Eosinophilic esophagitis: analysis of food impaction and perforation in 251 adolescent and adult patients

BACKGROUND ; AIMS: Eosinophilic esophagitis is a rapidly emerging, chronic inflammatory disorder. Prolonged inflammation evokes structural alterations and a fragile esophageal wall prone to perforation/rupture and food impaction. This report assesses the risk of spontaneously arising and procedure-induced complications and proposes practical recommendations. METHODS: The Swiss Esophageal Esophagitis Database documented 251 confirmed cases. A chart review identified which patients had required endoscopic bolus removal and/or experienced transmural esophageal perforation/rupture. In addition, a MEDLINE search for "eosinophilic esophagitis" with "esophageal perforation" or "esophageal rupture" was undertaken. RESULTS: During an 18-year period, 87 patients (34.7%) experienced 134 food impactions requiring flexible (124, 92.5%) or rigid (10, 7.5%) endoscopic bolus removal. Transmural perforation occurred in 20% (2/10) of rigid procedures, and 1 esophageal rupture (Boerhaave's syndrome) was observed. CONCLUSIONS: Bolus removal by rigid endoscopy is a high-risk procedure and should be avoided in eosinophilic esophagitis patients who require a gentler approach. Whether food impaction and esophageal wall remodeling can be prevented with anti-inflammatory medication is still undetermined. All Boerhaave's syndrome cases should be evaluated for underlying eosinophilic esophagitis.

Association Between Baseline Impedance Values and Response Proton Pump Inhibitorsin Patients With Heartburn

BACKGROUND & AIMS: Esophageal impedance measurements have been proposed to indicate the status of the esophageal mucosa, and might be used to study the roles of the impaired mucosal integrity and increased acid sensitivity in patients with heartburn. We compared baseline impedance levels among patients with heartburn who did and did not respond to proton pump inhibitor (PPI) therapy, along with the pathophysiological characteristics of functional heartburn (FH). METHODS: In a case-control study, we collected data from January to December 203 on patients with heartburn and normal findings from endoscopy who were not receiving PPI therapy and underwent impedance pH testing at hospitals in Italy. Patients with negative test results were placed on an 8-week course of PPI therapy (84 patients received esomeprazole and 36 patients received pantoprazole). Patients with more than 50% symptom improvement were classified as FH/PPI responders and patients with less than 50% symptom improvement were classified as FH/PPI nonresponders. Patients with hypersensitive esophagus and healthy volunteers served as controls. In all patients and controls, we measured acid exposure time, number of refluxes, baseline impedance, and swallow-induced peristaltic wave indices. RESULTS: FH/PPI responders had higher acid exposure times, numbers of reflux events, and acid refluxes compared with FH/PPI nonresponders (P < .05). Patients with hypersensitive esophagus had mean acid exposure times and numbers of reflux events similar to those of FH/PPI responders. Baseline impedance levels were lower in FH/PPI responders and patients with hypersensitive esophagus, compared with FH/PPI nonresponders and healthy volunteers (P < .001). Swallow-induced peristaltic wave indices were similar between FH/PPI responders and patients with hypersensitive esophagus. CONCLUSIONS: Patients with FH who respond to PPI therapy have impedance pH features similar to those of patients with hypersensitive esophagus. Baseline impedance measurements might allow for identification of patients who respond to PPIs but would be classified as having FH based on conventional impedance-pH measurements.

Risk of infections during interferon-based treatment in patients with chronic HCV infection and advanced hepatic fibrosis.

BACKGROUND & AIMS Pegylated interferon-based treatment is still the backbone of current hepatitis C therapy and is associated with bone marrow suppression and an increased risk of infections. The aim of this retrospective cohort study was to assess the risk of infections during interferon-based treatment among patients with chronic HCV infection and advanced hepatic fibrosis and its relation to treatment-induced neutropenia. METHODS This cohort study included all consecutive patients with chronic HCV infection and biopsy-proven bridging fibrosis or cirrhosis (Ishak 4-6) who started treatment between 1990 and 2003 in five large hepatology units in Europe and Canada. Neutrophil counts between 500/μL-749/μL and below 500/μL were considered as moderate and severe neutropenia, respectively. RESULTS This study included 723 interferon-based treatments, administered to 490 patients. In total, 113 infections were reported during 88 (12%) treatments, of which 24 (21%) were considered severe. Only one patient was found to have moderate neutropenia and three patients were found to have severe neutropenia at the visit before the infection. Three hundred and twelve (99.7%) visits with moderate neutropenia and 44 (93.6%) visits with severe neutropenia were not followed by an infection. Multivariable analysis showed that cirrhosis (OR 2.85, 95%CI 1.38-5.90, p=0.005) and severe neutropenia at the previous visit (OR 5.42, 95%CI 1.34-22.0, p=0.018) were associated with the occurrence of infection, while moderate neutropenia was not. Among a subgroup of patients treated with PegIFN, severe neutropenia was not significantly associated (OR 1.63, 95%CI 0.19-14.2, p=0.660). CONCLUSIONS In this large cohort of patients with bridging fibrosis and cirrhosis, infections during interferon-based therapy were generally mild. Severe interferon-induced neutropenia rarely occurred, but was associated with on-treatment infection. Moderate neutropenia was not associated with infection, suggesting that current dose reduction guidelines might be too strict.

