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Introduction: Early diagnosis of hepatocellular carcinoma (HCC) as well as evaluation of prognosis and prediction of treatment efficacy remains challenging due to the missing specific non-invasive biomarkers. The aim of this study was to identify disease-specific microRNA (miRNA) patterns for diagnosis, prediction of prognosis, and treatment response in patients with HCC. Methods: The study population included 42 HCC patients from SORAMIC clinical trial: 22 patients received sorafenib monotherapy, 20 patients underwent 90Y radioembolization in combination with sorafenib. 20 individuals were included in the control group. HCC patients underwent collection of plasma samples before and 7–9 weeks after the beginning of the treatment. Isolation of circulating miRNAs, preparation of small RNA sequencing libraries and next-generation sequencing were performed. Association analysis for novel diagnostic, prognostic, and treatment-related candidate biomarkers was performed. Results: A total of 42 differentially expressed (16 up-regulated and 26 down-regulated) miRNAs were identified comparing baseline and control group plasma samples. hsa-miR-215-5p and hsa-miR-192-5p were down-regulated, while hsa-miR-483-5p and hsa-miR-23b-3p were up-regulated comparing baseline and 7–9 weeks post-sorafenib monotherapy samples. hsa-miR-215-5p was the sole down-regulated miRNA in the same combination therapy comparison. hsa-miR-183-5p, hsa-miR-28-3p, and hsa-miR-1246 were found to be significantly up-regulated comparing non-responders versus responders to sorafenib. High hsa-miR-215-5p expression was significantly associated with worse HCC patients' prognosis. Conclusions: Systematic miRNA profiling of highly characterized samples from SORAMIC study revealed a subset of potential miRNA biomarkers for HCC diagnosis and prognosis of sorafenib-treated patients' survival. [ABSTRACT FROM AUTHOR]

Background:Helicobacter pylori (H. pylori) was discovered 40 years ago and has set a milestone in human medicine. The discovery led to rejection of the dogma of the acidic stomach as a sterile organ and requested to rewrite the chapters on gastric pathophysiology and gastroduodenal diseases. Summary: Over a period of 40 years following the discovery, more than 50,000 articles can be retrieved in PubMed as of today and illustrate the amount and the intensity of research around the role of this bacterium. H. pylori emerged as cause of chronic gastritis and principal cause of peptic ulcer disease (PUD). Eradication of H. pylori became standard of care in management in PUD. The importance of this was highlighted in 2005 with the Nobel Prize in Medicine awarded to Barry Marshall and Robin Warren. H. pylori became eventually recognized for its oncogenic potential in the stomach and as the main risk factor for gastric cancer development. Key Messages:H. pylori gastritis is defined as infectious disease and requires therapy in all infected individuals. Strategies of gastric cancer prevention and development of therapies to overcome the increasing antibiotic resistance are main targets in clinical research of today. [ABSTRACT FROM AUTHOR]

Introduction: In recent years, increasing options for systemic HCC treatment have become available. The development of therapy-specific prognostic scores has been encouraged. Tailoring therapy to individual patients requires prognostic scores for treatment success in addition to the Barcelona-Clinic-Liver-Cancer (BCLC) classification. We have developed and validated a prognostic score for patients treated with sorafenib. Methods: Prognostic factors identified in a multivariate analysis of 108 sorafenib patients were used to construct the Munich Sorafenib Evaluation (M-SE) score. M-SE and 9 established HCC prognostic systems were ranked according to concordance-index and AIC. External M-SE validation was performed in an independent HCC sorafenib cohort (n = 101) derived from the prospective multicenter randomized controlled SORAMIC trial. Results: Ascites (p < 0.0001; HR 2.923), tumor burden ≥50% of the liver (p = 0.0033; HR 1.946), and GOT (p < 0.0001; HR 1.716) were identified as independent prognostic parameters. All three M-SE stages were characterized by significantly different survival times (p < 0.0001). M-SE stage-A patients had a median OS of 18.7 months (95% CI: 15.6–21.8); patients in stage B and C showed a significantly shorter survival of 5.7 (2.7–8.7) and 2.0 months (1.6–2.4), respectively. M-SE (c-index 0.70; AIC 621) outperformed all other prognostic systems. External validation in a prospective cohort confirmed its superior prognostic performance. Conclusion: The M-SE score allows classification of sorafenib patients in three distinct prognostic stages. Provided that M-SE successfully passes prospective validation, it can help to predict the outcome of patients evaluated for sorafenib treatment. [ABSTRACT FROM AUTHOR]

Background: Dyspepsia is one of the most common complaints in gastroenterology. While its etiology is usually benign, rare cases of malignancy have to be identified. Individualized risk stratification is essential for cost-effective management of dyspepsia. Here, we discuss the challenges of investigating dyspepsia at the specialist level and provide a framework for rational workup and surveillance strategies. Summary: Causes of dyspepsia can be functional or organic, including gastritis, peptic ulcers, or malignancy. H. pylori gastritis represents a specific entity of dyspepsia and increases the risk of gastric cancer. H. pylori eradication can improve symptoms in a subset of patients and reduce gastric cancer risk. In young patients without alarm features, malignancy is rare, and noninvasive testing for H. pylori is appropriate. In elder patients and those with alarm features, high-quality endoscopy is the method of choice to rule out malignancy. Advanced corpus-predominant atrophic gastritis with or without intestinal metaplasia represent precancerous lesions. Key Messages: Symptom assessment requires to distinguish dyspepsia of functional or organic origin. Risk stratification in dyspeptic patients is based on age, alarm features, and H. pylori status. Noninvasive test-and-treat is recommended in patients with low gastric cancer risk, while endoscopy is recommended in individuals at increased risk. H. pylori infection should be eradicated in order to obtain a symptomatic benefit and reduce gastric cancer risk. Advanced preneoplastic lesions require endoscopic surveillance. [ABSTRACT FROM AUTHOR]

Background: COVID-19 was initially considered a respiratory disease but the SARS-CoV-2 virus can lead to serious systemic consequences affecting major organs including the digestive system. Summary: This review brings new clinically important information for the gastroenterologist. This includes: the mechanisms of tissue damage seen with the SARS-CoV-2 virus; the consequences of immunosuppression in patients with inflammatory bowel disease (IBD) and chronic liver disease with the additional risks of decompensation in patients with cirrhosis; the impact of COVID-19 on gastrointestinal emergencies, on gastrointestinal endoscopy, diagnosis and treatments. These highlight the need to understand the clinical pharmacology, toxicology and therapeutic implications of drugs commonly used by gastroenterologists and their links with COVID-19. Key Messages: Any part of the digestive system may be affected by the SARS-CoV-2 virus, and those with pre-existing disease are at greatest risk of adverse outcomes. The risk for drug-drug interactions is considerable in patients seriously ill with COVID-19 who often require mechanical ventilation and life support. Some repurposed drugs used against SARS-CoV-2 can cause or aggravate some of the COVID-19-related gastrointestinal symptoms and can also induce liver injury. Ongoing clinical studies will hopefully identify effective drugs with a more favourable risk-benefit ratio than many initially tried treatments. [ABSTRACT FROM AUTHOR]

