at least 4 weeks after treatment. RESULTS: The study was terminated after including 84 patients. H. pylori cure rates differed significantly: omeprazole-clarithromycin-amoxicillin: intention-to-treat, 43%; per protocol, 50%; omeprazole-bismuth subsalicylate-metronidazole-tetracycline: intention-to-treat, 68%; per protocol, 69%. The frequencies of resistance after first-line therapy were: metronidazole, 90%; clarithromycin, 71%; both combined, 68%. For clarithromycin resistance, H. pylori cure with omeprazole-clarithromycin-amoxicillin was 30% vs. 83% for clarithromycin susceptibility. CONCLUSIONS: Omeprazole-bismuth subsalicylate-metron- idazole-tetracycline was superior to omeprazole-clarithromycin-amoxicillin, but both therapies yielded unsatisfactory results. The high rate of post-therapeutic dual resistance has a negative impact on omepraz- ole-clarithromycin-amoxicillin, and probably also on omeprazole-bismuth subsalicylate-metronidazole-tetracycline, and limits the choice for second-line treatment.

Citric acid or orange juice for the 13C-urea breath test: the impact of pH and gastric emptying.

BACKGROUND: There is an ongoing debate about the optimal test drink to be used in the 13C-urea breath test (13C-UBT). We recently reported that a citric acid solution is the optimal test drink in the 13C-UBT, because it provides a high 13CO2 recovery and the excellent accuracy of the test appears optimal compared to other test meals. Orange juice, because of a better taste, is also propagated as a test drink in the 13C-UBT. AIM: To compare the diagnostic accuracy of the 13C-UBT with either orange juice or citric acid solution as a test drink. Furthermore, the effect of these test drinks on the gastric emptying rate was determined. METHODS: H. pylori status was assessed by histology, rapid urease test and culture in 50 consecutive dyspeptic patients. A 13C-UBT was performed on two consecutive days by giving 75 mg of 13C-urea randomly dissolved in 200 mL 0.1 M citric acid solution or 200 mL orange juice. The 13CO2/12CO2 ratio was measured in breath samples taken before and 15, 30, 45 and 60 min after administration of the test drink. The gastric emptying rate of orange juice and citric acid solution was compared to that of water in 10 healthy subjects on three consecutive days by means of a 13C-sodium acetate breath test; 50 mg of 13C-sodium acetate was dissolved in 200 mL of each solution and breath samples were collected before and every 10 min for 90 min after administration of the test drink. RESULTS: Twenty-six out of 50 patients (52%) were infected with H. pylori. Significantly higher values over baseline (35.7+/-5.2 per thousand vs. 23.2+/-3.4 per thousand, P<0.001) and higher area under the curve (1507+/-198 vs. 927+/-128, P<0.001) were observed in H. pylori-positive patients when citric acid solution was administered compared with orange juice. Sensitivity of the 13C-UBT was 100% when citric acid was used as a test drink and 88% with orange juice. Specificity was 100% with both test drinks. Gastric emptying of citric acid solution (t1/2 = 60.9+/-3.5 min) was significantly slower than that of orange juice (t1/2 = 49.7+/-3.1 min, P<0.001). CONCLUSION: 13C-UBT loses diagnostic accuracy when orange juice instead of citric acid is used as a test drink. The faster gastric emptying of orange juice might be responsible for the lower diagnostic accuracy of the 13C-UBT.

Validity of a modified 13C-urea breath test for pre- and posttreatment diagnosis of Helicobacter pylori infection in the routine clinical setting.