Improvement of platelets after SVR among patients with chronic HCV infection and advanced hepatic fibrosis.

BACKGROUND & AIMS Patients with chronic hepatitis C virus (HCV) infection may develop cirrhosis with portal hypertension, reflected by decreased platelet count and splenomegaly. This retrospective cohort study aimed to assess changes in platelet counts after antiviral therapy among chronic HCV-infected patients with advanced fibrosis. METHODS Platelet counts and spleen sizes were recorded in an international cohort of patients with Ishak 4-6 fibrosis who started antiviral therapy between 1990 and 2003. Last measured platelet counts and spleen sizes were compared to their pre-treatment values (within 6 six months prior to the start of therapy). All registered platelet count measurements from 24 week following cessation of antiviral therapy were included in repeated measurement analyses. RESULTS This study included 464 patients; 353 (76%) had cirrhosis and 187 (40%) attained sustained virological response (SVR). Among patients with SVR, median platelet count, increased by 35 x10(9) /L (IQR 7-62, p<0.001). In comparison, patients without SVR showed a median decline of 17 x10(9) /L (IQR -5-47, p<0.001). In a subgroup of 209 patients, median decrease in spleen size was 1.0 cm (IQR 0.3-2.0) for patients with SVR, while median spleen size increased with 0.6 cm (IQR -0.1-2.0, p<0.001) among those without SVR. The changes in spleen size and platelet count were significantly correlated (R=-0.41, p<0.001). CONCLUSIONS Among chronic HCV-infected patients with advanced hepatic fibrosis the platelet counts improved following SVR and the change in platelets correlated with the change in spleen size following antiviral therapy. These results suggest that HCV eradication leads to reduced portal pressure. This article is protected by copyright. All rights reserved.

Inverse Association Between Gluteofemoral Obesity and Risk of Barrett's Esophagus in a Pooled Analysis

BACKGROUND & AIMS: Gluteofemoral obesity (determined by measurement of subcutaneous fat in hip and thigh regions) could reduce risks of cardiovascular and diabetic disorders associated with abdominal obesity. We evaluated whether gluteofemoral obesity also reduces risk of Barrett's esophagus (BE), a premalignant lesion associated with abdominal obesity.

METHODS: We collected data from non-Hispanic white participants in 8 studies in the Barrett's and Esophageal Adenocarcinoma Consortium. We compared measures of hip circumference (as a proxy for gluteofemoral obesity) from cases of BE (n=1559) separately with 2 control groups: 2557 population-based controls and 2064 individuals with gastroesophageal reflux disease (GERD controls). Study-specific odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using individual participant data and multivariable logistic regression and combined using random effects meta-analysis.

RESULTS: We found an inverse relationship between hip circumference and BE (OR per 5 cm increase, 0.88; 95% CI, 0.81-0.96), compared with population-based controls in a multivariable model that included waist circumference. This association was not observed in models that did not include waist circumference. Similar results were observed in analyses stratified by frequency of GERD symptoms. The inverse association with hip circumference was only statistically significant among men (vs population-based controls: OR, 0.85; 95% CI, 0.76-0.96 for men; OR, 0.93; 95% CI, 0.74-1.16 for women). For men, within each category of waist circumference, a larger hip circumference was associated with decreased risk of BE. Increasing waist circumference was associated with increased risk of BE in the mutually adjusted population-based and GERD control models.

CONCLUSIONS: Although abdominal obesity is associated with increased risk of BE, there is an inverse association between gluteofemoral obesity and BE, particularly among men.