Introduction: Extrahepatic spread is reported as a prognostic factor in patients with advanced hepatocellular carcinoma (HCC) receiving systemic therapy. However, clinical studies have reported conflicting results for the clinical impact of the pattern of tumor progression during treatment and the role of new extrahepatic metastases in length of survival. Objective: To evaluate the impact of extrahepatic metastases on survival in patients with HCC treated with sorafenib or with a combination of sorafenib and selective internal radiation treatment (SIRT). Methods: SORAMIC is a randomized, controlled trial comprising diagnostic, local ablation, and palliative cohorts. In the palliative cohort, patients not eligible for transarterial chemoembolization (TACE) were randomized 11:10 to SIRT plus sorafenib (SIRT + sorafenib) or sorafenib alone. This exploratory subanalysis evaluated the impact of extrahepatic metastases on survival. Results: In the intent-to-treat cohort, 216 patients were randomized to SIRT + sorafenib and 208 to sorafenib alone. Seventeen patients with distant organ metastases (bone, n = 11; adrenal glands, n = 5; peritoneum, n = 1) and 262 without distant metastases at study entry were analyzed in this substudy. Patients with (Group A) and without (Group B) distant organ metastases at study entry presented with a median survival of 11.3 and 14.8 months, respectively (p = 0.2807). During follow-up of patients with no organ metastases at baseline, extrahepatic disease progression occurred in 50 patients (19.1%). No statistically significant difference in survival was observed between patients without extrahepatic progression and those with new extrahepatic disease during treatment (14.8 vs. 14.9 months; p = 0.6483). Development of new pulmonary metastases during treatment significantly shortened median survival (7.6 vs. 15.0 months, p = 0.0060). Conclusions: This subanalysis of the SORAMIC trial suggests that in patients with liver-dominant advanced HCC, metastases to distant organs with the exception of pulmonary metastases do not in general exert a negative impact on patient prognosis. The choice of palliative treatment should incorporate a personalized analysis of the pattern of tumor distribution. [ABSTRACT FROM AUTHOR]

Background: Herbal or complementary medicines are frequently used for the treatment of patients with functional gastrointestinal disorders (FGID). Regulatory requirements for herbal therapies are inconsistent and, in many jurisdictions, herbal therapies are either self-, minimally- or unregulated. Aim: To provide guidance for the appropriate and safe use of herbal medicines in patients with FGID patients with special consideration of the regulatory frameworks. Methods: A PubMed search of the literature was performed; relevant articles were included. Results: Similar to chemically defined therapies herbal medicines can cause adverse events. Thus, a risk-benefit appraisal should be undertaken for these therapies. While there is no disease specific mortality in FGID patients, patients with FGID who fail to respond to "empiric" chemically defined therapies undergo diagnostic and therapeutic measures that can be associated with appreciable morbidity and mortality. Thus, effective herbal treatments that subsequently reduce health-care utilization, reduce risks related to diagnostic or therapeutic measures that are initiated if no improvement of symptoms occurs. This "protective" effect of effective treatments for FGID needs to be taken in consideration when the risks and benefits of treatments are determined. In addition, standards that mirror regulations for chemically defined treatments should apply and the components of the respective preparations should undergo ongoing toxicological testing and rigorous quality assurance measures (including pharmacovigilance) applied. Conclusions: Some herbal therapies offer significant benefits for patients with FGID. To ensure the safety of these treatments, the regulatory requirements should mirror requirements for chemically defined treatments. [ABSTRACT FROM AUTHOR]

The incidence of peptic ulcer disease (PUD) peaked in the late 19th century while transiting into the 20th century. With entry in the new millennium a significant decrease of PUD has occurred. However, demographic changes with an increasing elderly population associated with multiple comorbidities and polypharmacy became responsible for a persistent high rate of peptic ulcer complications. The acid driven concept of PUD has directed the development of surgical procedures and drugs with an increasing potency in acid suppression. High speed of symptom resolution and rapid ulcer healing was obtained with the introduction of proton pump inhibitors, but cure of PUD has failed. The arrival of Helicobacter pylori has revolutionized the history of PUD which has become a curable disease by successful cure of the infection. However, new challenges have emerged with an increase of treatment failures due to increasing antibiotic resistance of H. pylori. The changing pattern in the prevalence of etiologies other than H. pylori demands for accurate identification of the ulcerogenic cause in the individual patient to allow for proper selection of therapy. Management of peptic ulcer bleeding remains a critical clinical challenge. The chapter of PUD is reduced in size and has become more heterogeneous – but is not closed! [ABSTRACT FROM AUTHOR]

Background: Blue light imaging (BLI) and linked color imaging (LCI) are new imaging modalities for the endoscopic evaluation of mucosal changes within the digestive tract. There is little experience with these modalities in the characterization of chronic gastritis (CG) intestinal metaplasia (IM) and atrophy in the stomach. Aims and Methods: In a single-center observational pilot study, we correlated endoscopic findings with histology in selected patients. Results: Findings from 29 patients were included in the analysis. Six patients had macroscopically normal gastric mucosa at endoscopy, and this was confirmed histologically in 5 of them. At endoscopy, 15 patients had the presence of IM in the antrum predicted, and this was confirmed histologically in 11 (73%). In the corpus, we predicted the presence of IM in 14 patients, and this was confirmed in 11 (78%) at histology. Eleven patients had the endoscopic suspicion of atrophy in antrum, which was confirmed in 9 patients (82%). In total, 14 patients had endoscopic suspicion of atrophy in corpus mucosa at endoscopy, but only 10 were confirmed in histology (71%). The concordance of endoscopic classification and histology was 93% for antrum and 88% for corpus. The positive predictive value and negative predictive value for IM were 0.74 and 0.83 and for atrophy 0.63 and 0.97, respectively. Conclusions: LCI and BLI are helpful in characterization of mucosal changes in CG. The ability to rule out premalignant conditions by endoscopy only reflects the clinical use and harbors significant clinical implications. [ABSTRACT FROM AUTHOR]

While the primary risk factor for oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO) is gastro-oesophageal reflux, the infection with Helicobacter pylori (H. pylori) is the dominant risk factor for gastric cancer. Reduction of reflux by dietary measures and proton pump inhibitors has some merits in OAC prevention, and the chemopreventive effect of Aspirin and statins is being widely investigated; however, improved outcome in OAC occurs primarily as the result of secondary prevention. Early detection of neoplastic lesions in Barrett's metaplasia can be achieved by surveillance endoscopies. Novel endoscopic imaging modalities carry similar importance as the endoscopic treatment techniques as without detection of early lesions, therapy cannot be applied. Minimally invasive approaches are currently being investigated to identify patients with BO who are at particular risk of neoplastic progression. While dietary factors also play an important role in the prevention of gastric cancer and chemoprevention seems to be promising, the most beneficial effect has been shown for the eradication of H. pylori infection, which results in at least a one third reduction of gastric cancer risk. This effect can be further improved if the eradication takes place prior to the development of pre-neoplastic gastric conditions such as mucosal atrophy or intestinal metaplasia (IM). The definition of the "point of no return", after which eradication is less effective, is of high importance, although H. pylori eradication can still be beneficial even at more advance stages of mucosal changes. For this reason, patients with advanced atrophy and IM should undergo endoscopic surveillance in the same way as patients with BO. There is also need for development of non-invasive tests to identify patients at high risk of progression to gastric cancer to improve outcome of these surveillance approaches. [ABSTRACT FROM AUTHOR]