OBJECTIVE: Citric acid meets the criteria of an optimal test drink for the 13C-urea breath test (13C-UBT) because it permits rapid, high level recovery of the 13C administered. In a previous study we reported that administration of 13C-urea dissolved in a citric acid solution provides results similar to those obtained with standard administration of the substrate 10 min after the test drink. The aim of this study was to evaluate the accuracy of this modified 13C-UBT for both primary and posttreatment diagnosis of Helicobacter pylori (H. pylori) infection in a large patient population in clinical practice. METHODS: The 13C-UBT was performed in 553 patients with dyspeptic symptoms by giving them 75 mg of 13C-urea either 10 min after administration of 200 ml of a test drink comprising 0.1 mol/L citric acid solution (protocol 1, n = 320) or dissolved in the same amount of this test drink (protocol 2, n = 233). All patients underwent an upper gastrointestinal endoscopy and the H. pylori-status was assessed by histology, rapid urease test, and culture. Sixty patients with proven H. pylori infection were reinvestigated by both endoscopy and 13C-UBT (protocol 2) 4 wk after completing eradication therapy. RESULTS: The accuracy of the two test protocols in the pretreatment diagnosis of H. pylori infection (95.6% and 96.6%), as well as of the modified 13C-UBT in the posttreatment evaluation of the infection (98.3%) was similar. More meaningful are the high PPV (>96%) and NPV (>93%) of the 13C-UBT under pre- and posttreatment conditions. CONCLUSIONS: The administration of 13C-urea dissolved in a citric acid solution simplifies the 13C-UBT, while preserving the high accuracy in the diagnosis of H. pylori infection. This modified 13C-UBT has equal accuracy in the pre- and the posttreatment situations.

The prevalence of Helicobacter pylori gastritis in patients with reflux oesophagitis: a case-control study.

OBJECTIVES: To investigate the prevalence of Helicobacter pylori in patients with erosive oesophagitis in comparison with asymptomatic subjects. DESIGN: Hospital based case-control study. METHODS: Two hundred and nineteen consecutive patients with erosive oesophagitis diagnosed over 2 years were studied. Patients with secondary gastro-oesophageal reflux disease, prior H. pylori eradication therapy, PPI or antibiotics were excluded and two case groups were formed: (1) patients with oesophagitis alone (OEA), and (2) patients with oesophagitis and concomitant peptic ulcer disease (OE&PUD). H. pylori was assessed by antral and corpus mucosa histology and the rapid urease test. Age- and sex-matched controls, who underwent voluntary screening for H. pylori by the 13C-urea breath test, had neither symptoms nor a history of upper gastrointestinal disease. RESULTS: The 130 patients in the OEA group had a prevalence of H. pylori of 38.5% compared with 75.6% in the 41 patients in the OE&PUD group and 88.5% in a subgroup of the latter with duodenal ulcer (26 patients). Infected and non-infected cases showed no significant differences in terms of grade of oesophagitis and incidence of Barrett's oesophagus. The prevalence of H. pylori infection in OEA was similar to that found in matched controls. In OE&PUD the relative risk of H. pylori infection was 3.6-fold higher than in controls [P = 0.0069, 95% confidence interval (CI), 1.401-9.195]. CONCLUSION: The prevalence of H. pylori in oesophagitis without PUD is similar to that of the asymptomatic population with no history of upper gastrointestinal disease. When oesophagitis and PUD occur together, the infection rate is within the range found in PUD alone.

13C-urea breath test for the diagnosis of Helicobacter pylori infection. A further simplification for clinical practice.

BACKGROUND: The 13C-urea breath test is the most accurate noninvasive method for the diagnosis of Helicobacter pylori infection. The oral administration of citric acid solution as test drink 10 min before administration of 13C-urea appears to be the most valuable test procedure hitherto reported. To simplify the test for clinical routine, we evaluated in a prospective, randomized, crossover study the accuracy of a new modification that consists in giving the 13C-urea dissolved in the test drink. METHODS: Forty dyspeptic patients were studied. H. pylori status was assessed by histology, rapid urease test, and culture. A 13C-urea breath test was performed on 2 consecutive days by giving 200 ml 0.1N citric acid solution either 10 min previous to (protocol 1) or simultaneously with (protocol 2) the administration of 75 mg 13C-urea in randomized order. The 13CO2/12CO2 ratio was measured in breath samples taken before and 10, 20, 30, 45, and 60 min after administration of 13C-urea. RESULTS: Twenty patients were H. pylori-positive. In these subjects maximal delta values (28.1 per thousand (21.4-34.9) versus 30.6 per thousand (22.8-38.4)), expired cumulative amount of 13C (9.3% (6.9-11.7) versus 10.2% (7.4-12.9)), and time to maximal delta value (33 min (26-39) versus 35 min (29-42)) obtained by applying test protocols 1 and 2, respectively, were similar. Both test protocols provided negative results in all H. pylori-negative subjects. The 13C-urea was stable in citric acid solution at room temperature for at least 2 weeks. CONCLUSIONS: The 13C-urea breath test for the diagnosis of H. pylori infection can be simplified by giving the substrate dissolved in the test drink. This modification is not associated with a loss of diagnostic accuracy.