Effect of a thrombin receptor (protease-activated receptor 1, PAR-1) gene polymorphism in chronic hepatitis C liver fibrosis

Background and Aim: Tissue injury leads to activation of coagulation and generation of thrombin. Inhibition of thrombin receptor protease-activated receptor 1 (PAR-1) has been shown to reduce liver fibrosis in animals. This study aimed to evaluate the effect of PAR-1 gene polymorphism on rate of liver fibrosis (RF) in chronic hepatitis C. Methods: Polymorphisms studied: C > T transition 1426 bp upstream of translation start site (-1426C/T), 13 bp repeat of preceding -506 5`-CGGCCGCGGGAAG-3` sequence (-506I/D), and A > T transversion in intervening sequence (IVS) 14 bp upstream of exon-2 start site (IVS-14A/T). A total of 287 European and 90 Brazilian patients were studied. Results: 1426C/T polymorphism: There was a trend to higher RF in patients with the TT genotype (P = 0.06) and an association between genotype CC and slow fibrosis (P = 0.03) in Europeans. In males, RF was significantly higher in those with the TT genotype compared to CT (P = 0.003) and CC (P = 0.007). There was a significant association between TT and fast fibrosis (P = 0.04). This was confirmed in an independent cohort of Brazilians where RF was higher in TT than in CC (P = 0.03). Analysis of -506I/D showed no difference in RF and distribution of slow/fast fibrosis among different genotypes in both populations. Analysis of IVS-14A/T showed no difference between genotypes. Conclusion: In conclusion, these findings suggest that PAR-1 receptor polymorphisms influence the progression of liver fibrosis.

Population screening for HFE-associated haemochromatosis: should we have to pay for our genes?

Haemochromatosis associated with mutations in the HFE gene is the most common inherited disorder in Caucasian populations. Early diagnosis and treatment allows for normal life expectancy whereas there is considerable morbidity and early mortality in those patients diagnosed late or untreated. Unfortunately, the development of symptoms and signs in haemochromatosis is usually associated with significant iron overload. For this reason, many clinicians and geneticists have advocated population screening. The recent identification of the HFE gene and the availability of a simple DNA-based diagnostic test have led to international debate as to the most cost-effective means of population screening for HFE-associated haemochromatosis. The present paper summarizes the evidence in favour of population screening and analyses the relative advantages of genotypic (DNA test) versus phenotypic (transferrin saturation) testing.

Emerging pathways in colorectal-cancer development

The past decade has seen the emergence of new pathways in the development of colorectal cancer. There is now clear evidence that subsets of these tumours do not show chromosomal instability and do not follow the suppressor pathway. Instead, about 15% of colorectal cancers are characterised by microsatellite instability (MSI). This feature arises through defective DNA mismatch repair, which is related either to a germline mutation (as in hereditary non-polyposis colorectal carcinoma) or to failure to express a mismatch-repair gene. CpG-island methylation has been linked to sporadic cancers with a high frequency of MSI. This type of methylation leads to loss of gene expression when it occurs in the promoter region of a gene. Tumours may have high or low type C (cancer-related) CpG-island methylation. When methylation affects hMLH1 (mismatch repair gene), the resultant cancer has high MSI.

Early-onset Crohn's disease is a risk factor for smaller final height.

OBJECTIVES: Growth retardation is a frequent complication of paediatric inflammatory bowel disease (IBD). Only a few studies report the final height of these patients, with controversial results. We compared adult height of patients with paediatric IBD with that of patients with adult-onset disease. METHODS: Height data of 675 women 19-44 years of age and 454 men 23-44 years of age obtained at inclusion in the Swiss IBD cohort study registry were grouped according to the age at diagnosis: (a) prepubertal (men≤13, women≤11 years), (b) pubertal (men 13-22, women 11-18 years) and (c) adult (men>22, women>18 years of age), and compared with each other and with healthy controls. RESULTS: Male patients with prepubertal onset of Crohn's disease (CD) had significantly lower final height (mean 172±6 cm, range 161-182) compared with men with pubertal (179±6 cm, 161-192) or adult (178±7 cm, 162-200) age at onset and the general population (178±7 cm, 142-204). Height z-scores standardized against heights of the normal population were significantly lower in all patients with a prepubertal diagnosis of CD (-0.8±0.9) compared with the other patient groups (-0.1±0.8, P<0.001). Prepubertal onset of CD emerged as a risk factor for reduced final height in patients with prepubertal CD. No difference for final height was found between patients with ulcerative or unclassified IBD diagnosed at prepubertal, pubertal or adult age. CONCLUSION: Prepubertal onset of CD is a risk for lower final height, independent of the initial disease location and the necessity for surgical interventions.

Advances in vaccination against Helicobacter pylori.

A vaccination against Helicobacter pylori may represent both prophylactic and therapeutic approaches to the control of H. pylori infection. Different protective H. pylori-derived antigens, such as urease, vacuolating cytotoxin A, cytotoxin-associated antigen, neutrophil-activating protein and others can be produced at low cost in prokaryote expression systems and most of these antigens have already been administered to humans and shown to be safe. The recent development by Graham et al. of the model of H. pylori challenge in humans, the recent published clinical trials and the last insight generated in animal models of H. pylori infection regarding the immune mechanisms leading to vaccine-induced Helicobacter clearance will facilitate the evaluation of immunogenicity and efficacy of H. pylori vaccine candidates in Phase II and III clinical trials.