Background: Gut microbiota play an essential role in the pathogenesis of hepatic encephalopathy (HE). Treatment strategies are directed to modulate intestinal microbiota profiles and their function by the administration of the non-absorbable disaccharide lactulose and the non-absorbable antibiotic rifaximin, which are required for long terms, but little is known on their long-term effect on gut microbiota composition and function. Aim: To characterize the active bacterial assemblages in duodenum and faeces in patients with minimal HE (MHE) before, during and after long-term therapy with rifaximin. Methods: We analysed the microbiota composition in 5 patients with liver cirrhosis and MHE treated either with rifaximin 550 mg bid alone continuously for a period of 3 months or combined with lactulose 30–60 mL daily for 3 months. In addition to clinical assessments of HE, biopsies from duodenum and stool samples were analysed for their specific bacterial community applying NGS after RNA isolation before treatment, after 3 months of treatment and 3 months after the end of treatment. Results: All 5 patients had a significant improvement of their MHE. Bacterial communities were different and distinct in duodenal samples and faeces. No statistically significant changes were found in the bacterial community profile at the different time points. Conclusion: Rifaximin therapy with and without lactulose over a period of 3 months does not affect the bacterial community composition. The improvement of HE with rifaximin is lasting also after the end of treatment and therefore a prolonged effect on microbiota metabolic function is suggested. [ABSTRACT FROM AUTHOR]

Background: Prospective data on the optimal management of patients with pancreatic ductal adenocarcinoma (PDA) and isolated local manifestation (ILM) after surgery are lacking. Hence, no statements with respect to this entity have been released from most international guidelines including European Society for Medical Oncology, National Comprehensive Cancer Network, and American Society for Clinical Oncology. Methods: We report for the first time a case-series of 3 patients with PDA and ILM receiving combined systemic chemotherapy and CT-guided high-dose-rate interstitial brachytherapy (CT-HDRBT). Results: CT-HDRBT allowed in all patients with pronounced chemotherapy-induced side effects either a pause of cytostatic treatment or de-escalation to a “maintenance” therapy (dose reduction, interval prolongation, scheme modification with withdrawal of most toxic drugs). Conclusion: Combining CT-HDRBT to systemic chemotherapy in patients with PDA and ILM is feasible and safe. As for patients with PDA and ILM no standard of care exists, designing an appropriate randomized prospective trial for this highly selected group of patients is challenging. [ABSTRACT FROM AUTHOR]

Background: Activation of protease-activated receptor-2 (PAR2) is involved in the mucosal immune pathogenesis of gastroesophageal reflux disease (GERD) that is characterized by proinflammatory cytokines such as interleukin-8 (IL-8). PAR2 activation on epithelial cells induces epithelial IL-8 secretion and initiates mucosal inflammation. Methods: A human primary esophageal epithelial cell model was established to investigate the effects of repeated stimulation with weakly acidic solutions and subsequent PAR2 activation. After creating a monolayer, cells were incubated under weakly acidic conditions for 7 h followed by 17 h at pH 7.4. This short-term exposure was repeated once. After weakly acidic stimulation, PAR2 activation was achieved by a synthetic agonist at pH 7.4. Results: After repeated weakly acidic incubation, PAR2 transcript levels were 3.6-fold upregulated (p = 0.001) and IL-8 transcripts were 2.4-fold enhanced (p = 0.034) compared to nonstimulated controls, while IL-8 protein in the cell pellet and supernatant was not increased. Only the additional PAR2 activation upon pH stimulation led to increased IL-8 secretion into the supernatant. Conclusions: We propose a 2-step mechanism in which repeated weakly acidic exposure leads to the upregulation of epithelial PAR2 expression. The subsequent activation of upregulated PAR2 contributes to the initiation of mucosal inflammation, which underlies the important role of esophageal epithelium in GERD pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic esophagitis (EoE) presents with dysphagia, but data about motility patterns using high-resolution manometry (HRM) are rare. We aimed at evaluating esophageal motility patterns in EoE and their correlation to endoscopic and dysphagia scores. Methods: Twenty-six EoE patients and 23 controls were included after 4 weeks of treatment with proton pump inhibitors. Dysphagia and endoscopic scores were evaluated before performing HRM. EoE patients were classified to have fibrostenotic (FS) or inflammatory (IF) type. HRM analysis was performed according to the Chicago classification (CC) system. Results: According to the CC, the HRM findings in EoE and controls were normal in 11 (42%) and 20 (88.5%), p < 0.0001. Weak and failed peristaltic integrity was only seen in EoE patients (failed 1/2.7%, weak 7/26.9%, p = 0.004). Of the EoE patients, 17 had IF and 9 presented with FS type. HRM parameters showed no differences according to the EoE subtype. The endoscopic score in the FS subtype was significantly higher than in EoE with IF subtype (5.33 vs. 3.58, p = 0.001). No significant difference was seen in dysphagia scores in EoE subtypes. Discussion: HRM findings in EoE are often diagnostic, but they are non-specific and do not correlate with the severity of dysphagia or endoscopic appearance. The clinical impact of HRM in EoE needs further evaluation. [ABSTRACT FROM AUTHOR]

Background: Functional gastrointestinal disorders (FGIDs) are very common and affect populations worldwide. A majority of patients are affected by a variety of heterogenous gastrointestinal symptoms (GIS) related to the upper and lower digestive system with frequent overlap and mostly of mild to moderate degree. The herbal medicinal preparation STW 5 is documented as an effective therapeutic option for treating FGID. Studies Conducted in Summary: STW 5 has been in use for more than 50 years in clinical practice and proven to be effective and safe in the management of FGID. The high efficacy of STW 5 on symptoms clustered in functional dyspepsia (FD) and irritable bowel syndrome (IBS) as well as on individual abdominal symptoms is demonstrated in 5 controlled, randomized double-blind studies in FD and in one trial conducted in patients with IBS. In addition the beneficial therapeutic effect of STW 5 on FGD as well as safety issues have been reported in a series of non interventional studies conducted in several thousands of adult patients and including 980 children. An additional study has been performed addressing the question as to how quickly the therapeutic effect is obtained after STW 5 administration. Key Messages from These Studies: STW 5 is an effective phyto-medication for treating patients with FD and IBS. STW 5 acts beneficially on abdominal symptom clusters as well as on individual GIS in adults and children. The time to onset of action is rapid, well tolerated and safe. The repetitive use of STW 5 is an appropriate option in clinical practice for patients with FGID. [ABSTRACT FROM AUTHOR]

The author discusses the complexities involved of treating functional gastrointestinal disorders (FGID). He offers overview of the background and diagnosis of the disease, and its impact on the patient's everyday activities and quality of life. He also asserts the need for clinicians to conduct a thorough diagnosis and treatment of the disease to ensure effectiveness.