Histological diagnosis of Helicobacter pylori gastritis is predictive of a high risk of gastric carcinoma.

Chronic Helicobacter pylori infection has been identified as a major risk factor for the subsequent development of gastric carcinoma On the basis of seroepidemiological studies the relative risk for infected persons was estimated to range between 3 and 6. Our study attempted to determine the relative risk of gastric carcinoma in H. pylori-infected individuals based on the histological evaluation of gastritis in gastric carcinoma patients in the light of a declining prevalence of H. pylori infection in Western countries. We histologically determined the H. pylori infection rate in 215 patients with early gastric carcinoma (tumor stage pT1), and compared it with that of 215 asymptomatic persons matched by age and sex who were tested by the 13C urea breath test. On the basis of these data an odds ratio of 16.7 (CI 9.6-29.1) was calculated for the relative risk of developing gastric carcinoma in H. pylori-infected people. The histological diagnosis of gastritis permits a separate risk assessment for patients with autoimmune gastritis, and by excluding these patients from the analysis we calculated an odds ratio for H. pylori-infected persons of 150 (CI 36.4-622.9). The endoscopic-histological diagnosis of H. pylori infection is associated with an increased risk of the subsequent development of gastric carcinoma of approximately 150-fold compared with H. pylori-negative patients who do not have chronic atrophic corpus gastritis of the autoimmune type (type A gastritis).

Transcript synthesis and surface expression of the interleukin-2 receptor (alpha-, beta-, and gamma-chain) by normal and malignant myeloid cells.

Expression of the interleukin-2 receptor alpha-(IL-2Ralpha-), IL-2Rbeta-, and the recently identified IL-2Rgamma-chain was examined on a wide range of cells of myeloid origin including neutrophils, monocytes, normal bone marrow-derived myeloid progenitors enriched for CD34+ cells, bone marrow blasts obtained from acute myelogenous leukemia (AML) patients, and permanent myeloid leukemia cell lines by reverse transcriptase-polymerase chain reaction and surface membrane analysis using receptor chain-specific monoclonal antibodies and flow cytometry. Expression of the p75 IL-2Rbeta- and the p64 IL-2Rgamma-chain was a common finding in most of the myeloid cell samples investigated, whereas IL-2Ralpha-chain was less frequently expressed. Although the high-affinity IL-2R form (ie, the alpha+, beta+, gamma+ IL-2R form) was detectable in a small minority of primary AML samples as well as the KG-1 cell line and IL-2 binding to these cells was sufficient to initiate signal transduction as evidenced by an increase in overall protein tyrosine phosphorylation and more specifically in tyrosine phosphorylation of the Janus kinase (JAK) 3, in none of these cell types did exposure to IL-2 affect cell growth kinetics. These results suggest that, in myeloid cells, the IL-2R may not stimulate mitogenic responses or that its components may be expressed in a combinational association with receptors for other cytokines and that IL-2Rgamma may play a regulatory role in normal and malignant myelopoiesis possibly independent from IL-2. Because recent studies by others have indicated that the IL-2Rgamma- chain may be shared by the IL-4R, the IL-7R, and most likely the IL-9R, expression of mRNA of these receptor types was also investigated in these cell samples. Surprisingly, in a substantial part of the myeloid lineage cells examined, an IL-2Rgamma+, IL-4R-, IL7R- configuration was noted that was, however, frequently associated with expression of IL-9R. Sharing of IL-9R/IL-2R components was furthermore suggested by inhibition of 125I-IL-2 binding to primary AML cells with excess of unlabeled IL-9.