The discovery of Helicobacter pylori changed the traditional view of the stomach as a hostile organ to bacterial survival. H. pylori induces chronic gastritis, which has the potential to progress to severe complications such as peptic ulcer disease and gastric neoplasia. The development of modern nucleotide sequencing techniques and new biocomputational tools allow the possibility of studying the diversity and complexity of the microbiome in the whole gastrointestinal (GI) tract and overcome the limitations of culturing techniques. However, the differentiation of alive resident and transient microbes in the upper GI tract and their role in the pathogenesis of gastroduodenal diseases requires an analysis beyond the detection of bacterial genomic material alone. Metabolomic and transcriptomic analyses of the bacteria may add important insights into their interaction with the host. Currently, the interaction of H. pylori with other microbes in the stomach and duodenum and their role for health and disease is poorly understood. This review provides a concise overview on the current knowledge of H. pylori and other gastric microbiota in the relationship with gastroduodenal pathologies. [ABSTRACT FROM AUTHOR]

Gastric atrophy (GA) and intestinal metaplasia are defined preneoplastic conditions of the stomach, whereas Helicobacter pylori gastritis by itself represents a risk condition for gastric cancer (GC) development. After H. pylori eradication, an overall reduction of GC incidence has been shown. However, this effect is lost once H. pylori gastritis has evolved to severe GA. On the other hand, only up to 5% of patients with severe GA may develop intestinal-type GC, and therefore the so-called 'point of no return' may not be appropriate to define the condition of all patients carrying preneoplastic changes in the gastric mucosa. Patients with the highest risk for GC are those who have already had GC that was cured by endoscopic resection. Prospective trials on the effect of H. pylori eradication in this high-risk group of patients showed inconsistent results, probably because of the inclusion of patients with and without baseline severe GA. Severe fundic GA determined by means of histology or serology represents the condition with the highest risk for metachronous neoplastic lesions in the stomach. In the present review, we focus on the effects of H. pylori eradication in patients with severe atrophy in terms of GC prevention. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Infection with Helicobacter pylori is established as the major risk factor for gastric cancer development. Damage of the mucosal barrier due to H. pylori-induced inflammation enhances the carcinogenic effect of other risk factors such as salt intake or tobacco smoking. The genetic disposition of both the bacterial strain and the host can increase the potential towards gastric cancer formation. Genetic variance of the bacterial proteins CagA and VacA is associated with a higher gastric cancer risk, as are polymorphisms and epigenetic changes in host gene coding for interleukins (IL1β, IL8), transcription factors (CDX2, RUNX3) and DNA repair enzymes. Application of high-throughput assays for genome-wide assessment of either genetic structural variance or gene expression patterns may lead to a better understanding of the pathobiological background of these processes, including the underlying signaling pathways. Understanding of the stepwise alterations that take place in the transition from chronic atrophic gastritis, via metaplastic changes, to invasive neoplasia is vital to define the 'point of no return' before which eradication of H. pylori has the potential to prevent gastric cancer. Currently, eradication as preventive strategy is only recommended for high-incidence regions in Asia; large population studies with an adequate follow-up are required to demonstrate the effectiveness of such an approach in Western populations. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is defined as a chronic immune/antigen-mediated esophageal disease characterized by clinical symptoms of esophageal dysfunction and histologically by eosinophil-predominant infiltration of the esophagus mucosa. Treatment of EoE should therefore lead to improvement of clinical symptoms and a histological decrease of eosinophilic inflammation. Topical corticosteroids (tCS; fluticasone, budesonide) have been demonstrated to be effective in treating EoE and therefore represent first-line therapy. To date, there is no approved therapy in the world for EoE. This is the reason why EoE patients are treated with medication such as inhalers or aqueous nebulizer solutions, which have to be swallowed. After administration, patients are not allowed to eat or drink for 45 min in order for the esophagus to become well coated so that the topical anti-inflammatory effect is maximized. For adults there are different dose ranges: fluticasone propionate 440-880 μg/day twice daily, budesonide 2 mg/day divided dose for inducing remission over a period of 4 to 8 weeks. Since EoE is a chronic disease known to relapse after termination of medication, maintenance therapy seems to be valuable, but there is no evidence from controlled studies with long-term follow-up. In several randomized trials, both tCS have been able to show a good safety profile. Candida esophagitis and oral candidiasis present the most common side effects of topical steroid therapy. At the moment, no data about tCS and long-term safety in EoE are available. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: In areas with high clarithromycin resistance, bismuth quadruple therapy (BQT) is recommended instead of clarithromycin triple therapy (CTT) as the first-line treatment for Helicobacter pylori eradication. Methods: Randomized clinical trials (RCTs) comparing BQT to CTT were identified through electronic and manual searches. A meta-analysis was performed to compare the efficacy and tolerability of these two regimens as first-line treatments for H. pylori infection. The effect of antibiotic resistance on treatment efficacy was also analyzed. Results: Twelve RCTs were included. BQT achieved eradication in 77.6% of patients, whereas CTT achieved an eradication rate of 68.9% [risk difference (RD) = 0.06, 95% CI: -0.01/0.13]. A high heterogeneity among the trials was found (χ2 = 50.16, p < 0.00001; I2 = 78%). In the subgroup analysis for treatment duration, the 10-day BQT was more effective than the 7-day CTT (RD = 0.25, 95% CI: 0.18/0.32), whereas no differences were observed between CTT and BQT given for 7 or 10 days. There were no statistical differences in side effects and compliance between both therapies (RD = 0.92, 95% CI: 0.76/1.12, and RD = -0.03, 95% CI: -0.05/0.00, respectively). The effect of antibiotic resistance on eradication rates was reported in 4 of the 12 RCTs. Clarithromycin resistance significantly affected the efficacy of CTT (RD = 0.75, 95% CI: 0.63/0.87), whereas BQT efficacy was not affected by metronidazole resistance (RD = 0.09, 95% CI: -0.06/0.25). Conclusions: The 10-day BQT was more effective than the 7-day CTT as a first-line therapy for H. pylori infection, whereas BQT and CTT for 7 or 10 days yielded similar eradication rates. Compliance and side effect rates were similar for both therapies. BQT overcomes clarithromycin resistance and its efficacy is not affected by metronidazole resistance. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: The incidence of hepatocellular cancer (HCC) continues to rise in Europe with a shift of the primary cause towards alcoholic and non-alcoholic fatty liver disease. Metabolic factors like diabetes mellitus and overweight have been identified as significant risk factors for HCC development. Patients and Methods: A retrospective analysis in a large single-center cohort of 650 patients diagnosed with HCC was performed. Demographic characteristics, risk factors, tumor stage at diagnosis and survival were evaluated. Results: Among 650 patients (aged 17-87 years, with a male: female ratio of 4:1), 80.8% had underlying liver cirrhosis. Alcohol abuse was identified as the only risk factor for liver cirrhosis in 52.2% of patients. Viral infection with hepatitis C and hepatitis B was present in 13.7 and 3.6% of patients, respectively. 66.1% of patients with HCC were overweight with a body mass index exceeding 25, 25.5% even exceeding 30; 52% of patients had diabetes mellitus. Conclusion: Strategies aiming at prevention and surveillance of patients at risk to develop HCC in the future need to widen the focus from patients with chronic viral hepatitis and a history of alcohol abuse to patients with metabolic risk factors. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Gastric cancer is a heterogeneous disease with currently still unknown mechanisms of development. Besides genetic and epigenetic mechanisms, microRNAs (miRNAs) have recently been discovered as one of the crucial players in gastric carcinogenesis through posttranscriptional regulation of tumor suppressor and oncogenes. A substantial number of deregulated miRNAs have been revealed in gastric cancer and the biological significance of those miRNAs has been confirmed in multiple functional experiments. A growing number of studies suggest involvement of miRNAs in various steps of gastric carcinogenesis: from gastritis toward metastatic disease. Great biological stability of miRNAs opens novel fields in biomarker research with potential clinical implementation in screening, diagnosis, prediction of prognosis and therapeutic management. In this review, we provide the basic knowledge of miRNA biogenesis and discuss extensively the role of miRNAs in gastric carcinogenesis, including Helicobacter pylori-related miRNA alterations and potential translational clinical implementations. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Only a small proportion of patients infected with Helicobacter pylori develop gastric cancer during their lifetime. At the same time, this type of cancer remains an important cause of mortality globally. The current interventional strategies have not been successful in decreasing the global burden of the disease; therefore, biomarkers for the identification of the individuals at high risk as well as those in the early stage of the disease is of high importance. In addition, predicting the point of no return for the development of the malignancy is of particular interest; whether atrophy, intestinal or spasmolytic polypeptide-expressing metaplasia, or some of their subtypes correspond to this point, still needs to be answered. The current review addresses the place of 'old markers', in particular pepsinogen tests for the identification of increased risk conditions. More data in Caucasian populations are required before these tests can be recommended for routine screening. Several of the host genetic factors are related to the development of sporadic gastric cancer; still their importance is probably not so high as initially thought, and at this stage host genetic factors cannot be used to identify high-risk groups. The detection of specific microRNAs could become a potential field in marker development, and several other new approaches for marker identification are emerging. To achieve the goal, a screening marker has to be not only accurate, but also available and cost-effective in the target populations, many of which are from low-income countries. This has to be considered when developing a marker or set of markers offered for gastric cancer screening programs. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Currently, more than 14% of the world's population is pre-obese or obese. The percentage is even higher in developed countries. Obesity is an important risk factor for a vast number of nonmalignant and malignant digestive diseases. Some of the more important examples are cholelithiasis, nonalcoholic fatty liver disease, and gastroesophageal reflux disease on the one hand and esophageal adenocarcinoma, gastric cardia adenocarcinoma, pancreatic cancer, liver cancer, gallbladder cancer, and colorectal cancer on the other hand. Their epidemic trends as reported in recent studies are reviewed here. Knowledge of their dependencies on obesity will yield a deeper understanding which is necessary to improve prevention and treatment concepts of this epidemic. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Probiotic bacteria are live microorganisms which contribute health benefits to their host. The numerous mechanisms of the probiotic-acting microorganisms include the induction of expression of certain cytokines and increasing the secretion of IgA and mucin. They activate lymphocytes and macrophages and inhibit the adhesion and invasion of epithelial cells. Escherichia coli Nissle 1917 (Mutaflor) is one of the most investigated probiotic bacteria. While the number of reports discussing the underlying mechanisms of Mutaflor has increased rapidly in recent years, novel clinical studies are missing. Here we provide an overview of the mechanisms of action and clinical studies related to Mutaflor. While most of the studies had positive outcomes, there are also a few in which Mutaflor did not perform to its expectations. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The diagnosis of eosinophilic esophagitis (EoE) and differentiation from gastroesophageal reflux disease (GERD) is potentially challenging and is based upon clinical signs and endoscopic and histological features. In order to alert the endoscopist to consider EoE in patients with esophageal symptoms before performing esophagogastroduodenoscopy, we aimed to identify a set of clinical and laboratory markers for predicting EoE. Methods: The study included 43 patients with either EoE (n = 23) or GERD (n = 20). The diagnosis of EoE was based on International Consensus Criteria. Age, gender, weight loss, history of atopy, dysphagia, history of food impaction, proton pump inhibitor (PPI) refractory heartburn, odynophagia, peripheral eosinophilia, and serum IgE were analyzed. Each symptom or sign was classified as '0' (absent, normal) or '1' (present, elevated), individually analyzed and statistically evaluated among the two groups of patients. Logistic regression analysis was carried out to identify a clinically applicable marker constellation to differentiate EoE from GERD. Results: Univariate analysis identified 6 out of the 10 variables to be significant between both groups. A stepwise procedure of logistic regression led to a model in which 3 out of the initial 10 items were found to be relevant for differentiating GERD and EoE. Derived from this model, an optimal differentiation was achieved by using the following simplified equation: peripheral eosinophilia + history of food impaction + PPI refractory heartburn leading to a maximal value of 3 (1 + 1 + 1). Based on a cut-off value of ≥2, sensitivity and specificity for diagnosing EoE were 91 and 100%, respectively. Conclusion: A defined set of markers including two clinical features and one laboratory parameter is highly predictive of EoE and thus allows physicians to distinguish EoE from GERD even before upper gastrointestinal endoscopy is performed. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: There are few reports focusing on therapeutic small bowel endoscopy. The aim of this study was to analyze the results of therapeutic small bowel endoscopy in a large cohort of patients. Methods: A retrospective study of a prospectively collected database comprising all patients undergoing diagnostic and therapeutic small bowel endoscopy in three centers. Results: A total of 614 double-balloon enteroscopies were performed in 534 patients. The most common pathological findings were angiodysplasias and vascular lesions (n = 98, 18%), mucosal ulcers and erosions (n = 95, 17.8%), polyps and tumors (including patients with familiar polyposis syndrome such as Peutz-Jeghers syndrome, familiar adenomatous polyps syndrome, neurofibromatosis, adenocarcinoma, neuroendocrine tumors and gastrointestinal stromal tumors) (n = 52, 9.7%), and strictures (Crohn's disease, ischemia, tumors) (n = 12, 2.2%). The mean duration of therapeutic small bowel enteroscopy was 67 min (range 30-115) compared to 50 min (range 25-105) for diagnostic procedures (p < 0.05). A therapeutic small bowel endoscopy was performed in 121 patients (22%). Therapeutic procedures included argon plasma coagulation of vascular lesions (n = 73), polypectomy (n = 49), mucosectomy (n = 5), stricture dilation (n = 7), foreign body extraction (n = 7), injection of fibrin glue (n = 10), and clip placement (n = 5). There were a total of 5 complications (0.9%; paralytic ileus, n = 2, pancreatitis, n = 1, bleeding n = 2). No perforations or deaths occurred. Conclusion: Endoscopists performing double-balloon enteroscopy should be trained and prepared to provide therapeutic interventions for small bowel disorders including argon plasma coagulation, injection, hemoclipping, polypectomy, mucosectomy and foreign body extraction. Therapeutic small bowel endoscopy, albeit associated with complications in about 1% of cases, can be considered a relatively safe procedure. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Recent studies suggest an increased Helicobacter pylori prevalence in patients with various extradigestive inflammatory diseases. Similar to H. pylori infection, many respiratory diseases are characterized by chronic inflammation as well as increased immune response. Recent studies have evaluated the relation between various respiratory disorders and H. pylori infection. The aim of this systematic review was to scrutinize the relevant literature and the mechanisms that could underlie a role for H. pylori infection in respiratory diseases. Methods: Relevant literature regarding pathophysiological mechanisms and clinical epidemiology of H. pylori and different respiratory diseases has been systematically identified and analyzed by two independent reviewers according to a PubMed search for English language (until week 14, April 2010). Conclusions: At present, there is no definite proof of a causal relationship between H. pylori and respiratory diseases. Both H. pylori and various respiratory diseases are characterized by the release of proinflammatory cytokines and attraction of granulocytes as well as B- and T-cell-mediated response, though a pathophysiological association has not been proven. Neither the role of genetic predisposition of the host nor the presence of virulence factors nor the impact of H. pylori eradication have been studied in detail and definitely need further evaluation. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Aim: Sorafenib has become the treatment standard for patients with advanced hepatocellular carcinoma (HCC). It is not clear whether patients with advanced liver function impairment (Child B) and patients undergoing additional locoregional therapy may tolerate treatment with sorafenib and benefit. We aimed to evaluate the tolerability and efficiency of sorafenib in patients with advanced HCC and different stages of liver cirrhosis, and in combination with locoregional therapy. Methods: In 50 patients with advanced HCC treated with sorafenib tolerability and efficiency of the therapy with respect to stage of liver cirrhosis, existence of extrahepatic tumor spread, and additional locoregional therapy were evaluated. Results: Fifty patients with advanced HCC were treated with sorafenib, and 13 received additional locoregional therapy. Tolerability of the systemic treatment was moderate in all patients, with no significant differences between the subgroups, while the median survival was better in patients with Child A than Child B cirrhosis. Conclusion: Tolerability and toxicity of a systemic treatment with sorafenib are moderate in patients with liver cirrhosis in Child A or B. Prospective randomized studies are required to evaluate the efficacy and tolerability of combined systemic and locoregional treatment approaches in patients with advanced HCC. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The majority of gastric adenocarcinomas are related to chronic inflammation induced by Helicobacter pylori infection. For intestinal-type gastric cancer, a multistep process of mucosal alterations leading from gastritis via glandular atrophy, intestinal metaplasia and dysplasia to invasive carcinoma is well recognized. Ongoing clinical studies focus on a 'point of no return'. It is defined as a situation when certain alterations are no longer reversible by H. pylori eradication and progression to gastric cancer may continue. H. pylori affects the mucosal as well as the systemic immune response by secretion of cytokines and the recruitment of distinct inflammatory cells. The immune response is characterized by a balance between a Th1-dominated response and the recruitment of antigen-specific regulatory T cells that allow the bacteria to persist in human gastric mucosa. Besides immune-mediated effects, H. pylori induces cellular alterations as well as genetic alterations in genes that are essential for the epigenetic integrity and mucosal homeostasis. These genetic alterations during gastric cancer development are in focus of intensive research and should ultimately allow the identification of risk factors involved in gastric carcinogenesis. The detection of individuals at high risk for gastric cancer would help to design appropriate strategies for prevention and surveillance. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Symptoms of gastroesophageal reflux are widely prevalent. There is a continuum between subjects with mild reflux symptoms and those severely affected by gastroesophageal reflux disease (GERD). Both groups may at times access over-the-counter (OTC) therapies. For the purpose of this review, relevant papers, including national and international guidelines were reviewed and recommendations made for appropriate use of OTC proton pump inhibitor (PPI) therapy. Results: PPIs are the gold standard for treatment of reflux symptoms. OTC therapy with histamine2 receptor antagonists (H2RAs) also plays a role. For the majority affected by reflux symptoms, effective symptom control is the most important outcome, as only a subgroup requires investigations or interventions. However, patients with alarm features (i.e. troublesome dysphagia, weight loss, predominant upper abdominal pain) are not recommended for OTC therapy and need prompt medical referral. Frequent relapses or failure to adequately respond to OTC therapy are additional triggers for medical assessment. Conclusions: OTC treatment of typical reflux symptoms (acid regurgitation, heartburn) with antacids and H2RAs is now accepted as safe and results in short-term relief of symptoms. There is no evidence of additional risk with OTC PPIs compared to these existing OTC therapies and PPIs are significantly more efficacious. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is technically challenging or impossible in patients with complex postsurgical anatomy. The aim of this cohort study was to assess the technical success of ERCP with the single balloon enteroscope (SBE) in patients with Roux-en-Y anastomosis. Patients: Patients with Roux-en-Y anastomosis presenting with cholestasis undergoing ERCP with the SBE technique in a tertiary university hospital. Diagnostic success was defined as successful duct cannulation or securing the diagnosis and therapeutic success was defined as the ability to successfully accomplish endoscopic therapy. Results: ERCP using the SBE was performed on 17 occasions in 13 patients (5 F, 8 M, mean age 66.5 years, range 25–77) with Roux-en-Y anastomosis. Indications for ERCP were biliary obstruction with common bile duct stones and/or cholangitis in all patients. The diagnostic success was 61.5% and the therapeutic success was 53.8%. Therapeutic interventions included dilation of common bile duct stenosis with a balloon (n = 4), biliary stent insertion (n = 2), removal of bile duct stones (n = 2), stent retrieval (n = 2), papillectomy (n = 1), and sphincterotomy (n = 1). No major complications occurred. Conclusions: ERCP using the SBE is feasible in patients with altered postsurgical anatomy presenting with biliary problems permitting diagnostic and therapeutic interventions. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide with about 600,000 patients dying from the disease annually. In 70–90%, HCC develops on the background of chronic liver cirrhosis or inflammation. Risk factors and etiologies vary among geographical regions. In regions with a high incidence the majority of cases are related to HBV and HCV hepatitis. In developed countries, in addition to virus-related HCC, high consumption of alcohol as well as non-alcoholic fatty liver disease often in the context of metabolic syndromes are the prevalent causes. Improvement in clinical management of patients with liver cirrhosis and the control of related complications are the key for the rising incidence of HCC. This review gives an overview on epidemiological trends and risk factors and their mechanisms involved in the hepatocarcinogenesis. Knowledge of these factors will help to improve current concepts for prevention, screening and treatment of this disease. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: To identify changes of liver function after single-fraction irradiation or yttrium-90 radioembolization (90Y-RE) of hepatocellular carcinoma associated with liver cirrhosis on the basis of laboratory data. Methods and Materials: 24 patients with primary liver carcinoma and liver cirrhosis classified Child-Pugh A or B were treated either by image-guided high-dose-rate brachytherapy (HDR-BT) (12 patients) or by 90Y-RE (12 patients). The following laboratory parameters were assessed 1 day before and 3 days, 6 weeks and 3 months after the intervention: total bilirubin and γ-glutamyl transpeptidase (GGTP) as parameters of detoxification function, albumin and cholinesterase (ChE) as direct synthesis parameters, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AP) as indicators of liver tissue damage. Preinterventional values were taken as baseline, following values were calculated as percentage changes from the baseline value. Statistical analysis was performed using the Wilcoxon-matched pairs test, comparing postinterventional with preinterventional values. Differences were considered statistically significant with a p value <0.05. Results: In all patients the median bilirubin, ALT, AP and albumin values remained within normal limits at any time of follow-up. AST levels in the RE group and GGTP in both groups have been already elevated over a normal range before the intervention, and in both groups both parameters showed a slight increase after interventions. ChE activity was lowered already in the baseline values and showed a further decrease 3 days after BT as well as 3 days and 6 weeks after RE, with final reconstitution to baseline values. All liver function test parameters showed mild changes shortly after radiation therapy but floating laboratory values recovering within 12 weeks to baseline values. Radiation or RE-induced liver disease was recorded in no patient. Conclusions: Liver function parameters show only mild changes shortly after intervention with recovery within 6–12 weeks to baseline values. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Barrett’s esophagus (BE) is established as the primary precursor lesion of esophageal adenocarcinoma (EAC). The risk of esophageal cancer is 30–125 times greater compared to an age-matched population and survival rates are low, with only 15% of patients being alive 5 years after initial diagnosis. Therefore, surveillance strategies in BE are recommended to detect intraepithelial neoplasia and early carcinoma which in turn can be resected using endoscopic methods. Nevertheless, surveillance strategies have not had a major benefit in decreasing the incidence of EAC. Thus, attention should also be given to potential targets for prevention strategies that might arrest or delay the progression of BE to EAC. This article focuses on known and postulated targets for prevention of distal esophageal cancer. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux disease (GERD) is a common disease that has a significant impact on patients’ health-related quality of life. While proton pump inhibitors have transformed GERD therapy, effective management of this disease is still a challenge. This review consolidates data from the recently published Burning Questions and Burning Desires surveys to provide a foundation for improved primary care management of GERD. First, the surveys confirm the significant troublesome impact of GERD on patients’ health-related quality of life. Negative effects on sleeping and eating were identified as the leading causes for concern among such patients. Second, a lack of symptom control was identified among patients receiving physician-guided care for GERD, with many patients experiencing persistent symptoms. This was likely to be responsible for the third major finding of these surveys – the high rate of concomitant over-the-counter medication use among patients receiving prescription therapy. The surveys also uncovered a disconnect between patients and physicians in terms of GERD symptom severity, and perceptions of GERD and its treatment. Such findings outline the requirement for improved management of GERD, including the need to identify patients who may benefit from reassessment and more effective therapies. Patient-reported, questionnaire-based tools may aid physicians in this regard. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Nocturnal acid breakthrough (NAB) is defined as gastric pH below 4 over 60 consecutive minutes at night-time in subjects who take proton pump inhibitors twice daily. The link between NAB and gastroesophageal reflux (GER) episodes has not been investigated using combined multichannel intraluminal impedance and pH-metry (MII-pH). Aims and Methods: The aim was to investigate the relationship between NAB and GER by means of MII and gastroesophageal pH-metry. We reanalyzed MII-pH recordings obtained in patients on twice-daily proton pump inhibitors. Results: Overall 15 eligible recordings were reanalyzed in detail (7 males, 8 females; age 59 ± 10 years, range 36–68 years). NAB was detected in 7/15 (46%) recordings with one NAB in 4 subjects and two 2 NABs in 3 subjects. In 6 of the cases with NAB, reflux symptoms were reported at night, but in no case did these occur in association with NAB. Patients with NAB reported significantly more typical than atypical symptoms (77 times vs. 47 times), whereas patients without NAB reported fewer typical than atypical symptoms (48 times vs. 60; p = 0.011). Over the total 24-hour period, acid reflux was more frequent (9 ± 11 times) in patients with NAB than in patients without NAB (1 ± 0.5 times; p = 0.04). Weakly acid reflux also occurred more frequently (15 ± 9 times) in subjects with NAB than in subjects without NAB (6 ± 4 times; p = 0.02). Weakly alkaline reflux occurred in equal frequencies in subjects with and without NAB (2 ± 4, 0 ± 0.4, respectively). Esophageal acid exposure in the upright position was not different between subjects with NAB and subjects without NAB, but subjects with NAB presented a higher recumbent esophageal acid exposure than subjects without NAB (2.0 ± 2.4 vs. 0%, respectively). Conclusion: Esophageal acid exposure is not increased during NAB episodes. However, over a period of 24 h, patients with NAB presented with increased gastroesophageal reflux. Although NAB and GER are not strongly associated, symptoms of patients with and without NAB are different. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Gastroesophageal reflux disease (GERD) leads to endoscopic and histomorphological changes in the gastroesophageal (GE) mucosa. Aims: To evaluate the expression of the cytokines interleukin-1β (IL-1β) and interleukin-8 (IL-8) in the GE mucosa in GERD patients and controls and to correlate the cytokine expression with the histomorphological parameters. Methods: One hundred and fifteen patients, 48 with erosive reflux disease (ERD) and 41 with non-erosive reflux disease (NERD) with typical GERD-related symptoms, and 26 controls were included. Endoscopic and histological characterization of esophagitis was performed according to the Los Angeles and Ismeil-Beigi/Vieth criteria, respectively. Mucosal gene expression levels of IL-1β and IL-8 were analyzed by real-time RT-PCR. Results: ERD and NERD patients revealed significant higher levels of IL-1β and IL-8 transcript levels in the cardia and esophageal mucosa than controls. The esophageal mucosa revealed elevated IL-8 (2.5- and 8.7-fold) and IL-1β (4.1- and 7.8-fold) transcript levels in NERD and ERD, respectively. Histological analysis demonstrated a stepwise increase of dilatation of intercellular spaces and the degree of basal cell hyperplasia from controls, NERD towards ERD. Gene expression levels of both cytokines correlated with histology. Conclusions: ERD and NERD are associated with an induction of the proinflammatory cytokines IL-1β and IL-8 that correlates with histomorphological changes in esophageal mucosa. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Heartburn is known to be common during pregnancy, however validated data on gastroesophageal reflux disease (GERD) are missing. The aim of this survey was to study the prevalence of GERD, the frequency and severity of typical GERD symptoms, and their impact on quality of life and therapeutic management in advanced pregnancy. Methods: One hundred and thirty-five consecutive pregnant women in the third trimester were included in a prospective study using validated questionnaires: RDQ, QOLRAD and a self-administered questionnaire detailing sociodemographic factors. Results: The prevalence for GERD in this unselected population was 56.3%. Among symptoms regurgitation was the most frequent with 47.3%, whereas heartburn was graded as the most severe symptom. The impact of GERD on the QOL of the pregnant women was significant (p < 0.001). 22.9% of the GERD population required medication because of severe symptoms, often reported to be insufficient for symptoms relief. Conclusion: GERD is common in late pregnancy with an important negative impact on the QOL. GERD in advanced pregnancy deserves more attention and better therapeutic management. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Bleeding gastric varices (BGV) are a severe complication of portal hypertension. Although the obliteration of gastric varices using cyanoacrylate has been shown effective to eradicate gastric varices, there are still few data available on its effectiveness for acutely BGV, cyanoacrylate-related complications and follow-up. Aims: To report on the feasibility, efficacy and outcomes of N-buytl-2-cyanoacrylate sclerotherapy in patients with BGV. Methods: This is a retrospective cohort study of consecutive patients who were evaluated for BGV at University of Magdeburg Medical Center. Data abstracted for analysis from the prospectively collected database included patient’s demographics, etiology of gastric varices, Child-Pugh score, effectiveness of endoscopic treatment, clinical and endoscopic follow-up. Immediate hemostasis was defined as visible and clinical arrest of bleeding. The following were considered as potential complications of the procedure: aspiration, fever, worsening hemorrhage due to the sclerotherapy and systemic embolization of cyanoacrylate. Results: 33 patients (17 F, 16 M; mean age 54 years, range 18–81) with BGV (29 had active bleeding and 4 had stigmata of recent bleeding) underwent endoscopic injections of N-butyl-2-cyanoacrylate for hemostasis over a 5-year period. Mean follow-up: 9 months (range: 1 month to 5 years). Initial hemostasis was achieved in 88%. Treatment-related complications occurred in 5 (15.1%), the most common being deep ulcerations, which also resulted in recurrent bleeding. One patient presented with distal cyanoacrylate embolization. During long-term follow-up, 6 patients died, 5 as a consequence of the underlying liver disease and 1 as a consequence of complications due to systemic cyanoacrylate embolization. Conclusions: N-butyl-2-cyanoacrylate sclerotherapy is highly effective for the treatment of BGV, with rare complications occurring both acutely and in the long term. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A difficult polyp is any flat or raised colonic mucosal lesion that given its size, shape or location makes it difficult for the colonoscopist to remove. Although many ‘difficult polyps’ will be an easy target for the advanced endoscopist, polyps that are >15 mm, have a large pedicle, are flat and extended, are difficult to see or are located in the cecum or any angulated portion of the colon should be always considered difficult. Post-polypectomy complications are more common in the presence of difficult polyps. This review describes several useful tips and tricks to deal with such polyps. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Chronic gastritis and esophagitis are associated with changes in mucosal glycosylation patterns. Lectins represent a group of specific carbohydrate binding proteins that can be used as sensitive tools for the analysis of glycosylation patterns. Aim: To investigate the binding patterns of lectins Ulex europaeus agglutinin-I (UEA-I), Dolichos biflorus agglutinin (DBA), Helix pomatia agglutinin (HPA) and peanut agglutinin (PNA) at the gastroesophageal junction in nonerosive (NERD), erosive reflux disease (ERD) and Barrett’s esophagus (BE). Methods: One hundred and twenty-two patients (female n = 53; male n = 69; controls n = 28; NERD n = 36; ERD n = 24 and BE n = 34) were included in this study. The binding patterns of lectins were examined immunohistochemically at the squamocolumnar junction, in squamous epithelium and columnar-lined epithelium. Staining patterns of lectins were semiquantitatively evaluated using an immunohistochemical score and the data were analyzed using non-parametric tests. Results: BE, as compared to the controls, was associated with specific lectin-binding patterns: lectin binding of UEA-I and DBA were significantly decreased at the superficial (p = 0.012; p = 0.00036, respectively) and at the deep glandular body (p = 0.045; p = 0.055, respectively). Comparisons of lectin-staining scores between GERD and BE revealed significant increases of UEA-I in both the stratum superficiale (p = 0.0155) and stratum spinosum (p = 0.0048) of SE in patients with BE. Notable, this change was specific for patients with BE, while no difference was observed between patients with GERD and controls. Conclusion: We found two major types of lectin-binding patterns. First, lectin-binding characteristics associated with GERD in general, and second, lectin-binding patterns which were specific for BE. Lectin UEA-I-binding proteins were specifically increased in the squamous epithelium of patients with BE. Thus, UEA-I may serve as a potential marker for BE, especially in patients with short segment BE. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In the developed world, most patients with gastroesophageal reflux disease (GERD) do not exhibit erosions when examined by standard white light endoscopy. Despite the high prevalence of such non-erosive reflux disease (NERD), relatively little is known of its underlying pathophysiology, hence there is no clear guide to clinical management. To establish areas of agreement or uncertainty in NERD, an international meeting was held in Vevey, Switzerland, in late 2007. The goal was to document current thinking in the areas of clinical presentation, assessment of clinical outcome, pathobiological mechanisms, and define optimal clinical strategies to diagnose and manage NERD. After extensive debates, the modified Delphi technique was utilized to reach a consensus on 85 specific statements. In addition, it was proposed that NERD be defined as ‘a subcategory of GERD characterised by troublesome reflux-related symptoms in the absence of esophageal mucosal erosions/breaks at conventional endoscopy and without recent acid suppressive therapy’. Evidence in support of this diagnosis may include responsiveness to acid suppression therapy, abnormal reflux monitoring or the identification of specific novel endoscopic findings. Defining the current state of knowledge in NERD should help improve the elucidation and management of this condition in the future. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are highly prevalent in the general population as does gastroesophageal reflux disease (GERD). Therefore, it is expected that these conditions may frequently overlap. Objective: We aimed at evaluating the presence ofFD and IBS symptoms in patients with erosive (ERD), non-erosive reflux disease (NERD) and Barrett’s esophagus (BE). Patients and Methods: 71 patients presenting at the reflux disease outpatient clinic were prospectively included in this study. 33 patients had NERD, 25 ERD and 13 BE according to the Montreal classification. All patients with ERD and NERD had typical reflux symptoms, as assessed by a validated GERD questionnaire (RDQ). The diagnosis of functional dyspepsia and IBS symptoms was assessed according to the Rome III criteria. Results: IBS symptoms (bloating, abdominal pain, constipation and diarrhea) were slightly more prevalent in NERD (54.6, 63.6, 21.20, 24.2%, respectively) than in ERD (48.0, 44.0, 12.0, 20.0%, respectively) and in BE (53.9, 23.10, 15,4, 23.1%, respectively), but none of these differences reached statistical significance. NERD patients had more FD symptoms than patients with ERD or BE, but again this difference did not reach statistical significance. Conclusion: Our data show that IBS and FD are common in the entire spectrum of GERD. The presence of these disorders might explain why many patients with GERD are deemed as treatment failures if they have no complete symptom relief with proton pump inhibitors. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]